Classifications

• • G—PHYSICS
  • G02—OPTICS
  • G02B—OPTICAL ELEMENTS, SYSTEMS OR APPARATUS
  • G02B1/00—Optical elements characterised by the material of which they are made; Optical coatings for optical elements
  • G02B1/04—Optical elements characterised by the material of which they are made; Optical coatings for optical elements made of organic materials, e.g. plastics
  • G02B1/041—Lenses
  • G02B1/043—Contact lenses

Definitions

• This invention relates to transparent plastic materials for optical use, and particularly to ocular devices which absorb ultraviolet radiation, and to their production from ultraviolet absorbing compounds, such as by copolymerizing the compounds with suitable reactive monomers.
• UV ultraviolet
• Contact lenses containing compounds for blocking ultraviolet (“UV”) light have been on the market for several years. Such lenses are useful to all who live in areas where bright sunlight is common. As UV radiation is likely to be a cause of cataracts and senile macular degeneration, everyone who wears contact lenses can benefit from the type which block this radiation. Younger persons, whose eye lenses transmit more ultraviolet radiation than do those of older persons, also should be concerned with providing additional protection. Ultraviolet blocking lenses are especially useful for those who have had the natural lens of the eye removed, since the natural lens has UV absorption properties that help to protect the interior of the eye. Hence, UN absorbing intraocular lenses (IOLs) are also highly desirable, since such lenses are implanted in place of the eye's natural lens.
• IOLs intraocular lenses
• Hydrogels are desirable for use in lenses, particularly IOLs.
• Prior art UV absorbers are generally hydrophobic and have limited solubility in hydrogels. Due in part to this limited solubility, it has been difficult to copolymerize UN absorbers with hydrogel forming monomers.
• UN absorbers are preferably copolymerized, rather than physically entrapped within the hydrogel, to prevent the absorber from being leached out of the UN absorbing hydrogel when the hydrogel is in the aqueous environment of the eye or stored in solution.
• UV absorbers having the required characteristics such as UV absorption between 300-400 nm and hydrolytic stability have been difficult to synthesize.
• Collins, et al. discovered a new class of benzotriazoles that are useful in soft contact lenses, as shown in U.S. Pat. No. 5,637,726.
• the compounds absorb UV light very well at the upper end of the UV spectrum.
• These benzotriazoles copolymerize well into hydrogel polymers without the problems of leaching out.
• effective amounts of these benzotriazoles incorporated into the contact lens polymer do not negatively affect the properties of the polymer.
• these compounds increase the refractive index and optic potential of the contact lenses, allowing for thinner lenses with enhanced oxygen permeability. These compounds also have a higher cut-off, up to 400nm, to block more light in the UNA range. While contact lenses containing a UV absorbing compound are now commercially available, these lenses do not block all of the UV light from entering the eye, and typically only block about 90% of the entire UV range. The UV range is generally broken in to two subranges, known as UVA and UVB. ANSI Class 1 specifications for UV absorption require an average percent transmittance of less than 1.0% at 280-315nm (UVB range) and only less than 10% at 316-
• UVA range UV range
• the difficulty in obtaining a UV blocking contact lens that meets Class 1 standards by using a benzotriazole, as described by Collins et al., is that one has to use so much benzotriazole that the lens also absorbs significant amount of light at the upper end of the UVA range and into the visible light range. This results in an observable yellowish tint in the contact lens, which is not appealing to consumers. More importantly, this yellowish tint throws off the cosmetic appearance of colored contact lenses.
• too much benzotriazole, or other UV absorbing compound can adversely affect the properties of the lens polymer, such as durability, flexibility, hydrophilicity, stability to sterilizing regimes, etc.
• the compound may be present in too high quantities for all of it to covalently bond with the other monomers during the polymerization, resulting in excessive residual monomer content that may gradually leach out during use.
• Hung et al. U.S. Patent No. 4,963,160, proposes a solution to some of these problems by bonding two different UV absorbing compounds that each have a different UV absorbing spectra onto a triazine derivative, which is then applied as a coating onto a polymeric lens.
• the UN absorbers are preferably selected to provide a UN absorbing agent with the broadest UN absorption range possible.
• Hung et al. disclosed embodiments of these UN absorbing agents that include p- aminobenzoic acid and a benzotriazole, or p-aminobenzoic acid and a benzophenone.
