Silicone hydrogel lens with a crosslinked hydrophilic coating

• US 8,529,057 B2
• Filed: 07/29/2011
• Issued: 09/10/2013
• Est. Priority Date: 07/30/2010
• Status: Active Grant

• Current Assignee: Alcon Incorporated
• Original Assignee: Novartis Ag
• Inventors: Qiu, Yongxing, Samuel, Newton T., Pruitt, John Dallas, Kolluru, Chandana, Medina, Arturo N., Winterton, Lynn Cook, Wu, Daqing, Qian, Xinming, Nelson, Jared
• Primary Examiner(s): GREECE, JAMES R
• Application Number:
  US13/193,651
• Publication Number:
  US 20120026457A1
• Time in Patent Office: 774 Days
• Field of Search: 359/159.01, 359/159.02, 359/159.33, 359/159.73, 427/2.1, 428/13
• US Class Current: 351/159.33
• CPC Class Codes: B29D 11/00067 Hydrating contact lenses
• CPC Class Codes: C08G 77/388 containing nitrogen
• CPC Class Codes: C08J 2383/04 Polysiloxanes
• CPC Class Codes: C08J 2383/08 containing silicon bound to organic groups containing atoms other than carbon, hydrogen, and oxygen
• CPC Class Codes: C08J 2433/02 Homopolymers or copolymers of acids; Metal or ammonium salts thereof
• CPC Class Codes: C08J 2433/26 Homopolymers or copolymers of acrylamide or methacrylamide
• CPC Class Codes: C08J 2487/00 Characterised by the use of unspecified macromolecular compounds, obtained otherwise than by polymerisation reactions only involving unsaturated carbon-to-carbon bonds
• CPC Class Codes: C08J 5/00 Manufacture of articles or shaped materials containing macromolecular substances manufacture of semi-permeable membranes B01D67/00 - B01D71/00
• CPC Class Codes: C08J 7/042 with two or more layers, where at least one layer of a composition contains a polymer binder
• CPC Class Codes: C08L 101/14 the macromolecular compounds being water soluble or water swellable, e.g. aqueous gels
• CPC Class Codes: C08L 83/04 Polysiloxanes
• CPC Class Codes: C09D 133/02 Homopolymers or copolymers of acids; Metal or ammonium salts thereof
• CPC Class Codes: C09D 133/14 of esters containing halogen, nitrogen, sulfur or oxygen atoms in addition to the carboxy oxygen
• CPC Class Codes: C09D 133/26 Homopolymers or copolymers of acrylamide or methacrylamide
• CPC Class Codes: C09D 171/02 Polyalkylene oxides
• CPC Class Codes: C09D 177/06 Polyamides derived from polyamines and polycarboxylic acids C09D177/10 takes precedence
• CPC Class Codes: C09D 5/1637 Macromolecular compounds
• CPC Class Codes: C09D 5/1681 Antifouling coatings characterised by surface structure, e.g. for roughness effect giving superhydrophobic coatings or Lotus effect
• CPC Class Codes: G02B 1/043 Contact lenses
• CPC Class Codes: G02B 1/10 Optical coatings produced by application to, or surface treatment of, optical elements G02B1/08 takes precedence
• CPC Class Codes: G02B 1/18 : Coatings for keeping optical surfaces clean, e.g. hydrophobic or photo-catalytic films G02B1/16 takes precedence
• CPC Class Codes: G02C 2202/06 : Special ophthalmologic or optometric aspects
• CPC Class Codes: G02C 2202/16 : Laminated or compound lenses
• CPC Class Codes: G02C 7/049 : Contact lenses having special fitting or structural features achieved by special materials or material structures

Abstract

The invention is related to a cost-effective method for making a silicone hydrogel contact lens having a crosslinked hydrophilic coating thereon. A method of the invention involves heating a silicone hydrogel contact lens in an aqueous solution in the presence of a water-soluble, highly branched, thermally-crosslinkable hydrophilic polymeric material having positively-charged azetidinium groups, to and at a temperature from about 40° C. to about 140° C. for a period of time sufficient to covalently attach the thermally-crosslinkable hydrophilic polymeric material onto the surface of the silicone hydrogel contact lens through covalent linkages each formed between one azetidinium group and one of the reactive functional groups on and/or near the surface of the silicone hydrogel contact lens, thereby forming a crosslinked hydrophilic coating on the silicone hydrogel contact lens. Such method can be advantageously implemented directly in a sealed lens package during autoclave.

