Method for producing contact lenses with durable lubricious coatings thereon

• US 9,810,812 B2
• Filed: 08/29/2016
• Issued: 11/07/2017
• Est. Priority Date: 09/04/2015
• Status: Active Grant

• Current Assignee: Alcon Incorporated
• Original Assignee: Novartis Ag
• Inventors: Qian, Xinming, Chang, Frank, Matsuzawa, Yasuo, Shankar, Venkat
• Primary Examiner(s): Greece, James
• Application Number:
  US15/249,587
• Publication Number:
  US 20170068019A1
• Time in Patent Office: 435 Days
• Field of Search: 35115933, 35115901, 35115902, 35115973
• CPC Class Codes: B29D 11/00048 composed of parts with dissimilar composition B29D11/00057 takes precedence
• CPC Class Codes: B29D 11/00067 Hydrating contact lenses
• CPC Class Codes: B29D 11/00125 Auxiliary operations, e.g. removing oxygen from the mould, conveying moulds from a storage to the production line in an inert atmosphere
• 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 2471/00 Characterised by the use of polyethers obtained by reactions forming an ether link in the main chain of polyacetals C08J2459/00; of epoxy resins C08J2463/00; of polythioether-ethers C08J2481/02; of polyethersulfones C08J2481/06; Derivatives of such polymers
• CPC Class Codes: C08J 2477/00 Characterised by the use of polyamides obtained by reactions forming a carboxylic amide link in the main chain of polyhydrazides C08J2479/06; of polyamide-imides or polyamide acids C08J2479/08; Derivatives of such polymers
• CPC Class Codes: C08J 7/123 Treatment by wave energy or particle radiation C08J7/18 takes precedence
• CPC Class Codes: G02B 1/043 Contact lenses

Abstract

The invention is related to a method for producing silicone hydrogel contact lenses with a stable lubricious hydrogel coating thereon. A method of the invention comprises forming a plasma-reactive hydrophilic polymer hybrid base coating having reactive functional groups on a silicone hydrogel contact lens and heating the silicone hydrogel contact lens with the hybrid base coating in an aqueous solution of a water-soluble and thermally crosslinkable hydrophilic polymeric material to form a stable lubricious hydrogel coating thereon.

Claims

1. A method for producing soft contact lenses, comprising the steps of:

(1) obtaining a preformed silicone hydrogel contact lens in a dry state;

(2) subjecting the preformed silicone hydrogel contact lens in the dry state to a surface treatment to obtain a silicone hydrogel contact lens with a base coating thereon, wherein the base coating comprises a prime plasma layer, a reactive polymer layer on top of the prime plasma layer, and reactive functional groups selected from the group consisting of carboxyl groups, primary amino groups, secondary amino groups, and combinations thereof, wherein the surface treatment comprises the sub-steps of

(a) plasma-treating the surface of the preformed silicone hydrogel contact lens in the dry state with a plasma to obtain a silicone hydrogel contact lens with the prime plasma layer thereon, wherein the plasma is generated in a plasma gas composed of air, N₂, O₂, CO₂, or a mixture of a C₁-C₆ hydrocarbon and a secondary gas selected from the group consisting of air, N₂, O₂, CO₂, and combinations thereof, wherein the prime plasma layer has a thickness of from about 0.5 nm to about 40 nm, and

(b) contacting the silicone hydrogel contact lens with the prime plasma layer thereon with a first aqueous solution including a reactive hydrophilic polymer having multiple reactive functional groups selected from the group consisting of carboxyl groups, primary amino groups, secondary amino groups, and combinations thereof to form the base coating which include the reactive polymer layer of the reactive hydrophilic polymer on top of the prime plasma layer; and

(3) heating the silicone hydrogel contact lens with the base coating thereon obtained in step (2), in a second aqueous solution which comprises a water-soluble and thermally-crosslinkable hydrophilic polymeric material having azetidinium groups and optionally primary or secondary amino groups and/or carboxyl groups, at a temperature of from about 60°

C. to about 140°

C. for a time period sufficient long to crosslink the water-soluble thermally-crosslinkable hydrophilic polymeric material and the base coating so as to form a hydrogel coating on the silicone hydrogel contact lens, wherein the silicone hydrogel contact lens in fully hydrated state has a WBUT of at least about 10 seconds and a friction rating of about 3 or lower.

