Background of the Invention

The present invention is directed to eye-compatible lenses, particularly hard contact lenses having excellent ⁵ oxygen permeability and wettability.

Contact lenses presently on the market are classi¬ fied into two large groups: soft contact lenses and hard contact lenses. Hard contact lenses are better able than soft contact lenses to retain visual characteristics, but 0 are less comfortable. The art has sought to increase oxygen permeability of hard contact lenses, to extend the length of time they can be worn without causing corneal d-amage or discomfort.

One proposed solution has been the formation of a

25 •copolymer of methyl methacrylate and a siloxane methacry- late compound. This solution has been less than satis¬ factory, since the lenses offered are not as hard, rigid, nor wettable as lenses formed from polymethyl methacryl¬ ate. In addition, such lenses are fragile and have poor

30 mechanical processability.

The object of the present invention is to overcome the deficiencies in the state of the art by offering lenses having a high degree of oxygen permeability, excellent wettability, and, if desired, ultraviolet ^{~ ~} absorption. The primary benefit of UV absorptivity is the resistance to user development of cataracts.

,.5us __i _* « * * SHEET

Summary of the Invention

The present invention is directed to oxygen- permeable lenses comprising copolymers of at least one unsaturated organosilicon monomer selected from alkyl or aryl siloxanes containing one or more unsaturated poly- merizable group(s) having the formula:

wherein: each R^ is independently an unsaturated polymer- izable methacrylate or acrylate group or hydrogen or "Z" group. "Z" group is acetoxy, carbomethoxy, glycidoxy, glyceryl, and carboxy. Acetoxy and carbomethoxy groups are preferred. At least one R-^ is a "Z" group; each R is independently an alkylene or cycloalkylene group having from 1 to about 10 carbon atoms, or an arylene group. Each "R" group may be the same or different. The arylene group is prefer¬ ably phenylene; each "a" is independently an integer from 0 to about 10 ; and n is an integer from 0 to about 10,

siloxyl alkyl esters of the formula:

R5-(0)

wherein:

R2 is selected from the class of hydrogen or methyl groups; b is an integer from 1 to 3 ; c and d are integers from 0 to 2; e is an integer of 0 or 1; A and R3 are selected from the class of methyl or phenyl groups; and R4 and R5 represent either no group (cyclic ring from "c" to "d") or methyl or phenyl groups. and/or

TITUTE SHEET

wherein:

X is an activated unsaturated group; Rg is a divalent hydrocarbon radical having from 1 to about 22 carbon atoms; R- ₇ is the same or different, and each one is of a monovalent hydrocarbon radical or a halogen- substituted onovalent hydrocarbon radical, each having from 1 to about 12 carbon atoms; and f is 0 or greater, and can range up to 800, but is ^* preferably less than about 25 for hard lenses, with at least one fluoroorgano monomer of the formula:

CH- C - M-

(4)

COO-(M) _g -(CH ₂ ) _h -Y

wherein:

M is hydrogen, alkyl, fluoroalkyl, alkyl carboxy, carboxy ester, alkyl carboxy ester, fluorinated carboxy ester, fluorinated alkyl carboxy ester, cyano, or phenyl; M is hydroxy alkyl, alkyl ether, or hydroxy alkyl ether; g is 0 or 1; h is from 0 to 4 ; and Y is a fluorocarbon group, preferably containing from about 2 to about 21 fluorine atoms. At least one hydrophilic monomer is included, preferably an unsaturated carboxylic acid capable of inducing wettability, and is present in an amount suffi¬ cient to provide in the resultant polymer a receding contact angle of about 45° or less. Methacrylic acid is preferred.

SUBSTITUT

At least one UV-absorbing agent may be included. The UV-absorbing agent may be a UV-absorbing monomer, preferably hydroxybenzophenone or a benzotriazole com¬ pound of the formula:

Z" (5)

wherein:

Rg is hydrogen or methyl; g is as defined above; i is from 1 to about 4; j is 1 or 2 ; and Z ¹ is:

^~ 9

wherein:

Rg is hydrogen, alkyl or hydroxy. Alternately or in addition, the UV-absorbing monomer nay be a benzotriazole of the formula:

SUBSTITUTE SHEET

wherein:

Rg and Rg are as defined above, and RlO is H or alkyl, preferably a Ci-Cio alkyl, pro¬ vided to induce UV absorbance to the lens. The UV-absorbing agent may also be non-polymerizable homopolymers and copolymers, preferably containing UV- absorbing units which are added to the monomer system that undergoes polymerization and which become physically entrained in the formed lens.