Claims

1. A method for producing silicone hydrogel contact lenses with crosslinked hydrophilic coatings thereon, comprising the steps of:

(a) obtaining a silicone hydrogel contact lens having amino groups and/or carboxyl groups on and/or near its surface and a water-soluble and thermally-crosslinkable hydrophilic polymeric material, wherein the silicone hydrogel contact lens comprises amino groups or carboxyl groups or both on and/or near the surface of the contact lens, wherein the hydrophilic polymeric material comprises (i) from about 20% to about 95% by weight of first polymer chains derived from an epichlorohydrin-functionalized polyamine or polyamidoamine, (ii) from about 5% to about 80% by weight of hydrophilic moieties or second polymer chains derived from at least one hydrophilicity-enhancing agent having at least one reactive functional group selected from the group consisting of amino group, carboxyl group, thiol group, and combination thereof, and (iii) positively-charged azetidinium groups which are parts of the first polymer chains or pendant or terminal groups covalently attached to the first polymer chains, wherein the hydrophilic moieties or second polymer chains are covalently attached to the first polymer chains through one or more covalent linkages each formed between one azetitdinium group of the epichlorohydrin-functionalized polyamine or polyamidoamine and one amino, carboxyl or thiol group of the hydrophilicity-enhancing agent; and

(b) heating the silicone hydrogel contact lens in an aqueous solution in the presence of the hydrophilic polymeric material to and at a temperature from about 40°

C. to about 140°

C. for a period of time sufficient to covalently attach the hydrophilic polymeric material onto the surface of the silicone hydrogel contact lens through second covalent linkages each formed between one azetidinium group of the hydrophilic polymeric material and one of the reactive functional groups on and/or near the surface of the contact lens, thereby forming a crosslinked hydrophilic coating on the silicone hydrogel contact lens, wherein the silicone hydrogel contact lens with the crosslinked hydrophilic coating thereon has a surface wettability characterized by having an averaged water contact angle of about 90 degrees or less.

2. The method of claim 1, wherein the hydrophilicity-enhancing agent is a hydrophilic polymers having one or more amino, carboxyl and/or thiol groups, wherein the content of monomeric units having an amino, carboxyl or thiol group in the hydrophilic polymer as the hydrophilicity-enhancing agent is less than about 40% by weight based on the total weight of the hydrophilic polymer.

3. The method of claim 2, wherein the hydrophilic polymer as the hydrophilicity-enhancing agent is:

a polyethylene glycol having one sole amino, carboxyl or thiol group;

a polyethylene glycol with two terminal amino, carboxyl and/or thiol groups;

multi-arm polyethylene glycol with one or more amino, carboxyl and/or thiol groups;

polyethylene glycol dendrimers with one or more amino, carboxyl and/or thiol groups.

4. The method of claim 2, wherein the hydrophilic polymer as the hydrophilicity-enhancing agent is a copolymer which is a polymerization product of a composition comprising (1) about 60% by weight or less by weight of at least one reactive vinylic monomer and (2) at least one non-reactive hydrophilic vinylic monomer and/or at least one phosphorylcholine-containing vinylic monomer;

or combinations thereof;

wherein the reactive vinylic monomer is selected from the group consisting of amino-C₁-C₆ alkyl(meth)acrylate, C₁-C₆ alkylamino-C₁-C₆ alkyl(meth)acrylate, allylamine, vinylamine, amino-C₁-C₆ alkyl(meth)acrylamide, C₁-C₆ alkylamino-C₁-C₆ alkyl (meth)acrylamide, acrylic acid, C₁-C₁₂ alkylacrylic acid, N,N-2-acrylamidoglycolic acid, beta-methyl-acrylic acid, alpha-phenyl acrylic acid, beta-acryloxy propionic acid, sorbic acid, angelic acid, cinnamic acid, 1-carobxy-4-phenyl butadiene-1,3, itaconic acid, citraconic acid, mesaconic acid, glutaconic acid, aconitic acid, maleic acid, fumaric acid, tricarboxy ethylene, and combinations thereof;

