CA1293082C - Substantially non-swellable contact lens containing block copolymer polysiloxane-polyoxyalkylene backbone units - Google Patents
Substantially non-swellable contact lens containing block copolymer polysiloxane-polyoxyalkylene backbone unitsInfo
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Abstract
Substantially Non-Swellable Contact Lens Containing Block Copolymer Polysiloxane-Polyoxyalkylene Backbone Units Abstract of the Disclosure Contact lenses which are optically clear, hydrolytically stable, biologically inert, wettable, flexible, substantially non-swellable in aqueous ocular tear fluid, oxygen permeable of a block copolymer containing polysiloxane and polyoxyalkylene oxide units are disclosed, as well as the preparation thereof and methods of treating vision defects therewith.
Description
V-16156/1+2/+~CGV 1230 Substantially Non-Swellable Contact Lens Containing Block Copolymer Polysiloxane-Polyoxyalkylene Backbone Units This invention relates to ophthalmlc devices, such as contact lenses and intraocular implants, and particularly contact lensas of a block copolymer containing polysiloxane and polyoxyalkylene oxide units po~sessing an advantageous blend of desirable properties including a) high oxygen permeability, b) good wettability, c) flexibility, d) optical clarity, and e) a substantial lack of a~ueous swell-ability in the ocular environment of ufie.
The use of siloxane containing materials of various types in the fabrication of ophthalmic devices is well known.
. .
Thus, in U.S. 3,996,187; 3,996,189; 3,341,490 and 3,228,741 there are described contact lenses fabricated from poly torganosiloxanes) containing filler~. While such lenses are generally soft and of high oxygen permeability, the use of flllers such as sllica, is indicated in order to increa~e the otherwise generally poor tear strength and tensile strength. Also, such gilicone rubber lenses are characteristically both hydrophobic and lipophilic.
U.S. 3,808,178 discloses hard contact lenses fabricated from copolymers of a polysiloxanylalkyl acrylate or methacrylate ester and an alkyl acrylate or methacrylate ester. The monomers and polymers of the patent are hydrophobic and are incompatlble with hydrophilic materials such as hydroxyethyl methacrylate. ~hile the disclosed lenses have increased oxygen permeability, they are rigid.
U.S. 4,136,250 discloses hydrogels of a copolymer of about 20 to about 90 % of a hydrophilic (or mixture of hydrophilic and hydrophobic) monomer and about 10 to about 80 % of a polyolefinic siloxAne macromer which can be used to fabricRte a contact lens.
~ypicallyl such hydrogels are recited to posse~s a degree of swelling of about 10 to about 12 %. It ha8 been found, however, that the pressnce of substantial amounts of water in such hydrogels limits the oxygen permeability of such materials.
U.S. 4,153,641 relates, in relevant part, to contact lenses fabricated from a polymer of a polyorganosiloxane terminated with vinylic groups, or copolymers thereof with other monomers. The exemplified products thereln are hydrophobic in nature.
U.S. 4,486,577 relAtes to copolymers of about 8 to 70 % of A
polysiloxane macromer containing at least two vinyl groups and 3~-92 % of B monomer which is at least predominantly water insoluble to make polymers useful, for example, as contact lenses.
Generally, such prior art contact lenses compositions are either insufficiently hydrophilic in terms of surfAce wettability to be acceptable to the contact lens profession, even though they may possess high oxygen permeability, or such contact lenses are of acceptable wettability but the hydrophilicity i~ coupled with water swellability, which tends to limit optimum oxygen permeability.
It is an object of the present invention to overcome these and other disadvantages of the art by provlding ophthalmic devices, such as contact lenses and corneal implants, possessing a high degree of surface wettability but which are substantially non-swellable in the aqueous environment of use, and possessing a high degree of oxygen permeability by employing a crosslinked block polymer containing polysiloxane and polyalkylene oxide units.
l~ Z
A further ob~ect of the inventlon is to provide a method of cor-recting visual defects in the form of refractive errors by fitting to the patient's eye ln need of the same a corrective contsct lens of such polymer. These and other ob~ects of the invention are apparent from ths following detailed description of the invention.
One embodiment of the present invention relates to an optlcally clear, hydrolytically stable, biologically inert, wettable, flexible, substantially non-swellable in aqueous ocular tear fluid, oxygen permeable ophthalmic device, such as a contact lens, which is fabricated from A crosslinked polymer of a crosslinkable monomer having a segment S" of the formula I, -(D-S'-L-D-A-L) - (I) wherein a is 1 to lO;
each D is independently oxygen or -N(R2l)-;
each S' is independently a ~egment of formula II, -(CH2)h (~iO)v-~i-(CH2)i-O- ; (II) each A is independently a segment of formula III, 3 ~s 7 9 1l l3 Is 17 19 _ _ ~ O__ _ ~ d ~~~~~ _ ~ )f- ~__O__ _ _ 8 X ID 12 14 Y 16 18 20 z q (III) the terminal oxygen within each unit of formula II and III being replaceable by -N(R2l)-;
each L is independently -BRB ' -, the terminal L group within any one monomer of formula I also being capable of being -BR-;
3~
whereln each b, d and f is lndependently O - 4; q is a number from 1 to 1000; each x, y and z is independently O to lOO provided at least one oE x, y and z i8 at least 1; such that (x~y~z) multiplied by q i8 4 to 1000, preferably 25 to 75;
each h and i is an integer from 1 to 6, v 18 an integer from 2 to 75, preferably 2 to 50, more preferably lO to 50, most preferably 15 to SO;
Rl and R2 are independently alkyl of up to 18 carbon atoms, or aryl of up to 12 carbon atoms, preferably lower alkyl or phenyl, most prefsrably methyl;
each of R3, R4, R7-RI0, Rl3-Rl6, Rl9 and R20 is independently selected from the group consisting of hydrogen, halogen, an ali-phatic, aromatic or heterocyclic containing radical such as:
unsubstituted C1-C16 alkyl; substituted C1-C16 alkyl; unsubstituted C2-Cl 6 alkenyl; and substituted C~-CI 6 alkenyl; wherein the alkyl and alkenyl substituents are independently selected from C1-Cl 6 alkoxycarbonyl, C2-CI6 alkenyloxycarbonyl, fluoro, aryl of up to 10 carbon atoms, C1-C16 alkoxy, Cl-C16 alkanoyloxy, aryloxy of up to lO carbon atoms, C3-C6 alkenoyloxy, aroyl of up to 10 carbon atoms, aroyloxy of up to 11 carbon atoms, C3-Cg cycloalkyl, C3-C8 cyclo-alkoxy, C3-Cg cycloalkyl-carbonyloxy, C3-C~ cycloalkoxy-carbonyl, oxacycloalkyl of up to 7 carbon atoms, oxacycloalkoxy of up to 7 carbon atoms, oxacycloalkoxy (up to 7 carbon atoms)-carbonyl, oxacycloalkyl (up to 7 carbon atoms)-carbonyloxy, and aryl (of up to 10 carbon atoms)-oxycarbonyl, each of said alkyl and alkenyl substituents being, in turn, optionally substituted by C1-C6 alkyl, fluoro or a C1-C6 alkoxy provided said last mentioned alkoxy is not bound to a carbon atom already singly bound to another oxygen atom;
R3, R~, R7-R~0, Rl3-Rl6, Rl9 and R2J being further independently selected from aryl of up to 10 carbon atoms, C3 Cg cycloalkyl, and oxacycloalkyl of up to 7 carbon atoms, each of which may be unsub-stituted or further substituted with a substituent selected ~rom the group of substituents for said-R3 alkyl set forth above R5, R6, Rl1, Rl2, Rl7 and Rls are selected from the same group set forth above for R3; and R5, R6, Rll, Rl2, Rl7 and Rl3 are further independently selected from Cl-Ct6 alkoxycarbonyl, C3-C16 alkenoyl-. .
oxy, C2-C16 alkenyloxycarbonyl, and Cl-CI6 alkanoyloxy, each of which may be further ~ubstituted by fluoro, aryl of up to 10 carbon atoms, or Cl-Cl6 alkoxy, and Rs, R6, R~l, Rl2, Rl7 and R~8 are still further independently selected from aryloxy of up to 10 carbon atoms, cycloalkoxy of up to 8 carbon atoms, cycloalkyl (of up to 8 carbon atoms)-carbonyloxy, cycloalkoxy (of up to 8 carbon atoms)-carbonyl, aroyloxy of up to 11 carbon atom~, oxacycloalkoxy of up to 7 carbon atoms, oxacycloalkenyloxy of up to 7 carbon atoms, oxa-cycloalkoxy (of up to 7 carbon atoms)-carbonyl, oxacycloalkyl (of up to 7 carbon atoms)-carbonyloxy, and aryloxy (of up to 10 carbon atoms)-carbonyl, each of which may be further substituted by fluoro, Cl-C6 alkyl or Cl-C6 alkoxy, provided that any substituent having a singly bound oxygen atom as its link to the rest of the molecule may not be a substituent on the ~ame carbon atom which is singly bonded to another oxygen atom; or 2 ad~acent group~, selected from R3-R20, together with the atoms to which they are attached may form a 5 - 8 membered cycloalkyl, oxacycloalkyl or bicycloalkyl ring.
Ihe monomer of formula I preferably is of formula Ia, -(D-A-L-S")-c (Is) or of formula Ib, -(S") -D-S'-L - (Ib) even more preferably of formula Ic, L' ~ (D-A-L)e-S ~ L (Ic) and more preferably said monomer being divinylic; wherein D, A, L, S', S" are as defined hereinbefore; snd wherein c i~ 1 to 10; e is zero or one; a times c is 1 to 10; L i9 selected from -BRB'- and -BR-; L' i6~ hydrogen, P'-RB'-, or P'-BRB'-; and L" is hydrogen, or -P', or, in ca~e that e is ~ero, also -D-S'-BR-P' or -D-S'-BRB'-P'.
.
1~ 82 R2l is independently selected from hydrogen, Cl-C4 alkyl and phenyl, and i~ preferably hydrogen.
Esch B and B' is se]ected from ~ V- and ~ NH-wlth the carbonyl group being bound to A, S', D or P':
each R i8 independently a dlvalent linking group preferably ~elected from a) a divalent aliphatic group of up to 25 carbon atoms which may be interrupted by oxy, carbonyloxy, amino, amlnocarbonyl, oxy-carbonyl, ureldo, oxycarbonylamino, or carbonylamino;
b) a divalent 5 - 7 membered cycloaliphatic group having 5 - 25 car-bon atoms;
c) a divalent arylene group having 6 - 25, preferably 7 - 15 carbon atoms; and d) a divslent aralkyl or alkaryl group having 7 to 25, preferably ô - 16 carbon atoms;
wherein groups b) and d) can be optionally interrupted by the same groups a8 in group a) and wherein the aryl rings in groups c) and d) may be further substituted with one or more substituent~ selected from halogen, preferably fluorine or chlorine, Cl-C4 alkyl, pre-ferably methyl, and Cl-C1z perhalo alkyl, especially Cl-C1z per-fluoro alkyl;
and P' is hydrogen, amino, hydroxy, or a moiety containing a crosslinkable group which may be crosslinked when coreacted with a suitable cros~linking agent or when irradiated by actinic radiation.
In the foregolng, all alkyl groups whether mentioned alone or as part of another group are preferably C1-C4 alkyl, such as methyl, ethyl, propyl and butyl, especially t-butyl, with the exception that ad~acent groups on aryl rings cannot each be t-butyl. These alkyl groups may be straight chain or branched chain. When the alkyl is a substituent on a phenyl ring, it is preferably attached at the para position. Preferably alkenyl groups, whether alone or as part of l~?3r 82 another group, are C2-C4 alkenyl, such aa ethenyll propenyl and butenyl. Preferred aryl groups (whether alone or as part of another group) are phenyl and nsphthyl, more preferably phenyl. Preferably the aryl groups are still further substituted by Cl-C4 alkyl, more preferably t-butyl, most preferably in the para position. Halogen may be chloro, bromo, iodo or fluoro.
Preferably b, d and f are independently O - 3, more preferably O - 2, most preferably O or l. While the group identified by formula I may be highly halogenated, it is preferably at least 25 %
halogen free, more preferably 30 %, still more preferably 40 %, and most preferably substantially halogen free. Nherever cyclo groups are indicated, whether carbocyclic or heterocycllc they preferably have 5 - 6 ring members and the heterocyclic* preferably have only carbon atoms and an oxygen atom as rine members.
Bicycloalkyl 18 understood to cover those groups when two adjacent R
groups in a segment of formula III together form a ring and one of them already is a cycloalkyl group. In other words a fused ring system made up of two geminal R groups and the carbon atom to which they are attached results. For example if R3 is cyclopropyl and R4 18 methyl then R3 and R4 together with the carbon to which it is attached could be (2,1,0~ cyclopent-2,2-diyl.
