Polymers and methods for ophthalmic applications

Abstract

The present invention relates to novel methods and materials particularly useful for ophthalmic applications and to methods for making and using the same. More particularly, the present invention relates to relatively soft, optically transparent, foldable, high refractive index materials particularly suited for use in the production of intraocular lenses, contact lenses, and other ocular implants and to methods for manufacturing and implanting IOLs made therefrom.

Claims

1. A method of determining post-implantation diopter of a lens pre-implantation comprising the steps of: (a) providing an intraocular lens (IOL) comprising a polymer for which the rigidity and refractive index is dependent upon its state of hydration, wherein the polymer comprises a first hydrophilic monomer and a second hydrophilic monomer selected from the group consisting of 2-phenylethyl acrylate, 2-phenylethyl methacrylate, hydroxyethylmethacrylate, and hydroxyethylacrylate, and further wherein one of the hydrophilic monomers is present in the polymer in an amount of about 70 weight percent; (b) exposing the IOL of step (a) before implantation to a hydrating liquid for a length of time that the polymer of the IOL hydrates to a state of hydration which is substantially similar to the state of hydration the IOL polymer will obtain post-implantation; (c) measuring the diopter value of the substantially hydrated IOL of step (b); (d) partially dehydrating the substantially hydrated IOL of step (c) to enhance its handling characteristics and ease of implantation in an eye, wherein the partially dehydrated IOL after implantation in the eye will obtain the diopter value substantially that of the IOL measured pre-implantation.

2. A method according to claim 1 further comprising implanting the partially dehydrated IOL in an eye, wherein the implanting step is accomplished using an IOL injector means.

3. A method according to claim 1 wherein the IOL polymer has equilibrium water content in the range of about 3% to about 15% by weight.

4. A method according to claim 1 wherein the IOL polymer has equilibrium water content in the range of about 4% to 10% by weight.

5. A method according to claim 2 wherein the implanted IOL exhibits reduced or eliminated glistenings as experienced by the wearer, post-implantation.

6. A method according to claim 2 wherein the implanted IOL exhibits reduced or eliminated glistenings as experienced by the wearer, post-implantation.

7. A method according to claim 1 wherein the polymer further comprises a crosslinker.

8. The method of claim 7, wherein said polymer further includes an ultraviolet light absorbing material.

9. The method of claim 7, wherein said polymer 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-hydroxybenzo-phenone, 2-(2′-methacryloxy-5′-methylphenyl)benzotriazole, 2-(2′-hydroxy-5′-methacryoxy-ethylphenyl)-2H-benzotriazole, 2-[3′-tert-Butyl-2′hydroxy-5′-(3″-methacyloyloxypropyl)phenyl]-5-chlorobenzotriazole, 2-(3′-tert-Butyl-5′-(3-dimethylvinylsilypropoxy)-2′-hydroxyphenyl]-5-methoxybenzo-triazole, 2-(3′-Allyl-2′-hydroxy-5-′methylphenyl)benzotriazole, 2-[3′tert′-Butyl-2′-hydroxy-5′-(3″-methacryloyl-oxypropoxy)phenyl]-5-methoxybenzotriazole and 2-[3′-tert-Butyl-2′-hydr-oxy-5′-(3″-methacryloyloxypropoxy)phenyl]-5-chloro-benzotriazole.

10. The method of claim 8, wherein the ultraviolet light absorbing material is vinyl anthracene or derivatives therein.

Description

DETAILED DESCRIPTION OF THE INVENTION

(1) Materials of the present invention with high refractive indexes are desirable to allow manufacturers to manufacture thinner IOLs. A thin IOL or thin IOL optic is critical in enabling a surgeon to minimize incision size. Keeping the surgical incision size to a minimum reduces intraoperative trauma and postoperative complications. A thin IOL is also critical for accommodating certain anatomical locations in the eye such as the anterior chamber and the ciliary sulcus. IOLs may be placed in the anterior chamber for increasing visual acuity in both aphakic and phakic eyes and placed in the ciliary sulcus for increasing visual acuity in phakic eyes.

(2) The preferred materials of the present invention have the flexibility required to allow the same to be folded or deformed so that IOLs made therefrom may be introduced into an eye through the smallest possible incision.

(3) The novel materials of the present invention are copolymers, trimers, tetramers, etc., comprising at least two monomeric components:

(4) a hydrophobic monomer, and a hydrophilic monomer. A cross linker generally is included as is a UV absorber.