wherein the non-reactive hydrophilic vinylic monomer is selected from the group consisting of acrylamide, methacrylamide, N,N-dimethylacrylamide, N,N-dimethylmethacrylamide, N-vinylpyrrolidone, N,N,-dimethylaminoethylmethacrylate, N,N-dimethylaminoethylacrylate, N,N-dimethylaminopropylmethacrylamide, N,N-dimethylaminopropylacrylamide, glycerol methacrylate, 3-acryloylamino-1-propanol, N-hydroxyethyl acrylamide, N-[tris(hydroxymethyl)methyl]-acrylamide, N-methyl-3-methylene-2-pyrrolidone, 1-ethyl-3-methylene-2-pyrrolidone, 1-methyl-5-methylene-2-pyrrolidone, 1-ethyl-5-methylene-2-pyrrolidone, 5-methyl-3-methylene-2-pyrrolidone, 5-ethyl-3-methylene-2-pyrrolidone, 2-hydroxyethyl(meth)acrylate, hydroxypropyl (meth)acrylate, C₁-C₄-alkoxy polyethylene glycol (meth)acrylate having a weight average molecular weight of up to 1500 Daltons, N-vinyl formamide, N-vinyl acetamide, N-vinyl isopropylamide, N-vinyl-N-methyl acetamide, allyl alcohol, vinyl alcohol (hydrolyzed form of vinyl acetate in the copolymer), and combinations thereof.

5. The method of claim 2, wherein the hydrophilic polymer as the hydrophilicity-enhancing agent is a monoamino-, monocarboxyl-, diamino- or dicarboxyl-terminated homo- or copolymer of a non-reactive hydrophilic vinylic monomer selected from the group consisting of acryamide, N,N-dimethylacrylamide, N-vinylpyrrolidone, N-vinyl-N-methyl acetamide, glycerol (meth)acrylate, hydroxyethyl(meth)acrylate, N-hydroxyethyl (meth)acrylamide, (meth)acryloyloxyethyl phosphorylcholine, C₁-C₄-alkoxy polyethylene glycol (meth)acrylate having a weight average molecular weight of up to 400 Daltons, vinyl alcohol, N-methyl-3-methylene-2-pyrrolidone, 1-methyl-5-methylene-2-pyrrolidone, 5-methyl-3-methylene-2-pyrrolidone, N,N-dimethylaminoethyl(meth)acrylate, N,N-dimethylaminopropyl (metha)crylamide, and combination thereof.

6. The method of claim 2, wherein the hydrophilic polymer as the hydrophilicity-enhancing agent is an amino- or carboxyl-containing polysaccharide, hyaluronic acid, chondroitin sulfate, and combinations thereof.

7. The method of claim 2, wherein the weight average molecular weight M_w of the hydrophilic polymer as the hydrophilicity-enhancing agent is from about 500 to about 1,000,000.

8. The method of claim 2, wherein the hydrophilicity-enhancing agent is:

amino-, carboxyl- or thiol-containing monosaccharides;

amino-, carboxyl- or thiol-containing disaccharides; and

amino-, carboxyl- or thiol-containing oligosaccharides.

9. The method of claim 2, wherein the step of heating is performed by autoclaving the silicone hydrogel contact lens immersed in a packaging solution in a sealed lens package at a temperature of from about 118°

C. to about 125°

C. for approximately 20-90 minutes to form the crosslinked hydrophilic coating on the silicone hydrogel contact lens, wherein the packaging solution comprises at least one buffering agent in an amount sufficient to maintain a pH of from about 6.0 to about 8.5 and has a tonicity of from about 200 to about 450 milliosmol (mOsm) and a viscosity of from about 1 centipoise to about 20 centipoises at 25°

C.