In formula I, when b i8 greater than one, each of the multiple Rs and R6 groups may be the same or different; however preferably all of the Rs groups are the same and all of the R6 groups are the same.
The same i9 true with respect to d, Rll, and Rl 2; and f, Rl7, and Rl 8, Preferably, each of b, d and f is independently an integer of O
to 2, and most preferably zero or one.
In one aspect of the invention, each of R3-R7, R9-R~3 and Rls-RI9 is hydrogen. PreferablY the substituents R8, Rl4 and RZ are alkyl of up to 16 carbon atoms; alkyl of up to 16 carbon atoms substituted by 3~æ,2 alkoxy of up to 8 carbon atoms, or fluoro; phenyl which is unsub-stituted or substituted by fluoro, alkoxy of up to 6 carbon atoms or alkyl of up to 6 carbon atoms; benzyl wherein the phenyl ring thereof is unsubstituted or substituted by fluoro, alkoxy of up to 6 carbon atoms or alkyl of up to 6 carbon atoms; cyclohexyl; or oxacycloalkyl of 4 or 5 ring carbon atoms.
A highly advantageous subembodiment relates to wettable, non-swell-able ophthalmic devices, preferably contact lenses, fabricated from a polymer of formula I wherein A is of the formula IV, [CH2-(CHz) ~ H~O]--[CHz--(CH2)d--CH--O~--[CH2--(CH2)f--~H--O]
IV
wherein b, d, f, q, x, y, z, R8, Rl4 and R20 are as defined above.
There are two very highly advantageous embodiments having formula IV
which are represented by either formula V
~ [(CH2) ~ H--O]--[(CH2)--CH2--O]E (cH2)~H--O]~ (v) wherein n i8 b + 1; m i9 d + 1, p is f + 1; n, m and p each indepen-dently being preferably 1 - 3, more preferably 1 or 2, most pre-ferably l; and x, y, z and q are as defined above; R8 and R20 are hydrogen or one is, but preferably both are, an aliphatic, aromatic, or heterocyclic radical, preferably alkyl of up to 6 carbon atoms, alkyl of up to 6 carbon atoms substltuted by alkoxy of up to 6 carbon atoms or fluoro phenyl which is unsubstituted or substi-tuted by fluoro, alkoxy of up to 6 carbon atoms or alkyl of up to 6 carbon atoms; benzyl wherein the phenyl ring thereof i5 unsub-stituted or substituted by flubro, alkoxy of up to 6 carbon atoms or alkyl of up to 6 carbon atoms; cyclohexyl or oxacycloalkyl of 4 or 5 ring carbon atoms; or which are represented by formula VI
3r ~il2 g c~ 1 [(CH2~--CH2-O~X [(CHz)m- H~03y [(CH2)p CH2-O~ ~ (VI) wherein n, m, p, x, y, z and q are 8S defined above for formula V
and Rl4 i8 preferably selected from the same group as R8 in for-mula V.
In the foregoing it is to be understood that the units of x, y and z may be positioned randomly, in block ~egments, or alternately.
Another preferred embodiment corresponds to formulae IV, V and VI
wherein z i8 zero.
Desirably, the polymer segments of formula III or IV in the completed polymer are predominantly and preferably flubstantially devoid of free hydroxyl groups in the interior of the polymer as such groups tend to reduce oxygen permeability.
Free hydroxy groups on the outer surfaces of the formed polymer are acceptable as they increase wettability without drawing water into the polymer matrix. However, it is still preferable to have as few free hydroxy groups in the finished polymer as practical if a contact lens having high oxygen permeability is to be prepared. A
suitable means of tying up the free hydroxy groups present would be to interact them wlth a color group.
Typical color group8 useful in these embodiments include, but are not limited to, the hydroxy-reactlve dyes known in the art under the tradename Remazol, manufactured by American Hoech~t. Examples of the Remazol dyes which are especially useful are:
`2 Dye Color Index Code Remazol Brill Blue RW Reactive Blue 19 Remazol Yellow GR Reactive Yellow 15 Remazol Black B Reactive Black 5 Remazol Golden Orange 3GA Reactive Orange 78 Remaæol Turquolse P Reactive Blue 21 all of which have at least one group of the formula -SO2-CHzCHzO-SO3 which reacts with the polymer or monomer hydroxy group to yield a cH 3 dye-SOz-CH2-CH2-O-polymer or dye-SO2- H-O-polymer group, preferably the for~er. In such a manner, both excess free hydroxy groups are disposed of and colored contact lenses can be realized simultaneously. The color group or former can be reacted with monomer before the monomer is incorporated into the structure of formula I or afterwards. Another means of disposing of these excessive hydroxy groups is to utilize their presence to form various degree~ and types of crosslinking.
A vinylic comonomer i~ fre~uently utilized to increase the hydrophillcity of the final product without substantially altering the other properties mentioned above. Typically, when the vinylic comonomer is a polyéthylene glycol of the formula Rd-RC-O-(CHzCH20)- R
or pyrrolidone of the formula with g being 1 - 25, R~ being hydrogen or methyl and Rd being CH2~CH-, CH23C~CH3)- or other VV curable moiety, the re~ultant polymer is more hydrophilic than previou~ly, but the Dk i~ es~en-tially the same as when the comonomer i~ absent.
Usually, when present, the vinylic comonomer i8 used in an amount of about 2 % to about 10 % by weight of the resultant polymer. Advan-tageously, no more than 5 % of vinylic comonomer is used when the compound of formula V has a molecular weight in excesæ of 8000.
Generally, when the compound of formula V has a molecular weight of under about 4000, up to 10 % by weight of vinylic comonomer can be used. When the compound of formula V has a molecular weight between 4000 and 8000, the maximum amount of vinylic comonomer i6 between 5 % and 10 % by weight.
When P' is a vinyl containing group, for example a group containing the moiety HÇ= Ç-Rb Ra with R and R as defined below (e.g. -o-CH2CHz-o~~~8~CH2)~
then the monomer of formula I can be crosslinked in the presence or absence of up to less than about 50 %, preferably up to about 50 %, most preferably up to about lO % by weight of other vinylic comonomers, provided that such comonomers are substantially free of hydroxy groups in the final product.
When P' does not have a vinylic group, but takes part in cross-linking, P' contains e.g. an active hydrogen. Preferably P' termi-nates in an OH, NHR , (R being hydrogen or lower alkyl), a leaving group bound directly to the B or B' carbonyl, a conventional acyl leaving group when not 80 bound, SCN- or OCN-. Crosslinking is then typically carrled out by condensation or addition with a bi- or polyfunctional coreactive monomer. For example, when P' i8 OH, then the coreactive monomer functional group can be -NHR , -COOH, OCN-, SCN-, etc.; when P' is NHR , the reactive comonomer functional group 3~2 can be a conventional acyl, or acyl bound to a conventional leaving group; and when P' has OCN- or SCN-, then th~ reactlve comonomer functional group can be OH. Similarly, the other coreactive func-tional groups mentioned in terms of elther P' or the coreactive monomer can be interchanged (Those mentioned as part of P' being on the coreactive monomer and those mentioned as part of the coreactive monomer being part of P').
Suitable vinylic comonomers and coreactive monomers for condensation are set forth below. However, the list i8 not exhaustive and tho~e of ordinary skill will appreciate the modifications, addition~, and alternatives which may also be employed.
When either or both L' and L" are hydrogen, or terminate in P' with P' being hydrogen, at least one additional cros~linkable moiety must be present a8 one of, or as substituent on one of, the groups R3-R2D.
Such crosslinkable groups may also be present as a substituent on or in place of one or more of R3-R20 even when one or both of L' and L"
have crosslinkable groups therein. However, the degree of cross-linking in the finished crosslinked polymer should not exceed 10 %, preferably not more than 5 %, and should be more preferably in the range of 1 - 4 %, most preferably in the range of 2 - 3 %.
Within the polymer fabricated from monomers of formula I, not more than 20-70 %, preferably not more than 50 % of the A groupc are polyethylene glycol.
The number of A units and the chsin length and nature of the substituents on the polyoxyethylene segment is determined by the degree of wettability desired in the polymer of the compound of formula I. In general, the polymer should be sufficiently hydro-philic ln its surface properties such that the polymer exhibits a contact angle with distllled water at 20C of less than 60, preferably less than 40, more preferably less than 25, ~till more preferably less than 15, mo~t preferably less than 10.
1~3~ 82 The greater the number of siloxane units, the greater the number of oxyalkylene units is generally required to reduce the contact angle to within the above limits.
Further, a large excess of unsubstituted oxyethylene units is to be avoided, as such excess units tend to cause the polymer to be swellable. As water is taken up, the oxygen permeability of such polymers tends to be drastically reduced. Advantageously, the instant polymers absorb less than about 10 % by weight water, preferably less than about 5 % by weight, most preferably less than 3 % by weight water.
Highly preferred are those polymers which exhibit a contact angle of eBs than 25, more prefersbly less than 15 and most preferably less than 10.
Preferred crosslinked polymers are those consisting essentially of a polymer of a divinylic monomer sccording to formula I wherein Rl and R2 are methyl, h and i are 2 to 4, v is 2-20; b, d and f are zero;
R3, R4 are hydrogen; R8, Rl~ and R20 are independently alkyl of up to 8 carbon atoms, (x+y+z) multiplied by q is 4-40 and P' is:
-CH~CH2 w1th R being hydrogen or methyl.
Very highly advantageous are those polymer~ of reactive vinylic monomers of the formula VII, ?3~2 ~ 14 -H2C'~ BRB' ~ D-(CH2- ~ -O)X-BRB' ~ D-(CH2)h'(~i)V ~ (C 2)i ~ ICH3 CIH3 -BRB'-D-(CH2-~H-O) -BRB' ~ ( 2)h (~ )v ~ ( 2)i ~7 -(CH2- H-O)x-BRB' ~ HCH2 (VII) k where one of e and k i8 one and the other zero; R 18 hydrogen or methyl;
each R ls a divalent arylene group of 6 to 15 carbon atoms, a divalent C6-C20-arylene-amlno carbonyloxy-C2-C6 alkylene;
or dlvalent C3-CIs cycloaliphatic;
B and B' are each -C-O- or -~
each R7 18 alkyl of l to 6 carbon atoms, or mixtures thereof withunlts wherein R7 i8 hydrogen, preferably with the proviso that R7 can be hydrogen in no more than about 75 %, more preferably 50 %, still more preferably no more than 30 %, of the units;
each x 18 4-75, preferably 6-70, more preferably 8-66; v is 2-66, preferably 2-25, more preferably 2-20; i and h are independently 2, 3 or 4; and a i~ an integer of 1-10, preferably 1-8, more preferably 1-6, still more preferably 1-4, most preferably 1-2.
Wlth~n this very highly advantageous embodiment, Ra is most preferably methyl; R is most preferably -phenylene-, -CH2CH20CONH-phenylene- or -CH2CH20CONH-tolylene-; R7 is methyl, x is most preferably 60 to 66; v 18 most preferably 15 to 20; a 1~ most preferably l to 3; ~ is most preferably zero; and e is most prefer-ably one.
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A very highly preferred embodiment are those polymers from monomers - 15 ~ 3~Z
of formula VII wherein each -C~l2- H-0-group i8 of the formula ~ ~22 1 ~ CHz H ~
where R2 2 i8 alkyl of 1 to 4 carbon atoms, most preferably methyl, and s i8 from about 6 to about 200, preferably from about 25 to about 100, and most preferably from about 50 to about 75.
Also highly preferred are those polymers of monomers of formula VII
l~-7 wherein each -CH2-~H-0-group i8 of the formula VIII
H2CH2 ~ CH2~H ~ H2CH2 ~ (VIII) wherein x i9 from about 2 to about 20, y is from about 8 to about 100, and z from about 4 to about 80. Another valuable embodi-ment requires the value of y to be at least about twice that of x or z and R2 2 to be alkyl of 1 to 4 carbon atoms, preferably methyl.
The reactive vinylic monomers of formula I can characteristically be polymerized to form crosslinked polymers under conventional polymerization condition~.
If desired, the monomer reactlon mixture may contain a catalytic amount of a conventional polymerization catalyst, preferably a free radical catalyst. Of psrticular interest are conventional peroxide and azo catalysts, such as hydrogen peroxide, benzoyl peroxide, tert-butyl peroctoate, benzoyl peroxide or azobis(isobutyronitrile).
The polymerization can generally be carried out at temperatures between about 20 and about 150C, for a period between about 1 and about 24 hours. It i9 understood that the time and temperature in such a reaction are inversely related. Thus, temperatures employed in the upper end of the temperature range will generally provide 3~ ~Z
reaction times near the lower end of the time range. Preferably, the polymerization is conducted in the presence of actinic radiation, such as W light.
