High refractive index hydrogel compositions for ophthalmic implants

• US 6,329,485 B1
• Filed: 12/11/1998
• Issued: 12/11/2001
• Est. Priority Date: 12/11/1998
• Status: Expired due to Term

• Current Assignee: Bausch & Lomb Incorporated (Bausch Health Cos., Inc.)
• Original Assignee: Bausch & Lomb Incorporated (Bausch Health Cos., Inc.)
• Inventors: Vanderbilt, David P.
• Primary Examiner(s): Wu, David W.
• Assistant Examiner(s): ZALUKAEVA, TATYANA
• Application Number:
  US09/209,552
• Time in Patent Office: 1,096 Days
• Field of Search: 526/318.1, 526/317.1, 526/318, 526/319, 526/320, 526/327, 623/6.11
• US Class Current: 526/318.1
• CPC Class Codes: A61L 2430/16 for reconstruction of eye parts, e.g. intraocular lens, cornea
• CPC Class Codes: A61L 27/16 obtained by reactions only involving carbon-to-carbon unsaturated bonds
• CPC Class Codes: C08F 220/26 Esters containing oxygen in addition to the carboxy oxygen
• CPC Class Codes: C08L 33/02 Homopolymers or copolymers of acids; Metal or ammonium salts thereof
• CPC Class Codes: C08L 33/14 of esters containing halogen, nitrogen, sulfur, or oxygen atoms in addition to the carboxy oxygen
• CPC Class Codes: G02B 1/043 Contact lenses

Abstract

Optically transparent, high refractive index hydrogels and intraocular lenses fabricated therefrom. The preferred hydrogels have a refractive index of 1.45 or above and a water content of approximately 5 to 30 percent by weight.

Claims

1. A hydrogel composition comprising:

a high refractive index monomer;

a hydrophilic monomer present in said composition in an amount greater than that of said high refractive index monomer;

a crosslinker; and

an initiator to form a hydrogel composition having a fully-hydrated water content less than approximately 20 percent by weight but at least approximately 5 percent by weight and a fully-hydrated refractive index of approximately 1.47 or greater to enable intraocular lenses made therefrom to be capable of passing through a 4.0 mm or smaller incision in a fully-hydrated state.

2. The hydrogel composition of claim 1 wherein said composition includes an ultraviolet light absorbing material.

3. The hydrogel composition of claim 1 wherein said composition includes an ultraviolet light absorbing material selected from the group consisting of beta-(4-benzotriazoyl-3-hydroxyphenoxy)ethyl acrylate, 4-(2-acryloxyethoxy)-2-hydroxybenzophenone, 4-methacryloxy-2-hydroxybenzophenone, 2-(2′

-methacryloxy-5′

-methylphenyl)benzotriazole, 2-(2′

-hydroxy-5′

-methacryoxyethylphenyl)-2H-benzotriazole, 2-[3′

-tert-Butyl-2′

-hydroxy-5′

-(3″

-methacryloyloxypropyl)phenyl]-5-chlorobenzotriazole, 2-(3′

-tert-Butyl-5′

-(3-dimethylvinylsilylpropoxy)-2′

-hydroxyphenyl]-5-methoxybenzotriazole, 2-(3′

-Allyl-2′

-hydroxy-5′

-methylphenyl)benzotriazole, 2-[3′

-tert-Butyl-2′

-hydroxy-5′

-(3″

-methacryloyloxypropoxy)phenyl]-5-methoxybenzotriazole and 2-[3′

-tert-Butyl-2′

-hydroxy-5′

-(3″

-methacryloyloxypropoxy)phenyl]-5-chlorobenzotriazole.

4. The hydrogel composition of claim 1 wherein said composition includes beta-(4-benzotriazoyl-3-hydroxyphenoxy)-ethyl acrylate as an ultraviolet light absorbing material.

5. The hydrogel composition of claim 1 wherein said initiator is selected from the group consisting of azobis(isobutyronitrile), 2,2′

-azobis(2,4-dimethylvaleronitrile), 2,2′

-azobis(methylbutyronitrile), 1,1′

-azobis(cyanocyclohexane), di-t-butyl peroxide, dicumyl peroxide, t-butylcumyl peroxide, 2,5-dimethyl-2,5-bis(2-ethylhexanoylperoxy)hexane, t-butylperoxyneodecanote, t-butyl peroxy 2-ethylhexanoate, di(4-t-butyl cyclohexyl) peroxydicarbonate, t-butyl peroxypivalate, decanoyl peroxide, lauroyl peroxide, benzoyl peroxide, 2,4-pentanedione peroxide, di(n-propyl)peroxydicarbonate, t-amyl peroxyneodecanoate and t-butyl peroxyacetate.

