SILICONE HYDROGEL LENS WITH A CROSSLINKED HYDROPHILIC COATING

• US 20130118127A1
• Filed: 11/13/2012
• Published: 05/16/2013
• Est. Priority Date: 11/15/2011
• Status: Active Grant

• Current Assignee: Alcon Incorporated
• Original Assignee: Novartis Ag
• Inventors: Kolluru, Chandana, Quinter, Bradley
• Granted Patent: US 9,505,184 B2
• Time in Patent Office: Days
• US Class Current: 53/431
• CPC Class Codes: B29C 2035/0827 using UV radiation
• CPC Class Codes: B29C 35/0805 using electromagnetic radiation
• CPC Class Codes: B29D 11/00038 Production of contact lenses
• CPC Class Codes: B29D 11/00048 composed of parts with dissimilar composition B29D11/00057 takes precedence
• CPC Class Codes: B29D 11/00134 Curing of the contact lens material
• CPC Class Codes: B29D 11/00865 Applying coatings; tinting; colouring printing, marking or copying processes B41M; identification in general G09F3/00; producing decorative effects in general B44C; positioning or marking of lenses B24B13/0055
• CPC Class Codes: B29K 2083/00 Use of polymers having silicon, with or without sulfur, nitrogen, oxygen, or carbon only, in the main chain, as moulding material
• CPC Class Codes: B29K 2105/0061 Gel or sol
• CPC Class Codes: B29K 2833/12 Polymers of methacrylic acid esters, e.g. PMMA, i.e. polymethylmethacrylate
• CPC Class Codes: B29K 2909/08 Glass
• CPC Class Codes: B29K 2995/0027 for light outside the visible spectrum
• CPC Class Codes: B29K 2995/0092 hydrophilic
• CPC Class Codes: B65B 5/04 Packaging single articles
• CPC Class Codes: C08L 101/02 characterised by the presence of specified groups , e.g. terminal or pendant functional groups
• CPC Class Codes: C08L 101/14 the macromolecular compounds being water soluble or water swellable, e.g. aqueous gels
• CPC Class Codes: G02B 1/043 Contact lenses
• 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 autoclaving, in a sealed lens package, a silicone hydrogel contact lens having a base coating of polyacrylic acid thereon in an aqueous solution in the presence of a water-soluble, crosslinkable hydrophilic polymeric material having epoxide groups, for a period of time sufficient to covalently attach the crosslinkable hydrophilic polymeric material onto the surface of the silicone hydrogel contact lens through covalent linkages each formed between one epoxide group and one of the carboxyl groups on and/or near the surface of the silicone hydrogel contact lens.

Claims

1. A method for producing silicone hydrogel contact lenses each having a crosslinked hydrophilic coating thereon, comprising the steps of:

(a) obtaining a silicone hydrogel contact lens;

(b) applying a layer of carboxyl-containing polymeric material onto the silicone hydrogel contact lens;

(c) placing the silicone hydrogel contact lens with the layer of carboxyl-containing polymeric material thereon into a lens package containing a packaging solution, wherein the packaging solution comprises one or more crosslinkable hydrophilic polymeric materials selected from the group consisting of (i) a water-soluble hydrophilic polymer polymeric material having epoxide groups, wherein the hydrophilic polymeric material is partial reaction product of a first multi-arm polyethyleneglycol having terminal epoxide groups and a first hydrophilicity-enhancing agent having at least one reactive functional group selected from the group consisting of amino group, carboxyl group, hydroxyl group, thiol group, and combination thereof, (ii) a second multi-arm polyethyleneglycol having terminal epoxide groups, (iii) a mixture of a third multi-arm polyethyleneglycol having terminal epoxide groups and a second hydrophilicity-enhancing agent having at least one reactive functional group selected from the group consisting of amino group, carboxyl group, hydroxyl group, thiol group, and combination thereof, and (iv) a combination thereof;

(d) sealing the package;

(e) autoclaving the sealed package with the silicone hydrogel contact lens therein at a temperature from about 115°

C. to about 125°

C. for at least about twenty minutes, thereby forming a non-silicone hydrogel coating on the silicone hydrogel contact lens, wherein the non-silicone hydrogel coating is a crosslinked polymeric material composed of the carboxyl-containing polymeric material crosslinked with the one or more crosslinkable material.

2. The method of claim 1, wherein the packaging solution comprises from about 0.01% to about 2% by weight of said one or more crosslinkable materials.

3. The method of claim 2, wherein the packaging solution comprises the water-soluble hydrophilic polymer polymeric material having epoxide groups, wherein the hydrophilic polymeric material is partial reaction product of a first multi-arm polyethyleneglycol having terminal epoxide groups and a first hydrophilicity-enhancing agent having at least one reactive functional group selected from the group consisting of amino group, carboxyl group, hydroxyl group, thiol group, and combination thereof.