Depending upon the nature of the polymer mixture, it may be desir-able for the polymers obtained from guch polymeri2ations to be post cured, e.g. at a somewhat elevated temperature such as between about 60C and about 150C.
For the preparation of contact lenges, the polymer mixture may be cast directly in the shape of the lens, or the polymerization may be carried out in a mold having a shape convenient for further pro-cessing, ~uch as in the shape of small cyclinders or "buttonfi", which can then be machined.
Minor amounts i.e. les~ than 50 %, preferably up to 30 %, and most preferably up to no more than about 10 % by weight, of conventional copolymeri2ible vlnyl monomerA, can be employed a~ extenders or hydrophilic modifiers, or the like, ln the preparation of the instant polymer, as copolymer constituents. Suitable vinyl monomers include:
acrylates and methacrylates of the general formula c~23 H2C~ -CooR24 where RZ3 is hydrogen or methyl and R24 is a stralght chaln or branched allphatic, cycloaliphatic or aromatic group having up to 20 carbon atoms whlch is unsubstituted or substituted by one or more alkoxy, alkanoyloxy or alkyl of up to 12 carbon atoms, or by halo, especially chloro or preferably fluoro, or C3-C5 polyalkyleneoxy of 2 to about 100 units;
acrylamides and methacrylamides of the general formula ,R23 HzC~C-CoNHR24 where R2 3 and R24 are defined above;
3(:~2 vinyl ether~ of the formula where R24 i8 as defined above;
vinyl esters of the formula HzC~CH-OOC-R2 "
where R24 is a3 defined above;
maleates and fumarates of the formula where R2 4 ls as defined above;
and vinylic substituted hydrocarbons of the formula R2 3 CH-.CHR2 4 where R23 and R24 are a~ defined above.
Useful monomers include, for example:
methyl-, ethyl-, propyl-, isopropyl-, butyl-, ethoxyethyl-, methoxy-ethyl-, ethoxypropyl-, phenyl-, benzyl-, cyclohexyl-, hexafluoro-isopropyl-, or n-octyl-acrylates and -methacrylates as well as the corresponding acrylamides and methacrylamides:
dimethylfumarate, dimethylmaleate, diethylfumarate, methyl vinyl ether, ethoxyethyl vinyl ether, vinyl acetate, vinyl propionate, vinyl benzoate, acrylonitrile, styrene, alphamethyl styrene, l-hexene, vinyl chloride, vinyl methyl ketone, vinyl stearate, 2-hexene and 2-ethylhexyl methacrylate.
As hydrophilic modifiers, to increase hydrophilicity without substantial 1088 of DK, the vinyl comonomer can be a N-(vinyl containing group)-pyrrolidone or a polyoxyethylene (of 1-25 repeat-ing units) acrylate or methacrylate. Such a hydrophilic modifier should not be present in exceas of about lO % by welght of the compound of formula I.
Most preferably, the instant polymers are free from copolymer units of such conventional vinyl monomers.
The vinyllc monomers of formula I can be prepared by methods known, per se.
1 ~3C 8;Z
For example, the slloxsne/polyalkylene oxide containing divinyllc monomer~ of formula I may be prepared by reacting a siloxane diol of the formula HO-(S')-H, wherein -S'- i6 a group of the formula II as deflned hereinbefore with a sufficient amount of a difunctional reactive group containing compound having the group -Q- or -Q-Y-, wherein the difunctional reactive group6 are isocyanate; activated carboxy, such as an anhydride, an acid halide or a carboxy ester; or i8 a leaving group, such as a halide, sulfato or the llke, to form the corresponding reactive group containing endcapped derivative.
The resulting endcapped siloxane derivative can then be reacted with a polyoxyalkylene diol of the formula HO-(A)-H, wherein -A- is a group of the formula III above to form the corresponding polyoxy-slkylene-slloxane-polyoxyalkylene diol. This diol can then be reacted with a reactive group containing vinylic monomer having the terminal H2C~C(R )-BR- moiety, wherein the reactive group is an lsocyanate; activated carboxy, such as an anhydride, an acid halide or carboxy ester, or is a leaving group such a~ halo, sulfato or the like to form the corresponding divinyl derivative where a is 1, and A is other than a direct bond. Alternatively, the aforementioned polyoxyalkylene - slloxane - polyoxyalkylene dlols can be further sequentlally reacted with a further difunctional reactlve group containing compound having the group -BR- or -BRB'-D- to form the correspondlng dl-functlonal reactive endcapped derivative which is then reacted with a siloxane dlol of the formula HO-(S'>-H. One may contlnue bullding up alternative polyoxyalkylene/slloxane unlt contalnlng dlols ln this manner, corresponding to the value of elther "c(a plus e)" or c(a plus k)". Then this diol may be endcapped wlth a reactlve group containing vinylic monomer havlng a termlnal H2C-C(R )-BR- moiety or the diol reacted with a sufficlent amount of dlfunctional reactlve group contalnlng compound to endcap the diol with a reactive group, such as eg. an lsocyanate, etc~
group whlch is then reacted wlth the appropriate vinylic containing ?3~ ~,Z
compound, such as an vinylic amine or alcohol, or other copoly-merizable monomer having a crosslinkable group to obtain the corresponding product of formula I.
Of course, instead of starting with a siloxane diol of the formula H0-(S')-H and building up the alternating sequence to the desired value of "a", one may instead begin with a polyoxyalkylene diol of the formula H0-(A)-H and, after endcapping the same with di-functional reactive groups, condense the same wlth the siloxane diol until the desired value of "a" is attained, and terminate the diol with vinylic groups as described above.
The above reactive vlnylic monomer~ are characteristically poly-merized under conventional polymerization conditions. In those vinylic monomers containing but one vinyl group, a minor amount e.g. from about 0.01 to about 5 weight percent, based on the monomer of formula I, of a conventional crosslinking agent, may be employed.
Suitable crosslinking agents include diolefinic monomer~ such as:
Allyl acrylate and methacrylate, alkylene glycol and polyalkylene glycol diacrylates and dimethacrylates, such as ethyleneglycol dimethacrylate, diethylene glycol dimethacrylate, and propylene glycol dimethacrylate; trimethylol propane triacrylate; penta-erythritol tetraacrylate, divinylbenzene; divinyl ether; divinyl sulfone; bisphenol A diacrylate or dimethacrylate; methylene bis-acrylamide; diallyl phthalate; triallyl melamine and hexamethylene diacrylate and dlmethacrylate. Also, such minor amounts of a crosslinking agent may be employed, if desired, in the polymeriza-tion of the di-vinyl monomer of formula I and VII.
When the monomers of formula I have free hydroxy, isocyanato, carboxylic or amine groups, suitable crosslinking agents contain di-or polyfunctional co-reactive groups to form addition or con-densation reactions linking 2 or more chains.
- 20 ~ 3~Z
If desired, the monomer reaction mixture may contain a catalytic amount of a conventional cataly~t, preferably a free rsdical catalyst. Of particular interest are conventional peroxide and azo cataly6ts, guch as hydrogen peroxide, benzoyl peroxide, tert-butyl, peroctoate, oenzoyl peroxide or azobis (isobutyronitrile).
The aforementioned reactions are generally straight forward additions or condensations and are typically conducted at a reaction temperature between about -10C and about 100C, depending upon the relative reactivity of the species involved, in the presence or absence of an inert diluent and in the optional presence of an addition or condensation catalyst if desired or appropriate. For reactions involving an isocyanate or acid halide, with a diol, for example, suitable optional catalysts include pyridine and triethyl-amine.
The siloxane diols of the formula H0-(S')-H are known in the art and many are commercially readily available.
Also, the polyoxyalkylene diols of the formula H0-A-H are known or can be prepared by known methods.
Thus, the polyols of the formula H0-A-~ are generally prepared by the addition reaction of xq moles of an epoxide of the formula IX, Cl ~ C ~ (IX) where R3-R3, b, ~, and q are as defined above, with yq moles of an epoxide of the formula X, Rj Rll R12 Rl3 f~c~7l (x) o 3(~Z
where R9-Rl4, d, y, and q are as defined above, and zq mole~ of an epoxide of the formula XI, R17 Rl8 ~ Iq ~ ~20 (XI) wherein R~s-R2~, f, ~, and q are as defined above, optionally in the presence of a conventional alkylation catalyst, ae atmospheric to elevated pressures of up to about 3000 kPa gauge, at temperatures between 0C and about 130C, optionally in the presence of an inert diluent. If desired, one may add to the reaction mixture, prior to the reaction of the epoxides, an aliphatic, aromatic or cycloali-phatic alcohol, acid or amine having up to 14 carbon atoms to prepare the corresponding mono-ol~ terminating in the group D.
The reaction between the epoxides, when mixture~ of different epoxides are employed to obtain the polyol of the formula H0-A-H, can be conducted by admixing the epoxides to obtain random copoly-mers or terpolymers, etc., or the addition can be conducted sequen-tially to form block copolymers having terminal hydroxy groups.
Suitable catalysts include alkaline earth oxides, alkaline earth carbonates, alkyl zinc compounds, aluminum alkoxides, hydrates of ferric chloride, bromide and acetate, and gamma radiation. The reaction may also be initisted by the presence of a glycol, such a8 ethylene glycol or propylene glycol or by a polyol of higher functionality such as sucrose, or by sn amine, such a8 ethylene diamine, toluenediamine, and so forth. Generally the length of time of the resction will depend in psrt on the alkylene oxide employed, but csn generally be from less than one to several score hours.
Thus, ethylene oxide generally is about three times as active as propylene oxide, which ln turn reacts more rapidly than 1,2-butylene oxide. The preparation of polyoxetanes and polytetrahydrofurans is generally initiated via ring opening oxonium formation using trialkyloxonium salts, carboxonium salts, scylium salts and the like.
1~3'~} ~2 Suitable diols of the formuls H0-A-H include those prepared from epoxldes such a9:
1,2-propylene oxide; 1,2-butylene oxide; 1,2-epoxydecane; 1,2-epoxy-dodecane; 1,2-epoxyoctane; 2,3-epoxynorbornane; 1,2-epoxy-3-ethoxy-propane; 1,2-epoxy-3-phenoxypropane; 2,3-epoxypropyl 4-methoxyphenyl ether; tetrahydrofuran; l,2-epoxy-3-cyclohexyloxypropane; oxetane;
1,2-epoxy-5-hexene; 1,2-epoxyethylbenzene; 1,2-epoxy-1-methoxy-2-methylpropane; perfluorohexylethoxypropylene oxide; benzyloxypro-pylene oxide, and the like. Also, the aforementioned epoxides may be employed as mixtures thereof. Further, certain cyclic ethers of formula IX, X or XI where b or d or f, respectively i9 3 and the carbocyclic portion of the ring is substituted are resistant to polymerization alone, but copolymerize quite readily with more reactive cycllc ethers. Suitable co-monomers include, for exAmpls, 2-methyl-tetrahydrofuran and 3-methyl-tetrahydrofuran. Also, while ethylene oxide may be employed as a co-monomer, ethylene oxide polymers, in the absence of more hydrophobic units, is character-istically too hydrophilic and absorbs too much aqueous fluid to be of use in accordance with the instant invention. However, ethylene oxide/propylene oxide copolymeric diols wherein there 18 30-80 %, preferably greater than 50 %, more preferably greater than 66 %
propylene oxlde, on a mole basis, is sufficiently hydrophobic 80 as to be substantially non-swellable in aqueous media, and yet sufficiently hydrophilic 80 as to exhibit a contact angle with water of less than 60; preferably less than 40, more preferably less than 25, more preferably less than 15, most preferably less than 10.
Many polymer diols of the formula H0-A-H are commercially available.
Thus, suitable diol products include poloxamers having the general formula HO(CH2CHzO) '-(CH(CH3)CH20)b'-(CH2CH20)c'-H
.
~ 3~Z
wharein b' has a value between sbout 16 and 100 and the sum of a and c' 18 between about 4 and about 100. Example8 of 8uch poloxa-merg, and their average values of a', b' and c', include poloxa-mer 101 (a' is 2, b' is 16, c' i~ 2~; poloxamer 122 (81 i~ 5, b~ 19 21, c' i9 5); poloxsmer 181 (a' is 3, b' ls 30, c' is 3);
poloxamer 212 (a' i8 8, b' is 35, c' i8 8); poloxamer 231 (a' is 6, b' 1B 39, c' is 6); poloxamer 282 (a' is 107 b' is 47, c' is 10);
poloxamer 331 (a' is 7, b' is 54, c' is 7); poloxamer 401 (a' is 6, b' is 67, c' is 6).