(5) The compositions comprise multimers including: a first monomer containing an aromatic, carbazole and or naphthyl moiety, the aromatic/carbazole/naphthyl moiety monomer being present in the composition at a concentration of at least 25% and preferably up to about 35-80%.

(6) The composition further includes a second monomer with a hydrophobic homopolymer, the hydrophobicity being defined as the homopolymer having a surface tension of about 50 dyn/cm or less, the second monomer being present in the copolymer in an amount of at least about 20 weight percent, preferably about 50-60 weight %.

(7) The composition then includes at least about 10 weight % of a hydrophilic monomer, preferably about 20-30 weight %. The composition then includes a crosslinking monomer, the crosslinking monomer being present at a concentration in the range up to 10 weight percent, preferably of about 1 weight % to about 8 weight %.

(8) Suitable hydrophilic monomers (i.e., monomers whose homopolymers are hydrophilic in accordance with this invention) include but are not limited to 2-hydroxyethylacrylate, 2-hydroxyethylmethacrylate, acrylamide, N-ornithine acrylamide, N-(2-hydroxypropyl)acrylamide, polyethyleneglycol acrylates, polyethyleneglycol methacrylates, N-vinyl pyrolidone, N-phenylacrylamide, dimethylaminopropyl methacrylamide, acrylic acid, benzylmethacrylamide, 4-hydroxybutylmethacrylate, glycerol mono methacrylate, glycerol mono acrylate, 2-sulfoethylmethacrylate, phenoxyethyl acrylate, phenoxy ethyl methacrylate, 2-(2-ethoxyethoxy)ethyl acrylate, 2-(2-ethoxyethoxy)ethyl methacrylate, furfuryl acrylate, furfuryl methacrylate, and methylthioethylacrylamide.

(9) Suitable hydrophobic monomers (i.e., monomers whose homopolymers are hydrophobic in accordance with this invention) include but are not limited to Lauryl methacrylate, Lauryl acrylate, 2-ethylhexyl acrylate, 2-ethylhexyl methacrylate, n-decyl acrylate, n-decyl methacrylate, hexyl acrylate, hexyl methacrylate, stearyl acrylate, stearyl methacrylate, isodecyl acrylate, isodecyl methacrylate, isobornyl acrylate, isobornyl methacrylate, vinyl laurate, vinyl stearate, 1-hexadecyl acrylate, 1-hexadecyl methacrylate, n-myristyl acrylate, n-myristyl methacrylate, n-dodecyl methacrylamide, butyl acrylate, n-butyl methacrylate, isooctyl acrylate, isotridecyl acrylate, isooctyl methacrylate, and isotridecyl methacrylate.

(10) Suitable crosslinkers include for example but are not limited to ethylene glycol dimethacrylate (EGDMDA), diethylene glycol dimethacrylate, triethylene glycol dimethacrylate and poly(ethylene glycol)dimethacrylate wherein ethylene glycol dimethacrylate is preferred. Suitable initiators include for example but are not limited to azobis(isobutyronitrile), 2,2′-azobis(2,4-dimethylvaleronitrile), 2,2′-azobis(methylbutyronitrile), 1,1′-azobis(cyanocyclo-hexane), di-t-butyl peroxide, dicumyl peroxide, t-butylcumyl peroxide, 2,5-dimethyl-2,5-bis(2-ethylhexanoyl peroxy)hexane, t-butyl peroxyneodecanote, 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 wherein 2,2′-azobis(isobutyronitrile) is preferred. Suitable ultraviolet light absorbers include for example but are not limited to beta-(4-benzotriazoyl-3-hydroxyphenoxy)ethyl acrylate, 4-(2-acryloxyethoxy)-2-hydroxybenzophenone, 4-methacryloxy-2-hydroxybenzo-phenone, 2-(2′-methacryloxy-5′-methylphenyl)benzotriazole, 2-(2′-hydroxy-5′-methacryoxyethylphenyl)-2H-benzotriazole, 2-[3′-tert-Butyl-2′-hydroxy-5′-(3″-methacryloyloxypropyl)phenyl]-5-chloro-benzotriazole, 2-(3′-tert-Butyl-5′-[3″-dimethyl-vinyisilylpropoxy)-2′-hydro-xyphenyl]-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″-methacryloyloxy-propoxy)phenyl]-5-chlorobenzotriazole wherein beta-(4-benzotriazoyl-3-hydroxyphen-oxy)ethyl acrylate is the preferred ultraviolet light absorber.

