Ultra violet, violet, and blue light filtering polymers for ophthalmic applications

Abstract

Opthalmic devices, particularly intraocular lenses (IOL), with improved contrast sensitivity and methods of making same. In one aspect, blue light blocking chromophores (BLBC) are diffused into, e.g. an IOL lens body to create a BLBC gradient in the lens. Orange dyes are preferred BLBCs.

Claims

1. A foldable intraocular lens comprising: a copolymer of vinyl carbazole, 2-ethylhexylacrylate, ethylene glycol dimethacrylate, and vinyl anthracene, the lens further comprising a substituted hydroxy benzotriazole moiety or a substituted hydroxy benzophenone moiety; and an orange dye wherein the orange dye is selected from the group consisting of: disperse orange 3 acrylamide, disperse orange 3 methacrylamide, disperse orange 3 acrylate, disperse orange 3 methacrylate, disperse orange 25 acrylamide, disperse orange 25 methacrylamide, disperse orange 25 acrylate, disperse orange 25 methacrylate, and 10-dodecylacridine orange bromide, wherein the orange dye is present in a concentration in the range of about 0.001% to 10% by weight, and further wherein the orange dye has a coefficient of extinction (e) of at least 1500 M-.sup.1 cm-.sup.1 for a region between 350 nanometers and 500 nm.

2. The foldable intraocular lens according to claim 1 wherein the orange dye is present in the range of about 0.002% to about 5% by weight.

3. The foldable intraocular lens according to claim 1 wherein the orange dye is present in the range of about 0.003% to about 3% by weight.

4. The foldable intraocular lens according to claim 1 further comprising hydroxyethylmethacrylate.

5. The foldable intraocular lens according to claim 1 further comprising hydroxyethylacrylate.

6. The foldable intraocular lens according to claim 1 wherein the substituted hydroxy benzotriazole moiety is 2-(2-methacryloxy-5-methylphenyl)benzotriazole.

7. The foldable intraocular lens according to claim 6, wherein the orange dye is disperse orange 25 methacrylamide.

8. The foldable intraocular lens according to claim 6, wherein the orange dye is disperse orange 3 acrylamide.

9. The foldable intraocular lens according to claim 6, wherein the orange dye is disperse orange 3 methacrylamide.

Description

DETAILED DESCRIPTION OF THE INVENTION

Ophthalmic Device Base Polymer

(1) Suitable monomers for use in polymeric ophthalmic device of the present invention include but are not limited to carbazole and/or naphthyl moiety, carbazole, naphthalene, or a naphthyl group such as vinyl carbazole, vinyl naphthalene, lauryl methacrylate, stearyl methacrylate, methyl methacrylate, 2-hydroxyethyl acrylate, 2-hydroxyethyl methacrylate, 3-hydroxypropyl acrylate, 3-hydroxypropyl methacrylate, n-vinyl pyrrolidone, styrene, eugenol (4-hydroxyvinylbenzene), alpha.-methylstyrene. In addition, for high-refractive index foldable lens applications, suitable monomers include, but are not limited to: 2-ethylphenoxy methacrylate, 2-ethylphenoxy acrylate, 2-ethylthiophenyl methacrylate, 2-ethylthiophenylacrylate, 2-ethylaminophenyl methacrylate, phenyl methacrylate, benzyl methacrylate, 2-phenylethyl methacrylate, 3-phenylpropyl methacrylate, 4-phenylbutyl methacrylate, 4-methylphenyl methacrylate, 4-methylbenzyl methacrylate, 2-2-methylphenylethyl methacrylate, 2-3-methylphenylethyl methacrylate, 2-4-methylphenylethyl methacrylate, 2-(4-propylphenyl)ethyl methacrylate, 2-(4-(1-methylethyl)phenyl)ethyl methacrylate, 2-(4-methoxyphenyl)ethyl methacrylate, 2-(4-cyclohexylphenyl)ethyl methacrylate, 2-(2-chlorophenyl)ethyl methacrylate, 2-(3-chlorophenyl)ethyl methacrylate, 2-(4-chloro-phenyl)ethyl methacrylate, 2-(4-bromophenyl)ethyl methacrylate, 2-(3-phenylphenyl)ethyl methacrylate, 2-(4-phenylphenyl)ethyl methacrylate), 2-(4-benzylphenyl)ethyl methacrylate, and the like, including the corresponding methacrylates and acrylates. N-vinyl pyrolidone, styrene, eugenol and .alpha.-methyl styrene may also be suitable especially for high-refractive index foldable lens applications.