Such poloxamers are available, e.g. from BASF Wyandotte under their Pluronic~ brand name. Also suitable are the "reverse poloxamers", having polyethylens glycol bounded on each side by polypropylene glycol.
Polypropylene ether glycols include commercially available products having a molecular weight range between about 400 and about 4,000.
As stated above, the polymers for use in the instant inventlon are those which exhibit a receding contact angle at 20C of less than 60, preferably le~s than 40, more preferably less than 25, more preferably less than 15 and most preferably less than 10. The measurement of such contact angle is conveniently performed using a modified "Wilhelmy Plate" technique, as described, for example, for J.D. Androde, et al. Surface and Interfacial Aspects of Biomedical Polymers, Vol. 1, Surface Chemistry and Physics, Plenum Pres~, 1985, wherein a specimen sample in the form of a plate of known dimensions is immersed into the wetting solution, pure water, at a slow controlled rate, e.g. at 2 - 20 mm per minute.
As mentioned above, the instant polymers for use in the present invention possess a high degree of oxygen permeability. The oxygen permeability, Dk(x10 ), is measured using a modification of ASTM
standard D3985-81 in that (a) there is used 21 % oxygen, i.e. air, instead of 99 - 100 % oxygen, (b) the ~urface area of sample 3~ ~2 employed iB 0. 50 square meters versus 100 square meters and the humldity i9 controlled to be at 95 - 100 % relatlve humidity lnstead of 0 % relative humidity. The unit of Dk is (mm-ml 02/cm2~sec~mmHg~.
Typically, conventional fully swollen polyhydroxyethyl methacrylate lenses which are sparingly crosslinked possess a Dk(xlO ), (mm~ml 02/cm2-sec~mmHg) value of about 5 - 7.
The instant polymers for use as an ophthalmic device, such as a contact lens, possess a Dk(x10 ) value generally greater than 7, preferably greater than about 15, more preferably greater than about 20 and most preferably greater than about 40.
The following examples are for illustrative purposes and are not to be construed a~ limiting the invention. All parts are by weight unless otherwise specified.
Table of abbreviation~ used throughout the examples:
PPG: polypropyleneglycol HEMA: hydroxyethyl methacrylate TDI: toluene diisocyanate PEG: polyethyleneglycol Example 1: To a dry, 0.25-liter, three-neck flask equipped with a thermometer, constant pressure dropping funnel, nitrogen inlet and condenser under a dry, nitrogen atmo~phere is added 1.74 g (0.010 moles) TDI, 10 ml dry dlchloromethane and 0.05 g tin octoate.
10.00 g (0.005 moles) poly(propylene oxide) in 40 ml of dry dichloromethane are added to the flask dropwise over a 40 minute period, maintaining a temperature less than 30C. The reaction is continued for 2 hours. After 2 hours, 14.65 g (0.010 moles) hydroxybutyl terminated polydimethylsiloxane in 30 ml of dry dichloromethane are sdded rapidly to the system and the reaction is allowed to continue 17 hours. Then 1.74 g (0.010 moles) TDI are sdded; after 3 hours, 1.30 g (0.010 moles) HEMA are added and the 3~ &Z
reaction i8 stirred 18 hours. After 18 hourfi, the isocyanate band ls not apparent in the infrared spectrum. The volatiles are then removed from the reaction system via vacuum rotary evaporation. The clear, viscous, reactive fluid is stored protected from light and thermal polymeri~ation.
To the clear, viscous fluid is added one percent Darocur 1173 (~V
initiator) and the mixture degassed and mixed via vacuum rotary evaporation. The material is then W cured in the appropriate molds under UV light with an intensity of 2 to 3 milliwatts. The resulting film has an advancing contact angle of 65.5 and a receding angle of 16.2.
Examples 2 to 3: Similar rections are conducted as described in example 1 but with reactive components of different molecular weight~ and other vAriations as outlined in Table 1. The solvents are adjusted proportionally based on the weight of the materials used.
Table 1*
Example Tin _ PPG Silicone TDI _ HEMA Octoate Darocur DK
2 30.23 40.03 6.96 2.60 0.06 1 % 159.0 (0.01) (0.02) ~0.04) (0.02) 3 6.40 10.77 1.12 0.42 0.0~ 1 % 257 (0.0016) (0.0032) (0.0064) (0.0032) * Weight in grams.
Number in parentheses is molar quantity.
Initlator expressed in terms of percent of prepolymer in grams.
DK expressed ln terms of DK units.
Example 4 To a dry, 100 ml, three-neck flask equipped with a thermometer, constant pressure dropping funnel, nitrogen inlet and condenser under a dry, nitrogen amosphere sre added 3.48 g - 26 ~ 3a &Z
(0.020 moles) TDI, 150 ml dry dichloromethane and dibutyl tin dilaurate and heat to reflux. 4-Hydroxybutyl polydimethyl6iloxane 14.65 g (0.010 moles) in 30 ml of dry dichloromethane are added dropwise to the flask. After 3 hours, 10.00 g (0.005 mol~s) poly-(ethylene oxide) are added to the flask dropwise. The reaction is stirred at reflux for four hours and 1.30 g (0.010 molefi) of HEMA
are charged to the flask. After 17 hours the isocyanate band is no longer observed in the lnfrared spectrum. The volatiles are removed via vacuum rotary evaporation. The clear, vi~cous, reactive fluid is protected from llght and thermal polymerization untll it is ready for use.
One percent Darocur 1173 is added to the prepolymer and the mixture degassed and mixed vla vacuum rotary evaporatlon. The prepolymer is transferred to the appropriate mold~ and cured under W light of 3 to 5 milliwatt intensity. The clear film~ produced in thi~ manner have oxygen permeabilities of 148.8 x 10 10.
Examples 5 to 11: Similar reactions are conducted as described in example 4 but with reactive components of different molecular weights and other variations as outlined in Table 2. The solvents are ad~usted proportionally oased on the weight of the materials u~ed .
Table 2*
Example Tin PPG Silicone TDI HEMA Octoate Darocur DK
50.72 37.158.83 3.30 0.02 1 % 125.4 (0.013) (0.025) (0.050) (0.025) 6 30.77 52.2012.40 4.64 0.030.5 % 133.1 (0.018) (0.036) (0.071) (0.036) 7 33.26 50.3111.96 4.47 0.03 1 % 179.1 (0.017) (0.034) (0.069) (0.034) 8 32.67 31.917.58 2.83 0.08 1 % 130.0 (0.011) (0.022) (0.044) (0.022) 1~?3(~ ~tZ
9 21.21 43.657~38 2.76 0.04 1 % 258.5 (0.011~ (0.021)(0.042) (0.021) 19.07 75.006.96 2.60 0.11 1 % 340.3 (0.01) (0.02)(0.04) (0.02) 11 19.08 55.276.96 2.61 0.7 1 % 388 (0.01~ (0.02)(0.04) (0.02) * Weight in grama.
Number in parentheses i~ molar quantity.
Initiator expressed in terms of percent of prepolymer in grams.
DK expressed in terms of DR units.
Example 12: To a dry, 100 ml, three-neck flask equipped with a thermometer, constant pressure dropping funnel, nitrogen inlet and condenser under a dry, nitrogen atmosphere are added 3.48 g (0.020 moles) TDI, 150 ml dry dichloromethane and dibutyl tin dilaurate and heat to reflux. 4-Hydroxybutyl polydimethylsiloxane 14.65 g (0.010 moles) in 30 ml of dry dichloromethane are added dropwise to the flask. After 3 hour~, 10.00 g (0.005 moles) poly(ethylene oxide) are added to the flaak dropwise. The reaction is ~tirred at reflux for four hours and 1.30 g (0.010 moles) of HEMA
are charged to the flask. After 17 hours the isocyanate band is no longer ob~erved in the infrared spectrum. The volatiles are removed via vacuum rotary evaporation. The clear, viscous, reactive fluid is protected from light and thermal polymerization until lt i8 ready for use.
20 % by weight of PPGMM (Alcolac) and 1 % Darocur 1173 are added to the prepolymer and the mixture is dega~sed and mixed via vacuum rotary evaporation. The prepolymer is transferred to the appropriate molds and cured under W light of 3 to 5 milliwatt per s~uare centimeter intensity. The clear films produced in this matter have oxygen permeabilities of 208.2 x 10
The use of siloxane containing materials of various types in the fabrication of ophthalmic devices is well known.
. .
Thus, in U.S. 3,996,187; 3,996,189; 3,341,490 and 3,228,741 there are described contact lenses fabricated from poly torganosiloxanes) containing filler~. While such lenses are generally soft and of high oxygen permeability, the use of flllers such as sllica, is indicated in order to increa~e the otherwise generally poor tear strength and tensile strength. Also, such gilicone rubber lenses are characteristically both hydrophobic and lipophilic.
U.S. 3,808,178 discloses hard contact lenses fabricated from copolymers of a polysiloxanylalkyl acrylate or methacrylate ester and an alkyl acrylate or methacrylate ester. The monomers and polymers of the patent are hydrophobic and are incompatlble with hydrophilic materials such as hydroxyethyl methacrylate. ~hile the disclosed lenses have increased oxygen permeability, they are rigid.
U.S. 4,136,250 discloses hydrogels of a copolymer of about 20 to about 90 % of a hydrophilic (or mixture of hydrophilic and hydrophobic) monomer and about 10 to about 80 % of a polyolefinic siloxAne macromer which can be used to fabricRte a contact lens.
~ypicallyl such hydrogels are recited to posse~s a degree of swelling of about 10 to about 12 %. It ha8 been found, however, that the pressnce of substantial amounts of water in such hydrogels limits the oxygen permeability of such materials.
U.S. 4,153,641 relates, in relevant part, to contact lenses fabricated from a polymer of a polyorganosiloxane terminated with vinylic groups, or copolymers thereof with other monomers. The exemplified products thereln are hydrophobic in nature.
U.S. 4,486,577 relAtes to copolymers of about 8 to 70 % of A
polysiloxane macromer containing at least two vinyl groups and 3~-92 % of B monomer which is at least predominantly water insoluble to make polymers useful, for example, as contact lenses.
Generally, such prior art contact lenses compositions are either insufficiently hydrophilic in terms of surfAce wettability to be acceptable to the contact lens profession, even though they may possess high oxygen permeability, or such contact lenses are of acceptable wettability but the hydrophilicity i~ coupled with water swellability, which tends to limit optimum oxygen permeability.
It is an object of the present invention to overcome these and other disadvantages of the art by provlding ophthalmic devices, such as contact lenses and corneal implants, possessing a high degree of surface wettability but which are substantially non-swellable in the aqueous environment of use, and possessing a high degree of oxygen permeability by employing a crosslinked block polymer containing polysiloxane and polyalkylene oxide units.
l~ Z
A further ob~ect of the inventlon is to provide a method of cor-recting visual defects in the form of refractive errors by fitting to the patient's eye ln need of the same a corrective contsct lens of such polymer. These and other ob~ects of the invention are apparent from ths following detailed description of the invention.