• the use of this UN absorbing agent has certain limitations because the UN absorbing compounds can only be used in a one-to-one mole ratio, so that the UN absorption spectra of the lens cannot be optimized. Also, there are difficulties to achieve consistent coating thicknesses.
• the present invention overcomes some of these problems unsolved by prior art UV blocking lenses by providing a plastic material, preferably in the form a of an ocular device such as a contact lens or an intraocular lens, comprising a polymer formed by incorporating one or more monomers suitable for use in making such lenses, and effective amounts of a combination of a first ultraviolet absorber and a second ultraviolet absorber, wherein the first UV absorber is a benzotriazole compound represented by the formula:
• R la , R , and R lc are independently hydrogen, halogen, C C 6 straight or branched chain alkoxy group, aryl or substituted aryl;
• R 2 is hydrogen, lower alkyl, preferably tert-butyl, aryl or substituted aryl;
• R 3 is hydrogen, lower alkyl, aryl , substituted aryl, or R 4 -R 5 -R 6 , where R 4 is an oxygen or is absent,
• R 5 is a linking group selected from -(CH 2 ) n O-, -CH(CH 3 )CH 2 O-, -CH 2 CH(CH 3 )O-, -(CH 2 ) deliberatelyOCH 2 -, -CH(CH 3 )CH 2 OCH 2 -, or -CH 2 CH(CH 3 )OCH 2 - group, or is absent;
• R 6 is acrylate, methacrylate, styrene or vinyl; and n is 2 or 3;
• R 7a , R 7b , and R 7c are independently hydrogen, halogen, C r C 6 straight or branched chain alkoxy group, aryl or substituted aryl;
• R 8 is a linking group selected from alkyl, -(CH 2 ) m O-, -CH(CH 3 )CH 2 O-, -CH 2 CH(CH 3 )O-, -(CH 2 ) m OCH 2 -, -CH(CH 3 )CH 2 OCH 2 -, or -CH 2 CH(CH 3 )OCH 2 - group, or is absent;
• R 9 is alkyl, acrylate, methacrylate, styrene or vinyl; and m is 2 or 3.
• Figure 1 shows the UV transmission spectra from the formulations of Example 5.
• Ocular devices contemplated in connection with the present invention include, without limitation, windows, lenses for eyeglasses and instruments such as binoculars, goggles, face shields, contact lenses, intraocular lenses and the like.
• Contact lenses can include both those for correcting defective visual acuity and the so-called “bandage lenses” which are used in treating eye disorders, as well as the purely cosmetic lenses used for purposes such as changing the apparent eye color.
• HEMA Hydroxyethyl methacrylate
• C 6 H 10 O 3 CH 2 C(CH 3 )CO 2 CH 2 CH 2 OH
• EOEMA Ethoxyethyl methacrylate
• CH 2 C(CH 3 )C ⁇ 2 CH 2 CH 2 ⁇ CH 2 CH 3
• VAZO 52 2,2'-azobis(2,4-dimethylpentanenitrile); C 14 H 24 N 4
• the present invention includes a contact lens, intraocular lens, or an optical quality plastic comprising a polymer formed by incorporating one or more monomers suitable for use in making such lenses, and effective amounts of a first ultraviolet absorber and a second ultraviolet absorber to provide amounts of UV absorption to meet ANSI Class 1 specifications without creating an observable yellowish tint to the lens, wherein the first UV absorber is a benzotriazole compound represented by the formula: where R la , R lh , and R lc are independently hydrogen, halogen, C C 6 straight or branched chain alkoxy group, aryl or substituted aryl; R 2 is hydrogen, lower alkyl, preferably tert-butyl, aryl or substituted aryl; R 3 is hydrogen, lower alkyl, aryl , substituted aryl, or R 4 -R 5 -R 6 , where R 4 is an oxygen or is absent, R 5 is a linking group selected from -(CH 2 ) contendO-, -CH(
• R , 7a , R D 7b , and R , 7c are independently hydrogen, halogen, C C 6 straight or branched chain alkoxy group, aryl or substituted aryl;
• R 8 is a linking group selected from alkyl, -(CH 2 ) m O-, -CH(CH 3 )CH 2 O-, -CH 2 CH(CH 3 )O-, -(CH 2 ) m OCH 2 -, -CH(CH 3 )CH 2 OCH 2 -, or -CH 2 CH(CH 3 )OCH 2 - group, or is absent; and
• R 9 is alkyl, acrylate, methacrylate, styrene or vinyl; and m is 2 or 3.