(2) A preferred lens-forming monomer mixture is the mixture of vinyl carbazole, lauryl methacrylate, and hydroxyethyl acrylate. Conventional methods for polymerization of the preferred monomer mixture to a preferred polymeric lens material would be well known to one skilled in the polymer art.

(3) A copolymerizable cross-linking agent is preferably used in the lens-materials of this invention such cross-linking may be any terminally or internally ethylenically unsaturated compound having more than one unsaturated group. Suitable cross-linking agents include, for example: ethylene glycol dimethacrylate, diethylene glycol dimethacrylate, allyl methacrylate, 1,3-propanediol dimethacrylate, allyl methacrylate, 1,6-hexanediol dimethacrylate, 1,4-butanediol dimethacrylate, and the like. A preferred cross-linking agent is ethylene glycol dimethacrylate. Suitable crosslinkers also include polymeric crosslinkers, such as, polyethylene glycol 1000 diacrylate, polyethylene glycol 1000 dimethacrylate, polyethylene glycol 600 dimethacrylate, polybutanediol 2000 dimethacrylate, polypropylene glycol 1000 diacrylate, polypropylene glycol 1000 dimethacrylate, polytetramethylene glycol 2000 dimethacrylate, and polytetramethylene glycol 2000 diacrylate.

(4) Chromophore System

(5) To achieve optimal light transmission and UV, violet, and blue light blocking, the chromophores described above may be used separately or in various combinations with concentrations varying from about 0.001% to 10% by weight comprises a mixture preferably about 0.002% to about 5% by weight, and most preferably about 0.003% to about 3% by weight. A preferred formulation contains one or more chromophores selected from each of the three classes of chromophores discussed above.

(6) Synthesis of Polymerizable Orange Dyes

(7) Disperse Orange 3 methacrylamide Synthesis

(8) 0.6 g of sodium hydride was added carefully to a 3 neck flask equipped with a condenser, addition funnel, and magnetic bar. 75 ml of anhydrous THF was added and the mixture stirred for 10 minutes. A solution of 4.0 g 4-(4-nitrophenylazo)aniline in 75 ml THF was added drop-wise and the flask stirred at 50 C. The temperature was raised to 95 C., and the mixture was refluxed for 6 hrs. The mixture was allowed to cool to room temperature and then 6.0 g of methacrylic acid in 20 ml THF was added drop-wise. The mixture was again refluxed for 8 hrs. The solution was cooled to room temperature. THF was evaporated to reveal a dark orange solid. The solid was washed thoroughly with dilute HCl and water. The product was recrystallized in 95% methanol. The yield was 56%.

(9) Disperse Orange 25 Methacrylamide Synthesis

(10) 3-[N-Ethyl-4-(4nitrophenylazo)phenylamino]propionitrile was used instead of 4-(4-nitrophenylazo)aniline in the above procedure. The yield was 42%.

(11) Disperse Orange 3 Acrylamide Synthesis

(12) 0.6 g of sodium hydride was added carefully to a 3 neck flask equipped with a condenser, addition funnel, and magnetic bar. 75 ml of methylene chloride was added and the mixture stirred for 10 minutes. A solution of 4.0 g 4-(4-nitrophenylazo)aniline in 75 ml methylene chloride was added drop-wise and the flask stirred at 50 C. The temperature was raised to 95 C., and the mixture was refluxed for 6 hrs. The mixture was allowed to cool to room temperature and then 6.0 g of acrylic acid in 20 ml methylene chloride was added drop-wise. The mixture was again refluxed for 8 hrs. The solution was cooled to room temperature. Methylene chloride was evaporated to reveal a dark orange solid. The solid was washed thoroughly with dilute HCl and water. The product was recrystallized in 95% methanol. The yield was 35%.

(13) Disperse Orange 25 Acrylamide Synthesis

(14) 3-[N-Ethyl-4-(4nitrophenylazo)phenylamino]propionitrile was used instead of 4-(4-nitrophenylazo)aniline in the above procedure. The yield was 38%.