(11) A UV absorber optionally may be added to the copolymer compositions. A novel, preferred, UV/blue light absorber, i.e., vinyl anthracene, may be added to the copolymer compositions. Conventional UV absorbers such as a vinyl benzophenone or a vinyl benzotriazole also may be used.

(12) TABLE-US-00001 TABLE 1 Examples 1-8: Concen- ΔD upon Example Monomer tration RI % EWC Tg ° C. hydration 1 PEA 70 1.5341 7 2 0.6 HEA 27 EGDM 3 2 PEMA 67 1.5401 6 12 0.6 HEA 30 EGDM 3 3 PEA 67 1.5441 8 16 0.8 HEMA 30 EGDM 3 4 BA 70 1.5241 9 10 1.0 HEA 27 EGDM 3 5 POEA 70 1.5201 10 19 1.0 HEMA 27 EGDM 3 6 BMA 60 1.5312 8 18 0.8 HEA 20 LM 17 EGDM 3 7 VC 27 1.5213 6 10 0.5 HEA 20 LM 50 EGDM 3 8 VC 30 1.5422 14 7 0.8 EHA 42 HEA 25 EGDM 3 0.3% by weight of MEB was used in all copolymer compositions. PEA: 2-phenylethyl acrylate PEMA: 2-phenylethyl methacrylate POEA: Phenoxyethyl acrylate BA: Benzyl acrylate BMA: Benzyl methacrylate VC: vinyl carbazole EHA: 2-ethylhexylacrylate LM: Lauryl methacrylate HEMA; Hyroxyethylmethacrylate HEA: Hydroxyethylacrylate EGDM: ethylene glycol dimethacrylates MEB: 2-(2′-Methacryloxy-5′methylphenyl)benzotriazole

General Preparation Steps for Polymers of Table 1, Example 1-8

(13) The comonomers listed above were mixed in a glass flask using a magnetic stir bar for at least 30 minutes followed by sonication for the times indicated, and then stirring again for another 30 minutes.

(14) We found that sonicating for about 30 minutes at a power setting of 100% on a Branson 5510 provides optically clear materials with adequate optical and physical properties. The monomer solution is degassed with argon and poured in 6 in.×6 in. molds made from glass plates separated by a silicone gasket. The molds were kept at 60° C. for 6 hours and then post-cured in vacuo at 100° C. for 12 hours.

(15) The resulting copolymers are rigid enough to be machined at around room temperature. A unique aspect of the present invention is that the refractive index of these materials is so high that lenses are made thin enough to be folded without further processing or hydration.

(16) IOLs are machined from the copolymers to exact diopters. The IOLs are hydrated in distilled water for 3 hours at 50° C. and the diopter measured again in a hydrated state. The value obtained is the actual power of the lens that should be used for labeling purposes.

(17) Alternatively, a mathematical formula relating the diopter of a dry lens to that of the same lens hydrated may be developed from data such as that discussed below and used to label the IOLs.

(18) Empirical Estimation of In-Vivo Lens Diopter

(19) Unlike conventional hydrogel where lens hydration results into a significant decrease in diopter due to a decrease of RI of the polymer upon absorbing water, the lenses of the present invention exhibit a relatively modest change in diopter upon hydration due to the small amount of water absorbed and a counterbalancing effect of the lens swelling and concomitant steepening of the radius of curvature. Lenses were lathe cut from sheets made from polymer compositions made according to the procedure described previously. Ten (10) lenses were selected for each composition. Table 2 below shows the diopter of 20 D lenses made from polymer examples 1-8 before and after hydration:

(20) TABLE-US-00002 TABLE 2 Examples 1-8: % Diopter before Diopter after Example RI EWC hydration (D) SD* hydration (D) SD 1 1.5341 7 20.0 0.1 20.6 0.3 2 1.5401 6 20.0 0.2 20.6 0.3 3 1.5441 8 20.0 0.1 20.8 0.2 4 1.5241 9 20.0 0.1 21.0 0.2 5 1.5201 10 20.0 0.2 21.0 0.1 6 1.5312 8 20.0 0.2 20.8 0.3 7 1.5213 6 20.0 0.2 20.5 0.2 8 1.5422 14 20.0 0.2 20.8 0.3 *Standard deviation, of diopter measurement, n = 10.