• R 1 are H, Cl and CH 3 O-, more preferably CH O-.
• R la and R ic are hydrogen when R lb is methoxy.
• the preferred substituent group for R 2 is tert-butyl.
• R 3 is preferably oxygen.
• R 4 is preferably oxygen.
• R 5 is preferably selected from -(CH 2 ) 3 OCH 2 - and -(CH 2 ) 2 OCH 2 -, more preferably R 5 is -(CH 2 ) 3 OCH 2 -.
• R 6 is preferably methacrylate or styrene.
• the more preferred compound is one wherein R 1 is CH 3 O-; R 2 is -C(CH 3 ) 3 ; R 4 is O; R 5 is -(CH 2 ) 3 OCH 2 -; and R 6 is styrene.
• the aryl group may optionally be substituted with halogen, alkyl, halogenated alkyl, alkoxy, alkenyl, alkynyl, and amino groups.
• benzotriazole derivatives that have UV absorbing qualities comparable to those described specifically in this application, may be useful alternatives to those defined by this invention.
• One skilled in the art may be able to find or synthesize such compounds and apply them in accordance with the teaching of this invention without undue experimentation.
• a preferred class of benzotriazole compounds are represented by the formula:
• R 1 and R 5 are as defined above.
• the starting benzotriazole can be prepared by the method described in Examples 1-3 of U.S. Pat. No. 4,716,234 to Dunks et al., which is incorporated herein by reference, substituting 4-halo-2-nitroaniline for the 4- methoxy-2-nitroaniline when it is desired to make a halogen group, and using any of 3-chloro-l-propanol, 2-chloroethanol, 2-chloro- 1 -propanol or l-chloro-2- propanol to produce the desired group for R 2 .
• the first UN absorbing compound may preferably be a benzotriazole derivative represented by the formula:
• R 1 is a hydrogen, halogen or lower alkoxy
• R 2 and R 3 are independently hydrogen or lower alkyl.
• R 1 is halogen, with chlorine being more preferred.
• R 2 and R 3 are independently hydrogen, methyl or tert-butyl. More preferably, R 2 is tert-butyl.
• the non-polymerizable benzotriazole derivative of this formula is preferably used for rigid gas permeable contact lenses.
• a preferred compound is 2-(2'-hydroxy-3 '-tert-butyl- 5 '-methyl- phenyl)-5-chlorobenzotriazole, which is manufactured by Ceiba-Geigy Co ⁇ ., and commercially available under the trademark TI ⁇ UVI ⁇ -326.
• the benzophenone compounds preferably R 7 is hydrogen, halogen or alkoxy. More preferably, R 7 is hydrogen or p is zero.
• R 8 is preferably alkyl, -(CH 2 ) n O-, or absent.
• R 9 is preferably is alkyl, acrylate, or methacrylate.
• the second UV absorbers are selected from the group exemplified by 2-hydroxy-4-acryloxyethoxy-benzophenone, 2-hydroxy-4-methacryloxy- benzophenone, and 2-hydroxy-4-methoxy-benzophenone. More preferably, the selected compounds are 2-hydroxy-4-acryloxyethoxy-benzophenone or 2- hydroxy-4-methacryloxy-benzophenone.
• 2-hydroxy-4- acryloxyethoxy-benzophenone is selected for use in hydrogel lenses.
• 2-hydroxy-4- methoxy-benzophenone is preferred for rigid gas permeable contact lenses or other rigid plastics.
• useful amounts of the UV absorbing compounds in a polymer range from about 0.01 percent to about 25 percent, depending upon the intended use for the polymer. In general, it will be desirable to minimize the amount of compound used, so that the physical and chemical properties of the base polymer (other than UV abso ⁇ tion) will not be significantly or detrimentally effected.
• about 0.05 to about 10 percent of UV absorbers can be used.
• the preferred total amounts of UV absorbers are between about 0.8 and about 3.0 percent, with between about 1.0 and about 2.0 percent being more preferred.
• the desired ratio of the amount of the first UN absorber to the second UN absorber is between about 5: 1 and about 1 :3, preferably between about 3 : 1 and 1 :3.