10 In the polymerized state, the UV-absorbing monomers act as a UV filter or screen capable of preventing UV transmission to the eye. It is important that in this regard most of the complications associated with cornea aphakia and retina problems can be prevented. In addi- ⁵ tion, the phenolic moiety enhances wettability of the lens. Moreover, being compatible with the other monomers, the UV-absorbing monomers are readily copolymerized and permanently retained in the polymer chain. Migration to the polymer surface and leaching are avoided.

2° A final component is a crosslinking monomer which is a crosslinking agent, preferably a silicon monomer, present in an amount up to about 5, preferably up to about 2, percent by weight.

It has been found that the total organosilicon-

~^ monomer content of the polymer may range from about 10 to about 40 percent by weight, preferably from about 10 to about 35 percent by weight, more preferably 30 percent by weight. The hydrophilic monomer may be present in an amount of from about 1 to about 15 percent by weight,

3° preferably from about 2 to about 10 percent by weight. The UV agent may be present in an amount of from about 0 to about 20 percent, preferably from about 0.1 to about 20 percent, more preferably from about 2 to about 10 per¬ cent by weight, and the crosslinking monomer may be

35 present in an amount up to about 2 percent by weight.

All percentages are based on the total weight of the monomers and, if present, the UV-absorbing agent. The balance of the monomer system may be solely the fluoro¬ organo monomers. It is desired that the lens have a Shore D hardness greater than about 78, preferably from about 80 to about 85. There may be desirably included other monomers such as acrylates, methacrylates, itaconic esters, styrenes, fluorinated styrenes, alkyl styrenes, fluorinated alkyl styrenes, and the like, present in a concentration of up to about 50 percent by weight of the concentration of the fluoroorgano monomer, typically in a concentration of up to about 5 percent by weight based on the total weight of the UV-absorbing agent and the mono¬ mers. Such monomers are used to modify properties such as hardness, machinability, wettability, oxyqen permea¬ bility, and the like.

It is desired to provide an oxygen permeability at 35°C greater than 50 x 10 ^" ^(cm ² /sec. ) (ml 0 ₂ /ml x mm Hg) . When using low-cost fluoroorgano compounds such as 2,2,2-trifluoroethylmethacrylate, the organosilicon content of the monomer system must be high, typically in the range of from 25 percent to 30 percent or more by weight based on the total weight of the UV-absorbing agent and the monomers. Organosilicon monomer content can be advantageously reduced, however, by inclusion of high-performance fluoroorganomonomers such as hexafluoro- isopropylmethacrylate.

SUBSTITUTE

Detailed Description

The present invention is directed to eye-compatible, i.e., ocular-compatible, lenses, in particular, hard contact lenses, formed of an interpolymerized amount of at least one organosilicon monomer, at least one fluoro¬ organo compound, at least one monomeric unsaturated carboxylic-acid wetting agent, and a UV-absorbing agent which is preferably a monomer of benzotriazole and/or benzophenone , and at least one crosslinking monomer. Other reactive monomers such as acrylates, methacrylates, itaconic esters, styrenes, fluorinated styrenes, alkyl styrenes, fluorinated alkyl styrenes, and the like, may be included as part of the polymerizable composition, to achieve a lens of desired hardness, wettability, oxygen permeability, machinability, and the like.

The organosilicon monomers which may be used in accordance with the instant invention include alkyl or aryl siloxanes containing one or more unsaturated poly¬ merizable group(s) having the formula:

S

-9- wherein: each R-^ is independently an unsaturated polymer¬ izable methacrylate or acrylate group or hydrogen or "Z" group. "Z" group is acetoxy, carbomethoxy, glycidoxy, glyceryl, and carboxy. Acetoxy and carbomethoxy groups.are preferred. At least one -^ is a " 2 ^~ group; each R is independently an alkylene or cycloalkylene group having from 1 to about 10 carbon atoms, or an arylene group. Each "R" group may be the same or different. The arylene group is prefer¬ ably phenylene; each "a" is independently an integer from 0 to about 10; and n is an integer from 0 to about 10, siloxyl alkyl esters of the formula: :

SUBSTITUTE SHEET

wherein:

R ₂ is selected from the class of hydrogen or methyl groups; b is an integer from 1 to 3 ; c and d are integers from 0 to 2 ; e is an integer of 0 or 1; A and R3 are selected from the class of methyl or phenyl groups; and R ₄ and R5 represent either no group (cyclic ring from "c" to ^H d") or methyl or phenyl groups, and/or

wherein:

X is an activated unsaturated group;

Rg is a divalent hydrocarbon radical having from 1 to about 22 carbon atoms;

R7 is the s-ame or different, and each one is of a monovalent hydrocarbon radical or a halogen- substituted monovalent hydrocarbon radical, each having from 1 to about 12 carbon atoms; and f is 0 or greater, and can range up to 800, but is preferably less than about 25 for hard lenses.

