Organosilicon biomedical devices with polymerizable glycosaminoglycans

Abstract

An organosilicon biomedical device is disclosed. The organosilicon biomedical device comprises a polymeric product of a mixture forming the biomedical device, the mixture containing (a) one or more grafted glycosaminoglycan polymers comprising glycosaminoglycans having a polymer backbone and one or more side chains, the one or more side chains comprising olefinically unsaturated reactive residues grafted onto the polymer backbone, and (b) one or more monomers forming the organosilicon biomedical device comprising at least one hydrogen-donating group.

Description

[0001] Priority requirements

[0002] This application claims priority to U.S. Provisional Patent Application Serial No. 63 / 622,213, filed January 18, 2024, entitled “Silicone Biomedical Device with Polymerizable Glycosaminoglycans”, the contents of which are incorporated herein by reference in their entirety. Background Technology

[0003] Ideally, contact lenses should be as comfortable as possible for the wearer. Contact lens manufacturers constantly strive to improve lens comfort. However, many contact lens wearers still experience dryness or eye irritation throughout the day, especially towards the end. At any point, an insufficiently moistened lens will cause noticeable discomfort for the wearer. While moistening drops can be used to alleviate this discomfort as needed, it would be ideal if it didn't occur in the first place.

[0004] Contact lenses made from silicone-containing materials have been studied for many years. These materials can generally be divided into two main categories: hydrogels and non-hydrogels. Non-hydrogels do not absorb a significant amount of water, while hydrogels can absorb and maintain water in equilibrium. Hydrogels typically have a water content greater than about five percent by weight, and more commonly between about 10 percent by weight and about 80 percent by weight. Regardless of their water content, both non-hydrogel and hydrogel silicone contact lenses tend to have a relatively hydrophobic, non-wetting surface.

[0005] Glycosaminoglycans (GAGs) are a group of polysaccharides composed of repeating disaccharide units. Due to their high polarity and hydrophilicity, they can be found in many systems of the human and animal bodies. For example, GAGs are found on the surface of cells and in the extracellular matrix of animal organisms such as skin, cartilage, and lungs.

[0006] Each GAG (glucuronic acid glycosides) possesses a chemical structure comprising a repeating basic disaccharide structure composed of uronic acid and hexosamine, optionally sulfated to varying degrees. GAGs are primarily classified into three groups based on their constituent disaccharides: the first group consists of compounds composed of chondroitin sulfate or dermatan sulfate; the second group consists of compounds composed of heparan sulfate or heparin; and the third group consists of hyaluronic acid compounds. For example, compounds composed of chondroitin sulfate or dermatan sulfate consist of the disaccharide: uronic acid (glucuronic acid or iduronic acid) (β1→3) N-acetylgalactosamine; compounds composed of heparan sulfate or heparin consist of the disaccharide: uronic acid (glucuronic acid or iduronic acid) (β1→4) N-acetylglucosamine; and hyaluronic acid consists of the disaccharide: glucuronic acid (β1→3) N-acetylglucosamine. Furthermore, the structures are highly diverse due to modifications involving sulfation.

[0007] These GAGs are referred to as biomaterials, possessing physicochemical properties derived from characteristic viscoelasticity and biological properties mediated by interactions with various functional proteins, depending on molecular size and sulfation patterns. Summary of the Invention

[0008] According to one illustrative embodiment, the organosilicon biomedical device comprises a polymeric product forming a mixture of the organosilicon biomedical device, the mixture comprising:

[0009] (a) One or more grafted glycosaminoglycan polymers comprising a polymer backbone and one or more side chains, the side chains comprising olefinically unsaturated reactive residues grafted onto the polymer backbone; and

[0010] (b) One or more monomers that form organosilicon biomedical devices, wherein the monomer contains at least one hydrogen-donating group.

[0011] According to another illustrative embodiment, a method for fabricating an organosilicon biomedical device includes:

[0012] (a) A mixture for forming an organosilicon biomedical device, the mixture comprising (i) one or more grafted glycosaminoglycan polymers having a polymer backbone and one or more side chains, the one or more side chains comprising olefinically unsaturated reactive residues grafted onto the polymer backbone, and (ii) one or more monomers for forming an organosilicon biomedical device comprising at least one hydrogen-donating group.

[0013] (b) subjecting a mixture to polymerization conditions to provide a polymerizable organosilicon biomedical device; and

[0014] (c) Hydrate the polymerized organosilicon biomedical device. Detailed Implementation

[0015] The various non-limiting illustrative embodiments described herein relate to organosilicon biomedical devices obtained from one or more grafted glycosaminoglycan polymers comprising a polymer backbone and one or more side chains, the side chains comprising olefinically unsaturated reactive residues grafted onto the polymer backbone, the one or more grafted glycosaminoglycan polymers being polymerized with one or more monomers comprising at least one hydrogen-donating group that form organosilicon biomedical devices.

[0016] 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 factors that must be carefully balanced to provide usable contact lenses. For example, since the cornea obtains its oxygen supply through contact with the atmosphere, good oxygen permeability is an important characteristic of some contact lens materials. Wetting is also important because if the lens is not adequately wetted, it cannot remain lubricated and therefore cannot be worn comfortably in the eye. Therefore, the best contact lenses will have at least excellent oxygen permeability and excellent tear film wettability.

[0017] While lenses with high water content are softer, smoother, and more comfortable to wear, they may lack one or more properties that provide comfortable and safe contact lens wear. Hydrogels represent a class of ideal materials for many biomedical applications, including contact lenses and intraocular lenses. A hydrogel is a hydrated, cross-linked polymeric system that contains water in equilibrium. Silicone hydrogels are a class of known hydrogels and are characterized by containing silanoxy groups. One advantage of silicone hydrogels over non-silicone hydrogels is that silicone hydrogels generally have higher oxygen permeability due to the presence of silanoxy-containing monomers. For example, the currently available non-silicone hydrogels shown in Table 1 below have the following water content and oxygen permeability (Dk).

[0018] Table 1

[0019]

[0020] Furthermore, a problem associated with glycosaminoglycans is that they are known to be incompatible with organosilicon monomers when combined in water.

[0021] The organosilicon biomedical devices described in the exemplary embodiments herein overcome the aforementioned disadvantages and advantageously contain high water content and are optically transparent. For example, the organosilicon biomedical devices described herein overcome the aforementioned disadvantages by being formed from a polymeric product of a mixture forming an organosilicon biomedical device, the mixture comprising one or more grafted glycosaminoglycan polymers containing glycosaminoglycans having a polymer backbone and one or more side chains containing olefinically unsaturated reactive residues grafted onto the polymer backbone, and one or more monomers forming an organosilicon biomedical device containing at least one hydrogen-donating group, which are optically transparent compared to the organosilicon biomedical device obtained from the polymeric product of the mixture, the mixture comprising one or more grafted glycosaminoglycan polymers containing glycosaminoglycans having a polymer backbone and one or more side chains containing olefinically unsaturated reactive residues grafted onto the polymer backbone, and one or more monomers forming an organosilicon biomedical device without hydrogen-donating groups.

[0022] Therefore, the organosilicon biomedical devices disclosed herein will exhibit suitable physical and chemical properties, such as oxygen permeability, lubricity, and wettability, for long-term contact with the body. Furthermore, the grafted glycosaminoglycan polymers used to fabricate the organosilicon biomedical devices are considered to advantageously exhibit less enzymatic, oxidative, and thermal degradation, and thus possess greater stability, longer shelf life, and the rigidity of the desired conformation.

[0023] The silicone 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 tissues or fluids (and preferably in or on human tissues or fluids). Representative examples of biomedical devices include, but are not limited to, artificial ureters, diaphragms, intrauterine devices, heart valves, catheters, denture pads, prosthetic devices, and ophthalmic lens applications, wherein the lens is intended for direct placement inside or on the eye, such as, for example, intraocular devices and contact lenses. In one illustrative embodiment, the silicone biomedical device is a silicone ophthalmic device, particularly a silicone contact lens, and more particularly a silicone contact lens made of silicone hydrogel.

[0024] As used herein, the term "ophthalmic device" refers to a device that resides in or on the eye. These devices can provide optical correction, wound care, drug delivery, diagnostic functionality, or cosmetic enhancement or effect, or a combination of these properties. Useful ophthalmic devices include, but are not limited to, ophthalmic lenses such as soft contact lenses, such as soft hydrogel lenses, soft non-hydrogel lenses, etc., rigid contact lenses, such as rigid gas-permeable lens materials, etc., intraocular lenses, overlapping lenses, ocular inserts, optical inserts, etc. As will be understood by those skilled in the art, a lens is considered "soft" if it can fold back on itself without breaking.

[0025] In one non-limiting illustrative embodiment, the organosilicon biomedical device disclosed herein will be a high-water-content organosilicon biomedical device. For example, in one illustrative embodiment, the high-water-content organosilicon biomedical device will have an equilibrium water content of at least about 70% by weight. In another illustrative embodiment, the high-water-content organosilicon biomedical device will have an equilibrium water content of about 70% by weight to about 90% by weight. In another illustrative embodiment, the high-water-content organosilicon biomedical device will have an equilibrium water content of at least about 75% by weight. In yet another illustrative embodiment, the high-water-content organosilicon biomedical device will have an equilibrium water content of about 75% by weight to about 90% by weight.

[0026] In a non-limiting illustrative embodiment, the organosilicon biomedical device disclosed herein is formed from a polymeric product of a mixture forming an organosilicon biomedical device, the mixture comprising: (a) one or more grafted glycosaminoglycan polymers having a polymer backbone and one or more side chains comprising olefinically unsaturated reactive residues grafted onto the polymer backbone, and (b) one or more monomers forming an organosilicon biomedical device comprising at least one hydrogen-donating group.

[0027] Glycosaminoglycans (GAGs) are molecules having many alternating subunits. Typically, GAGs are represented by the formula ABABAB, where A is a uronic acid and B is an amino sugar that may or may not be O- or N-sulfated, where the A and B units can be heterogeneous in terms of epimeric content or sulfation. Any natural or synthetic polymer containing a uronic acid can be used. Other GAGs are sulfated with different sugars. Many different types of GAGs with generally understood structures exist, such as, for example, chondroitin sulfate (e.g., 4- and 6-chondroitin sulfate), heparin, heparan sulfate, proheparin, dermatan, dermatan sulfate, hyaluronic acid or its salts (e.g., sodium or potassium hyaluronic acid), keratin sulfate, and other disaccharides such as sucrose, lactulose, lactose, maltose, trehalose, cellobiose, mannobiose, and chitobiose. Glycosaminoglycans are available from Sigma and many other biochemical suppliers such as HTL Biotechnology (France). For example, in one illustrative embodiment, the GAG ​​is hyaluronic acid or its salt. In another illustrative embodiment, GAG is chondroitin sulfate.

[0028] GAG possesses reactive functional groups in its polymer backbone, allowing for the grafting of olefinically unsaturated reactive residues onto the backbone. Suitable reactive functional groups in the polymer backbone include carboxylic acid ester groups, hydroxyl groups, organosilicon groups, sulfur-containing groups (such as thiols), and other groups including polymerizable functional groups (such as allyl, vinyl, acrylate, methacrylate, methacrylamide, etc.). Additionally, the sugar ring of GAG can open to form aldehydes for further functionalization. The GAGs used in this paper can have a weight-average molecular weight in the range of about 10,000 Daltons (Da) to about 3,000,000 Da, with the lower limit being about 10,000 Da, about 20,000 Da, about 30,000 Da, about 40,000 Da, about 50,000 Da, about 60,000 Da, about 70,000 Da, about 80,000 Da, about 90,000 Da, or about 100,000 Da, and the upper limit being about 200,000 Da, about 300,000 Da, about 400,000 Da, about 500,000 Da, about 600,000 Da, about 700,000 Da, about 800,000 Da, about 900,000 Da, about 1,000,000 Da, or up to about 2,800,000 Da. Da, where any lower bound can be combined with any upper bound.

[0029] Hyaluronic acid is a well-known, naturally occurring, water-soluble, biodegradable polymer composed of two alternating sugars (D-glucuronic acid and N-acetylglucosamine) linked by alternating β-(1,4) and β-(1,3) glycosidic bonds. Hyaluronic acid is a non-sulfated GAG. The polymer is hydrophilic and exhibits high viscosity in aqueous solutions with relatively low solute concentrations. It is typically found naturally as sodium hyaluronate. However, other salts, such as potassium hyaluronate, are contemplated herein. Methods for preparing commercially available hyalurones and their salts are well known. Hyalurones are available from Seikagaku Company, Clear Solutions Biotech, Inc., Pharmacia Inc., Sigma Inc., and many other suppliers such as HTL Biotechnology, Contipro, and Bloomage Biotechnology Corporation. Hyaluronic acid has repeating units in a structure represented by the following formula:

[0030] .