10. The method of claim 9, wherein the packaging solution comprises from about 0.01% to about 2% by weight of the thermally-crosslinkable hydrophilic polymeric material.

11. The method of claim 9, wherein the method further comprises:

before the step of heating, contacting at room temperature the silicone hydrogel contact lens with an aqueous solution of the thermally-crosslinkable hydrophilic polymeric material to form a top layer of the thermally-crosslinkable hydrophilic polymeric material on the surface of the silicone hydrogel contact lens, immersing the silicone hydrogel contact lens with the top layer of the thermally-crosslinkable hydrophilic polymeric material in the packaging solution in the lens package; and

sealing the lens package.

12. The method of claim 9, wherein the silicone hydrogel contact lens is made by polymerizing a silicone hydrogel lens formulation comprising from about 0.1% to about 10% by weight of a reactive vinylic monomer selected from the group consisting of amino-C₂-C₆ alkyl (meth)acrylate, C₁-C₆ alkylamino-C₂-C₆ alkyl(meth)acrylate, allylamine, vinylamine, amino-C₂-C₆ alkyl(meth)acrylamide, C₁-C₆ alkylamino-C₂-C₆ alkyl(meth)acrylamide, acrylic acid, C₁-C₁₂ alkylacrylic acid, N,N-2-acrylamidoglycolic acid, beta methyl-acrylic acid, alpha-phenyl acrylic acid, beta-acryloxy propionic acid, sorbic acid, angelic acid, cinnamic acid, 1-carobxy-4-phenyl butadiene-1,3, itaconic acid, citraconic acid, mesaconic acid, glutaconic acid, aconitic acid, maleic acid, fumaric acid, tricarboxy ethylene, and combinations thereof.

13. The method of claim 12, wherein the silicone hydrogel contact lens comprises a reactive base coating including amino and/or carboxyl groups.

14. The method of claim 13, wherein the reactive base coating comprises at least one layer of a reactive polymer having pendant amino groups and/or carboxyl groups and is obtained by contacting the silicone hydrogel contact lens with a solution of the reactive polymer, wherein the reactive polymer is:

a homopolymer of amino-C₁ to C₄ alkyl(meth)acrylamide, amino-C₁ to C₄ alkyl(meth)acrylate, C₁ to C₄ alkylamino-C₁ to C₄ alkyl(meth)acrylamide, C₁ to C₄ alkylamino-C₁ to C₄ alkyl(meth)acrylate, allylamine, or vinylamine;

polyethyleneimine;

a polyvinylalcohol with pendant amino groups;

a linear or branched polyacrylic acid;

a homopolymer of C₁ to C₁₂ alkylacrylic acid;

a copolymer of amino-C₂ to C₄ alkyl(meth)acrylamide, amino-C₂ to C₄ alkyl(meth)acrylate, C₁ to C₄ alkylamino-C₂ to C₄ alkyl(meth)acrylamide, C₁ to C₄ alkylamino-C₂ to C₄ alkyl(meth)acrylate, acrylic acid, C₁ to C₁₂ alkylacrylic acid, maleic acid, and/or fumaric acid, with at least one non-reactive hydrophilic vinylic monomer;

a carboxyl-containing cellulose;

hyaluronate;

chondroitin sulfate;

poly(glutamic acid);

poly(aspartic acid);

or combinations thereof.

15. The method of claim 13, wherein the reactive polymer for forming a base coating is polyacrylic acid, polymethacrylic acid, poly(C₂-C₁₂ alkylacrylic acid), poly[acrylic acid-co-methacrylic acid], poly[C₂-C₁₂ alkylacrylic acid-co-(meth)acrylic acid], poly(N,N-2-acrylamidoglycolic acid), poly[(meth)acrylic acid-co-acrylamide], poly[(meth)acrylic acid-co-vinylpyrrolidone], poly[C₂-C₁₂ alkylacrylic acid-co-acrylamide], poly[C₂-C₁₂ alkylacrylic acid-co-vinylpyrrolidone], hydrolyzed poly[(meth)acrylic acid-co-vinylacetate], hydrolyzed poly[C₂-C₁₂ alkylacrylic acid-co-vinylacetate], polyethyleneimine (PEI), polyallylamine hydrochloride (PAH) homo- or copolymer, polyvinylamine homo- or copolymer, or combinations thereof.