6. The hydrogel composition of claim 1 wherein said initiator is azobis(isobutyronitrile).

7. The composition of claim 1 wherein said crosslinker is selected from the group consisting of ethylene glycol dimethacrylate, diethylene glycol dimethacrylate, triethylene glycol dimethacrylate and poly(ethylene glycol) dimethacrylate.

8. The composition of claim 1 wherein said crosslinker is ethylene glycol dimethacrylate.

9. The composition of claim 1 wherein said hydrophilic monomer is a monomer represented by the formula:

wherein R₁ is selected from the group consisting of hydrogen and C_1-6 alkyl and R₂ is selected from the group consisting of hydrogen, an alkali metal, an alkaline earth metal, C_1-6 hydroxyalkyl, C_4-12 hydroxyalkoxyalkyl, C_4-12 hydroxyalkoxyalkyl, C_2-12 alkoxyalkyl, C_3-12 polyalkoxyalkyl, C_3-15 polyalkoxyhydroxyalkyl and C_2-12 dihydroxyalkyl.

10. The composition of claim 1 wherein said hydrophilic monomer is selected from the group consisting of 2-hydroxyethyl methacrylate, hydroxyethoxyethyl methacrylate, hydroxydiethoxyethyl methacrylate, methoxyethyl methacrylate, methoxyethoxyethyl methacrylate, methoxydiethoxyethyl methacrylate, poly(ethylene glycol) methacrylate, methoxy-poly(ethylene glycol) methacrylate, methacrylic acid, sodium methacrylate, glycerol methacrylate, hydroxypropyl methacrylate, and hydroxybutyl methacrylate.

11. The composition of claim 1 wherein said hydrophilic monomer is 2-hydroxyethyl methacrylate.

12. The composition of claim 1 wherein said high refractive index monomer is a monomer represented by one of the formulas:

wherein R₃ is selected from the group consisting of hydrogen and C_1-6, alkyl, R₄ is selected from the group consisting of C_6-25 aryl, C_6-25 hydroxyaryl, C_6-25 aryloxyaryl, C_12-25 polyhydroxyaryl, C_12-35 polyaryl, C_6-15 arylalkyl, C_12-35 polyarylalkyl, C_6-15 alkoxyaryl, C_6-15 aryl halides, C_6-15 aryloxyalkyl, C_1-7 alkyl halides, C_6-15 arylthioalkyl, C_6-15 aryloxyalkyl halides and C_6-15 aryloxyalkoxyalkyl, and R₅ is selected from the group consisting of hydrogen, C_1-3 alkyl and C_6-15 alkylaryl.

13. The composition of claim 1 wherein said high refractive index monomer is selected from the group consisting of phenyl acrylate, phenyl methacrylate, benzyl acrylate, benzyl methacrylate, 2-phenylethyl acrylate, 2-phenylethyl methacrylate, 2-phenoxyethyl acrylate, 2-phenoxyethyl methacrylate, phenylthioethyl acrylate, phenylthioethyl methacrylate, 2,4,6-tribromophenyl acrylate, 2,4,6-tribromophenyl methacrylate, pentabromophenyl acrylate, pentabromophenyl methacrylate, pentachlorophenyl acrylate, pentachlorophenyl methacrylate, 2,3-dibromopropyl acrylate, 2,3-dibromopropyl methacrylate, 2-naphthyl acrylate, 2-naphthyl methacrylate, 4-methoxybenzyl acrylate, 4-methoxybenzyl methacrylate, 2-benzyloxyethyl acrylate, 2-benzyloxyethyl methacrylate, 4-chlorophenoxyethyl acrylate, 4-chlorophenoxyethyl methacrylate, 2-phenoxyethoxyethyl acrylate, 2-phenoxyethoxyethyl methacrylate, N-phenyl acrylamide, N-phenyl methacrylamide, N-benzyl acrylamide, N-benzyl methacrylamide, N,N-dibenzyl acrylamide, N,N-dibenzyl methacrylamide, N-diphenylmethyl acrylamide, N-(4-methylphenyl)methyl acrylamide, N-1-naphthyl acrylamide, N-4-nitrophenyl acrylamide, N-(2-phenylethyl) acrylamide, N-triphenylmethyl acrylamide, N-(4-hydroxyphenyl) acrylamide, N,N-methylphenyl acrylamide, N,N-phenyl phenylethyl acrylamide, N-diphenylmethyl methacrylamide, N-(4-methyl phenyl)methyl methacrylamide, N-1-naphthyl methacrylamide, N-4-nitrophenyl methacrylamide, N-(2-phenylethyl) methacrylamide, N-triphenylmethyl methacrylamide, N-(4-hydroxyphenyl) methacrylamide, N,N-methylphenyl methacrylamide, N,N′