[0031] Therefore, the repeating unit in hyaluronic acid can be as follows:

[0032]

[0033] Typically, hyaluronic acid or its salts can have about 2 to about 1,500,000 disaccharide units. In one embodiment, hyaluronic acid or a salt thereof may have a weight-average molecular weight in the range of about 10,000 Daltons (Da) to about 3,000,000 Da, wherein the lower limit is about 10,000 Da, about 20,000 Da, about 30,000 Da, about 40,000 Da, about 50,000 Da, about 60,000 Da, about 70,000 Da, about 80,000 Da, about 90,000 Da, or about 100,000 Da, and the upper limit is about 200,000 Da, about 300,000 Da, about 400,000 Da, about 500,000 Da, about 600,000 Da, about 700,000 Da, about 800,000 Da, about 900,000 Da, about 1,000,000 Da, or about up to 2,800,000 Da. Da, where any lower bound can be combined with any upper bound.

[0034] Chondroitin sulfate is a linear sulfated polysaccharide composed of repeating β-D-glucuronic acid (GlcA) and N-acetyl-β-D-galactosamine (GalNAc) units arranged sequentially via GlcA-β(1,3)-GalNAc-β(1,4) glycosidic bonds. In one embodiment, chondroitin sulfate has one or more repeating units with a structure represented by the following formula:

[0035]

[0036] In one illustrative embodiment, chondroitin sulfate has repeating units of a structure represented by the following formula:

[0037] .

[0038] Typically, chondroitin sulfate can have approximately 2 to approximately 1,500,000 repeating units. In one embodiment, chondroitin sulfate may have a weight-average molecular weight in the range of about 10,000 Da to about 3,000,000 Da, wherein the lower limit is about 5,000 Da, 10,000 Da, about 20,000 Da, about 30,000 Da, about 40,000 Da, about 50,000 Da, about 60,000 Da, about 70,000 Da, about 80,000 Da, about 90,000 Da, or about 100,000 Da, and the upper limit is about 200,000 Da, about 300,000 Da, about 400,000 Da, about 500,000 Da, about 600,000 Da, about 700,000 Da, about 800,000 Da, about 900,000 Da, about 1,000,000 Da, or about 3,000,000 Da. Da, where any lower bound can be combined with any upper bound.

[0039] In one illustrative embodiment, dermatin sulfate has repeating units of a structure represented by the following formula:

[0040] .

[0041] Typically, dermatin sulfate can have approximately 2 to approximately 1,500,000 repeating units. In one embodiment, chondroitin sulfate may have a weight-average molecular weight in the range of about 10,000 Da to about 3,000,000 Da, wherein the lower limit is about 5,000 Da, 10,000 Da, about 20,000 Da, about 30,000 Da, about 40,000 Da, about 50,000 Da, about 60,000 Da, about 70,000 Da, about 80,000 Da, about 90,000 Da, or about 100,000 Da, and the upper limit is about 200,000 Da, about 300,000 Da, about 400,000 Da, about 500,000 Da, about 600,000 Da, about 700,000 Da, about 800,000 Da, about 900,000 Da, about 1,000,000 Da, or about 3,000,000 Da. Da, where any lower bound can be combined with any upper bound.

[0042] In one illustrative embodiment, heparin and heparan sulfate have repeating units of a structure represented by the following formula:

[0043] .

[0044] Typically, heparin and heparin sulfate can have approximately 2 to approximately 1,500,000 repeating units. In one embodiment, chondroitin sulfate may have a weight-average molecular weight in the range of about 10,000 Da to about 3,000,000 Da, wherein the lower limit is about 5,000 Da, 10,000 Da, about 20,000 Da, about 30,000 Da, about 40,000 Da, about 50,000 Da, about 60,000 Da, about 70,000 Da, about 80,000 Da, about 90,000 Da, or about 100,000 Da, and the upper limit is about 200,000 Da, about 300,000 Da, about 400,000 Da, about 500,000 Da, about 600,000 Da, about 700,000 Da, about 800,000 Da, about 900,000 Da, about 1,000,000 Da, or about 3,000,000 Da. Da, where any lower bound can be combined with any upper bound.

[0045] In one illustrative embodiment, keratin sulfate has repeating units of a structure represented by the following formula:

[0046] .

[0047] Typically, keratin sulfate can have approximately 2 to approximately 1,500,000 repeating units. In one embodiment, chondroitin sulfate may have a weight-average molecular weight in the range of about 10,000 Da to about 3,000,000 Da, wherein the lower limit is about 5,000 Da, 10,000 Da, about 20,000 Da, about 30,000 Da, about 40,000 Da, about 50,000 Da, about 60,000 Da, about 70,000 Da, about 80,000 Da, about 90,000 Da, or about 100,000 Da, and the upper limit is about 200,000 Da, about 300,000 Da, about 400,000 Da, about 500,000 Da, about 600,000 Da, about 700,000 Da, about 800,000 Da, about 900,000 Da, about 1,000,000 Da, or about 3,000,000 Da. Da, where any lower bound can be combined with any upper bound.

[0048] The olefinically unsaturated reactive residues on the reactive functional groups grafted into the polymer backbone of the GAG ​​are derived from monomers containing olefinically unsaturated reactive groups and at least one reactive end group. In one embodiment, the olefinically unsaturated reactive residue is a methacrylate-containing residue. The at least one reactive end group contains a reactive functional group capable of being grafted onto a complementary reactive functional group in the GAG ​​polymer backbone. Suitable reactive functional groups of monomers containing olefinically unsaturated reactive groups and at least one reactive end group include, for example, halogens, acid anhydrides, amino groups, aldehyde groups, carboxylic acid groups, alcohol groups, thiols, hydrazides, glycidyl groups, etc. In one non-limiting illustrative embodiment, the olefinically unsaturated reactive residues can be derived from, for example, methacrylic anhydride, methacryloyl chloride, 2-isocyanoethyl methacrylate, 3-(trimethoxysilyl)propyl methacrylate, 3-(chlorodimethylsilyl)propyl methacrylate, glycidyl methacrylate, methacrylhydrazine, aminoethyl methacrylate, vinyl chloroformate, allyl chloride, acryloyl chloride, and acrylic anhydride. However, the foregoing list is merely exemplary, and other monomers for forming olefinically unsaturated reactive residues on the polymer backbone of GAGs are contemplated herein.

[0049] The grafted glycosaminoglycan polymers disclosed herein can be obtained by grafting at least one reactive end group of one or more monomers containing an olefinically unsaturated reactive group onto a complementary reactive functional group in the polymer backbone of a glycosaminoglycan. For example, in one illustrative embodiment, an anhydride group of one or more monomers containing an olefinically unsaturated reactive group can be grafted onto a carboxylic acid group in the polymer backbone of a glycosaminoglycan. In a non-limiting illustrative embodiment, the graft polymerization reaction can achieve a grafting degree in the range of about 0.5% to about 50%, i.e., the number of side chains in the polymer backbone containing olefinically unsaturated reactive residues. In another illustrative embodiment, the grafting degree can be in the range of about 2% to about 30%. In another illustrative embodiment, the grafting degree can be in the range of about 5% to about 20%. In yet another illustrative embodiment, the grafting degree can be in the range of about 5% to about 15%. In yet another illustrative embodiment, the grafting degree can be in the range of about 5% to about 10%.

[0050] Typically, GAG and monomers containing olefinically unsaturated reactive groups and at least one reactive end group can be added sequentially or simultaneously to the reaction mixture. The reaction can be carried out at a suitable temperature for a period of time to maximize the yield of the product, i.e., the olefinically unsaturated reactive residues grafted onto the polymer backbone of the glycosaminoglycan. For example, in one illustrative embodiment, suitable temperature and time period include a temperature in the range of about 10°C to about 40°C and a time period in the range of about 4 hours to about 48 hours. In another illustrative embodiment, suitable temperature and time period include a temperature in the range of about 15°C to about 25°C and a time period in the range of about 8 hours to about 24 hours.

[0051] In one illustrative embodiment, glycosaminoglycans may be added to the reaction mixture in an amount ranging from about 0.5% to about 5% by weight, based on the total weight of the reaction mixture. In another illustrative embodiment, glycosaminoglycans may be added to the reaction mixture in an amount ranging from about 1% to about 3% by weight, based on the total weight of the reaction mixture.

[0052] In one illustrative embodiment, a monomer comprising an olefinically unsaturated reactive group and at least one reactive end group may be added to the reaction mixture in an amount ranging from about 0.1 wt% to about 5 wt%, based on the total weight of the reaction mixture. In another illustrative embodiment, a monomer comprising an olefinically unsaturated reactive group and at least one reactive end group may be added to the reaction mixture in an amount ranging from about 0.5 wt% to about 2 wt%, based on the total weight of the reaction mixture.

[0053] In one non-limiting illustrative embodiment, the olefinically unsaturated reactive residue is a methacrylate-containing residue derived from a methacrylate-containing monomer as described above, and the degree of methacrylate can range from about 0.5% to about 50%. In another illustrative embodiment, the degree of methacrylate can range from about 2% to about 30%. In yet another illustrative embodiment, the degree of methacrylate can range from about 5% to about 15%.

[0054] The resulting grafted glycosaminoglycan polymer can be a random copolymer or a block copolymer. In one illustrative embodiment, the grafted glycosaminoglycan polymer disclosed herein may have a weight-average molecular weight in the range of about 20,000 Da to about 6,000,000 Da, wherein the lower limit is about 20,000 Da, about 30,000 Da, about 40,000 Da, about 50,000 Da, about 60,000 Da, about 70,000 Da, about 80,000 Da, about 90,000 Da, or about 100,000 Da, and the upper limit is about 100,000 Da, about 150,000 Da, about 200,000 Da, about 300,000 Da, about 400,000 Da, about 500,000 Da, about 600,000 Da, about 700,000 Da, about 800,000 Da, about 900,000 Da, or about 1,000,000 Da. Da, approximately 2,000,000 Da, approximately 3,000,000 Da, approximately 4,000,000 Da, approximately 5,000,000 Da, or up to approximately 6,000,000 Da, where any lower limit can be combined with any upper limit.

[0055] In a non-limiting illustrative embodiment, as may be combined with one or more of the foregoing paragraphs, the grafted glycosaminoglycan polymer may be present in the mixture forming the organosilicon biomedical device in an amount ranging from about 0.1 wt% to about 1.0 wt% based on the total weight of the mixture forming the organosilicon biomedical device. In another embodiment, the grafted glycosaminoglycan polymer may be present in the mixture forming the organosilicon biomedical device in an amount ranging from about 0.25 wt% to about 0.5 wt% based on the total weight of the mixture forming the organosilicon biomedical device.

[0056] In a non-limiting illustrative embodiment, as may be combined with one or more of the foregoing paragraphs, the mixtures described herein for forming organosilicon biomedical devices further comprise one or more monomers for forming organosilicon biomedical devices, which contain at least one hydrogen-donating group.

[0057] As used herein, the term "hydrogen-donating group" refers to a hydrogen atom capable of forming a reversible (intermolecular or intramolecular) physical interaction with another atom or group. In one illustrative embodiment, suitable hydrogen-donating groups include, for example, hydroxyl (OH) groups, amino (NH, NH2) groups, SH groups, and carboxyl groups, such as COOH and COSH. In one illustrative embodiment, the hydrogen-donating group is OH or NH. However, these are merely illustrative, and any hydrogen-donating group is contemplated herein.

[0058] Monomers forming organosilicon biomedical devices that include at least one hydrogen-donating group will have a suitable silicon-to-hydrogen-donating group ratio to provide the required compatibility. In a non-limiting illustrative embodiment, as may be combined with one or more of the foregoing paragraphs, monomers forming organosilicon biomedical devices that include at least one hydrogen-donating group may have a silicon-to-hydrogen-donating group ratio of about 1:1 to about 9:1. In a non-limiting illustrative embodiment, monomers forming organosilicon biomedical devices that include at least one hydrogen-donating group may have a silicon-to-hydrogen-donating group ratio of about 1:1 to about 4:1. In a non-limiting illustrative embodiment, monomers forming organosilicon biomedical devices that include at least one hydrogen-donating group may have a silicon-to-hydrogen-donating group ratio of about 1:1 to about 1:5.

[0059] In addition to at least one hydrogen-donating group, the monomer forming the organosilicon biomedical device will also contain at least one olefinically unsaturated reactive group for polymerization with the olefinically unsaturated reactive group of the grafted glycosaminoglycan polymer. olefinically unsaturated reactive end groups are well known to those skilled in the art. Suitable olefinically unsaturated polymerizable groups include, for example, (meth)acrylates, vinyl carbonates, urethane O-vinyl esters, urethane N-vinyl esters, styrene-containing groups, and (meth)acrylamide. As used herein, the term "(meth)" indicates an optional methyl substituent. Thus, terms such as "(meth)acrylate" indicate methacrylates or acrylates, and "(meth)acrylamide" indicates methacrylamide or acrylamide. In one embodiment, the olefinically unsaturated reactive end group can be represented by the following general formula:

[0060]

[0061] Where R 1 It is independently hydrogen, fluorine, or methyl; R 2 It can be hydrogen, fluorine, an alkyl radical having 1 to 6 carbon atoms, or -CO-YR. 3 Free radicals, where Y is -O-, -S-, or -NH-, and R 3 It is a divalent alkylene radical having 1 to about 10 carbon atoms.