One embodiment of the present invention relates to an optlcally clear, hydrolytically stable, biologically inert, wettable, flexible, substantially non-swellable in aqueous ocular tear fluid, oxygen permeable ophthalmic device, such as a contact lens, which is fabricated from A crosslinked polymer of a crosslinkable monomer having a segment S" of the formula I, -(D-S'-L-D-A-L) - (I) wherein a is 1 to lO;
each D is independently oxygen or -N(R2l)-;
each S' is independently a ~egment of formula II, -(CH2)h (~iO)v-~i-(CH2)i-O- ; (II) each A is independently a segment of formula III, 3 ~s 7 9 1l l3 Is 17 19 _ _ ~ O__ _ ~ d ~~~~~ _ ~ )f- ~__O__ _ _ 8 X ID 12 14 Y 16 18 20 z q (III) the terminal oxygen within each unit of formula II and III being replaceable by -N(R2l)-;
each L is independently -BRB ' -, the terminal L group within any one monomer of formula I also being capable of being -BR-;
3~
whereln each b, d and f is lndependently O - 4; q is a number from 1 to 1000; each x, y and z is independently O to lOO provided at least one oE x, y and z i8 at least 1; such that (x~y~z) multiplied by q i8 4 to 1000, preferably 25 to 75;
each h and i is an integer from 1 to 6, v 18 an integer from 2 to 75, preferably 2 to 50, more preferably lO to 50, most preferably 15 to SO;
Rl and R2 are independently alkyl of up to 18 carbon atoms, or aryl of up to 12 carbon atoms, preferably lower alkyl or phenyl, most prefsrably methyl;
each of R3, R4, R7-RI0, Rl3-Rl6, Rl9 and R20 is independently selected from the group consisting of hydrogen, halogen, an ali-phatic, aromatic or heterocyclic containing radical such as:
unsubstituted C1-C16 alkyl; substituted C1-C16 alkyl; unsubstituted C2-Cl 6 alkenyl; and substituted C~-CI 6 alkenyl; wherein the alkyl and alkenyl substituents are independently selected from C1-Cl 6 alkoxycarbonyl, C2-CI6 alkenyloxycarbonyl, fluoro, aryl of up to 10 carbon atoms, C1-C16 alkoxy, Cl-C16 alkanoyloxy, aryloxy of up to lO carbon atoms, C3-C6 alkenoyloxy, aroyl of up to 10 carbon atoms, aroyloxy of up to 11 carbon atoms, C3-Cg cycloalkyl, C3-C8 cyclo-alkoxy, C3-Cg cycloalkyl-carbonyloxy, C3-C~ cycloalkoxy-carbonyl, oxacycloalkyl of up to 7 carbon atoms, oxacycloalkoxy of up to 7 carbon atoms, oxacycloalkoxy (up to 7 carbon atoms)-carbonyl, oxacycloalkyl (up to 7 carbon atoms)-carbonyloxy, and aryl (of up to 10 carbon atoms)-oxycarbonyl, each of said alkyl and alkenyl substituents being, in turn, optionally substituted by C1-C6 alkyl, fluoro or a C1-C6 alkoxy provided said last mentioned alkoxy is not bound to a carbon atom already singly bound to another oxygen atom;
R3, R~, R7-R~0, Rl3-Rl6, Rl9 and R2J being further independently selected from aryl of up to 10 carbon atoms, C3 Cg cycloalkyl, and oxacycloalkyl of up to 7 carbon atoms, each of which may be unsub-stituted or further substituted with a substituent selected ~rom the group of substituents for said-R3 alkyl set forth above R5, R6, Rl1, Rl2, Rl7 and Rls are selected from the same group set forth above for R3; and R5, R6, Rll, Rl2, Rl7 and Rl3 are further independently selected from Cl-Ct6 alkoxycarbonyl, C3-C16 alkenoyl-. .
oxy, C2-C16 alkenyloxycarbonyl, and Cl-CI6 alkanoyloxy, each of which may be further ~ubstituted by fluoro, aryl of up to 10 carbon atoms, or Cl-Cl6 alkoxy, and Rs, R6, R~l, Rl2, Rl7 and R~8 are still further independently selected from aryloxy of up to 10 carbon atoms, cycloalkoxy of up to 8 carbon atoms, cycloalkyl (of up to 8 carbon atoms)-carbonyloxy, cycloalkoxy (of up to 8 carbon atoms)-carbonyl, aroyloxy of up to 11 carbon atom~, oxacycloalkoxy of up to 7 carbon atoms, oxacycloalkenyloxy of up to 7 carbon atoms, oxa-cycloalkoxy (of up to 7 carbon atoms)-carbonyl, oxacycloalkyl (of up to 7 carbon atoms)-carbonyloxy, and aryloxy (of up to 10 carbon atoms)-carbonyl, each of which may be further substituted by fluoro, Cl-C6 alkyl or Cl-C6 alkoxy, provided that any substituent having a singly bound oxygen atom as its link to the rest of the molecule may not be a substituent on the ~ame carbon atom which is singly bonded to another oxygen atom; or 2 ad~acent group~, selected from R3-R20, together with the atoms to which they are attached may form a 5 - 8 membered cycloalkyl, oxacycloalkyl or bicycloalkyl ring.
Ihe monomer of formula I preferably is of formula Ia, -(D-A-L-S")-c (Is) or of formula Ib, -(S") -D-S'-L - (Ib) even more preferably of formula Ic, L' ~ (D-A-L)e-S ~ L (Ic) and more preferably said monomer being divinylic; wherein D, A, L, S', S" are as defined hereinbefore; snd wherein c i~ 1 to 10; e is zero or one; a times c is 1 to 10; L i9 selected from -BRB'- and -BR-; L' i6~ hydrogen, P'-RB'-, or P'-BRB'-; and L" is hydrogen, or -P', or, in ca~e that e is ~ero, also -D-S'-BR-P' or -D-S'-BRB'-P'.
.
1~ 82 R2l is independently selected from hydrogen, Cl-C4 alkyl and phenyl, and i~ preferably hydrogen.
Esch B and B' is se]ected from ~ V- and ~ NH-wlth the carbonyl group being bound to A, S', D or P':
each R i8 independently a dlvalent linking group preferably ~elected from a) a divalent aliphatic group of up to 25 carbon atoms which may be interrupted by oxy, carbonyloxy, amino, amlnocarbonyl, oxy-carbonyl, ureldo, oxycarbonylamino, or carbonylamino;
b) a divalent 5 - 7 membered cycloaliphatic group having 5 - 25 car-bon atoms;
c) a divalent arylene group having 6 - 25, preferably 7 - 15 carbon atoms; and d) a divslent aralkyl or alkaryl group having 7 to 25, preferably ô - 16 carbon atoms;
wherein groups b) and d) can be optionally interrupted by the same groups a8 in group a) and wherein the aryl rings in groups c) and d) may be further substituted with one or more substituent~ selected from halogen, preferably fluorine or chlorine, Cl-C4 alkyl, pre-ferably methyl, and Cl-C1z perhalo alkyl, especially Cl-C1z per-fluoro alkyl;
and P' is hydrogen, amino, hydroxy, or a moiety containing a crosslinkable group which may be crosslinked when coreacted with a suitable cros~linking agent or when irradiated by actinic radiation.
In the foregolng, all alkyl groups whether mentioned alone or as part of another group are preferably C1-C4 alkyl, such as methyl, ethyl, propyl and butyl, especially t-butyl, with the exception that ad~acent groups on aryl rings cannot each be t-butyl. These alkyl groups may be straight chain or branched chain. When the alkyl is a substituent on a phenyl ring, it is preferably attached at the para position. Preferably alkenyl groups, whether alone or as part of l~?3r 82 another group, are C2-C4 alkenyl, such aa ethenyll propenyl and butenyl. Preferred aryl groups (whether alone or as part of another group) are phenyl and nsphthyl, more preferably phenyl. Preferably the aryl groups are still further substituted by Cl-C4 alkyl, more preferably t-butyl, most preferably in the para position. Halogen may be chloro, bromo, iodo or fluoro.
Preferably b, d and f are independently O - 3, more preferably O - 2, most preferably O or l. While the group identified by formula I may be highly halogenated, it is preferably at least 25 %
halogen free, more preferably 30 %, still more preferably 40 %, and most preferably substantially halogen free. Nherever cyclo groups are indicated, whether carbocyclic or heterocycllc they preferably have 5 - 6 ring members and the heterocyclic* preferably have only carbon atoms and an oxygen atom as rine members.
Bicycloalkyl 18 understood to cover those groups when two adjacent R
groups in a segment of formula III together form a ring and one of them already is a cycloalkyl group. In other words a fused ring system made up of two geminal R groups and the carbon atom to which they are attached results. For example if R3 is cyclopropyl and R4 18 methyl then R3 and R4 together with the carbon to which it is attached could be (2,1,0~ cyclopent-2,2-diyl.
In formula I, when b i8 greater than one, each of the multiple Rs and R6 groups may be the same or different; however preferably all of the Rs groups are the same and all of the R6 groups are the same.
The same i9 true with respect to d, Rll, and Rl 2; and f, Rl7, and Rl 8, Preferably, each of b, d and f is independently an integer of O
to 2, and most preferably zero or one.
In one aspect of the invention, each of R3-R7, R9-R~3 and Rls-RI9 is hydrogen. PreferablY the substituents R8, Rl4 and RZ are alkyl of up to 16 carbon atoms; alkyl of up to 16 carbon atoms substituted by 3~æ,2 alkoxy of up to 8 carbon atoms, or fluoro; phenyl which is unsub-stituted or substituted by fluoro, alkoxy of up to 6 carbon atoms or alkyl of up to 6 carbon atoms; benzyl wherein the phenyl ring thereof is unsubstituted or substituted by fluoro, alkoxy of up to 6 carbon atoms or alkyl of up to 6 carbon atoms; cyclohexyl; or oxacycloalkyl of 4 or 5 ring carbon atoms.
A highly advantageous subembodiment relates to wettable, non-swell-able ophthalmic devices, preferably contact lenses, fabricated from a polymer of formula I wherein A is of the formula IV, [CH2-(CHz) ~ H~O]--[CHz--(CH2)d--CH--O~--[CH2--(CH2)f--~H--O]
IV
wherein b, d, f, q, x, y, z, R8, Rl4 and R20 are as defined above.
There are two very highly advantageous embodiments having formula IV
which are represented by either formula V
~ [(CH2) ~ H--O]--[(CH2)--CH2--O]E (cH2)~H--O]~ (v) wherein n i8 b + 1; m i9 d + 1, p is f + 1; n, m and p each indepen-dently being preferably 1 - 3, more preferably 1 or 2, most pre-ferably l; and x, y, z and q are as defined above; R8 and R20 are hydrogen or one is, but preferably both are, an aliphatic, aromatic, or heterocyclic radical, preferably alkyl of up to 6 carbon atoms, alkyl of up to 6 carbon atoms substltuted by alkoxy of up to 6 carbon atoms or fluoro phenyl which is unsubstituted or substi-tuted by fluoro, alkoxy of up to 6 carbon atoms or alkyl of up to 6 carbon atoms; benzyl wherein the phenyl ring thereof i5 unsub-stituted or substituted by flubro, alkoxy of up to 6 carbon atoms or alkyl of up to 6 carbon atoms; cyclohexyl or oxacycloalkyl of 4 or 5 ring carbon atoms; or which are represented by formula VI
3r ~il2 g c~ 1 [(CH2~--CH2-O~X [(CHz)m- H~03y [(CH2)p CH2-O~ ~ (VI) wherein n, m, p, x, y, z and q are 8S defined above for formula V
and Rl4 i8 preferably selected from the same group as R8 in for-mula V.
In the foregoing it is to be understood that the units of x, y and z may be positioned randomly, in block ~egments, or alternately.
Another preferred embodiment corresponds to formulae IV, V and VI
wherein z i8 zero.
Desirably, the polymer segments of formula III or IV in the completed polymer are predominantly and preferably flubstantially devoid of free hydroxyl groups in the interior of the polymer as such groups tend to reduce oxygen permeability.
Free hydroxy groups on the outer surfaces of the formed polymer are acceptable as they increase wettability without drawing water into the polymer matrix. However, it is still preferable to have as few free hydroxy groups in the finished polymer as practical if a contact lens having high oxygen permeability is to be prepared. A
suitable means of tying up the free hydroxy groups present would be to interact them wlth a color group.
Typical color group8 useful in these embodiments include, but are not limited to, the hydroxy-reactlve dyes known in the art under the tradename Remazol, manufactured by American Hoech~t. Examples of the Remazol dyes which are especially useful are:
`2 Dye Color Index Code Remazol Brill Blue RW Reactive Blue 19 Remazol Yellow GR Reactive Yellow 15 Remazol Black B Reactive Black 5 Remazol Golden Orange 3GA Reactive Orange 78 Remaæol Turquolse P Reactive Blue 21 all of which have at least one group of the formula -SO2-CHzCHzO-SO3 which reacts with the polymer or monomer hydroxy group to yield a cH 3 dye-SOz-CH2-CH2-O-polymer or dye-SO2- H-O-polymer group, preferably the for~er. In such a manner, both excess free hydroxy groups are disposed of and colored contact lenses can be realized simultaneously. The color group or former can be reacted with monomer before the monomer is incorporated into the structure of formula I or afterwards. Another means of disposing of these excessive hydroxy groups is to utilize their presence to form various degree~ and types of crosslinking.
A vinylic comonomer i~ fre~uently utilized to increase the hydrophillcity of the final product without substantially altering the other properties mentioned above. Typically, when the vinylic comonomer is a polyéthylene glycol of the formula Rd-RC-O-(CHzCH20)- R
or pyrrolidone of the formula with g being 1 - 25, R~ being hydrogen or methyl and Rd being CH2~CH-, CH23C~CH3)- or other VV curable moiety, the re~ultant polymer is more hydrophilic than previou~ly, but the Dk i~ es~en-tially the same as when the comonomer i~ absent.
Usually, when present, the vinylic comonomer i8 used in an amount of about 2 % to about 10 % by weight of the resultant polymer. Advan-tageously, no more than 5 % of vinylic comonomer is used when the compound of formula V has a molecular weight in excesæ of 8000.
Generally, when the compound of formula V has a molecular weight of under about 4000, up to 10 % by weight of vinylic comonomer can be used. When the compound of formula V has a molecular weight between 4000 and 8000, the maximum amount of vinylic comonomer i6 between 5 % and 10 % by weight.