Illustrative, but no wise limiting, of the organo¬ silicon monomers wh.ich may be used in accordance with the invention there may be mentioned: l-γ-methacryloxymethyl-3-(3-acetoxypropyl)-l, 1,3,3-tetra- methyldisiloxane, γ-methacryloxypropyl-bis( trimethyls iloxy) M 3-acetoxy- propyldimethylsiloxy)silane, γ-methacryloxypropyl-bis( trimethylsiloxy)-( 3-carbo- methoxypropyldimethylsiloxyjsilane, γ-methacryloxypropyl-bis( trimethylsiloxy)-(3-hydroxy- propyldimethylsiloxy)silane, γ-methacryloxypropyl-bis(trimethylsiloxy)-( 3-carboxy- propyldimethylsiloxy)silane, γ-methacryloxypropyl-bis( 3-acetoxypropyldimethylsiloxy) -(trimethylsiloxy)silane, γ-methacryloxypropyl-bis( 3-carbomethoxypropyldimethyl- ^: siloxy)-(trimethylsiloxy)silane, γ-methacryloxypropyl-bis( 3-hydroxypropyldimethylsiloxy) -(trimethylsiloxy)silane, γ-methacryloxypropyl-bis( 3-carboxypropyldimethylsiloxy) -(trimethylsiloxy)silane, γ-methacryloxypropyl-tris( 3-acetoxypropyldimethylsiloxy) silane, γ-methacryloxypropyl-tris ( 3-carbomethoxypropyldimethyl- siloxy)silane, γ-methacryloxypropyl-tris( 3-hydroxypropyldimethylsiloxy) silane , Y-methacryloxypropyl-bis( penta ethyldisiloxanyl )- ( 3-acetσxypropyldimethylsiloxy)silane, γ-methacryloxypropyl-bis ( pentamethyldis iloxanyl ) - ( 3-car borne thoxypropyldimethy Is iloxy) silane, γ-methacryloxypropyl-bis ( pentamethyldis iloxanyl )-

( 3-hydroxypropyldime thy Is iloxy) silane, γ-methacryloxypropyl-bis( pentame hyldisiloxanyl) - ( car bo xypropyldine thy Is iloxy) silane,

wo _ i i *_j ; &ϊsπc _.

l-(Υ-methacryloxypropyl)-3-(3-acetoxypropyl)-tetra(tri¬ methyIsiloxy)disiloxane, l-(Y-methacryloxypropyl)-3-(3-carbomethoxypropyl)-tetra (trimethyIsiloxy)disiloxane, l-(Y-methacryloxypropyl)-3-(3-hydroxypropyl)-tetra(tri- methylsiloxy)disiloxane, l-(β-methacryloxypropyl)-3-(3-carboxypropyl)-tetra(tri- methylsiloxy)disiloxane, l,3-bis(Y-methacryloxypropyl)-l,l,3,3-tetra(3-acetoxy- propyIdimethyIsiloxy)disiloxane, Y-methacryloxypropyl-tris(4-acetoxyphenyldimeth lsiloxy) silane, Y-methacryloxypropyl-tris(2-carboxyethyldimethylsiloxy) silane, Y-methacryloxypropyl-tris(2-acetoxyethyldimethylsiloxy) silane, methacryloyloxymethylpentamethyIdisiloxane, methacryloyloxypropyl-tris(trimethylsilyDsiloxane, methacryloyloxymethylheptame hyleyclotetrasiloxane, ethacryloyloxypropylheptamethylcyclotetrasiloxane, and the like, and activated unsaturated group end-capped poly- siloxanes, i.e., monomers prepared by equilibrating the appropriately substituted disiloxane, for example, 1,3- bis(4-methacryloxybutyl)tetramethyldisiloxane, with a suitable amount of a cyclic diorganosiloxane, e.g., hexa- ethylcyclotrisiloxane, octaphenylcyclotetrasiloxane, hexapheny1eyelotrisiloxane, 1,2,3-1rimethy1eyelotri- siloxane, 1,2,3-triphenylcyclotrisiloxane, 1,2,3,4- tetrame hylcyclotrisiloxane, 1,2,3,4-tetraphenylcyclo- tetrasiloxane and the like, in the presence of an acid or base catalyst, as more particularly defined in U.S. Patents 4,142,508 and 4,463,141 to Ellis, and 4,153,641 to Deichert et al. all incorporated herein by reference.