[0062] In another illustrative embodiment, the (meth)acrylic group of the heterocyclic (meth)acrylic acid monomer is a reactive end group containing a (meth)acrylate. Suitable reactive end groups containing (meth)acrylates can be those represented by the following structures:

[0063]

[0064] Where R is hydrogen or methyl; L is O, NR 1 Or S, where R 1 It is H, CH3, CH2CH3, or CH(CH3)2; m is an integer from 0 to 4, and R* is a linking group or bond. Suitable linking groups include, for example, any divalent hydrocarbon radical or moiety, such as independently linear or branched, substituted or unsubstituted C1-C6 alkyl groups, or -OR 2 Group, wherein R 2 It is an alkyl group with 1 to 6 carbon atoms.

[0065] In some embodiments, the monomers forming organosilicon biomedical devices are hydroxyl-functionalized monomers. In a non-limiting illustrative embodiment, a class of hydroxyl-functionalized monomers forming organosilicon biomedical devices includes monomers of formulas I and II:

[0066] (I)

[0067] (II)

[0068] in:

[0069] n is an integer between 3 and 35 or between 4 and 25;

[0070] R 1 Is it hydrogen or C? 1-6 alkyl;

[0071] R 2 R 3 and R 4 C is either substituted or unsubstituted independently. 1-6 Alkyl, C 1-6 Three Cs 1-6 Alkylsiloxy, phenyl, naphthyl, substituted phenyl, or substituted naphthyl, wherein the alkyl substituent includes, for example, C 1-6 alkoxycarbonyl, C 1-6 Alkyl, C 1-6 Alkoxy, amide, halogen, hydroxyl, carboxyl, C 1-6 Alkyl carbonyl and formyl groups, wherein aromatic substituents include, for example, C 1-6 alkoxycarbonyl, C1-6 Alkyl, C 1-6 Alkoxy, amide, halogen, hydroxyl, carboxyl, C 1-6 Alkyl carbonyl and formyl groups;

[0072] R 5 It is a hydroxyl group, an alkyl group containing one or more hydroxyl groups; or (CH2(CR) 9 R 10 ) y O) x )-R 11 Where y is 1 to 5 or 1 to 3, and x is an integer from 1 to 100, preferably 2 to 90, and more preferably 10 to 25; R 9 -R 11 The alkyl group is independently selected from H, alkyl groups having up to 10 carbon atoms, and alkyl groups having up to 10 carbon atoms substituted with at least one polar functional group;

[0073] R 6 It is a divalent group containing up to 20 carbon atoms;

[0074] R 7 It is a free radical reactive group;

[0075] R 8 It is a divalent or trivalent group containing up to 20 carbon atoms.

[0076] In one illustrative embodiment, for a monofunctional hydroxyl-functionalized organosilicon monomer, R 1 It is hydrogen, and R 2 R 3 and R 4 It is C 1-6 Alkyl and tri-C 1-6 Alkylsiloxy groups, such as methyl and trimethylsiloxy groups. In one illustrative embodiment, for multifunctionality (bifunctional or higher functionality), R 1 -R 4 Independently contains olefinically unsaturated polymerizable groups, such as acrylates, styrene, C... 1-6 Alkyl acrylates, acrylamide, C 1-6 Alkylacrylamide, N-vinyllactam, N-vinylamide, C 2-12 alkenyl, C 2-12 alkenylphenyl, C 2-12 alkenylnaphthyl or C 2-6 alkenylphenyl C 1-6 alkyl.

[0077] In some embodiments, R5 is a hydroxyl group, -CH2OH, -CH2CHOHCH2OH, or -(OCH2CH2). xOH, of which the hydroxyl group is the most preferred.

[0078] In some implementation schemes, R 6 Is it a divalent or unsubstituted C? 1-6 Alkyl, substituted or unsubstituted C 1-6 Alkoxy, substituted or unsubstituted C 1-6 Alkoxy C 1-6 Alkyl, substituted or unsubstituted phenylene, substituted or unsubstituted naphthalene, substituted or unsubstituted C 1-12 cycloalkyl, substituted or unsubstituted C 1-6 Alkoxycarbonyl, substituted or unsubstituted amide, substituted or unsubstituted carboxyl, substituted or unsubstituted C 1-6 Alkyl carbonyl, carbonyl and substituted or unsubstituted C 1-6 alkoxy groups, wherein the substituents include, for example, C 1-6 alkoxycarbonyl, C 1-6 Alkyl, C 1-6 Alkoxy, amide, halogen, hydroxyl, carboxyl, C 1-6 Alkyl carbonyl and formyl groups. In some embodiments, R 6 It is a divalent methyl (methylene).

[0079] In some implementation schemes, R 7 Contains free radical reactive groups, such as acrylate, styrene, vinyl, vinyl ether, itaconic acid ester group, C 1-6 Alkyl acrylates, acrylamide, C 1-6 Alkylacrylamide, N-vinyllactam, N-vinylamide, C 2-12 alkenyl, C 2-12 alkenylphenyl, C 2-12 alkenylnaphthyl or C 2-6 alkenylphenyl C 1-6 Alkyl or cationic reactive groups, such as vinyl ethers or epoxide groups. In some embodiments, R 7 It contains methacrylates.

[0080] In some implementation schemes, R 8 Is it a divalent or unsubstituted C? 1-6 Alkyl, substituted or unsubstituted C 1-6 Alkoxy, substituted or unsubstituted C 1-6 Alkoxy C 1-6 Alkyl, substituted or unsubstituted phenylene, substituted or unsubstituted naphthalene, substituted or unsubstituted C 1-12 cycloalkyl, substituted or unsubstituted C 1-6 Alkoxycarbonyl, substituted or unsubstituted amide, substituted or unsubstituted carboxyl, substituted or unsubstituted C 1-6Alkyl carbonyl, carbonyl, substituted or unsubstituted C 1-6 alkoxy groups, wherein the substituents include, for example, C 1-6 alkoxycarbonyl, C 1-6 Alkyl, C 1-6 Alkoxy, amide, halogen, hydroxyl, carboxyl, C 1-6 Alkyl carbonyl and formyl groups. In some embodiments, R 8 It is C 1-6 Alkyloxy C 1-6 alkyl.

[0081] Representative examples of monomers for forming organosilicon biomedical devices with hydroxyl functionalization of Formula I include 2-acrylic acid, 2-methyl-2-hydroxy-3-[3-[1,3,3,3-tetramethyl-1-[(trimethylsilyl)oxy]disiloxyl]propoxy]propyl ester (also known as ((3-methacryloyloxy-2-hydroxypropoxy)propylbis(trimethylsiloxy)methylsilane), which has the following structure:

[0082]

[0083] The above-described compound ((3-methacryloyloxy-2-hydroxypropoxy)propylbis(trimethylsiloxy)methylsilane) can be formed from an epoxide, which can produce an 80:20 mixture of the compound shown above and (2-methacryloyloxy-3-hydroxypropoxy)propylbis(trimethylsiloxy)methylsilane. In some embodiments, a certain amount of primary hydroxyl groups is present, such as greater than about 10% by weight or at least about 20% by weight.

[0084] In some embodiments, suitable hydroxyl-functionalized monomers for forming organosilicon biomedical devices include (3-methacryloyloxy-2-hydroxypropoxy)propyltris(trimethylsilyloxy)silane, which has the following structure:

[0085] ,

[0086] Bis-3-methacryloyloxy-2-hydroxypropoxypropyl polydimethylsiloxane, which has the following structure:

[0087] ,

[0088] 3-Methacryloxy-2-(2-hydroxyethoxy)propoxy)propylbis(trimethylsiloxy)methylsilane has the following structure:

[0089] ,as well as

[0090] N,N,N′,N′-Tetra(3-methacryloyloxy-2-hydroxypropyl)-α,ω-bis-3-aminopropyl-polydimethylsiloxane.

[0091] In some embodiments, suitable hydroxyl-functionalized monomers for forming silicone biomedical devices include the reaction product of glycidyl methacrylate and amino-functionalized polydimethylsiloxane. Other suitable hydroxyl-functionalized monomers for forming silicone biomedical devices include those disclosed in columns 6, 7, and 8 of U.S. Patent No. 5,994,488, and monomers disclosed in U.S. Patent Nos. 4,235,985, 4,259,467, 4,260,725, 4,261,875, 4,649,184, 4,139,513, 4,139,692, US 2002 / 0016383, U.S. Patent Nos. 4,139,513, and 4,139,692. All such and any other patents or applications cited herein are incorporated herein by reference.

[0092] In some embodiments, suitable hydroxyl-functionalized monomers for forming organosilicon biomedical devices include those having the following structures:

[0093]

[0094] Where n = 1-50, and R independently contains H or a polymerizable unsaturated group, wherein at least one R contains a polymerizable group, and at least one R, and preferably three to eight Rs, contains H.

[0095] In some embodiments, another class of hydroxyl-functionalized monomers for forming organosilicon biomedical devices includes monomers of formula III:

[0096] (III)

[0097] Where R 1 R 5 R 7 and R 8 Having the aforementioned meaning, where R 5 At least one of them is an OH group. In some embodiments, R 5 At least two of them are OH groups. In some embodiments, each R 1 It's hydrogen, each R 5 It is an OH group, R 7 It is a methacrylate end group, and R 8 It is C 1-6Alkyl groups. A representative example of a monomer of Formula III is 3-(trihydroxysilyl)propyl methacrylate. Monomers of Formula III can be prepared by methods known in the art, and as described in the examples.

[0098] In some embodiments, the monomer forming the organosilicon biomedical device is an amino-functionalized monomer forming the organosilicon biomedical device. In a non-limiting illustrative embodiment, a class of amino-functionalized monomers forming organosilicon biomedical devices includes monomers of formula IV:

[0099] (IV)

[0100] Where R 1 R 2 R 3 and R 4 Independently, it is hydrogen, alkyl group, haloalkyl group, cycloalkyl group, heterocycloalkyl group, alkenyl group, haloalkenyl group, aryl group, and heteroaryl group; R 5 R 6 and R 7 It is independently a straight-chain or branched alkyl group; x is 1 to 6; and y is 3 to 7.

[0101] In some embodiments, the R of the monofunctional organosilicon monomer represented by the structure of formula IV 1 R 2 R 3 and R 4 Independently, it is hydrogen, C1 to C 12 alkyl groups, C1 to C 12 Haloalkyl groups, C3 to C 12 Cycloalkyl groups, C3 to C 12 Heterocyclic alkyl groups, C2 to C 12 alkenyl groups, C2 to C 12 Haloalkenyl groups, C6 to C 12 Aromatic groups and C6 to C 12 heteroaromatic groups; R 5 R 6 and R 7 Independently, they are either straight or branched, C1 to C2. 12 Alkyl group; x is 1 to 6; and y is 3 to 7.

[0102] In some embodiments, the R of the monofunctional organosilicon monomer represented by the structure of formula IV 1 R 2 R 3 and R 4 Independently, it is hydrogen, C1 to C6 alkyl group; R 5 R 6 and R7 Independently, it is a straight-chain or branched C1 to C6 alkyl group; x is 1 to 6; and y is 3 to 7.

[0103] In some embodiments, the R of the monofunctional organosilicon monomer represented by the structure of formula IV 1 R 2 R 3 and R 4 Independently, it is a C1 to C3 alkyl group; R 5 and R 6 Independently, it is a C1 to C3 alkyl group; R 7 It is a straight-chain or branched C3 to C6 alkyl group; x is 2 to 4; and y is 3 to 7.

[0104] Representative examples of alkyl groups used for purposes herein include, by way of example, straight-chain or branched alkyl chain groups containing one to about 30 carbon atoms, one to about 12 carbon atoms, or one to about 6 carbon atoms, the remainder of the molecule having or not having unsaturation, such as methyl, ethyl, n-propyl, 1-methylethyl (isopropyl), n-butyl, n-pentyl, methylene, ethylene, etc., optionally containing one or more heteroatoms (e.g., O and N) or one or more halogen atoms (e.g., fluorine, chlorine, bromine, and iodine) to form a haloalkyl group.

[0105] Representative examples of cycloalkyl groups used for the purposes of this document include, by way of example, substituted or unsubstituted non-aromatic monocyclic or polycyclic systems having about 3 to about 30 carbon atoms, or 3 to about 12 carbon atoms, or 3 to about 6 carbon atoms, such as, for example, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, perhydronaphthyl, adamantyl and norbornel groups, bridging cyclic groups, or spirobicyclic groups, such as spiro-(4,4)-non-2-yl, etc., optionally containing one or more heteroatoms, such as O and N, to form a heterocyclic alkyl group.