2. The method of claim 1, wherein the plasma is generated in a plasma gas compose of CO₂, or a mixture of methane and CO₂.

3. The method of claim 1, wherein the first aqueous solution has a pH from about 1.0 to about 3.0, and wherein the reactive hydrophilic polymer is a polyanionic polymer comprising carboxyl groups and having a weight average molecular weight of at least 1000 Daltons.

4. The method of claim 3, wherein the polyanionic polymer is selected from the group consisting of polyacrylic acid, polymethacrylic acid, polyethylacrylic acid, poly(acrylic acid-co-methacrylic acid), poly(acrylic acid-co-ethacrylic acid), poly(methacrylic acid-co-ethacrylic acid), and a mixture thereof.

5. The method of claim 1, wherein the first aqueous solution has a pH from about 9.5 to about 11.0, wherein the reactive hydrophilic polymer is a polycationic polymer comprising primary and/or secondary amino groups and having a weight average molecular weight of at least 1000 Daltons.

6. The method of claim 5, wherein the polycationic polymer is selected from the group consisting of polyethyleneimine, polyallylamine, polyvinylamine, polyamidoamine, and a mixture thereof.

7. The method of claim 1, wherein the reactive hydrophilic polymer comprises azetidinium groups and reactive functional groups selected from the group consisting of primary groups, secondary amino groups, carboxyl groups, and combinations thereof, wherein the reactive hydrophilic polymer has a weight average molecular weight of at least 1000 Daltons, wherein the first aqueous solution has a pH of less than about 8.0.

8. The method of claim 7, wherein the reactive hydrophilic polymer is a chemically-modified poly(2-oxazoline-co-ethyleneimine)-epichlorohydrin, a chemically-modified polyamidoamine-epichlorohydrin, or combinations thereof, wherein the chemically-modified poly(2-oxazoline-co-ethyleneimine)-epichlorohydrin or the chemically-modified polyamidoamine-epichlorohydrin comprises (i) from about 20% to about 95% by weight of first polymer chains derived from a polyamidoamine-epichlorohydrin or a poly(2-oxazoline-co-ethyleneimine)-epichlorohydrin, (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 two reactive functional groups selected from the group consisting of amino group, carboxyl group, and combination thereof, 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 polyamidoamine-epichlorohydrin or the poly(2-oxazoline-co-ethyleneimine)-epichlorohydrin and one amino, carboxyl or thiol group of the hydrophilicity-enhancing agent, and (iii) azetidinium groups which are parts of the first polymer chains or pendant or terminal groups covalently attached to the first polymer chains.

9. The method of claim 1, wherein the water-soluble thermally crosslinkable hydrophilic polymeric material is a poly(2-oxazoline-co-ethyleneimine)-epichlorohydrin, a chemically-modified poly(2-oxazoline-co-ethyleneimine)-epichlorohydrin, a chemically-modified polyamidoamine-epichlorohydrin, or combinations thereof, wherein the chemically-modified poly(2-oxazoline-co-ethyleneimine)-epichlorohydrin or the chemically-modified polyamidoamine-epichlorohydrin comprises (i) from about 20% to about 95% by weight of first polymer chains derived from a polyamidoamine-epichlorohydrin or a poly(2-oxazoline-co-ethyleneimine)-epichlorohydrin, (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, 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 polyamidoamine-epichlorohydrin or the poly(2-oxazoline-co-ethyleneimine)-epichlorohydrin and one amino, carboxyl or thiol group of the hydrophilicity-enhancing agent, and (iii) azetidinium groups which are parts of the first polymer chains or pendant or terminal groups covalently attached to the first polymer chains.