SUBST

16700 -13-

While concentrations of organosilicon monomers may range from about 10 to about 40 parts by weight based on the total weight of the UV-absorbing agent, if employed, and the monomers, the preferred range is from about 10 to about 35, more preferably from about 20 to about 30 parts by weight. Oxygen permeability (all other factors being constant) will increase with an increase in organosilicon monomer content. At higher levels, the lens becomes more difficult to machine, requiring the inclusion of monomers as part of the monomer system, as mentioned above, to yield a lens having a Shore D hardness greater than about 78, preferably from about 80 to about 85.

The fluoroorgano monomers utile in the practice of the instant invention are generally compounds of the formula:

CH ₂ = C - Mi I - (4)

COO-(M) _g -(CH ₂ ) _h -Y wherein:

Mi is hydrogen, alkyl, fluoroalkyl, alkyl carboxy, carboxy ester, alkyl carboxy ester, fluorinated carboxy ester, fluorinated alkyl carboxy ester, cyano, or phenyl; M is hydroxy alkyl, alkyl ether, or hydroxy alkyl ether; g and h are as defined above; and

Y is a fluorocarbon group, preferably containing from about 2 to about 21 fluorine atoms.

Preferably, Y has the formula:

n ^F 2n+l -~ ^c n ^F 2n ^H<

Illustrative of fluoroorgano monomers are: 2,2,2-trifluoroethylmethacrylate, hexafluorobutylmeth- acrylate, hexafluoroisopropylmethacrylate, pentafluoro- n-propylmethacrylate, and the like. Trifluoroisopropyl¬ methacrylate is the preferred monomer for oxygen permea¬ bility, with 2,2,2-trifluoroethylmethacrylate being preferred for cost. Perfluoro or fluorinated styrenes may also be used.

Hydrophilic monomers are included in the composition to enhance wettability. They preferably comprise an unsaturated carboxylic acid, most preferably methacrylic acid, for compatability of monomers and wearer comfort. Acrylic acid is functional but less desirable. Other monomers such as 2-hydroxyethylmethacrylate and the like may be used. Concentration may be from about 0.1 to about 15 or more percent by weight, preferably from about 2 ^" to about 10 percent by weight based on the total weight of the UV-absorbing agent and the monomers.

The amount of hydrophilic monomer present depends on the amount of UV-absorbing agent, as described below, is employed, as the latter also has the capability of being a hydrophilic agent. Whether in monomeric or in poly¬ meric form, its concentration may range from 0 to about 20 percent by weight, preferably from about 0.1 to about 20 percent by weight, more preferably from about 2 to about 10 percent by weight based on the total weight of the monomers. The UV-absorbing agents used herein are preferably in a polymerized form and cooperate with the hydrophilic monomer to induce wettability and antiseptic- ability, i.e., self-sterilizable, in consequence of hydroxy-substituted benzene moieties. In the polymerized state, the UV absorbers absorb in the range of from about 300nm to about 450nm, preferably with no less than about 70% UV radiation at 3.70nm. Preferred UV-absorbing agents are, or are formed of, monomers of the formula:

"

-15-

₂ ^> ( 5 )

wherein :

R8 is hydrogen or methyl ; g is 0 or 1 ; i is from about 1 to about 4; j is 1 or 2; and

Z ¹ is:

R ₉

wherein:

Rg is hydrogen; an alkyl, preferably a C1-C5 alkyl or hydroxyl. In the alternative or in addition, there may be employed a phenyl benzotriazole of the formula:

SUBSTϊTUTΞ SHS

wherein:

R8 and Rg are as defined above. Preferred UV absorbers include: 2-hydroxy-4-(2-methacryloyloxyethoxy)benzophenone, 2-hydroxy-4-(2-acryloyloxyethoxy)benzophenone,

2-hydroxy-4-( 2-hydroxy-3-methacryloxypropyl)benzophenone, 2-(2-hydroxy-5-vinylphenyl)-2H-benzotriazole, and the like.