[0106] Representative examples of cycloalkyl groups used for the purposes of this document include, by way of example, groups containing a substituted or unsubstituted cyclic ring having about 4 to about 30 carbon atoms or 3 to about 6 carbon atoms directly attached to an alkyl group, which is then attached to the main structure of the monomer at any carbon of the alkyl group to produce a stable structure, such as, for example, cyclopropylmethyl, cyclobutylethyl, cyclopentylethyl, etc., wherein the cyclic ring may optionally contain one or more heteroatoms, such as O and N, to form a heterocyclic alkyl group.

[0107] Representative examples of cycloalkenyl groups used for the purposes of this document include, by way of example, groups containing substituted or unsubstituted cyclic rings having about 3 to about 30 carbon atoms or 3 to about 6 carbon atoms having at least one carbon-carbon double bond, such as, for example, cyclopropenyl, cyclobutenyl, cyclopentenyl, etc., wherein the cyclic ring may optionally contain one or more heteroatoms, such as O and N, to form a heterocyclic alkenyl group.

[0108] Representative examples of aryl groups used for the purposes of this document include, by way of example, substituted or unsubstituted monoaromatic or polyaromatic groups containing about 6 to about 30 carbon atoms or about 6 to about 12 carbon atoms, such as, for example, phenyl, naphthyl, tetrahydronaphthyl, indenyl, biphenyl, etc., optionally containing one or more heteroatoms, such as O and N, to form a heteroaryl group.

[0109] In one illustrative embodiment, the monofunctional organosilicon monomer represented by the structure of Formula IV is commercially available from sources such as ShinEtsu or can be prepared by methods within the scope of those skilled in the art. For example, in one illustrative embodiment, the monofunctional organosilicon monomer represented by the structure of Formula IV can be prepared according to the following reaction scheme I.

[0110] Option I

[0111]

[0112] In a non-limiting illustrative embodiment, as may be combined with one or more of the foregoing paragraphs, the monomers forming the organosilicon biomedical device may be present in the mixture forming the organosilicon biomedical device in an amount ranging from about 1 wt% to about 30 wt%, based on the total weight of the mixture forming the organosilicon biomedical device. In another embodiment, the monomers forming the organosilicon biomedical device may be present in the mixture forming the organosilicon biomedical device in an amount ranging from about 1 wt% to about 15 wt%, based on the total weight of the mixture forming the organosilicon biomedical device.

[0113] In non-limiting illustrative embodiments, the mixtures described herein for forming organosilicon biomedical devices may also contain one or more hydrophilic monomers, as can be combined with one or more of the foregoing paragraphs. Suitable one or more hydrophilic monomers include, for example, unsaturated carboxylic acids, acrylamides, vinyl lactams, poly(alkoxy(meth)acrylates), hydroxyl-containing (meth)acrylates, hydrophilic ethylene carbonates, hydrophilic urethanes, hydrophilic oxazolones, and poly(olefin glycol) functionalized with polymerizable groups, as well as mixtures thereof. Representative examples of unsaturated carboxylic acids include methacrylic acid, acrylic acid, and mixtures thereof. Representative examples of amides include alkylamides, such as N,N-dimethylacrylamide, N,N-dimethylmethacrylamide, and mixtures thereof. Representative examples of cyclic lactams include N-vinyl-2-pyrrolidone, N-vinylcaprolactam, N-vinyl-2-piperidinone, and mixtures thereof. Representative examples of hydroxyl-containing (meth)acrylates include hydroxyethyl 2-methacrylate, glyceryl methacrylate, and mixtures thereof. Representative examples of functionalized poly(olefin glycols) include poly(diethylene glycol) with different chain lengths containing monomethacrylate or dimethacrylate end caps. In one embodiment, the poly(olefin glycol) polymer contains at least two olefin glycol monomer units. Further examples are the hydrophilic ethylene carbonate or urethane monomers disclosed in U.S. Patent No. 5,070,215, and the hydrophilic oxazolone monomer disclosed in U.S. Patent No. 4,910,277. Other suitable hydrophilic monomers will be apparent to those skilled in the art. Mixtures of the aforementioned hydrophilic monomers can also be used in the monomer mixtures described herein.

[0114] In a non-limiting illustrative embodiment, as may be combined with one or more of the foregoing paragraphs, one or more hydrophilic monomers may be present in the mixture forming the organosilicon biomedical device in an amount ranging from about 30% to about 90% by weight, based on the total weight of the mixture forming the organosilicon biomedical device. In another illustrative embodiment, one or more hydrophilic monomers may be present in the mixture forming the organosilicon biomedical device in an amount ranging from about 45% to about 75% by weight, based on the total weight of the mixture forming the organosilicon biomedical device. In yet another illustrative embodiment, one or more hydrophilic monomers may be present in the mixture forming the organosilicon biomedical device in an amount ranging from greater than or equal to about 50% to about 75% by weight, based on the total weight of the mixture forming the organosilicon biomedical device.

[0115] In a non-limiting illustrative embodiment, the mixture forming the organosilicon biomedical device may further comprise one or more hydrophobic monomers, as can be combined with one or more of the foregoing paragraphs. Suitable hydrophobic monomers include olefinically unsaturated hydrophobic monomers, such as, for example, hydrophobic monomers containing (meth)acrylates, hydrophobic monomers containing N-alkyl (meth)acrylamide, hydrophobic monomers containing alkyl vinyl carbonates, hydrophobic monomers containing alkyl vinyl carbamates, hydrophobic monomers containing fluoroalkyl (meth)acrylates, hydrophobic monomers containing N-fluoroalkyl (meth)acrylamide, hydrophobic monomers containing N-fluoroalkyl vinyl carbonates, hydrophobic monomers containing N-fluoroalkyl vinyl carbamates, hydrophobic monomers containing organosilicon (meth)acrylates, hydrophobic monomers containing (meth)acrylamide, hydrophobic monomers containing vinyl carbonates, hydrophobic monomers containing vinyl carbamates, hydrophobic monomers containing styrene, hydrophobic monomers containing polyoxypropylene (meth)acrylates and the like, and mixtures thereof.

[0116] In a non-limiting illustrative embodiment, the one or more hydrophobic monomers can be represented by the structure of formula V:

[0117] (V)

[0118] Where R 1 It is methyl or hydrogen; R 2 It is -O- or -NH-; R 3 and R 4 Independently, it is a divalent group selected from the group consisting of: -CH2-, -CHOH-, and -CHR. 6 -;R 5 and R 6 Independently, it is a branched C3-C8 alkyl group; R 7 It is hydrogen or -OH; n is an integer of at least 1, and m and p are independently integers of 0 or at least 1, provided that the sum of m, p and n is 2, 3, 4 or 5.

[0119] Representative examples of one or more hydrophobic monomers represented by the structure of Formula V include, but are not limited to, 4-tert-butyl-2-hydroxycyclohexyl methacrylate (TBE); 4-tert-butyl-2-hydroxycyclopentyl methacrylate; 4-tert-butyl-2-hydroxycyclohexylmethacrylamide (TBA); 6-isopentyl-3-hydroxycyclohexyl methacrylate; 2-isohexyl-5-hydroxycyclopentylmethacrylamide, 4-tert-butylcyclohexyl methacrylate, isobornyl methacrylate, adamantyl methacrylate, n-butyl methacrylate, n-hexyl methacrylate, lauryl methacrylate, benzyl methacrylate, etc. In one embodiment, one or more hydrophobic monomers comprise compounds of Formula V, wherein R 3It is -CH2-, m is 1 or 2, p is 0, and the sum of m and n is 3 or 4.

[0120] In a non-limiting illustrative embodiment, as may be combined with one or more of the foregoing paragraphs, one or more hydrophobic monomers may be present in the mixture forming the organosilicon biomedical device in an amount ranging from about 0.5 wt% to about 25 wt%, based on the total weight of the mixture forming the organosilicon biomedical device. In another illustrative embodiment, one or more hydrophobic monomers will be present in the mixture forming the organosilicon biomedical device in an amount ranging from about 1 wt% to about 10 wt%, based on the total weight of the mixture forming the organosilicon biomedical device.

[0121] In non-limiting illustrative embodiments, mixtures forming organosilicon biomedical devices may further comprise one or more crosslinking agents, as can be combined with one or more of the agents mentioned in the foregoing paragraphs. Crosslinking agents suitable for use herein are known in the art. In illustrative embodiments, one or more crosslinking agents are bifunctional or polyfunctional crosslinking agents comprising two or more reactive functional groups. In one embodiment, one or more crosslinking agents have at least two polymerizable functional groups. Representative examples of crosslinking agents include divinylbenzene, allyl methacrylate, ethylene glycol dimethacrylate, tetraethylene glycol dimethacrylate, 1,4-butanediol diglycidyl ether, polyethylene glycol dimethacrylate, vinyl carbonate derivatives of ethylene glycol dimethacrylate, and methacryloyloxyethyl vinyl carbonate. However, other crosslinking agents are contemplated, and the foregoing list is merely exemplary.

[0122] In a non-limiting illustrative embodiment, as may be combined with one or more of the preceding paragraphs, one or more crosslinking agents are used in the mixture forming the organosilicon biomedical device in an amount less than or equal to about 5% by weight, and typically less than or equal to about 2% by weight, for example, about 0.1% by weight to about 5% by weight or about 0.1% by weight to about 2% by weight, based on the total weight of the mixture forming the organosilicon biomedical device.

[0123] In non-limiting illustrative embodiments, mixtures forming organosilicon biomedical devices, as can be combined with one or more of the foregoing paragraphs, may also contain one or more wetting agents. In one embodiment, suitable one or more wetting agents include, for example, poly(vinyl alcohol) (PVA), poly(N-vinylpyrrolidone) (PVP), polymers containing carboxylic acid functional groups, such as polymers containing poly(acrylic acid) (PAA), the aforementioned copolymers, etc. Another class of suitable wetting agents includes non-polymeric wetting agents. Representative examples of such wetting agents include glycerol, propylene glycol and other non-polymeric glycols and glycols.

[0124] In a non-limiting illustrative embodiment, as may be combined with one or more of the foregoing paragraphs, one or more wetting agents may be present in the mixture forming the organosilicon biomedical device in an amount ranging from about 0% to about 10% by weight, based on the total weight of the mixture forming the organosilicon biomedical device. In another embodiment, one or more wetting agents may be present in the mixture forming the organosilicon biomedical device in an amount ranging from about 0.1% to about 10% by weight, based on the total weight of the mixture forming the organosilicon biomedical device. In yet another embodiment, one or more wetting agents may be present in the mixture forming the organosilicon biomedical device in an amount ranging from about 0.5% to about 5% by weight, based on the total weight of the mixture forming the organosilicon biomedical device.

[0125] In a non-limiting illustrative embodiment, the mixture forming the organosilicon biomedical device may also contain one or more surfactants, such as end-functionalized surfactants, as can be combined with one or more of the foregoing paragraphs. Suitable end-functionalized surfactants include, for example, one or more end-functionalized polyethers. The useful polyether to be end-functionalized comprises one or more chain or polymeric components having one or more (-OR-) repeating units, wherein R is an alkylene or aromatic group having 2 to about 6 carbon atoms. The polyether can be derived from block copolymers formed from ethylene oxide (EO) and propylene oxide (PO) components in different ratios. Such polyethers and their respective component segments may include different attached hydrophobic and hydrophilic chemical functional groups and segments.

[0126] A representative example of a suitable polyether that can be terminally functionalized is poloxamer block copolymers. A specific class of poloxamer block copolymers are those available under the trademark Pluronic (BASF Wyandotte Corp., Wyandotte, .M.). Poloxamers include Pluronics and reverse Pluronics. Pluronics are a series of ABA block copolymers consisting of poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) blocks, typically as shown in Formula VI:

[0127] HO(C2H4O) a (C3H6O) b (C2H4O) a H(VI)

[0128] Where a is independently at least 1, and b is at least 1.

[0129] Reverse Pluronics are a series of BAB block copolymers composed of poly(propylene oxide)-poly(ethylene oxide)-poly(propylene oxide) blocks, typically as shown in Formula VII:

[0130] HO(C3H6O) b (C2H4O) a (C3H6O) b H(VII)

[0131] Where a is at least 1, and b is independently at least 1. The poly(ethylene oxide) (PEO) blocks are hydrophilic, while the poly(propylene oxide) (PPO) blocks are hydrophobic. Poloxamers in each series have different proportions of PEO and PPO, which ultimately determine the hydrophilic-lipophilic balance (HLB) of the material. That is, changing the HLB value is based on changing the 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.

[0132] Poloxamer and reverse poloxamer have terminal hydroxyl groups that can be terminally functionalized. Examples of terminally functionalized poloxamers discussed below are poloxamer dimethacrylates (e.g., Pluronic) disclosed in U.S. Patent Application Publication No. 2003 / 0044468. ® F127 dimethacrylate). Other examples include glycidyl-terminated copolymers of polyethylene glycol and polypropylene glycol disclosed in U.S. Patent No. 6,517,933.