-phenyl phenylethyl methacrylamide, N-vinylcarbazole, 4-vinylpyridine, 2-vinylpyridine, styrene, 2-chlorostyrene, 3-chlorostyrene, 4-chlorostyrene, 2-bromostyrene, 3-bromostyrene, 4-bromostyrene, 2,6-dichlorostyrene, 2-iodostyrene, 3-iodostyrene, 4-iodostyrene, pentabromostyrene, 4-phenylstyrene, 1-vinylnaphthalene, 2-vinylnaphthalene, 9-vinylanthracene and 4-phenoxystyrene.

14. The composition of claim 1 wherein said high refractive index monomer and said hydrophilic monomer comprise at least about 70 percent by weight of said composition.

15. The composition of claim 1 wherein said high refractive index monomer and said hydrophilic monomer comprise approximately 75 percent by weight of said composition.

16. A composition poly(2-hydroxyethyl methacrylate-co-phenyl methacrylate) having a fully-hydrated water content less than approximately 20 percent by weight but at least approximately 5 percent by weight and a fully-hydrated refractive index of approximately 1.47 or greater to enable intraocular lenses made therefrom to be capable of passing through a 4.0 mm or smaller incision in a fully-hydrated state.

17. A composition poly(2-hydroxyethyl methacrylate-co-benzyl acrylate) having a fully-hydrated water content less than approximately 20 percent by weight but at least approximately 5 percent by weight and a fully-hydrated refractive index of approximately 1.47 or greater to enable intraocular lenses made therefrom to be capable of passing through a 4.0 mm or smaller incision in a fully-hydrated state.

18. A composition poly(2-hydroxyethyl methacrylate-co-benzyl methacrylate) having a fully-hydrated water content less than approximately 20 percent by weight but at least approximately 5 percent by weight and a fully-hydrated refractive index of approximately 1.47 or greater to enable intraocular lenses made therefrom to be capable of passing through a 4.0 mm or smaller incision in a fully-hydrated state.

19. A composition poly(2-hydroxyethyl methacrylate-co-2-phenylethyl acrylate) having a fully-hydrated water content less than approximately 20 percent by weight but at least approximately 5 percent by weight and a fully-hydrated refractive index of approximately 1.47 or greater to enable intraocular lenses made therefrom to be capable of passing through a 4.0 mm or smaller incision in a fully-hydrated state.

20. A composition poly(2-hydroxyethyl methacrylate-co-2-phenylethyl methacrylate) having a fully-hydrated water content less than approximately 20 percent by weight but at least approximately 5 percent by weight and a fully-hydrated refractive index of approximately 1.47 or greater to enable intraocular lenses made therefrom to be capable of passing through a 4.0 mm or smaller incision in a fully-hydrated state.

21. A composition poly(2-hydroxyethyl methacrylate-co-2-phenoxyethyl acrylate) having a fully-hydrated water content less than approximately 20 percent by weight but at least approximately 5 percent by weight and a fully-hydrated refractive index of approximately 1.47 or greater to enable intraocular lenses made therefrom to be capable of passing through a 4.0 mm or smaller incision in a fully-hydrated state.

22. A composition poly(2-hydroxyethyl methacrylate-co-2-phenoxyethyl methacrylate) having a fully-hydrated water content less than approximately 20 percent by weight but at least approximately 5 percent by weight and a fully-hydrated refractive index of approximately 1.47 or greater to enable intraocular lenses made therefrom to be capable of passing through a 4.0 mm or smaller incision in a fully-hydrated state.

23. A composition poly(2-hydroxyethyl methacrylate-co-N-benzyl methacrylamide) having a fully-hydrated water content less than approximately 20 percent by weight but at least approximately 5 percent by weight and a fully-hydrated refractive index of approximately 1.47 or greater to enable intraocular lenses made therefrom to be capable of passing through a 4.0 mm or smaller incision in a fully-hydrated state.

24. A composition poly(2-hydroxyethyl methacrylate-co-N-vinylcarbazole) having a fully-hydrated water content less than approximately 20 percent by weight but at least approximately 5 percent by weight and a fully-hydrated refractive index of approximately 1.47 or greater to enable intraocular lenses made therefrom to be capable of passing through a 4.0 mm or smaller incision in a fully hydrated state.