4. The method of claim 3, wherein the water-soluble hydrophilic polymer polymeric material having epoxide groups comprises from about 20% to about 95% by weight of first polymer chains derived from the first multi-arm polyethyleneglycol having terminal epoxide groups and from about 5% to about 80% by weight of hydrophilic moieties or second polymer chains derived from said at least one hydrophilicity-enhancing agent having at least one reactive functional group selected from the group consisting of amino group, carboxyl group, hydroxyl, thiol group, and combination thereof.

5. The method of claim 4, wherein at least one of the first and second hydrophilicity-enhancing agents is selected from the group consisting of amino-containing monosaccharides;

carboxyl-containing monosaccharides;

thiol-containing monosaccharides;

amino-containing disaccharides;

carboxyl-containing disaccharides;

thiol-containing disaccharides;

amino-containing oligosaccharides;

carboxyl-containing oligosaccharides;

thiol-containing oligosaccharides; and

combinations thereof.

6. The method of claim 4, wherein at least one of the first and second hydrophilicity-enhancing agents is a hydrophilic polymer having one or more amino, carboxyl and/or thiol groups, wherein the content of monomeric units having an amino (—

NHR′

with R′

as defined above), carboxyl (—

COOH) and/or thiol (—

SH) group in the hydrophilic polymer as a hydrophilicity-enhancing agent is less than about 40% by weight based on the total weight of the hydrophilic polymer.

7. The method of claim 4, wherein at least one of the first and second hydrophilicity-enhancing agents are selected from the group consisting of carboxymethylcellulose, carboxyethylcellulose, carboxypropylcellulose, hyaluronic acid, chondroitin sulfate, and combinations thereof.

8. The method of claim 4, wherein at least one of the first and second hydrophilicity-enhancing agents are selected from the group consisting of PEG-N H₂;

PEG-SH;

PEG-COOH;

H₂N-PEG-N H₂;

HOOC-PEG-COOH;

HS-PEG-SH;

H₂N-PEG-COOH;

HOOC-PEG-SH;

H₂N-PEG-SH;

multi-arm PEG with at least one amino group;

multi-arm PEG with at least one carboxyl group;

multi-arm PEG with at least one thiol group;

PEG dendrimers with at least one amino group;

PEG dendrimers with at least one carboxyl group;

PEG dendrimers with at least one thiol group;

a monoamino-, monocarboxyl-, diamino- or dicarboxyl-terminated homo- or copolymer of a non-reactive hydrophilic vinylic monomer selected from the group consisting of acryamide (AAm), N,N-dimethylacrylamide (DMA), N-vinylpyrrolidone (NVP), N-vinyl-N-methyl acetamide, glycerol(meth)acrylate, hydroxyethyl(meth)acrylate, N-hydroxyethyl(meth)acrylamide, 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, (meth)acryloyloxyethyl phosphorylcholine, and combinations thereof;

a copolymer which is a polymerization product of a composition comprising (1) from about 0.1% to about 30% by weight of (meth)acrylic acid, C₂-C₁₂ alkylacrylic acid, vinylamine, allylamine and/or amino-C₂-C₄ alkyl(meth)acrylate, and (2) (meth)acryloyloxyethyl phosphorylcholine and/or at least one 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, C₁-C₄-alkoxy polyethylene glycol (meth)acrylate having a weight average molecular weight of up to 400 Daltons, vinyl alcohol, and combination thereof.

9. The method of claim 1, wherein the packaging solution comprises a mixture of a third multi-arm polyethyleneglycol having terminal epoxide groups and a second hydrophilicity-enhancing agent having at least one reactive functional group selected from the group consisting of amino group, carboxyl group, hydroxyl group, thiol group, and combination thereof.

10. The method of claim 9, wherein at least one of the first and second hydrophilicity-enhancing agents is selected from the group consisting of amino-containing monosaccharides;

carboxyl-containing monosaccharides;

thiol-containing monosaccharides;

amino-containing disaccharides;

carboxyl-containing disaccharides;

thiol-containing disaccharides;

amino-containing oligosaccharides;

carboxyl-containing oligosaccharides;

thiol-containing oligosaccharides; and

combinations thereof.

11. The method of claim 9, wherein at least one of the first and second hydrophilicity-enhancing agents is a hydrophilic polymer having one or more amino, carboxyl and/or thiol groups, wherein the content of monomeric units having an amino (—

NHR′

with R′

as defined above), carboxyl (—

COOH) and/or thiol (—

SH) group in the hydrophilic polymer as a hydrophilicity-enhancing agent is less than about 40% by weight based on the total weight of the hydrophilic polymer.

12. The method of claim 9, wherein at least one of the first and second hydrophilicity-enhancing agents are selected from the group consisting of carboxymethylcellulose, carboxyethylcellulose, carboxypropylcellulose, hyaluronic acid, chondroitin sulfate, and combinations thereof.