The UV-absorbing agents are either part of the mono- mer system or are high-molecular-weight, non-polymerizable homopolymers or copolymers preferably containing such monomers as described above or other UV-absorbing units. They are reacted as such with the polymerizable monomer system and are entrained in the polymerization product. The lenses of the instant invention are formulated to have high oxygen permeability (Dk) of at least about 15 and preferably greater than 50, as expressed in units of .llml 0 ₂ /ml x mm- Hg) and as determined at 35°C.

Values are achieved using high concentrations of the organonosilicon monomer and/or selection of the fluoroor¬ gano monomer. With compositions of high organosilicon- monomer content there are displayed increased brittleness and a reduction in capability to undergo machining. At least one crosslinking agent, such as a multi-functional organosilicon monomer, a fluoroorgano monomer, or other modifying monomer, is employed in an amount sufficient to control hardness of the lens in the range of Shore D hardness of from about 80 to about 85. A highly multi¬ functional organosilicon monomer is preferred, as it does not interfere with oxygen permeability. Other crosslink¬ ing agents which may be used include ethylene glycol dimethacrylate, ethylene glycol diacrylate, diethylene glycol dimethacrylate, diethylene glycol diacrylate, and the like.

^■

Lens formation is by free radical polymerization such as azobisisobutyronitrile (AIBN) and peroxide catalysts under conditions set forth in U.S. Patent 3,808,179, incorporated herein by reference. Colorants and the like may be added prior to monomer polymerization. It is preferred to form the lens base in sheet form between layers of a non-adherent surface. The sheet is cut into smaller lense precursors from which the lens is ground to user specifications. Spin-casting, as described for instance in U.S. Patent 3,408,429, incorporated herein by reference, may also be used.

Because of high oxygen permeability and wettability, and UV absorbance if desired, the lenses formed in accord¬ ance with the instant invention may be used for any lens application desired.

In any instance, oxygen-permeability values of the lens may be determined using a test method developed by Dr. Irving Fatt of Berkeley, California, and disclosed in the paper, entitled: "Oxygen Transmissibility and Permeability o Gas Permeable Hard Contact Lenses and Materials" by Irving Fatt, Ph.D., International Contact Lens Clinic, Vol. 11, No. 3, March 1984. The instrument was a polarographic cell with a curved surface for finished lenses, polarographic amplifier, recorder and a constant temperature chamber equipped with a temperature control unit. The measurements were made at 35°C and the units of oxygen permeability (Dk) are (cm /sec.) (ml 0 /ml x mm Hg)

The water wettability of the contact lens material was determined by the sesile drop method using a Rame- Hart goniometer with an environmental chamber. Both the advancing and the receding contact angles are determined. The hardness is measured as Shore D at 22°C using a hardness tester, and percent light transmission is mea¬ sured using a recording spectrophotometer. The absorption spectra of the copolymers are deter¬ mined on a "Perkin Elmer" UV-Vis spectrophotometer using 0.1-0.15mm-t in optically polished discs. The amount of

SUBSTITUTE SHEET

materials extractable from the lenses is evaluated by. first storing them in a saline solution for 10 days at 35°C. The lenses are then rinsed with distilled water, dried, weighed, and placed in stoppered, 25cc volumetric flasks, again containing saline as the extracting medium. The saline is analyzed daily for its extracted ultraviolet absorber by placing 4cc of the extract in a spectrophoto¬ meter cell and determining the absorption at 320nm. The absorption values are compared against the calibration curve made for the pure ultraviolet absorber. Extract- ables can also be determined by the Soxhlet extraction method, using water as the solvent.

Leachability-diffusibility may be evaluated by cyto- toxicity assay-agar overlay method.

The assay is based on the method described by Guess, W.L. , Rosenbluth, S.A. , Schmidt, B. , and Autian, J. , in "Agar Diffusion Method for Toxicity Screening of Plastics on Cultured Cell Monolayers" , J. Pharm. Sci. 54:1545-1547, 1965, incorporated herein by reference, and is designed to detect the response of a mammalian monolayer cell culture to readily diffusible components from materials or test solutions applied to the surface of an agar layer overlaying the monolayer.

The response of the cell monolayer is evaluated, with respect to the discoloration of the red-stained mono- layer, under and around the sample when the petri dish is viewed against a white background. Loss of color of the stained cells is considered to be a physiologically sig¬ nificant reaction of the cells. The extent of discolora¬ tion is confirmed by examination of the monolayer on an inverted microscope, and the extent of lysis of the cells within the discoloration zone is estimated. Typically, discoloration of cells precedes lysis, as manifested by a region and a region . showing lysis. A sample is reported as "cytotoxic" only if lysis is observed.

SUBSTITUTE SHEET