[0133] Another example of a suitable polyether that can be terminally functionalized is poloxamine block copolymers. While poloxamers and reverse poloxamers are considered bifunctional molecules (based on terminal hydroxyl groups), poloxamines exist in a tetrafunctional form, meaning the molecule is a tetrafunctional block copolymer with primary hydroxyl groups at the ends and linked by a central diamine. A specific class of poloxamine block copolymers is those available under the trademark Tetronic (BASF). Poloxamines include Tetronic and reverse Tetronics. Poloxamine has the general structure of the following formula VIII:

[0134] (VIII),

[0135] Where a is independently at least 1, and b is independently at least 1.

[0136] Poloxamer and / or poloxamine are functionalized to provide the desired reactivity at the ends of the molecule. The functional groups can be modified and determined based on the intended use of the functionalized PEO and PPO-containing block copolymer. That is, the PEO and PPO-containing block copolymer is reacted to provide terminal functional groups complementary to the monomer mixture intended to form the device. The term "block copolymer" as used herein should be understood to mean that poloxamer and / or poloxamine have two or more blocks in their polymer backbone.

[0137] Typically, the choice of functional end groups depends on the functional groups of the reactive molecules in the mixture. For example, if the reactive molecule contains a carboxylic acid group, glycidyl methacrylate can provide a methacrylate end group. If the reactive molecule contains a hydroxyl or amino functional group, ethyl methacrylate isocyanate or (meth)acryloyl chloride can provide a methacrylate end group, and vinyl chloroformate can provide a vinyl end group. A variety of suitable combinations of alkenyl unsaturated end groups and reactive molecules will be apparent to those skilled in the art. For example, the functional group can include a moiety selected from amines, hydrazides, acylhydrazides, thiols (nucleophiles), carboxylic acids, carboxylic acid esters (including imide esters), orthoesters, carbonates, isocyanates, isothiocyanates, aldehydes, ketones, thioketones, alkenyl groups, acrylates, methacrylates, acrylamides, sulfones, maleimides, disulfides, iodine, epoxy, sulfonates, thiosulfonates, silanes, alkoxysilanes, halosilanes, and phosphoramides. More specific examples of these groups include succinimide esters or carbonates, imidazole esters or carbonates, benzotriazole esters or carbonates, p-nitrophenyl carbonates, vinyl sulfones, chloroethyl sulfones, vinylpyridines, pyridyl disulfides, iodoacetamides, glyoxal, diketones, methanesulfonates, toluenesulfonates, and trifluoroethyl sulfonates. Other activated carboxylic acid derivatives are also included, as well as hydrates or protected derivatives of any of the foregoing moieties (e.g., aldehyde hydrates, hemiacetals, acetals, ketone hydrates, hemiketals, ketals, thioketals, thioacetals). Preferred electrophilic groups include succinimide carbonates, succinimide esters, maleimides, benzotriazole carbonates, glycidyl ethers, imidazole esters, p-nitrophenyl carbonates, acrylates, trifluoroethyl sulfonates, aldehydes, and o-pyridyl disulfides.

[0138] Representative examples of the reaction sequence in which block copolymers containing PEO and PPO can be terminally functionalized are provided below.

[0139]

[0140] This document also provides some exemplary, but non-limiting, reaction examples for providing functionalized ends to block copolymers containing PEO and PPO. It should be understood that those skilled in the art will be able to identify other reaction methods without extensive experimentation. It should also be understood that any particular block copolymer molecule shown is merely one chain length of a polydisperse population of the reference material.

[0141] In one illustrative embodiment, the mixture forming the silicone biomedical device comprises one or more block copolymers containing PEO and PPO. An example of such a copolymer that can be used in monomer mixtures is Pluronic. ® F127, a type of [(polyethylene oxide)] 99 -(polypropylene oxide) 66 -(polyethylene oxide) 99 Block copolymers of [ ]. The terminal hydroxyl groups of the copolymer are functionalized to allow the copolymer to react with other monomers that form ophthalmic devices. Another example includes Pluronic 407 dimethacrylate having the following structure:

[0142] .

[0143] In one illustrative embodiment, the terminally functionalized surfactant is selected from the group consisting of: poloxamer having at least one terminal functionalization, trans-poloxamer having at least one terminal functionalization, poloxamine having at least one terminal functionalization, trans-poloxamine having at least one terminal functionalization, and mixtures thereof.

[0144] In a non-limiting illustrative embodiment, as may be combined with one or more of the foregoing paragraphs, the surfactant may be present in the mixture forming the organosilicon biomedical device in an amount ranging from about 0.01 wt% to about 20 wt%, based on the total weight of the mixture forming the organosilicon biomedical device. In another illustrative embodiment, the surfactant may be present in the mixture forming the organosilicon biomedical device in an amount ranging from about 1 wt% to about 10 wt%, based on the total weight of the mixture forming the organosilicon biomedical device.

[0145] In a non-limiting illustrative embodiment, the mixture forming the organosilicon biomedical device may further comprise a reactive (polymerizable) ultraviolet (UV) absorber and / or a reactive blue light absorber, as may be combined with one or more of the foregoing paragraphs. Suitable reactive UV absorbers may be any known reactive UV absorber. In a non-limiting illustrative embodiment, suitable reactive UV absorbers include, for example, 2-(2'-hydroxy-3'-methylallyl-5'-methylphenyl)benzotriazole (tradely known as o-methylallyl Tinuvin P (“oMTP”), commercially available from Polysciences, Inc., Warrington, Pennsylvania), 3-(2H-benzo[d][1,2,3]triazol-2-yl)-4-hydroxyphenyl ethyl methacrylate, and 2-(3-(tert-butyl)-4-hydroxy-5-(5-methoxy-2H-benzo[d][1,2,3]triazol-2-yl)phenoxy)ethyl methacrylate.

[0146] In one illustrative embodiment, a suitable UV absorber comprises, for example, one or more compounds having the following formula:

[0147] ,

[0148]

[0149] (2-Acrylic acid, 2-methyl, 2-(4-benzoyl-3-hydroxyphenoxy)-1-[(4-benzoyl-3-hydroxyphenoxy)methyl ester),

[0150] ,

[0151] ,

[0152] ,as well as

[0153] .

[0154] These compounds are illustrative only and are not intended to be limiting. Any known or subsequently developed UV absorbers are contemplated for use herein.

[0155] In an illustrative embodiment, the UV absorber may be present in the monomer mixture in an amount ranging from about 0.1 wt% to about 5 wt% based on the total weight of the monomer mixture. In another illustrative embodiment, the UV absorber may be present in the monomer mixture in an amount ranging from about 1.5 wt% to about 2.5 wt% based on the total weight of the monomer mixture. In yet another non-limiting illustrative embodiment, the UV absorber may be present in the monomer mixture in an amount ranging from about 1.5 wt% to about 2 wt% based on the total weight of the monomer mixture.

[0156] Many reactive blue light absorbing compounds are known. Preferred reactive blue light absorbing compounds are those described in U.S. Patents 5,470,932, 8,207,244, and 8,329,775, the contents of which are hereby incorporated by reference. In one embodiment, the blue light absorbing dye is N-2-[3-(2'-methylphenylazo)-4-hydroxyphenyl]ethylmethacrylamide. In an illustrative embodiment, the blue light absorber may be present in the monomer mixture in an amount ranging from about 0.005% by weight to about 1% by weight, based on the total weight of the monomer mixture. In another illustrative embodiment, the blue light absorber may be present in the monomer mixture in an amount ranging from about 0.01% by weight to about 1% by weight, based on the total weight of the monomer mixture.

[0157] As needed and to the extent that it does not prejudice the purpose and effect of the illustrative embodiments disclosed herein, the mixtures for forming organosilicon biomedical devices disclosed herein may also contain various additives, such as antioxidants, colorants, toughening agents and the like, as well as other components known in the art.

[0158] The illustrative embodiments of the silicone biomedical device (e.g., contact lens or intraocular lens) can be prepared by polymerizing the aforementioned mixture for forming the silicone biomedical device to form a product, which can then be shaped into a suitable form by, for example, machining, injection molding, compression molding, cutting, etc. For example, in producing a contact lens, the initial mixture can be polymerized in a tube to provide a rod-shaped article, which is then cut into button-shaped pieces. These button-shaped pieces can then be machined into the contact lens.

[0159] Alternatively, silicone biomedical devices (such as contact lenses) can be directly cast from the mixture into a mold (e.g., a polypropylene mold) using methods such as spin casting and static casting. Spin casting is disclosed in U.S. Patent Nos. 3,408,429 and 3,660,545, and static casting is disclosed in U.S. Patent Nos. 4,113,224, 4,197,266, and 5,271,875. Spin casting involves injecting a mixture to be polymerized into a mold and rotating the mold in a controlled manner while exposing the mixture to a radiation source (such as UV light). Static casting involves injecting a monomer mixture between two mold portions, one mold portion shaped to form a front lens surface and the other mold portion shaped to form a rear lens surface, and curing the mixture while retaining it in the mold assembly to form a lens, for example, through free radical polymerization of the mixture.

[0160] Examples of free radical reaction techniques used to cure eyeglass materials include thermal radiation, infrared radiation, electron beam radiation, gamma radiation, ultraviolet (UV) radiation, etc.; or combinations of such techniques may be used. U.S. Patent No. 5,271,875 describes a static casting method that allows molded finished lenses in a cavity defined by a rear mold and a front mold. As another method, U.S. Patent No. 4,555,732 discloses a method in which excess mixture is cured by spin casting in a mold to form a molded article having a front spectacle surface and a relatively large thickness, and the rear surface of the cured spin-cast article is subsequently machined by lathe to provide a contact lens with the desired thickness and rear spectacle surface.

[0161] Polymerization can be promoted by exposing the mixture to heat and / or radiation (such as ultraviolet, visible, or high-energy radiation). A polymerization initiator can be included in the mixture to promote the polymerization step. Representative examples of free radical thermal polymerization initiators include organic peroxides such as acetyl peroxide, lauroyl peroxide, decanoyl peroxide, stearyl peroxide, benzoyl peroxide, tert-butyl perpentyl peroxide, and dicarbonate peroxide. Representative UV initiators are those known in the art and include benzoin methyl ether, benzoin ethyl ether, and Darocure. ® 1173, 1164, 2273, 1116, 2959, 3331 (EMIndustries) and Irgacure ® Examples include 651, 184, and 2959 (Ciba-Geigy), and 2,2'-azobis(2-methylpropionitrile) (VAZO64). Typically, the initiator is used in the mixture at a concentration of about 0.01% to about 5% by weight of the total mixture.

[0162] Polymerization is typically carried out in a reaction medium, such as a solution or dispersion of a solvent, like water, or an alkanol containing one to four carbon atoms (e.g., methanol, ethanol, or propan-2-ol). Alternatively, a mixture of any of the solvents described above may be used.

[0163] Typically, polymerization can be carried out in an inert atmosphere, such as nitrogen or argon, for about 15 minutes to about 72 hours. If necessary, the resulting polymer can be dried under vacuum for, for example, about 5 hours to about 72 hours, or left in an aqueous solution before use.

[0164] The polymerization of mixtures forming silicone biomedical devices will produce a polymer that, upon hydration, preferably forms a hydrogel. When producing hydrogel lenses, the mixtures forming silicone biomedical devices may also contain at least one diluent, which is ultimately replaced by water when the polymer product is hydrated to form a hydrogel. The amount of diluent used should be less than about 50% by weight, and in most cases, the diluent content will be less than about 30% by weight. However, in a particular polymer system, the practical limit will be determined by the solubility of the various monomers in the diluent. For the production of optically transparent copolymers, it is important that no phase separation occurs between the comonomers and the diluent, or between the diluent and the final copolymer, resulting in visual opacity.

[0165] Furthermore, 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, when the diluent is replaced by water during hydration, may cause or result in copolymer collapse. Suitable diluents include, but are not limited to, ethylene glycol, glycerol, liquid poly(ethylene glycol), alcohols, alcohol / water mixtures, ethylene oxide / propylene oxide block copolymers, low molecular weight linear poly(2-hydroxyethyl methacrylate), glycol esters of lactic acid, formamide, ketones, dialkyl sulfoxides, butyl carbitol and the like, and mixtures thereof.

[0166] If necessary, it may be desirable to remove residual diluent from the lens prior to an edge finishing operation, which can be performed by evaporation at or near ambient pressure or under vacuum. Increased temperatures can be used to shorten the time required for diluent evaporation. As will be readily apparent to those skilled in the art, the time, temperature, and pressure conditions for the solvent removal step will vary depending on factors such as the volatility of the diluent and specific monomer components. If desired, the mixture used to produce the hydrogel lens may also contain crosslinking agents and wetting agents known in the art for preparing hydrogel materials.

[0167] In the case of intraocular lenses, the mixture to be polymerized to form an organosilicon biomedical device may also contain monomers for increasing the refractive index of the resulting polymer. Examples of such monomers include aromatic (meth)acrylates, such as phenyl (meth)acrylate, 2-phenylethyl (meth)acrylate, 2-phenoxyethyl methacrylate, and benzyl (meth)acrylate.