13. The method of claim 9, wherein at least one of the first and second hydrophilicity-enhancing agents are selected from the group consisting of PEG-N H₂;

PEG-SH;

PEG-COOH;

H₂N-PEG-N H₂;

HOOC-PEG-COOH;

HS-PEG-SH;

H₂N-PEG-COOH;

HOOC-PEG-SH;

H₂N-PEG-SH;

multi-arm PEG with one or more amino, carboxyl or thiol groups;

PEG dendrimers with one or more amino, carboxyl or thiol groups;

a monoamino-, monocarboxyl-, diamino- or dicarboxyl-terminated homo- or copolymer of a non-reactive hydrophilic vinylic monomer selected from the group consisting of acryamide (AAm), N,N-dimethylacrylamide (DMA), N-vinylpyrrolidone (NVP), N-vinyl-N-methyl acetamide, glycerol(meth)acrylate, hydroxyethyl(meth)acrylate, N-hydroxyethyl(meth)acrylamide, 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, (meth)acryloyloxyethyl phosphorylcholine, and combinations thereof;

a copolymer which is a polymerization product of a composition comprising (1) from about 0.1% to about 30% by weight of (meth)acrylic acid, C₂-C₁₂ alkylacrylic acid, vinylamine, allylamine and/or amino-C₂-C₄ alkyl (meth)acrylate, and (2) (meth)acryloyloxyethyl phosphorylcholine and/or at least one 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, C₁-C₄-alkoxy polyethylene glycol(meth)acrylate having a weight average molecular weight of up to 400 Daltons, vinyl alcohol, and combination thereof.

14. The method of claim 2, wherein the packaging solution comprises a second multi-arm polyethyleneglycol having terminal epoxide groups.

15. The method of claim 4, wherein the carboxyl-containing polymeric material is:

a homopolymer of a carboxyl-containing vinylic monomer;

a copolymer of two or more carboxyl-containing vinylic monomers;

a copolymer of a carboxyl-containing vinylic monomer with one or more vinylic monomers;

a carboxyl-containing cellulose;

poly(glutamic acid);

poly(aspartic acid);

or combinations thereof,

wherein the carboxyl-containing vinylic monomer is selected from the group consisting of acrylic acid, a C₁-C₄ alkylacrylic acid, N,N-2-acrylamidoglycolic acid, beta methyl-acrylic acid (crotonic 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, and combination thereof,

wherein the non-reactive hydrophilic vinylic monomer is selected from the group consisting of acrylamide (AAm), methacrylamide N,N-dimethylacrylamide (DMA), N,N-dimethylmethacrylamide (DMMA), N-vinylpyrrolidone (NVP), N,N,-dimethylaminoethylmethacrylate (DMAEM), N,N-dimethylaminoethylacrylate (DMAEA), N,N-dimethylaminopropylmethacrylamide (DMAPMAm), N,N-dimethylaminopropylacrylamide (DMAPAAm), 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), a phosphorylcholine-containing vinylic monomer, and combinations thereof.

16. The method of claim 9, wherein the carboxyl-containing polymeric material is:

a homopolymer of a carboxyl-containing vinylic monomer;

a copolymer of two or more carboxyl-containing vinylic monomers;

a copolymer of a carboxyl-containing vinylic monomer with one or more vinylic monomers;

a carboxyl-containing cellulose;

poly(glutamic acid);

poly(aspartic acid);

or combinations thereof,

wherein the carboxyl-containing vinylic monomer is selected from the group consisting of acrylic acid, a C₁-C₄ alkylacrylic acid, N,N-2-acrylamidoglycolic acid, beta methyl-acrylic acid (crotonic 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, and combination thereof,

wherein the non-reactive hydrophilic vinylic monomer is selected from the group consisting of acrylamide (AAm), methacrylamide N,N-dimethylacrylamide (DMA), N,N-dimethylmethacrylamide (DMMA), N-vinylpyrrolidone (NVP), N,N,-dimethylaminoethylmethacrylate (DMAEM), N,N-dimethylaminoethylacrylate (DMAEA), N,N-dimethylaminopropylmethacrylamide (DMAPMAm), N,N-dimethylaminopropylacrylamide (DMAPAAm), 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), a phosphorylcholine-containing vinylic monomer, and combinations thereof.

17. The method of claim 16, wherein the carboxyl-containing polymeric material is polyacrylic acid, polymethacrylic acid, poly(C₂-C₁₂ alkylacrylic acid), poly[acrylic acid-co-methacrylic 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.

18. The method of claim 16, wherein the weight average molecular weight M_w of the carboxyl-containing polymeric material is at least about 10,000 Daltons.

19. The method of claim 1, wherein the step (b) is performed by dipping the silicone hydrogel contact lens in a solution of the carboxyl-containing polymeric material, wherein the solution is prepared by dissolving the carboxyl-containing polymeric material in a mixture of water and one or more organic solvents, an organic solvent, or a mixture of one or more organic solvent.

20. A silicone hydrogel contact lens which has a crosslinked hydrophilic coating thereon and is obtained according to a method of claim 1, wherein the silicone hydrogel contact lens has at least one of the properties 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 from about 18% to about 70% by weight when fully hydrated;

or combinations thereof.