• the amounts of the individual UN absorbing compounds used depend on the polymer base, thickness of the lens, water or solids content and desired level of UN abso ⁇ tion. The preferred amounts will, of course, vary depending upon the water content and thickness of the lenses. For example, a lens that is twice as thick will need only half the concentration of UN absorber, assuming its water content is the same. On the other hand, a lens twice as thick with doubled water content will require the same concentration of UN absorber.
• the first and second UV absorbers are present in amounts to provide an enhanced reduction in the level of UV transmission compared to the level of UV transmission than can be achieved by using the same total amount of one UV absorbing compound alone.
• the two UV absorbing compounds in combination enhance the total effective UV light blockage. Greater blocking of UV light can be achieved using lesser total amounts of the combination of BZT and BP than using a like amount of either BZT or BP alone.
• the UV absorbing compounds can be copolymerized with a large number of unsaturated and other monomers to produce polymers having enhanced UV blocking properties. Representative useful monomers include, without limitation:
• olefins either straight- or branched-chain, including ethylene, propene, butenes, pentenes and the like;
• dienes such as butadiene, and trienes;
• the present invention is directed to UV absorbing hydrogels having the following characteristics.
• the UV absorbing monomer of the UV blocking hydrogel should block UV radiation between about 300-400 nm, because the pu ⁇ ose of inco ⁇ orating a UV absorber into a hydrogel is to prevent transmittance of UV radiation to the retina. As previously discussed, this function is normally performed by the eye's natural lens, which, however, is damaged by UV radiation.
• the UV blocking hydrogel should block UV radiation between about 300 to 400 nm, it is desirable that absorbance sha ⁇ ly decrease above 400 nm. If absorbance does not sha ⁇ ly decrease above 400 nm, the UV absorbing hydrogel will take on a significant yellow tint. In some cases, however, some yellow tint may be desired. For example, it has been thought that increased light absorbance in this range by spectacles, goggles, contact lenses, etc., enhances visual acuity.
• the UV absorbing hydrogel be stable as a copolymer and in particular exhibit long-term hydrolytic stability. This is a particularly important requirement when the hydrogel is to be used as an IOL and surgically implanted within the eye, since IOLs are generally intended to remain in the eye indefinitely.
• the UV absorbing compound to be inco ⁇ orated into the hydrogel must be soluble in the hydrogel-forming monomer so that it can be copolymerized with the hydrogel-forming monomer. It is necessary that the UV absorber be copolymerized with the hydrogel-forming monomer due to the expanded nature of hydrogels. Because of this expanded structure it is impractical to rely on imbedding or dispersing UV-absorbing compounds within the hydrogel as can be done with rigid-gas-permeable (RGP) type lenses. Moreover, copolymerization prevents the UV absorber from being leached from the hydrogel while in the eye or in a storage solution. At a minimum, the UV absorbing monomer should be soluble in the hydrogel forming monomer in an amount sufficient to provide the desired degree of UV absorbance in the UV blocking hydrogel.
• Ocular devices or UV blocking optical plastics may be produced by inco ⁇ orating a first UV absorbing compound, a second UV absorbing compound, and at least one monomeric compound suitable for producing an ocular device, preferably in the case of contact and intraocular lenses, hydroxyethyl methacrylate, N- vinyl pyrrolidone, alkyl methacrylates such as methyl methacrylate, aryl methacrylates, silicone methacrylate, glyceryl methacrylate, fluorinated methacrylates, alkyl substituted styrene, or combination thereof.
• hydroxyethyl methacrylate such as methyl methacrylate, aryl methacrylates, silicone methacrylate, glyceryl methacrylate, fluorinated methacrylates, alkyl substituted styrene, or combination thereof.
• other lens-producing monomers may be used.
• Contact and intraocular lenses in accordance with invention may be hydrophilic, hard, or rigid-gas-permeable (RGP), depending on the monomer or combination thereof in which the UV-absorbing compounds of the invention are inco ⁇ orated.
• RGP rigid-gas-permeable
• the UV absorbers dispersed in the polymer matrix.
• hydrophilic lenses it is preferred to have the UV absorbers copolymerized with the base lens monomers.
• Copolymerization may take place by any of the methods well known within the ocular device industry, e.g., by heat or UV light, or with a suitable initiator. Polymerization temperatures are typically 25° to 140°C, more preferably 30° to
• Suitable polymerization catalysts include azobisisobutyronitrile, available from E. I. DuPont de Nemours Corporation, Wilmington, Del. U.S.A. as Nazo 64TM, 2,2'- azobis (2,4-dimethylpentanenitrile), available from DuPont as Nazo 52TM, and 2,5- dimethyl-2,5-bis(2-ethylhexanoylperoxy) hexane, available from Elf-Atochem, Buffalo, ⁇ .Y. U.S.A. as Lupersol 256TM, as well as other peroxides.