[0168] The silicone biomedical devices (such as contact lenses) obtained in this paper can undergo optional machining operations. For example, optional machining steps may include grinding or polishing the lens edges and / or surfaces. Typically, such machining processes can be performed before or after the product is released from the mold part, for example, by removing the lens from the mold using vacuum tweezers to dry release the lens from the mold, and then transferring the lens to a second set of vacuum tweezers using mechanical tweezers and placing it against a rotating surface to smooth the surface or edges. The lens can then be flipped over to machine the other side of the lens.

[0169] The lenses can then be transferred to individual lens packages containing a buffered saline solution. The saline solution can be added to the package before or after lens transfer. Suitable packaging designs and materials are known in the art. Plastic packaging is releasably 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 methods and conditions are known in the art and include, for example, autoclaving.

[0170] As will be readily understood by those skilled in the art, other steps may be included in the molding and packaging process described above. Such other steps may include, for example, coating the formed lens, surface treating the lens during formation (e.g., by transfer via a mold), inspecting the lens, discarding defective lenses, cleaning the half-mold, reusing the half-mold, and combinations thereof.

[0171] The following examples are provided to enable those skilled in the art to practice the invention, and these examples are merely illustrative. The examples should not be construed as limiting the scope of the invention as defined in the claims.

[0172] The following describes the formation of various polymerization products and their characterization using standard testing procedures, such as:

[0173] Water %: Blot two sets of six hydrated lenses or films dry on a filter paper to remove excess water, and weigh the samples (wet weight). Then, place the samples in a wide-mouth bottle containing desiccant and heat in a microwave oven for 10 minutes. Then let the samples stand for 30 minutes to equilibrate to room temperature and weigh again (dry weight). The percentage of water is calculated from the dry and wet weights.

[0174] Contact Angle: Capture bubble contact angle data were collected on a first-ten Å FTA-1000 pillar-shaped instrument. Prior to analysis, all samples were rinsed in HPLC-grade water to remove components of the packaging solution from the sample surface. The surface tension of the water used for all experiments was measured using the pendant drop method before data collection. A surface tension of 70 to 72 dynes / cm was desired for the water to be suitable for use. All lens samples were placed on a curved sample holder and immersed in a quartz unit filled with HPLC-grade water. The advancing and receding capture bubble contact angles were collected for each sample. The advancing contact angle is defined as the angle measured in water as the bubble retracts from the lens surface (water advances across the surface). All capture bubble data were collected using a high-speed digital camera focused on the sample / bubble interface. The contact angle was calculated at the digital frame just before the contact line moves across the sample / bubble interface. The receding contact angle is defined as the angle measured in water as the bubble expands on the sample surface (water recedes from the surface).

[0175] The modulus (g / mm²) was measured using an Instron (model 4502) instrument according to ASTM 1708. 2 The membrane sample is immersed in borate-buffered saline solution; the appropriate size of the membrane sample is a gauge length of 22 mm and a width of 4.75 mm, wherein the sample further has an end that forms a dog bone shape (to accommodate clamping the sample with the Instron instrument) and has a thickness of 100 ± 50 micrometers.

[0176] In the embodiments, the following abbreviations are used.

[0177] NVP: N-vinyl-2-pyrrolidone.

[0178] TBE: 4-tert-butyl-2-hydroxycyclopentyl methacrylate.

[0179] DMA: N,N-dimethylacetamide

[0180] EGDMA: Ethylene dimethacrylate

[0181] AMA: Allyl methacrylate.

[0182] HA: Hyaluronic acid.

[0183] HA-MA: Methacrylated hyaluronic acid represented by the following structure:

[0184] .

[0185] TrisMA: Tris(trimethylsiloxy)methylpropyl methacrylate.

[0186] X-22-1666: N-[3-(9-butyl-1,1,3,3,5,5,7,7,9,9-decamethyl-1-pentasiloxane)propyl]-2-acrylamide represented by the following structure:

[0187] .

[0188] X-22-1666C: An organosilicon monomer represented by the following structure and available from ShinEtsu:

[0189] .

[0190] SIGMA: (3-Methacryloxy-2-hydroxypropoxy)propylbis(trimethylsiloxy)methylsilane having the following structure:

[0191] .

[0192] M1EDS6: A compound with the following structure that is available from the gelest:

[0193] .

[0194] MCR-M11: Compounds with the following structure:

[0195] .

[0196] Vazo TM 64: Azobisisobutyronitrile (AIBN).

[0197] Irgacure 2959: 2-hydroxy-4'-(2-hydroxyethoxy)-2-methylphenylacetone,

[0198] PVP: Polyvinylpyrrolidone (K90).

[0199] UV416: 2-(4-benzoyl-3-hydroxyphenoxy)ethyl acrylate.

[0200] Reactive Blue 69: 1-Amino-4-[[4-[(2-bromo-1-oxoallyl)amino]-2-sulfonate phenyl]amino]-9,10-dihydro-9,10-dioxanthracene-2-sulfonate disodium salt,

[0201] P407DM: Poloxamer 407 dimethacrylate having the following structure:

[0202] .

[0203] Example 1

[0204] Preparation of HA-MA.

[0205] Add 490 mL of deionized (DI) water to a 1-liter flask equipped with a stir bar. Add 10 g of HA (M n ~115 kDa) was dissolved in the stirred solution. A pH meter was immersed in the HA solution. Methacrylic anhydride (1.91 g, 12.4 mmol) was added to the solution at room temperature. The pH of the solution was maintained between 8.0 and 8.5 for 6 hours by adding NaOH solution (20 wt%), and then the solution was stirred overnight. The product was purified by dialyzing against RO water (MWCO 6 kDa to 8 kDa) for two days, followed by lyophilization for two days. The product was redissolved in 300 mL of DI, purified by dialyzing, and lyophilized again to obtain a white HA-MA powder with 10% methacrylate.

[0206] Example 2

[0207] X-22-1666, having the following structure, was prepared using a general reaction scheme:

[0208] .

[0209]

[0210] Under a nitrogen atmosphere, 2,2,4,4,6,6,8,8-octamethyl-1,3,5,7,2,4,6,8-tetraoxatetrasiloxane (29.6 g, 0.1 mol) and anhydrous cyclohexane (150 mL) were added to an oven-dried flask equipped with a magnetic stir bar and a condenser. Butyllithium (6.4 g, 0.1 mol) was added to the reaction mixture, followed by cyclohexane (25 mL). After stirring for one hour, tetrahydrofuran (THF) (70 mL, distilled on sodium / benzophenone) was added, and the reaction mixture was stirred for another 16 hours. Next, N-(3-(chlorodimethylsilyl)propyl)acrylamide (20.5 g, 0.1 mol) was added, and the mixture was stirred for another 24 hours. The reaction mixture was then filtered, and silica gel (3.5 g, dried at 160 °C for 3 h) was added, and the reaction mixture was stirred for another 4 hours. The reaction mixture was filtered through a diatomaceous earth pad (20 g), and butylated hydroxytoluene (BHT) (5 mg) was added to the filtrate. The filtrate was then concentrated under vacuum (40 °C / 0.3 mm Hg). Heptane (200 mL) was added to the concentrate with stirring, and the mixture was washed with DI water (100 mL), NaHCO3 aqueous solution (2 × 100 mL, prepared by dissolving 10 g NaHCO3 in 200 mL of DI water), brine (100 mL), and finally with DI water (100 mL). Heptane (50 mL) was added, and the mixture was dried over MgSO4 (15 g) for 20 h. The MgSO4 was filtered off, and the solvent was removed using a rotary evaporator. The crude product was stirred over activated basic alumina (30 g for 24 h) and then filtered through a thin diatomaceous earth pad. Any residual solvent was removed at 25 °C and 0.2 mm Hg for 30 min to produce 40 g of the desired product as a clear oil.

[0211] Examples 3 to 5 and Comparative Examples A to D

[0212] Manufacturing contact lenses.

[0213] Contact lenses were prepared using the reaction components listed in Table 2 below by weight percentage. Lenses were prepared by mixing the reaction components together in a scintillation bottle with stirring or rolling for at least approximately 1 hour until all components were dissolved. The reaction mixture was then dispensed into a thermoplastic contact lens mold assembly and heat-cured at 90°C for 2 hours after purging with nitrogen to form the contact lens. The resulting lens was demolded from the mold and extracted with water for 2 × 3 minutes to remove residual monomers.

[0214] Once the lens has been extracted, place it in a vial or blister pack filled with buffered saline. Seal the vial or blister pack with a stopper or foil and autoclave at approximately 121°C for about 30 minutes. The properties of the resulting contact lenses are also shown in Table 3 below.

[0215] Table 2

[0216]

[0217] Table 3

[0218]

[0219] The data in Table 3 show that, compared with the contact lenses of Comparative Examples B to D, which were prepared from the polymer product of a mixture of grafted glycosaminoglycan polymers (including glycosaminoglycans having a polymer backbone and one or more side chains containing olefinically unsaturated reactive residues grafted onto the polymer backbone) and monomers containing at least one hydrogen-donating group that form organosilicon biomedical devices, the contact lenses of Examples 3 to 5 were optically transparent (Comparative Examples B to D).

[0220] Example 6 and Comparative Examples E to G

[0221] Manufacturing contact lenses.

[0222] Contact lenses were prepared using the reaction components listed in Table 4 below, by weight percentage. First, 3-(trihydroxysilyl)propyl methacrylate was prepared by mixing 5% by weight of 3-(trimethoxysilyl)propyl methacrylate with 2% HA-MA in water and heating at 35°C until the mixture became clear. This reaction is a hydrolysis of the methoxy substituent to give 3-(trihydroxysilyl)propyl methacrylate. The mixture of water, HA-MA, and 3-(trihydroxysilyl)propyl methacrylate was then directly incorporated into the monomer formulation.

[0223] Lenses were prepared by mixing the reaction components together in a scintillation bottle with stirring or rolling for at least about 1 hour until all components dissolved. The reaction mixture was then dispensed into a thermoplastic contact lens mold assembly and irradiated with UV rays for 20 seconds to form contact lenses. The resulting lenses were demolded from the mold, extracted with water for 3 minutes, and placed in a buffer salt solution to remove residual monomers.

[0224] Once the lens has been extracted, place it in a vial or blister pack filled with buffered saline. Seal the vial or blister pack with a stopper or foil and autoclave at approximately 121°C for about 30 minutes. The properties of the resulting contact lenses are also shown in Table 5 below.

[0225] Table 4

[0226]

[0227] Table 5

[0228]

[0229] The data in Table 5 show that, compared to the contact lenses of Comparative Examples F to G, which were prepared from a polymer product of a grafted glycosaminoglycan polymer (including a glycosaminoglycan having a polymer backbone and one or more side chains containing olefinically unsaturated reactive residues grafted onto the polymer backbone) and a monomer containing at least one hydrogen-donating group that forms an organosilicon biomedical device, the contact lenses of Example 6 (Comparative Examples F to G) are optically transparent.

[0230] Unless otherwise stated, although compositions and methods are described in accordance with the principle of “comprising” various components or steps, compositions and methods may also be “substantially composed of various components or steps” or “composed of various components or steps”.

[0231] The terms “a / an” and “the” are intended to include plural alternatives, such as at least one. Unless otherwise specified, the terms “including,” “with,” and “having” as used herein are defined as encompassing (i.e., open language).

[0232] This document discloses various numerical ranges. Unless otherwise stated, when an applicant discloses or claims protection for any type of range, the applicant's intent is to individually disclose or claim protection for every possible number that such range can reasonably cover, including the endpoints of the range and any subranges and combinations thereof covered therein. For example, unless otherwise specified, all numerical endpoints of the ranges disclosed herein are approximate values.

[0233] In this document, a value or range may be expressed as “about”, from “about” a specific value and / or to “about” another specific value. When such a value or range is expressed, other disclosed embodiments include the listed specific value, from one specific value and / or to another specific value. Similarly, when a value is expressed as an approximation using the antecedent “about”, it should be understood that the specific value forms another embodiment. It will be further understood that multiple values ​​are disclosed, and each value is also disclosed herein as “about” that specific value in addition to the value itself. On the other hand, the use of the term “about” means ±20% of the value, ±15% of the value, ±10% of the value, ±5% of the value, ±3% of the value, or ±1% of the value.

[0234] If the applicant chooses to claim a measure smaller than the full scope of this disclosure for any reason, such as taking into account references that the applicant may not have been aware of at the time of filing this application, the applicant reserves the right to exclude or not include any individual member (including any sub-scopes or combinations of sub-scopes) of any stated value or range group that can be claimed under scope or in any similar manner. Furthermore, the applicant reserves the right to exclude or not include any member of the claimed group.

[0235] According to one aspect of this disclosure, an organosilicon biomedical device comprises a polymeric product forming a mixture of biomedical devices, the mixture comprising (a) one or more grafted glycosaminoglycan polymers having a polymer backbone and one or more side chains having glycosaminoglycans having olefinically unsaturated reactive residues grafted onto the polymer backbone; and (b) one or more monomers forming organosilicon biomedical devices having at least one hydrogen-donating group.