10. The method of claim 9, wherein the water-soluble thermally crosslinkable hydrophilic polymeric material is a chemically-modified poly(2-oxazoline-co-ethyleneimine)-epichlorohydrin or a chemically-modified polyamidoamine-epichlorohydrin, wherein the chemically-modified poly(2-oxazoline-co-ethyleneimine)-epichlorohydrin and the chemically-modified polyamidoamine-epichlorohydrin independently of each other comprise:

(i) from about 20% to about 95% by weight of first polymer chains derived from a polyamidoamine-epichlorohydrin or a poly(2-oxazoline-co-ethyleneimine)-epichlorohydrin;

(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 polyamidoamine-epichlorohydrin or the poly(2-oxazoline-co-ethyleneimine)-epichlorohydrin and one amino, carboxyl or thiol group of the hydrophilicity-enhancing agent.

11. The method of claim 10, wherein the hydrophilicity-enhancing agent is a hydrophilic polymer having one or more amino, carboxyl and/or thiol groups, wherein the content of the amino, carboxyl and/or thiol groups 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.

12. The method of claim 10, wherein the hydrophilicity-enhancing agent is:

PEG-NH₂;

PEG-SH;

PEG-COOH;

H₂N-PEG-NH₂;

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 diamino-, dicarboxyl-, monoamino- or monocarboxyl-terminated homo- or co-polymer of a non-reactive hydrophilic vinylic monomer;

or combinations thereof, wherein PEG is a polyethylene glycol segment, wherein the non-reactive 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, a phosphorylcholine-containing vinylic monomer, 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.

13. The method of claim 10, 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 from about 1% to about 15%, by weight of at least one reactive vinylic monomer and (2) at least one non-reactive hydrophilic vinylic monomer, 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-C₄ 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 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, a phosphorylcholine-containing vinylic monomer, 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.

14. The method of claim 10, wherein the hydrophilic polymer as the hydrophilicity-enhancing agent is an amino- or carboxyl-containing polysaccharide, hyaluronic acid, chondroitin sulfate, and combinations thereof.

15. The method of claim 10, wherein the weight average molecular weight M_w of the hydrophilicity-enhancing agent is from about 500 to about 1,000,000 Daltons.

16. The method of claim 10, 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.

17. The method of claim 10, wherein the first polymer chains are derived from the polyamidoamine-epichlorohydrin.

18. The method of claim 10, wherein the first polymer chains are derived from the poly(2-oxazoline-co-ethyleneimine)-epichlorohydrin.

19. The method of claim 1, wherein the step of heating is carried out directly in a sealed lens package containing a packaging solution including the water-soluble and thermally-crosslinkable hydrophilic polymeric material during sterilization by autoclave at a temperature from about 115°

C. to about 125°

C. for at least about 20 minutes under pressure;

wherein the packaging solution comprises from about 0.01% to about 2% by weight of the water-soluble and thermally-crosslinkable hydrophilic polymeric material;

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 5 centipoises, at 25°

C.

20. A silicone hydrogel contact lens, comprising:

a silicone hydrogel substrate;

a base coating on the surface of the silicone hydrogel substrate, wherein the base coating comprises a prime plasma layer and a reactive polymer layer on top of the prime plasma layer, wherein the plasma prime layer has a thickness of from about 0.5 nm to about 40 nm, wherein the reactive polymer comprises reactive functional groups selected from the group consisting of carboxyl groups, primary amino groups, secondary amino groups, and combinations thereof; and

a non-silicone hydrogel coating covalently attached onto the base coating, wherein the non-silicone hydrogel coating is covalently attached onto the reactive polymer layer through multiple reactive functional groups,

wherein the silicone hydrogel contact lens in a fully-hydrated state has an oxygen permeability of at least about 40 barrers, a WBUT of at least about 10 seconds, a friction rating of about 3 or lower, and a water contact angle of about 80 degrees or less.