When P' is a vinyl containing group, for example a group containing the moiety HÇ= Ç-Rb Ra with R and R as defined below (e.g. -o-CH2CHz-o~~~8~CH2)~
then the monomer of formula I can be crosslinked in the presence or absence of up to less than about 50 %, preferably up to about 50 %, most preferably up to about lO % by weight of other vinylic comonomers, provided that such comonomers are substantially free of hydroxy groups in the final product.
When P' does not have a vinylic group, but takes part in cross-linking, P' contains e.g. an active hydrogen. Preferably P' termi-nates in an OH, NHR , (R being hydrogen or lower alkyl), a leaving group bound directly to the B or B' carbonyl, a conventional acyl leaving group when not 80 bound, SCN- or OCN-. Crosslinking is then typically carrled out by condensation or addition with a bi- or polyfunctional coreactive monomer. For example, when P' i8 OH, then the coreactive monomer functional group can be -NHR , -COOH, OCN-, SCN-, etc.; when P' is NHR , the reactive comonomer functional group 3~2 can be a conventional acyl, or acyl bound to a conventional leaving group; and when P' has OCN- or SCN-, then th~ reactlve comonomer functional group can be OH. Similarly, the other coreactive func-tional groups mentioned in terms of elther P' or the coreactive monomer can be interchanged (Those mentioned as part of P' being on the coreactive monomer and those mentioned as part of the coreactive monomer being part of P').
Suitable vinylic comonomers and coreactive monomers for condensation are set forth below. However, the list i8 not exhaustive and tho~e of ordinary skill will appreciate the modifications, addition~, and alternatives which may also be employed.
When either or both L' and L" are hydrogen, or terminate in P' with P' being hydrogen, at least one additional cros~linkable moiety must be present a8 one of, or as substituent on one of, the groups R3-R2D.
Such crosslinkable groups may also be present as a substituent on or in place of one or more of R3-R20 even when one or both of L' and L"
have crosslinkable groups therein. However, the degree of cross-linking in the finished crosslinked polymer should not exceed 10 %, preferably not more than 5 %, and should be more preferably in the range of 1 - 4 %, most preferably in the range of 2 - 3 %.
Within the polymer fabricated from monomers of formula I, not more than 20-70 %, preferably not more than 50 % of the A groupc are polyethylene glycol.
The number of A units and the chsin length and nature of the substituents on the polyoxyethylene segment is determined by the degree of wettability desired in the polymer of the compound of formula I. In general, the polymer should be sufficiently hydro-philic ln its surface properties such that the polymer exhibits a contact angle with distllled water at 20C of less than 60, preferably less than 40, more preferably less than 25, ~till more preferably less than 15, mo~t preferably less than 10.
1~3~ 82 The greater the number of siloxane units, the greater the number of oxyalkylene units is generally required to reduce the contact angle to within the above limits.
Further, a large excess of unsubstituted oxyethylene units is to be avoided, as such excess units tend to cause the polymer to be swellable. As water is taken up, the oxygen permeability of such polymers tends to be drastically reduced. Advantageously, the instant polymers absorb less than about 10 % by weight water, preferably less than about 5 % by weight, most preferably less than 3 % by weight water.
Highly preferred are those polymers which exhibit a contact angle of eBs than 25, more prefersbly less than 15 and most preferably less than 10.
Preferred crosslinked polymers are those consisting essentially of a polymer of a divinylic monomer sccording to formula I wherein Rl and R2 are methyl, h and i are 2 to 4, v is 2-20; b, d and f are zero;
R3, R4 are hydrogen; R8, Rl~ and R20 are independently alkyl of up to 8 carbon atoms, (x+y+z) multiplied by q is 4-40 and P' is:
-CH~CH2 w1th R being hydrogen or methyl.
Very highly advantageous are those polymer~ of reactive vinylic monomers of the formula VII, ?3~2 ~ 14 -H2C'~ BRB' ~ D-(CH2- ~ -O)X-BRB' ~ D-(CH2)h'(~i)V ~ (C 2)i ~ ICH3 CIH3 -BRB'-D-(CH2-~H-O) -BRB' ~ ( 2)h (~ )v ~ ( 2)i ~7 -(CH2- H-O)x-BRB' ~ HCH2 (VII) k where one of e and k i8 one and the other zero; R 18 hydrogen or methyl;
each R ls a divalent arylene group of 6 to 15 carbon atoms, a divalent C6-C20-arylene-amlno carbonyloxy-C2-C6 alkylene;
or dlvalent C3-CIs cycloaliphatic;
B and B' are each -C-O- or -~
each R7 18 alkyl of l to 6 carbon atoms, or mixtures thereof withunlts wherein R7 i8 hydrogen, preferably with the proviso that R7 can be hydrogen in no more than about 75 %, more preferably 50 %, still more preferably no more than 30 %, of the units;
each x 18 4-75, preferably 6-70, more preferably 8-66; v is 2-66, preferably 2-25, more preferably 2-20; i and h are independently 2, 3 or 4; and a i~ an integer of 1-10, preferably 1-8, more preferably 1-6, still more preferably 1-4, most preferably 1-2.
Wlth~n this very highly advantageous embodiment, Ra is most preferably methyl; R is most preferably -phenylene-, -CH2CH20CONH-phenylene- or -CH2CH20CONH-tolylene-; R7 is methyl, x is most preferably 60 to 66; v 18 most preferably 15 to 20; a 1~ most preferably l to 3; ~ is most preferably zero; and e is most prefer-ably one.
.
A very highly preferred embodiment are those polymers from monomers - 15 ~ 3~Z
of formula VII wherein each -C~l2- H-0-group i8 of the formula ~ ~22 1 ~ CHz H ~
where R2 2 i8 alkyl of 1 to 4 carbon atoms, most preferably methyl, and s i8 from about 6 to about 200, preferably from about 25 to about 100, and most preferably from about 50 to about 75.
Also highly preferred are those polymers of monomers of formula VII
l~-7 wherein each -CH2-~H-0-group i8 of the formula VIII
H2CH2 ~ CH2~H ~ H2CH2 ~ (VIII) wherein x i9 from about 2 to about 20, y is from about 8 to about 100, and z from about 4 to about 80. Another valuable embodi-ment requires the value of y to be at least about twice that of x or z and R2 2 to be alkyl of 1 to 4 carbon atoms, preferably methyl.
The reactive vinylic monomers of formula I can characteristically be polymerized to form crosslinked polymers under conventional polymerization condition~.
If desired, the monomer reactlon mixture may contain a catalytic amount of a conventional polymerization catalyst, preferably a free radical catalyst. Of psrticular interest are conventional peroxide and azo catalysts, such as hydrogen peroxide, benzoyl peroxide, tert-butyl peroctoate, benzoyl peroxide or azobis(isobutyronitrile).
The polymerization can generally be carried out at temperatures between about 20 and about 150C, for a period between about 1 and about 24 hours. It i9 understood that the time and temperature in such a reaction are inversely related. Thus, temperatures employed in the upper end of the temperature range will generally provide 3~ ~Z
reaction times near the lower end of the time range. Preferably, the polymerization is conducted in the presence of actinic radiation, such as W light.
Depending upon the nature of the polymer mixture, it may be desir-able for the polymers obtained from guch polymeri2ations to be post cured, e.g. at a somewhat elevated temperature such as between about 60C and about 150C.
For the preparation of contact lenges, the polymer mixture may be cast directly in the shape of the lens, or the polymerization may be carried out in a mold having a shape convenient for further pro-cessing, ~uch as in the shape of small cyclinders or "buttonfi", which can then be machined.
Minor amounts i.e. les~ than 50 %, preferably up to 30 %, and most preferably up to no more than about 10 % by weight, of conventional copolymeri2ible vlnyl monomerA, can be employed a~ extenders or hydrophilic modifiers, or the like, ln the preparation of the instant polymer, as copolymer constituents. Suitable vinyl monomers include:
acrylates and methacrylates of the general formula c~23 H2C~ -CooR24 where RZ3 is hydrogen or methyl and R24 is a stralght chaln or branched allphatic, cycloaliphatic or aromatic group having up to 20 carbon atoms whlch is unsubstituted or substituted by one or more alkoxy, alkanoyloxy or alkyl of up to 12 carbon atoms, or by halo, especially chloro or preferably fluoro, or C3-C5 polyalkyleneoxy of 2 to about 100 units;
acrylamides and methacrylamides of the general formula ,R23 HzC~C-CoNHR24 where R2 3 and R24 are defined above;
3(:~2 vinyl ether~ of the formula where R24 i8 as defined above;
vinyl esters of the formula HzC~CH-OOC-R2 "
where R24 is a3 defined above;
maleates and fumarates of the formula where R2 4 ls as defined above;
and vinylic substituted hydrocarbons of the formula R2 3 CH-.CHR2 4 where R23 and R24 are a~ defined above.
Useful monomers include, for example:
methyl-, ethyl-, propyl-, isopropyl-, butyl-, ethoxyethyl-, methoxy-ethyl-, ethoxypropyl-, phenyl-, benzyl-, cyclohexyl-, hexafluoro-isopropyl-, or n-octyl-acrylates and -methacrylates as well as the corresponding acrylamides and methacrylamides:
dimethylfumarate, dimethylmaleate, diethylfumarate, methyl vinyl ether, ethoxyethyl vinyl ether, vinyl acetate, vinyl propionate, vinyl benzoate, acrylonitrile, styrene, alphamethyl styrene, l-hexene, vinyl chloride, vinyl methyl ketone, vinyl stearate, 2-hexene and 2-ethylhexyl methacrylate.
As hydrophilic modifiers, to increase hydrophilicity without substantial 1088 of DK, the vinyl comonomer can be a N-(vinyl containing group)-pyrrolidone or a polyoxyethylene (of 1-25 repeat-ing units) acrylate or methacrylate. Such a hydrophilic modifier should not be present in exceas of about lO % by welght of the compound of formula I.
Most preferably, the instant polymers are free from copolymer units of such conventional vinyl monomers.
The vinyllc monomers of formula I can be prepared by methods known, per se.
1 ~3C 8;Z
For example, the slloxsne/polyalkylene oxide containing divinyllc monomer~ of formula I may be prepared by reacting a siloxane diol of the formula HO-(S')-H, wherein -S'- i6 a group of the formula II as deflned hereinbefore with a sufficient amount of a difunctional reactive group containing compound having the group -Q- or -Q-Y-, wherein the difunctional reactive group6 are isocyanate; activated carboxy, such as an anhydride, an acid halide or a carboxy ester; or i8 a leaving group, such as a halide, sulfato or the llke, to form the corresponding reactive group containing endcapped derivative.
The resulting endcapped siloxane derivative can then be reacted with a polyoxyalkylene diol of the formula HO-(A)-H, wherein -A- is a group of the formula III above to form the corresponding polyoxy-slkylene-slloxane-polyoxyalkylene diol. This diol can then be reacted with a reactive group containing vinylic monomer having the terminal H2C~C(R )-BR- moiety, wherein the reactive group is an lsocyanate; activated carboxy, such as an anhydride, an acid halide or carboxy ester, or is a leaving group such a~ halo, sulfato or the like to form the corresponding divinyl derivative where a is 1, and A is other than a direct bond. Alternatively, the aforementioned polyoxyalkylene - slloxane - polyoxyalkylene dlols can be further sequentlally reacted with a further difunctional reactlve group containing compound having the group -BR- or -BRB'-D- to form the correspondlng dl-functlonal reactive endcapped derivative which is then reacted with a siloxane dlol of the formula HO-(S'>-H. One may contlnue bullding up alternative polyoxyalkylene/slloxane unlt contalnlng dlols ln this manner, corresponding to the value of elther "c(a plus e)" or c(a plus k)". Then this diol may be endcapped wlth a reactlve group containing vinylic monomer havlng a termlnal H2C-C(R )-BR- moiety or the diol reacted with a sufficlent amount of dlfunctional reactlve group contalnlng compound to endcap the diol with a reactive group, such as eg. an lsocyanate, etc~
group whlch is then reacted wlth the appropriate vinylic containing ?3~ ~,Z
compound, such as an vinylic amine or alcohol, or other copoly-merizable monomer having a crosslinkable group to obtain the corresponding product of formula I.
Of course, instead of starting with a siloxane diol of the formula H0-(S')-H and building up the alternating sequence to the desired value of "a", one may instead begin with a polyoxyalkylene diol of the formula H0-(A)-H and, after endcapping the same with di-functional reactive groups, condense the same wlth the siloxane diol until the desired value of "a" is attained, and terminate the diol with vinylic groups as described above.
The above reactive vlnylic monomer~ are characteristically poly-merized under conventional polymerization conditions. In those vinylic monomers containing but one vinyl group, a minor amount e.g. from about 0.01 to about 5 weight percent, based on the monomer of formula I, of a conventional crosslinking agent, may be employed.