[0236] In a non-limiting illustrative embodiment, as may be combined with one or more of the preceding paragraphs, one or more grafted glycosaminoglycan polymers are selected from the group consisting of: chondroitin, chondroitin sulfate, dermatan, dermatan sulfate, heparin, heparan sulfate, heparin precursor, hyaluronic acid, and salts thereof.

[0237] In a non-limiting illustrative embodiment, as may be combined with one or more of the preceding paragraphs, one or more grafted glycosaminoglycan polymers have a grafting degree in the range of about 2% to about 30%.

[0238] In a non-limiting illustrative embodiment, as may be combined with one or more of the foregoing paragraphs, the olefinically unsaturated reactive residue is a (meth)acrylate-containing residue.

[0239] In a non-limiting illustrative embodiment, as may be combined with one or more of the preceding paragraphs, one or more grafted glycosaminoglycan polymers have a degree of methacrylation ranging from about 0.5% to about 50%.

[0240] In a non-limiting illustrative embodiment, as may be combined with one or more of the foregoing paragraphs, the glycosaminoglycan is hyaluronic acid or a salt thereof, and the olefinically unsaturated reactive residue is a (meth)acrylate-containing residue.

[0241] In a non-limiting illustrative embodiment, as may be combined with one or more of the preceding paragraphs, at least one hydrogen-donating group includes one or more of hydroxyl, amino, SH and carboxyl groups.

[0242] In a non-limiting illustrative embodiment, such as in combination with one or more of the preceding paragraphs, at least one hydrogen-donating group is OH or NH.

[0243] In a non-limiting illustrative embodiment, as may be combined with one or more of the foregoing paragraphs, one or more monomers forming organosilicon biomedical devices are one or more hydroxyl-functionalized monomers forming organosilicon biomedical devices.

[0244] In a non-limiting illustrative embodiment, as may be combined with one or more of the foregoing paragraphs, the monomers for forming organosilicon biomedical devices that are one or more hydroxyl-functionalized monomers include one or more monomers of formula I, II, or III:

[0245] (I)

[0246] (II)

[0247] in:

[0248] n is an integer between 3 and 35 or between 4 and 25;

[0249] R 1 Is it hydrogen or C? 1-6 alkyl;

[0250] R 2 R 3 and R 4 C is either substituted or unsubstituted independently. 1-6 alkyl groups, C 1-6 Three Cs 1-6 Alkyl siloxy group, phenyl group, naphthyl group, substituted phenyl group and substituted naphthyl group;

[0251] R 5 It is a hydroxyl group, an alkyl group containing one or more hydroxyl groups, or (CH2(CR)9 R 10 ) y O) x )-R 11 , where y is from 1 to 5, and x is an integer from 1 to 100;

[0252] R 6 It is a divalent group containing up to 20 carbon atoms;

[0253] R 7 It is a free radical reactive group;

[0254] R 8 It is a divalent or trivalent group containing up to 20 carbon atoms; and

[0255] R 9 -R 11 Independently hydrogen, optionally substituted with at least one polar functional group, or an alkyl group having at most 10 carbon atoms, or:

[0256] (III)

[0257] Where R 1 R 5 R 7 and R 8 It has the aforementioned meaning.

[0258] In a non-limiting illustrative embodiment, as may be combined with one or more of the foregoing paragraphs, the monomers for forming organosilicon biomedical devices with hydroxyl functionalization include monomers represented by the following structures:

[0259] .

[0260] In a non-limiting illustrative embodiment, as may be combined with one or more of the foregoing paragraphs, one or more monomers forming organosilicon biomedical devices are one or more amino-functionalized monomers forming organosilicon biomedical devices.

[0261] In a non-limiting illustrative embodiment, as can be combined with one or more of the foregoing paragraphs, the monomer for forming an organosilicon biomedical device with one or more amino-functionalized forms is represented by the structure of Formula IV:

[0262] (IV)

[0263] Where R 1 R 2 R 3 and R 4Independently, it is hydrogen, alkyl group, haloalkyl group, cycloalkyl group, heterocycloalkyl group, alkenyl group, haloalkenyl group, aryl group, and heteroaryl group; R 5 R 6 and R 7 It is independently a straight-chain or branched alkyl group; x is 1 to 6; and y is 3 to 7.

[0264] In a non-limiting illustrative embodiment, as may be combined with one or more of the foregoing paragraphs, one or more monomers forming an organosilicon biomedical device further comprise at least one olefinically unsaturated reactive group.

[0265] In a non-limiting illustrative embodiment, as may be combined with one or more of the foregoing paragraphs, one or more monomers forming an organosilicon biomedical device have a silicon atom to hydrogen-donating group ratio of about 1:1 to about 9:1.

[0266] In a non-limiting illustrative embodiment, as may be combined with one or more of the foregoing paragraphs, one or more monomers forming an organosilicon biomedical device have a silicon atom to hydrogen-donating group ratio of about 1:1 to about 4:1.

[0267] In a non-limiting illustrative embodiment, as may be combined with one or more of the foregoing paragraphs, one or more monomers forming an organosilicon biomedical device have a silicon atom to hydrogen-donating group ratio of about 1:1 to about 1:5.

[0268] In a non-limiting illustrative embodiment, a mixture that can be combined with one or more of the foregoing paragraphs to form an organosilicon biomedical device comprises:

[0269] Based on the total weight of the mixture forming the organosilicon biomedical device, approximately 0.1 wt% to approximately 1.0 wt% of one or more grafted glycosaminoglycan polymers; and

[0270] Based on the total weight of the mixture forming the organosilicon biomedical device, about 1% to about 30% of one or more monomers forming the organosilicon biomedical device.

[0271] In a non-limiting illustrative embodiment, such as when combined with one or more of the foregoing paragraphs, the mixture forming the organosilicon biomedical device further comprises one or more monomers that form a non-organosilicon biomedical device.

[0272] In a non-limiting illustrative embodiment, as may be combined with one or more of the foregoing paragraphs, one or more monomers forming a non-organosilicon biomedical device are selected from the group consisting of: unsaturated carboxylic acids, acrylamide, vinyl lactam, poly(alkyleneoxy(meth)acrylate, (meth)acrylic acid, hydroxyl-containing (meth)acrylate, hydrophilic ethylene carbonate, hydrophilic urethane monomer, hydrophilic oxazolone monomer, and mixtures thereof.

[0273] In a non-limiting illustrative embodiment, as may be combined with one or more of the foregoing paragraphs, the mixture forming the organosilicon biomedical device comprises about 30% to about 90% by weight of one or more monomers forming non-organosilicon biomedical devices, based on the total weight of the mixture forming the organosilicon biomedical device.

[0274] In a non-limiting illustrative embodiment, the mixture forming the organosilicon biomedical device may, as can be combined with one or more of the foregoing paragraphs, further comprise one or more crosslinking agents.

[0275] In a non-limiting illustrative embodiment, such as in combination with one or more of the foregoing paragraphs, the mixture forming the organosilicon biomedical device further comprises one or more components selected from the group consisting of wetting agents, surfactants, and ultraviolet (UV) blockers.

[0276] In a non-limiting illustrative embodiment, as may be combined with one or more of the preceding paragraphs, the organosilicon biomedical device has a water content of at least about 70% by weight.

[0277] In a non-limiting illustrative embodiment, such as in combination with one or more of the preceding paragraphs, the organosilicon biomedical device is optically transparent.

[0278] In a non-limiting illustrative embodiment, as may be combined with one or more of the preceding paragraphs, the silicone biomedical device is one of contact lenses, artificial lenses, and hydrogels.

[0279] According to another aspect of this disclosure, a method for fabricating an organosilicon biomedical device includes:

[0280] (a) Providing a mixture for forming an organosilicon biomedical device, the mixture comprising (i) one or more grafted glycosaminoglycan polymers having a polymer backbone and one or more side chains having glycosaminoglycans having olefinically unsaturated reactive residues grafted onto the polymer backbone, and (ii) one or more monomers for forming an organosilicon biomedical device having at least one hydrogen-donating group.

[0281] (b) subjecting a mixture to polymerization conditions to provide a polymerizable organosilicon biomedical device; and

[0282] (c) Hydrate the polymerized organosilicon biomedical device.

[0283] In a non-limiting illustrative embodiment, as may be combined with one or more of the preceding paragraphs, one or more grafted glycosaminoglycan polymers are selected from the group consisting of: chondroitin, chondroitin sulfate, dermatan, dermatan sulfate, heparin, heparan sulfate, heparin precursor, hyaluronic acid, and salts thereof.

[0284] In a non-limiting illustrative embodiment, as may be combined with one or more of the preceding paragraphs, one or more grafted glycosaminoglycan polymers have a grafting degree in the range of about 2% to about 30%.

[0285] In a non-limiting illustrative embodiment, as may be combined with one or more of the foregoing paragraphs, the olefinically unsaturated reactive residue is a (meth)acrylate-containing residue.

[0286] In a non-limiting illustrative embodiment, as may be combined with one or more of the preceding paragraphs, one or more grafted glycosaminoglycan polymers have a degree of methacrylation ranging from about 0.5% to about 50%.

[0287] In a non-limiting illustrative embodiment, as may be combined with one or more of the foregoing paragraphs, the glycosaminoglycan is hyaluronic acid or a salt thereof, and the olefinically unsaturated reactive residue is a (meth)acrylate-containing residue.

[0288] In a non-limiting illustrative embodiment, as may be combined with one or more of the preceding paragraphs, at least one hydrogen-donating group includes one or more of hydroxyl, amino, SH and carboxyl groups.

[0289] In a non-limiting illustrative embodiment, such as in combination with one or more of the preceding paragraphs, at least one hydrogen-donating group is OH or NH.

[0290] In a non-limiting illustrative embodiment, as may be combined with one or more of the foregoing paragraphs, one or more monomers forming organosilicon biomedical devices are one or more hydroxyl-functionalized monomers forming organosilicon biomedical devices.

[0291] In a non-limiting illustrative embodiment, as may be combined with one or more of the foregoing paragraphs, the monomers for forming organosilicon biomedical devices that are one or more hydroxyl-functionalized include monomers of formulas I, II, and III:

[0292] (I)

[0293] (II)

[0294] in:

[0295] n is an integer between 3 and 35 or between 4 and 25;

[0296] R 1 Is it hydrogen or C? 1-6 alkyl;

[0297] R 2 R 3 and R 4 C is either substituted or unsubstituted independently. 1-6 alkyl groups, C 1-6 Three Cs 1-6 Alkyl siloxy group, phenyl group, naphthyl group, substituted phenyl group and substituted naphthyl group;

[0298] R 5 It is a hydroxyl group, an alkyl group containing one or more hydroxyl groups, or (CH2(CR) 9 R 10 ) y O) x )-R 11 , where y is from 1 to 5, and x is an integer from 1 to 100;

[0299] R 6 It is a divalent group containing up to 20 carbon atoms;

[0300] R 7 It is a free radical reactive group;

[0301] R 8 It is a divalent or trivalent group containing up to 20 carbon atoms; and

[0302] R 9 -R 11 Independently hydrogen, optionally substituted with at least one polar functional group, or an alkyl group having at most 10 carbon atoms, or:

[0303] (III)

[0304] Where R 1 R 5 R 7 and R 8 It has the aforementioned meaning.

[0305] In a non-limiting illustrative embodiment, as may be combined with one or more of the foregoing paragraphs, the monomers for forming organosilicon biomedical devices that are one or more hydroxyl-functionalized include monomers represented by the following structures:

[0306] .

[0307] In a non-limiting illustrative embodiment, as may be combined with one or more of the foregoing paragraphs, one or more monomers forming organosilicon biomedical devices are one or more amino-functionalized monomers forming organosilicon biomedical devices.

[0308] In a non-limiting illustrative embodiment, as can be combined with one or more of the foregoing paragraphs, the monomer for forming an organosilicon biomedical device with one or more amino-functionalized forms is represented by the structure of Formula IV:

[0309] (IV)

[0310] Where R 1 R 2 R 3 and R 4 Independently, it is hydrogen, alkyl group, haloalkyl group, cycloalkyl group, heterocycloalkyl group, alkenyl group, haloalkenyl group, aryl group, and heteroaryl group; R 5 R 6 and R 7 Independently, it is a straight-chain or branched alkyl group; x is 1 to 6; and y is 3 to 15.

[0311] In a non-limiting illustrative embodiment, as may be combined with one or more of the foregoing paragraphs, one or more monomers forming an organosilicon biomedical device further comprise at least one olefinically unsaturated reactive group.

[0312] In a non-limiting illustrative embodiment, as may be combined with one or more of the foregoing paragraphs, one or more monomers forming an organosilicon biomedical device have a silicon atom to hydrogen-donating group ratio of about 1:1 to about 9:1.