16. The method of claim 15, wherein the reactive polymer is dissolved in a mixture of water and one or more organic solvents, an organic solvent, or a mixture of one or more organic solvents.

17. The method of claim 13, wherein the reactive base coating on the contact lens is obtained by polymerizing at least one amino-containing or carboxyl-containing vinylic monomer under the effect of a plasma.

18. A silicone hydrogel contact lens product obtained according to a method of claim 16, wherein the silicone hydrogel contact lens has at least one property selected from the group consisting of:

an oxygen permeability of at least about 40 barrers;

an elastic modulus of about 1.5 MPa or less;

an lonoflux Diffusion Coefficient, D, of, at least about 1.5×

10<sup>−

6</sup> mm²/min;

a water content of preferably from about 18% to about 70% by weight when fully hydrated; and

combinations thereof.

19. An ophthalmic lens product, which comprises a sterilized and sealed lens package,

wherein the lens package comprises:

a post-autoclave lens packaging solution and a readily-usable silicone hydrogel contact lens immersed therein,

wherein the readily-usable silicone hydrogel contact lens comprises a crosslinked hydrophilic coating obtained by autoclaving an original silicone hydrogel contact lens having amino groups and/or carboxyl groups on and/or near the surface of the original silicone hydrogel contact lens in a pre-autoclave packaging solution containing a water-soluble and thermally-crosslinkable hydrophilic polymeric material,

wherein the thermally-crosslinkable hydrophilic polymeric material comprises (i) from about 20% to about 95% by weight of first polymer chains derived from an epichlorohydrin-functionalized polyamine or polyamidoamine, (ii) from about 5% to about 80% by weight of hydrophilic moieties or second polymer chains derived from at least one hydrophilicity-enhancing agent having at least one reactive functional group selected from the group consisting of amino group, carboxyl group, thiol group, and combination thereof, and (iii) azetidinium groups which are parts of the first polymer chains or pendant or terminal groups covalently attached to the first polymer chains,

wherein the thermally-crosslinkable hydrophilic polymeric material is covalently attached onto the original silicone hydrogel contact lens through first covalent linkages each formed between one amino or carboxyl group on and/or near the surface of the original silicone hydrogel contact lens and one azetidinium group of the thermally-crosslinkable hydrophilic polymeric material,

wherein the post-autoclave packaging solution comprises at least one buffering agent in an amount sufficient to maintain a pH of from about 6.0 to about 8.5 and has a tonicity of from about 200 to about 450 milliosmol, and a viscosity of from about 1 centipoise to about 20 centipoises at 25°

C.,

wherein the post-autoclave packaging solution comprises a polymeric wetting material which is an hydrolyzed product of the thermally-crosslinkable hydrophilic polymeric material after autoclave,

wherein the readily-usable silicone hydrogel contact lens has a surface hydrophilicity/wettability characterized by having an averaged water contact angle of about 90 degrees or less.

20. A water-soluble and thermally-crosslinkable hydrophilic polymeric material, comprising:

(a) from about 20% to about 95% by weight of first polymer chains derived from an epichlorohydrin-functionalized polyamine or polyamidoamine;

(b) from about 5% to about 80% by weight of second polymer chains derived from at least one hydrophilicity-enhancing polymeric agent having at least one reactive functional group selected from the group consisting of amino group, carboxyl group, thiol group, and combination thereof, wherein the second polymer chains are covalently attached to the first polymer chains through one or more covalent linkages each formed between one azetitdinium group of the epichlorohydrin-functionalized polyamine or polyamidoamine and one amino, carboxyl or thiol group of the hydrophilicity-enhancing polymeric agent; and

(c) azetidinium groups which are parts of the first polymer chains or pendant groups covalently attached to the first polymer chains.