Suitable crosslinking agents include diolefinic monomer~ such as:
Allyl acrylate and methacrylate, alkylene glycol and polyalkylene glycol diacrylates and dimethacrylates, such as ethyleneglycol dimethacrylate, diethylene glycol dimethacrylate, and propylene glycol dimethacrylate; trimethylol propane triacrylate; penta-erythritol tetraacrylate, divinylbenzene; divinyl ether; divinyl sulfone; bisphenol A diacrylate or dimethacrylate; methylene bis-acrylamide; diallyl phthalate; triallyl melamine and hexamethylene diacrylate and dlmethacrylate. Also, such minor amounts of a crosslinking agent may be employed, if desired, in the polymeriza-tion of the di-vinyl monomer of formula I and VII.
When the monomers of formula I have free hydroxy, isocyanato, carboxylic or amine groups, suitable crosslinking agents contain di-or polyfunctional co-reactive groups to form addition or con-densation reactions linking 2 or more chains.
- 20 ~ 3~Z
If desired, the monomer reaction mixture may contain a catalytic amount of a conventional cataly~t, preferably a free rsdical catalyst. Of particular interest are conventional peroxide and azo cataly6ts, guch as hydrogen peroxide, benzoyl peroxide, tert-butyl, peroctoate, oenzoyl peroxide or azobis (isobutyronitrile).
The aforementioned reactions are generally straight forward additions or condensations and are typically conducted at a reaction temperature between about -10C and about 100C, depending upon the relative reactivity of the species involved, in the presence or absence of an inert diluent and in the optional presence of an addition or condensation catalyst if desired or appropriate. For reactions involving an isocyanate or acid halide, with a diol, for example, suitable optional catalysts include pyridine and triethyl-amine.
The siloxane diols of the formula H0-(S')-H are known in the art and many are commercially readily available.
Also, the polyoxyalkylene diols of the formula H0-A-H are known or can be prepared by known methods.
Thus, the polyols of the formula H0-A-~ are generally prepared by the addition reaction of xq moles of an epoxide of the formula IX, Cl ~ C ~ (IX) where R3-R3, b, ~, and q are as defined above, with yq moles of an epoxide of the formula X, Rj Rll R12 Rl3 f~c~7l (x) o 3(~Z
where R9-Rl4, d, y, and q are as defined above, and zq mole~ of an epoxide of the formula XI, R17 Rl8 ~ Iq ~ ~20 (XI) wherein R~s-R2~, f, ~, and q are as defined above, optionally in the presence of a conventional alkylation catalyst, ae atmospheric to elevated pressures of up to about 3000 kPa gauge, at temperatures between 0C and about 130C, optionally in the presence of an inert diluent. If desired, one may add to the reaction mixture, prior to the reaction of the epoxides, an aliphatic, aromatic or cycloali-phatic alcohol, acid or amine having up to 14 carbon atoms to prepare the corresponding mono-ol~ terminating in the group D.
The reaction between the epoxides, when mixture~ of different epoxides are employed to obtain the polyol of the formula H0-A-H, can be conducted by admixing the epoxides to obtain random copoly-mers or terpolymers, etc., or the addition can be conducted sequen-tially to form block copolymers having terminal hydroxy groups.
Suitable catalysts include alkaline earth oxides, alkaline earth carbonates, alkyl zinc compounds, aluminum alkoxides, hydrates of ferric chloride, bromide and acetate, and gamma radiation. The reaction may also be initisted by the presence of a glycol, such a8 ethylene glycol or propylene glycol or by a polyol of higher functionality such as sucrose, or by sn amine, such a8 ethylene diamine, toluenediamine, and so forth. Generally the length of time of the resction will depend in psrt on the alkylene oxide employed, but csn generally be from less than one to several score hours.
Thus, ethylene oxide generally is about three times as active as propylene oxide, which ln turn reacts more rapidly than 1,2-butylene oxide. The preparation of polyoxetanes and polytetrahydrofurans is generally initiated via ring opening oxonium formation using trialkyloxonium salts, carboxonium salts, scylium salts and the like.
1~3'~} ~2 Suitable diols of the formuls H0-A-H include those prepared from epoxldes such a9:
1,2-propylene oxide; 1,2-butylene oxide; 1,2-epoxydecane; 1,2-epoxy-dodecane; 1,2-epoxyoctane; 2,3-epoxynorbornane; 1,2-epoxy-3-ethoxy-propane; 1,2-epoxy-3-phenoxypropane; 2,3-epoxypropyl 4-methoxyphenyl ether; tetrahydrofuran; l,2-epoxy-3-cyclohexyloxypropane; oxetane;
1,2-epoxy-5-hexene; 1,2-epoxyethylbenzene; 1,2-epoxy-1-methoxy-2-methylpropane; perfluorohexylethoxypropylene oxide; benzyloxypro-pylene oxide, and the like. Also, the aforementioned epoxides may be employed as mixtures thereof. Further, certain cyclic ethers of formula IX, X or XI where b or d or f, respectively i9 3 and the carbocyclic portion of the ring is substituted are resistant to polymerization alone, but copolymerize quite readily with more reactive cycllc ethers. Suitable co-monomers include, for exAmpls, 2-methyl-tetrahydrofuran and 3-methyl-tetrahydrofuran. Also, while ethylene oxide may be employed as a co-monomer, ethylene oxide polymers, in the absence of more hydrophobic units, is character-istically too hydrophilic and absorbs too much aqueous fluid to be of use in accordance with the instant invention. However, ethylene oxide/propylene oxide copolymeric diols wherein there 18 30-80 %, preferably greater than 50 %, more preferably greater than 66 %
propylene oxlde, on a mole basis, is sufficiently hydrophobic 80 as to be substantially non-swellable in aqueous media, and yet sufficiently hydrophilic 80 as to exhibit a contact angle with water of less than 60; preferably less than 40, more preferably less than 25, more preferably less than 15, most preferably less than 10.
Many polymer diols of the formula H0-A-H are commercially available.
Thus, suitable diol products include poloxamers having the general formula HO(CH2CHzO) '-(CH(CH3)CH20)b'-(CH2CH20)c'-H
.
~ 3~Z
wharein b' has a value between sbout 16 and 100 and the sum of a and c' 18 between about 4 and about 100. Example8 of 8uch poloxa-merg, and their average values of a', b' and c', include poloxa-mer 101 (a' is 2, b' is 16, c' i~ 2~; poloxamer 122 (81 i~ 5, b~ 19 21, c' i9 5); poloxsmer 181 (a' is 3, b' ls 30, c' is 3);
poloxamer 212 (a' i8 8, b' is 35, c' i8 8); poloxamer 231 (a' is 6, b' 1B 39, c' is 6); poloxamer 282 (a' is 107 b' is 47, c' is 10);
poloxamer 331 (a' is 7, b' is 54, c' is 7); poloxamer 401 (a' is 6, b' is 67, c' is 6).
Such poloxamers are available, e.g. from BASF Wyandotte under their Pluronic~ brand name. Also suitable are the "reverse poloxamers", having polyethylens glycol bounded on each side by polypropylene glycol.
Polypropylene ether glycols include commercially available products having a molecular weight range between about 400 and about 4,000.
As stated above, the polymers for use in the instant inventlon are those which exhibit a receding contact angle at 20C of less than 60, preferably le~s than 40, more preferably less than 25, more preferably less than 15 and most preferably less than 10. The measurement of such contact angle is conveniently performed using a modified "Wilhelmy Plate" technique, as described, for example, for J.D. Androde, et al. Surface and Interfacial Aspects of Biomedical Polymers, Vol. 1, Surface Chemistry and Physics, Plenum Pres~, 1985, wherein a specimen sample in the form of a plate of known dimensions is immersed into the wetting solution, pure water, at a slow controlled rate, e.g. at 2 - 20 mm per minute.
As mentioned above, the instant polymers for use in the present invention possess a high degree of oxygen permeability. The oxygen permeability, Dk(x10 ), is measured using a modification of ASTM
standard D3985-81 in that (a) there is used 21 % oxygen, i.e. air, instead of 99 - 100 % oxygen, (b) the ~urface area of sample 3~ ~2 employed iB 0. 50 square meters versus 100 square meters and the humldity i9 controlled to be at 95 - 100 % relatlve humidity lnstead of 0 % relative humidity. The unit of Dk is (mm-ml 02/cm2~sec~mmHg~.
Typically, conventional fully swollen polyhydroxyethyl methacrylate lenses which are sparingly crosslinked possess a Dk(xlO ), (mm~ml 02/cm2-sec~mmHg) value of about 5 - 7.
The instant polymers for use as an ophthalmic device, such as a contact lens, possess a Dk(x10 ) value generally greater than 7, preferably greater than about 15, more preferably greater than about 20 and most preferably greater than about 40.
The following examples are for illustrative purposes and are not to be construed a~ limiting the invention. All parts are by weight unless otherwise specified.
Table of abbreviation~ used throughout the examples:
PPG: polypropyleneglycol HEMA: hydroxyethyl methacrylate TDI: toluene diisocyanate PEG: polyethyleneglycol Example 1: To a dry, 0.25-liter, three-neck flask equipped with a thermometer, constant pressure dropping funnel, nitrogen inlet and condenser under a dry, nitrogen atmo~phere is added 1.74 g (0.010 moles) TDI, 10 ml dry dlchloromethane and 0.05 g tin octoate.
10.00 g (0.005 moles) poly(propylene oxide) in 40 ml of dry dichloromethane are added to the flask dropwise over a 40 minute period, maintaining a temperature less than 30C. The reaction is continued for 2 hours. After 2 hours, 14.65 g (0.010 moles) hydroxybutyl terminated polydimethylsiloxane in 30 ml of dry dichloromethane are sdded rapidly to the system and the reaction is allowed to continue 17 hours. Then 1.74 g (0.010 moles) TDI are sdded; after 3 hours, 1.30 g (0.010 moles) HEMA are added and the 3~ &Z
reaction i8 stirred 18 hours. After 18 hourfi, the isocyanate band ls not apparent in the infrared spectrum. The volatiles are then removed from the reaction system via vacuum rotary evaporation. The clear, viscous, reactive fluid is stored protected from light and thermal polymeri~ation.
To the clear, viscous fluid is added one percent Darocur 1173 (~V
initiator) and the mixture degassed and mixed via vacuum rotary evaporation. The material is then W cured in the appropriate molds under UV light with an intensity of 2 to 3 milliwatts. The resulting film has an advancing contact angle of 65.5 and a receding angle of 16.2.
Examples 2 to 3: Similar rections are conducted as described in example 1 but with reactive components of different molecular weight~ and other vAriations as outlined in Table 1. The solvents are adjusted proportionally based on the weight of the materials used.
Table 1*
Example Tin _ PPG Silicone TDI _ HEMA Octoate Darocur DK
2 30.23 40.03 6.96 2.60 0.06 1 % 159.0 (0.01) (0.02) ~0.04) (0.02) 3 6.40 10.77 1.12 0.42 0.0~ 1 % 257 (0.0016) (0.0032) (0.0064) (0.0032) * Weight in grams.
Number in parentheses is molar quantity.
Initlator expressed in terms of percent of prepolymer in grams.
DK expressed ln terms of DK units.
Example 4 To a dry, 100 ml, three-neck flask equipped with a thermometer, constant pressure dropping funnel, nitrogen inlet and condenser under a dry, nitrogen amosphere sre added 3.48 g - 26 ~ 3a &Z
(0.020 moles) TDI, 150 ml dry dichloromethane and dibutyl tin dilaurate and heat to reflux. 4-Hydroxybutyl polydimethyl6iloxane 14.65 g (0.010 moles) in 30 ml of dry dichloromethane are added dropwise to the flask. After 3 hours, 10.00 g (0.005 mol~s) poly-(ethylene oxide) are added to the flask dropwise. The reaction is stirred at reflux for four hours and 1.30 g (0.010 molefi) of HEMA
are charged to the flask. After 17 hours the isocyanate band is no longer observed in the lnfrared spectrum. The volatiles are removed via vacuum rotary evaporation. The clear, vi~cous, reactive fluid is protected from llght and thermal polymerization untll it is ready for use.
One percent Darocur 1173 is added to the prepolymer and the mixture degassed and mixed vla vacuum rotary evaporatlon. The prepolymer is transferred to the appropriate mold~ and cured under W light of 3 to 5 milliwatt intensity. The clear film~ produced in thi~ manner have oxygen permeabilities of 148.8 x 10 10.
Examples 5 to 11: Similar reactions are conducted as described in example 4 but with reactive components of different molecular weights and other variations as outlined in Table 2. The solvents are ad~usted proportionally oased on the weight of the materials u~ed .