[0313] In a non-limiting illustrative embodiment, as may be combined with one or more of the foregoing paragraphs, one or more monomers forming an organosilicon biomedical device have a silicon atom to hydrogen-donating group ratio of about 1:1 to about 4:1.

[0314] In a non-limiting illustrative embodiment, as may be combined with one or more of the foregoing paragraphs, one or more monomers forming an organosilicon biomedical device have a silicon atom to hydrogen-donating group ratio of about 1:1 to about 1:5.

[0315] In a non-limiting illustrative embodiment, a mixture that can be combined with one or more of the foregoing paragraphs to form an organosilicon biomedical device comprises:

[0316] Based on the total weight of the mixture forming the organosilicon biomedical device, approximately 0.1 wt% to approximately 1.0 wt% of one or more grafted glycosaminoglycan polymers; and

[0317] Based on the total weight of the mixture forming the organosilicon biomedical device, about 1% to about 30% of one or more monomers forming the organosilicon biomedical device.

[0318] In a non-limiting illustrative embodiment, such as when combined with one or more of the foregoing paragraphs, the mixture forming the organosilicon biomedical device further comprises one or more monomers that form a non-organosilicon biomedical device.

[0319] In a non-limiting illustrative embodiment, as may be combined with one or more of the foregoing paragraphs, one or more monomers forming a non-organosilicon biomedical device are selected from the group consisting of: unsaturated carboxylic acids, acrylamide, vinyl lactam, poly(alkyleneoxy(meth)acrylate, (meth)acrylic acid, hydroxyl-containing (meth)acrylate, hydrophilic ethylene carbonate, hydrophilic urethane monomer, hydrophilic oxazolone monomer, and mixtures thereof.

[0320] In a non-limiting illustrative embodiment, as may be combined with one or more of the foregoing paragraphs, the mixture forming the organosilicon biomedical device comprises about 30% to about 90% by weight of one or more monomers forming non-organosilicon biomedical devices, based on the total weight of the mixture forming the organosilicon biomedical device.

[0321] In a non-limiting illustrative embodiment, the mixture forming the organosilicon biomedical device may, as can be combined with one or more of the foregoing paragraphs, further comprise one or more crosslinking agents.

[0322] In a non-limiting illustrative embodiment, such as in combination with one or more of the foregoing paragraphs, the mixture forming the organosilicon biomedical device further comprises one or more components selected from the group consisting of wetting agents, surfactants, and ultraviolet (UV) blockers.

[0323] In a non-limiting illustrative embodiment, as may be combined with one or more of the preceding paragraphs, the organosilicon biomedical device has a water content of at least about 70% by weight.

[0324] In a non-limiting illustrative embodiment, such as in combination with one or more of the preceding paragraphs, the organosilicon biomedical device is optically transparent.

[0325] In a non-limiting illustrative embodiment, as may be combined with one or more of the preceding paragraphs, the silicone biomedical device is one of contact lenses, artificial lenses, and hydrogels.

[0326] For the sake of brevity, the various features disclosed herein, described in the context of a single embodiment, may also be provided individually or in any suitable sub-combination. All combinations of embodiments are specifically covered by the illustrative embodiments disclosed herein, as if each combination were individually and explicitly disclosed. Furthermore, all sub-combinations listed in embodiments describing such variables are also explicitly covered by the inventive compositions and disclosed herein, as if each such sub-combination were individually and explicitly disclosed herein.

[0327] 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 an example 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 can be implemented by those skilled in the art without departing from the scope and spirit of the invention. Furthermore, those skilled in the art will contemplate other modifications within the scope and spirit of the appended features and advantages.

Claims

1. An organosilicon biomedical device comprising a polymeric product of a mixture forming the biomedical device, said mixture comprising: (a) One or more grafted glycosaminoglycan polymers comprising a polymer backbone and one or more side chains, said one or more side chains comprising olefinically unsaturated reactive residues grafted onto the polymer backbone; and (b) One or more monomers that form organosilicon biomedical devices, wherein the monomer contains at least one hydrogen-donating group.

2. The organosilicon biomedical device according to claim 1, wherein the one or more grafted glycosaminoglycan polymers are selected from the group consisting of: chondroitin, chondroitin sulfate, dermatan, dermatan sulfate, heparin, heparan sulfate, heparin precursor, hyaluronic acid, and salts thereof.

3. The organosilicon biomedical device according to claim 1 or 2, wherein the one or more grafted glycosaminoglycan polymers have a grafting degree in the range of about 2% to about 30%.

4. The organosilicon biomedical device according to any one of claims 1 to 3, wherein the olefinically unsaturated reactive residue is a (meth)acrylate residue.

5. The organosilicon biomedical device according to claim 4, wherein the one or more grafted glycosaminoglycan polymers have a degree of methacrylation in the range of about 0.5% to about 50%.

6. The organosilicon biomedical device according to any one of claims 1 to 3, wherein the glycosaminoglycan is hyaluronic acid or a salt thereof, and the olefinically unsaturated reactive residue is a (meth)acrylate-containing residue.

7. The organosilicon biomedical device according to any one of claims 1 to 6, wherein the at least one hydrogen-donating group comprises one or more of a hydroxyl group, an amino group, an SH group, and a carboxyl group.

8. The organosilicon biomedical device according to claim 1, wherein the at least one hydrogen-donating group is OH or NH.

9. The organosilicon biomedical device according to claim 1, wherein the one or more monomers forming the organosilicon biomedical device include one or more hydroxyl-functionalized monomers forming the organosilicon biomedical device.

10. The organosilicon biomedical device according to claim 9, wherein the one or more hydroxyl-functionalized monomers forming the organosilicon biomedical device comprise one or more monomers of formula I, II, or III: (I) (II) in: n is an integer between 3 and 35 or between 4 and 25; R 1 is hydrogen or C 1-6 alkyl; R 2 , R 3 , and R 4 are independently substituted or unsubstituted C 1-6 alkyl groups, C 1-6 triC 1-6 alkylsilyloxy groups, phenyl groups, naphthyl groups, substituted phenyl groups, and substituted naphthyl groups; R 5 is a hydroxyl group, an alkyl group containing one or more hydroxyl groups or (CH2(CR 9 R 10 ) y O) x )-R 11 wherein y is 1 to 5 and x is an integer from 1 to 100; R 6 is a divalent group comprising up to 20 carbon atoms; R 7 It is a free radical reactive group; R 8 It is a divalent or trivalent group containing up to 20 carbon atoms; and R 9 -R 11 Independently hydrogen, optionally substituted with at least one polar functional group, or an alkyl group having at most 10 carbon atoms, or: (III) Where R 1 R 5 R 7 and R 8 It has the aforementioned meaning.

11. The organosilicon biomedical device according to any one of claims 1 to 8, wherein the one or more monomers forming the organosilicon biomedical device comprise one or more amino-functionalized monomers forming the organosilicon biomedical device.

12. The organosilicon biomedical device according to claim 11, wherein the one or more amino-functionalized monomers forming the organosilicon biomedical device are represented by the structure of formula IV: (IV) Where R 1 R 2 R 3 and R 4 Independently, it is hydrogen, alkyl group, haloalkyl group, cycloalkyl group, heterocycloalkyl group, alkenyl group, haloalkenyl group, aryl group, and heteroaryl group; R 5 R 6 and R 7 It is independently a straight-chain or branched alkyl group; x is 1 to 6; and y is 3 to 7.

13. The organosilicon biomedical device according to any one of claims 1 to 12, wherein one or more monomers forming the organosilicon biomedical device have a silicon atom to hydrogen-donating group ratio of about 1:1 to about 9:

1.

14. The organosilicon biomedical device according to any one of claims 1 to 12, wherein one or more monomers forming the organosilicon biomedical device have a silicon atom to hydrogen-donating group ratio of about 1:1 to about 1:

5.

15. The organosilicon biomedical device according to any one of claims 1 to 14, wherein the mixture forming the organosilicon biomedical device comprises: Based on the total weight of the mixture forming the organosilicon biomedical device, approximately 0.1 wt% to approximately 1.0 wt% of the one or more grafted glycosaminoglycan polymers; and Based on the total weight of the mixture forming the organosilicon biomedical device, about 1% to about 30% of the one or more monomers forming the organosilicon biomedical device.

16. The organosilicon biomedical device according to any one of claims 1 to 15, wherein the mixture forming the organosilicon biomedical device further comprises one or more monomers forming a non-organosilicon biomedical device.

17. The organosilicon biomedical device according to any one of claims 1 to 16, having a water content of at least about 70% by weight.

18. The organosilicon biomedical device according to any one of claims 1 to 17, wherein it is optically transparent.

19. The organosilicon biomedical device according to any one of claims 1 to 18, wherein it is one of an organosilicon contact lens, an organosilicon intraocular lens, or an organosilicon hydrogel.

20. A method for fabricating an organosilicon biomedical device, comprising: (a) Providing a mixture for forming an organosilicon biomedical device, the mixture comprising (i) one or more grafted glycosaminoglycan polymers having a polymer backbone and one or more side chains, the one or more side chains having olefinically unsaturated reactive residues grafted onto the polymer backbone, and (ii) one or more monomers for forming an organosilicon biomedical device having at least one hydrogen-donating group. (b) subjecting the mixture to polymerization conditions to provide a polymerized organosilicon biomedical device; as well as (c) Hydrate the polymerized organosilicon biomedical device.

21. The method of claim 20, wherein the one or more grafted glycosaminoglycan polymers are selected from the group consisting of chondroitin, chondroitin sulfate, dermatan, dermatan sulfate, heparin, heparan sulfate, heparin precursor, hyaluronic acid, and salts thereof.

22. The method of claim 20 or 21, wherein the one or more grafted glycosaminoglycan polymers have a grafting degree in the range of about 2% to about 30%.

23. The method according to any one of claims 20 to 22, wherein the olefinically unsaturated reactive residue is a (meth)acrylate residue, and the one or more grafted glycosaminoglycan polymers have a degree of methacrylation in the range of about 0.5% to about 50%.

24. The method according to any one of claims 20 to 23, wherein the at least one hydrogen-donating group comprises one or more of a hydroxyl group, an amino group, an SH group, and a carboxyl group.

25. The method of claim 20, wherein the at least one hydrogen-donating group is OH or NH.

26. The method according to any one of claims 20 to 25, wherein the one or more monomers forming organosilicon biomedical devices comprise one or more hydroxyl-functionalized monomers forming organosilicon biomedical devices.

27. The method of claim 26, wherein the one or more hydroxyl-functionalized monomers forming organosilicon biomedical devices comprise one or more monomers of formula I, II, or III: (I) (II) in: n is an integer between 3 and 35 or between 4 and 25; R 1 Is it hydrogen or C? 1-6 alkyl; R 2 R 3 and R 4 C is either substituted or unsubstituted independently. 1-6 alkyl groups, C 1-6 Three Cs 1-6 Alkyl siloxy group, phenyl group, naphthyl group, substituted phenyl group and substituted naphthyl group; R 5 It is a hydroxyl group, an alkyl group containing one or more hydroxyl groups, or (CH2(CR) 9 R 10 ) y O) x )-R 11 , where y is from 1 to 5, and x is an integer from 1 to 100; R 6 It is a divalent group containing up to 20 carbon atoms; R 7 It is a free radical reactive group; R 8 It is a divalent or trivalent group containing up to 20 carbon atoms; and R 9 -R 11 Independently hydrogen, optionally substituted with at least one polar functional group, or an alkyl group having at most 10 carbon atoms, or: (III) Where R 1 R 5 R 7 and R 8 It has the aforementioned meaning.

28. The method according to any one of claims 20 to 25, wherein the one or more monomers forming organosilicon biomedical devices comprise one or more amino-functionalized monomers forming organosilicon biomedical devices.

29. The method according to claim 28, wherein the monomer for forming the organosilicon biomedical device, which is one or more amino-functionalized, is represented by the structure of formula IV: (IV) Where R 1 R 2 R 3 and R 4 Independently, it is hydrogen, alkyl group, haloalkyl group, cycloalkyl group, heterocycloalkyl group, alkenyl group, haloalkenyl group, aryl group, and heteroaryl group; R 5 R 6 and R 7 It is independently a straight-chain or branched alkyl group; x is 1 to 6; and y is 3 to 7.

30. The method according to any one of claims 20 to 29, wherein the one or more monomers forming the organosilicon biomedical device have a silicon atom to hydrogen-donating group ratio of about 1:1 to about 9:

1.

31. The method according to any one of claims 20 to 29, wherein the one or more monomers forming the organosilicon biomedical device have a silicon atom to hydrogen-donating group ratio of about 1:1 to about 1:

5.

32. The method according to any one of claims 20 to 31, wherein the mixture forming the organosilicon biomedical device comprises: Based on the total weight of the mixture forming the organosilicon biomedical device, approximately 0.1 wt% to approximately 1.0 wt% of the one or more grafted glycosaminoglycan polymers; and Based on the total weight of the mixture forming the organosilicon biomedical device, about 1% to about 30% of the one or more monomers forming the organosilicon biomedical device.

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