(15) Commercially available chromophores may in some instances be used. Care must be taken to remove any residual initiators, processing aids or other extraneous additives, including unpolymerized monomer(s), which might not be suitable for long-term exposure to ophthalmic fluid or to the ophthalmic environment.

(16) Methods of Manufacture

(17) General Preparation Steps for Polymers of Example 1-10

(18) The comonomers listed below were mixed in a glass flask using a magnetic stir bar for at least 30 minutes followed by sonication for 30 minutes at a power setting of 100% on a Branson 5510 and then stirring again for another 30 minutes. The combination of sonication and hydrophilic/hydrophobic repulsion forces allows the formation of nanoclusters. AIBN was added at a concentration of 0.2% by weight. The comonomer mixture was vacuum degassed and placed in a Teflon tubular mold. The mold was placed in water bath at 70 C. for 12 hours than cured at 100 C. for 12 hours. A polymer rod measuring 19 mm in diameter and 6 inches in length was removed from the mold, cured for 12 hours at 100 C. and annealed for 14 hours at 100 C. for further processing. The polymer rod was machined into 17 mm2 mm disks and IOLs were cut from the samples.

(19) The refractive index was measured using a CLR 12-70 refractometer from Index Instrument. The optical properties of the IOLs were measured by UV/VIS spectroscopy using a DU-50 spectrophotometer from Beckman Instruments. To assess the efficiency of UV light and blue light blocking, percent light transmittance was measured at key wavelengths including 400, 420, and 470 nm. A comparative analysis with a commercially available IOL containing a yellow dye (Acrysof Natural) was included in the studies.

Examples 1-10

(20) TABLE-US-00001 % Transmittance Monomer Conc. RI 400 nm 420 nm 470 nm 1. VC 30 1.569 10 23 53 LM 37 HEMA 29.5 EGDM 2.92 DOM2 0.08 5 0.5 VA 2. VC 30 1.568 14 27 65 LM 36.7 HEA 30 EGDM 2.92 DOA3 0.08 MEB 0.3 3. VC 30 1.563 4 15 54 EHA 36.2 HEMA 30 EGDM 2.95 DOM2 0.05 5 0.5 VA 0.3 MEB 4. VC 30 1.562 8 19 65 EHA 36.1 HEA 30 EGDM 2.95 DOM3 0.05 VA 0.6 MEB 0.3 5. VN 30 1.554 7 9 54 EHA 36.3 HEMA 30 EGDM 2.95 DOM2 0.05 5 0.4 VA 0.3 MEB 6. VC 29 1.551 1 2 48 EHA 37 HEA 30 EGDM 2.98 DOA3 0.02 VA 1.0

(21) TABLE-US-00002 PREFERRED FORMULATIONS 7. VC 21. 1.539 1 19 62 HEA 3 LM 28. EGD 0 M 46. DOM 7 3 2.9 VA 85 MEB 0.0 15 0.7 0.3 8. VC 21. 1.536 1 15 60 HEA 3 LM 28. EGD 0 M 46. DOM 7 3 2.9 VA 82 MEB 0.0 18 0.7 0.3 9. VC 21. 1.535 1 14 50 HEA 3 LM 28. EGD 0 M 46. DOM 7 3 2.9 VA 7 MEB 0.0 3 0.7 0.3 10. VC 21. 1.537 1 19 55 HEA 3 LM 28. EGD 0 M 46. DOM 7 3 2.9 VA 8 MEB 0.0 2 0.7 0.3 Acrysof Natural not known 6 28 57 VC: vinyl carbazole VN: 2-vinyl naphthalene EHA: 2-ethylhexylacrylate LM: Lauryl methacrylate HEMA; Hydroxyethylmethacrylate HEA: Hydroxyethylacrylate EGDM: ethylene glycol dimethacrylate VA: vinyl anthracene MEB: 2-(2-Methacryloxy-5methylphenyl)benzotriazole DOM3: Disperse Orange 3 Methacrylamide DOA3: Disperse Orange 3 Acrylamide DOM25: Disperse Orange 25 Methacrylamide

(22) The results show that the novel chromophore system provides excellent UV, violet, and blue light filtering without compromising light transmission at higher wavelengths.