• azobisisobutyronitrile available from E. I. DuPont de Nemours Corporation, Wilmington, Del. U.S.A. as Nazo 64TM, 2,2'- azobis (2,4-dimethylpentanenitrile), available from DuPont as Nazo 52TM, and 2,5- dimethyl-2,5-bis(2-ethylhexanoylper
• UN light is used to initiate the polymerization, its intensity should be about 0.1 to about 50 milliwatts per square centimeter, more preferably 1 to 5 mW/cm 2 .
• the time required is from 1 minute to 10 hours, preferably from 5 minutes to 2 hours.
• the temperature is between about 20 and 50°C, preferably 25-30°C.
• Light-created radicals are derived from the initiators such as
• Lenses of the invention may also be produced by first polymerizing a rod of the copolymer, cutting the rod into bonnets or buttons, and machining the bonnets or buttons into lenses, as is well known in the art. If the polymer undergoes a UV cure, the monomer mixture may also be heat cured after exposure to the UN source. Alternatively, the lenses may be produced by any of the known molding or casting techniques, such as the methods referred to by Kindt-Larsen et al. in U.S. Pat. No. 5,039,459. The exact manner used for polymerization and lens shaping is a matter of choice and is not critical to this invention.
• the hydrated lens had a water content of 53% with a center thickness of
• Example 2 NVP based Class I lens
• the hydrated lens had a water content of 74%
• the hydrated lens had a water content of 38%
• the solids content of these lenses are shown on a dry basis.
• the hydrated lenses had a water content as shown in the table.
• the lenses were made by placing the monomer formulation in to the contact lens mold at 70°C for 30 minutes, then ramping up to 120°C over 10 minutes and holding for 30 minutes. The lenses were cooled down and cycled through an autoclave in saline solution.
• UV transmission spectra for the lenses of Examples 5 a through 5h are shown in FIG. 1.
• a stock solution of the above polymer base ingredients was prepared, and varying amounts of Tinuvin-326 and MBP were added to separate portions of the polymer base to individually obtain formulae 7a-7f.
• Rods were filled and warmed at 48°C for 24 hours; then cured at 110°C for 24 hours. The rods were annealed by ramping the temperature to 110°C over 2 hours and holding for 70 hours, then cooling over a 2 hour period. The rods were irradiated with 1.0 mRad from a Co- 60 source. The rods were sliced into buttons and then machined and polished into 8 mm diameter lenses. Five lenses for each UV absorber formulation, Example 7a through 7f, were measured for UV abso ⁇ tion. The results were averaged and listed above.
• a polymer base was prepared according to the following shown on a total wet basis:
• This amount of BZT added is equivalent to 1.42% by weight of dry polymer.
• the resulting contact lenses had average transmittance values of 6.8% for 280-315nm (UVB) and 2.1% for 316-380nm (UVA). At 280nm, the transmittance was 18.72%, which is equivalent to 0.73 Absorbance units.
• Example 8(b) To the same polymer base as above 0.75% BZT and 0.79% BP on a dry basis was added, for a total of 1.54% UV absorbers on a dry weight basis. The resulting contact lenses had average transmittance values of 1.03% for 280-315nm (UVB) and 4.07% for 316-380nm (UVA). At 280nm, the transmittance was 1.89%), which is equivalent to 1.72 Absorbance units. Comparison of Examples 8(a) and 8(b):
• UV-blocking monomers BP and BZT
• BP and BZT were used individually and in combination at the same levels to make molded experimental RGP lenses.
• the averaged percent transmission data in the UVA and UVB range are reported below.
• Lenses were filled on a LCCM type filler/sealer using hand filling of cavities. Lenses were hydrated and processed as follows:
• the UV/V spectra was run using a Perkin-Elmer spectrophotometer fitted with an integrating sphere detector. The percent transmissions of the different lens formulations were averaged over the UVA and UVB region and listed in categories according to UV monomer composition, as shown below.

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• 1998
  • 1998-07-21 US US09/121,071 patent/US6244707B1/en not_active Expired - Lifetime
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