Table 2*
Example Tin PPG Silicone TDI HEMA Octoate Darocur DK
50.72 37.158.83 3.30 0.02 1 % 125.4 (0.013) (0.025) (0.050) (0.025) 6 30.77 52.2012.40 4.64 0.030.5 % 133.1 (0.018) (0.036) (0.071) (0.036) 7 33.26 50.3111.96 4.47 0.03 1 % 179.1 (0.017) (0.034) (0.069) (0.034) 8 32.67 31.917.58 2.83 0.08 1 % 130.0 (0.011) (0.022) (0.044) (0.022) 1~?3(~ ~tZ
9 21.21 43.657~38 2.76 0.04 1 % 258.5 (0.011~ (0.021)(0.042) (0.021) 19.07 75.006.96 2.60 0.11 1 % 340.3 (0.01) (0.02)(0.04) (0.02) 11 19.08 55.276.96 2.61 0.7 1 % 388 (0.01~ (0.02)(0.04) (0.02) * Weight in grama.
Number in parentheses i~ molar quantity.
Initiator expressed in terms of percent of prepolymer in grams.
DK expressed in terms of DR units.
Example 12: To a dry, 100 ml, three-neck flask equipped with a thermometer, constant pressure dropping funnel, nitrogen inlet and condenser under a dry, nitrogen atmosphere are added 3.48 g (0.020 moles) TDI, 150 ml dry dichloromethane and dibutyl tin dilaurate and heat to reflux. 4-Hydroxybutyl polydimethylsiloxane 14.65 g (0.010 moles) in 30 ml of dry dichloromethane are added dropwise to the flask. After 3 hour~, 10.00 g (0.005 moles) poly(ethylene oxide) are added to the flaak dropwise. The reaction is ~tirred at reflux for four hours and 1.30 g (0.010 moles) of HEMA
are charged to the flask. After 17 hours the isocyanate band is no longer ob~erved in the infrared spectrum. The volatiles are removed via vacuum rotary evaporation. The clear, viscous, reactive fluid is protected from light and thermal polymerization until lt i8 ready for use.
20 % by weight of PPGMM (Alcolac) and 1 % Darocur 1173 are added to the prepolymer and the mixture is dega~sed and mixed via vacuum rotary evaporation. The prepolymer is transferred to the appropriate molds and cured under W light of 3 to 5 milliwatt per s~uare centimeter intensity. The clear films produced in this matter have oxygen permeabilities of 208.2 x 10
Claims (55)
1. An optically clear, wettable, flexible, substantially non-swellable in aqueous ocular tear fluid, oxygen permeable ophthalmic device, fabricated from a crosslinked polymer of a crosslinkable monomer having a segment S" of the formula I, -(D-S'-L-D-A-L)? (I) wherein a is 1 to 10;
each D is independently oxygen or -N(R21)-;
each S' is independently a segment of formula II, (II) each A is independently a segment of formula III, the terminal oxygen within each unit of formula II and III being replaceable by -N(R21)-;
each L is independently -BRB'-, the terminal L group within any one monomer of formula I also being capable of being -BR-;
wherein each b, d and f is independently 0 - 4; q is a number from 1 to 1000; each x, y and z is independently 0 to 100 provided at least one of x, y and z is at least 1; such that (x+y+z) multiplied by q is 4 to 1000;
each h and i is an integer from 1 to 6, v is an integer from 2 to 75;
R1 and R2 are independently alkyl of up to 18 carbon atoms, or aryl of up to 12 carbon atoms;
each of R3, R4, R7-R10, R13-R16, R19 and R20 is independently selected from the group consisting of hydrogen, halogen, an ali-phatic, aromatic or heterocyclic containing radical selected from unsubstituted C1-C16 alkyl; substituted C1-C16 alkyl; unsubstituted C2-C16 alkenyl; and substituted C2-C16 alkenyl; wherein the alkyl and alkenyl substituents are independently selected from C1-C16 alkoxycarbonyl, C2-C16 alkenyloxycarbonyl, fluoro, aryl of up to 10 carbon atoms, C1-C16 alkoxy, C1-C16 alkanoyloxy, aryloxy of up to 10 carbon atoms, C3-C6 alkenoyloxy, aroyl of up to 10 carbon atoms, aroyloxy of up to 11 carbon atoms, C3-C8 cycloalkyl, C3-C9 cyclo-alkoxy, C3-C8 cycloalkyl-carbonyloxy, C3-C8 cycloalkoxy-carbonyl, oxacycloalkyl of up to 7 carbon atoms, oxacycloalkoxy of up to 7 carbon atoms, oxacycloalkoxy (up to 7 carbon atoms)-carbonyl, oxacycloalkyl (up to 7 carbon atoms)-carbonyloxy, and aryl (of up to 10 carbon atoms)-oxycarbonyl, each of said alkyl and alkenyl substituents being, in turn, optionally substituted by C1-C6 alkyl, fluoro or a C1-C6 alkoxy provided said last mentioned alkoxy is not bound to a carbon atom already singly bound to another oxygen atom;
R3, R4, R7-R10, R13-R16, R19 and R20 being further independently selected from aryl of up to 10 carbon atoms, C3-C9 cycloalkyl, and oxacycloalkyl of up to 7 carbon atoms, each of which may be unsub-stituted or further substituted with a substituent selected from the group of substituents for said R3 alkyl set forth above;
R5, R6, R11, R12, R17 and R18 are selected from the same group set forth above for R3; and R5, R6, R11, R12, R17 and R8 are further independently selected from C1-C16 alkoxycarbonyl, C3-C16 alkenoyl-oxy, C2-C16 alkenyloxycarbonyl, and C1-C16 alkanoyloxy, each of which may be further substituted by fluoro, aryl of up to 10 carbon atoms, or C1-C16 alkoxy, and R5, R6, R11, R12, R17 and R18 are still further independently selected from aryloxy of up to 10 carbon atoms, cycloalkoxy of up to 8 carbon atoms, cycloalkyl (of up to 8 carbon atoms)-carbonyloxy, cycloalkoxy (of up to 8 carbon atoms)-carbonyl, aroyloxy of up to 11 carbon atoms, oxacycloalkoxy of up to 7 carbon atoms, oxacycloalkenyloxy of up to 7 carbon atoms, oxa-cycloalkoxy (of up to 7 carbon atoms)-carbonyl, oxacycloalkyl (of up to 7 carbon atoms)-carbonyloxy, and aryloxy (of up to 10 carbon atoms)-carbonyl, each of which may be further substituted by fluoro, C1-C6 alkyl or C1-C6 alkoxy, provided that any substituent having a singly bound oxygen atom as its link to the rest of the molecule may not be a substituent on the same carbon atom which is singly bonded to another oxygen atom; or 2 adjacent groups, selected from R3-R20, together with the atoms to which they are attached may form a 5 - 8 membered cycloalkyl, oxacycloalkyl or bicycloalkyl ring; R21 is independently selected from hydrogen, C1-C4 alkyl and phenyl; and wherein each B and B' is selected from -?-, -?-O-; and -?NH-with the carbonyl group being bound to A, S' or D;
each R is independently a divalent linking group selected from a) a divalent aliphatic group of up to 25 carbon atoms which may be interrupted by oxy, carbonyloxy, amino, aminocarbonyl, oxy-carbonyl, ureido, oxycarbonylamino, or carbonylamino;
b) a divalent 5 - 7 membered cycloaliphatic group having 5 - 25 car-bon atoms;
c) a divalent arylene group having 6 - 25 carbon atoms; and d) a divalent aralkyl or alkaryl group having 7 to 25 carbon atoms;
wherein groups b) and d) can be optionally interrupted by the same groups as in group a) and wherein the aryl rings in groups c) and d) may be further substituted with one or more substituents selected from halogen, C1-C4 alkyl, and C1-C12 perhalo alkyl; said device having a receding contact angle of less than 60°; having absorbed less than about 10 % water in its swollen state; and having a Dk x10-10(mm?ml O2/cm2?sec?mmHg) of at least about 7.
each D is independently oxygen or -N(R21)-;
each S' is independently a segment of formula II, (II) each A is independently a segment of formula III, the terminal oxygen within each unit of formula II and III being replaceable by -N(R21)-;
each L is independently -BRB'-, the terminal L group within any one monomer of formula I also being capable of being -BR-;
wherein each b, d and f is independently 0 - 4; q is a number from 1 to 1000; each x, y and z is independently 0 to 100 provided at least one of x, y and z is at least 1; such that (x+y+z) multiplied by q is 4 to 1000;
each h and i is an integer from 1 to 6, v is an integer from 2 to 75;
R1 and R2 are independently alkyl of up to 18 carbon atoms, or aryl of up to 12 carbon atoms;
each of R3, R4, R7-R10, R13-R16, R19 and R20 is independently selected from the group consisting of hydrogen, halogen, an ali-phatic, aromatic or heterocyclic containing radical selected from unsubstituted C1-C16 alkyl; substituted C1-C16 alkyl; unsubstituted C2-C16 alkenyl; and substituted C2-C16 alkenyl; wherein the alkyl and alkenyl substituents are independently selected from C1-C16 alkoxycarbonyl, C2-C16 alkenyloxycarbonyl, fluoro, aryl of up to 10 carbon atoms, C1-C16 alkoxy, C1-C16 alkanoyloxy, aryloxy of up to 10 carbon atoms, C3-C6 alkenoyloxy, aroyl of up to 10 carbon atoms, aroyloxy of up to 11 carbon atoms, C3-C8 cycloalkyl, C3-C9 cyclo-alkoxy, C3-C8 cycloalkyl-carbonyloxy, C3-C8 cycloalkoxy-carbonyl, oxacycloalkyl of up to 7 carbon atoms, oxacycloalkoxy of up to 7 carbon atoms, oxacycloalkoxy (up to 7 carbon atoms)-carbonyl, oxacycloalkyl (up to 7 carbon atoms)-carbonyloxy, and aryl (of up to 10 carbon atoms)-oxycarbonyl, each of said alkyl and alkenyl substituents being, in turn, optionally substituted by C1-C6 alkyl, fluoro or a C1-C6 alkoxy provided said last mentioned alkoxy is not bound to a carbon atom already singly bound to another oxygen atom;
R3, R4, R7-R10, R13-R16, R19 and R20 being further independently selected from aryl of up to 10 carbon atoms, C3-C9 cycloalkyl, and oxacycloalkyl of up to 7 carbon atoms, each of which may be unsub-stituted or further substituted with a substituent selected from the group of substituents for said R3 alkyl set forth above;
R5, R6, R11, R12, R17 and R18 are selected from the same group set forth above for R3; and R5, R6, R11, R12, R17 and R8 are further independently selected from C1-C16 alkoxycarbonyl, C3-C16 alkenoyl-oxy, C2-C16 alkenyloxycarbonyl, and C1-C16 alkanoyloxy, each of which may be further substituted by fluoro, aryl of up to 10 carbon atoms, or C1-C16 alkoxy, and R5, R6, R11, R12, R17 and R18 are still further independently selected from aryloxy of up to 10 carbon atoms, cycloalkoxy of up to 8 carbon atoms, cycloalkyl (of up to 8 carbon atoms)-carbonyloxy, cycloalkoxy (of up to 8 carbon atoms)-carbonyl, aroyloxy of up to 11 carbon atoms, oxacycloalkoxy of up to 7 carbon atoms, oxacycloalkenyloxy of up to 7 carbon atoms, oxa-cycloalkoxy (of up to 7 carbon atoms)-carbonyl, oxacycloalkyl (of up to 7 carbon atoms)-carbonyloxy, and aryloxy (of up to 10 carbon atoms)-carbonyl, each of which may be further substituted by fluoro, C1-C6 alkyl or C1-C6 alkoxy, provided that any substituent having a singly bound oxygen atom as its link to the rest of the molecule may not be a substituent on the same carbon atom which is singly bonded to another oxygen atom; or 2 adjacent groups, selected from R3-R20, together with the atoms to which they are attached may form a 5 - 8 membered cycloalkyl, oxacycloalkyl or bicycloalkyl ring; R21 is independently selected from hydrogen, C1-C4 alkyl and phenyl; and wherein each B and B' is selected from -?-, -?-O-; and -?NH-with the carbonyl group being bound to A, S' or D;
each R is independently a divalent linking group selected from a) a divalent aliphatic group of up to 25 carbon atoms which may be interrupted by oxy, carbonyloxy, amino, aminocarbonyl, oxy-carbonyl, ureido, oxycarbonylamino, or carbonylamino;
b) a divalent 5 - 7 membered cycloaliphatic group having 5 - 25 car-bon atoms;
c) a divalent arylene group having 6 - 25 carbon atoms; and d) a divalent aralkyl or alkaryl group having 7 to 25 carbon atoms;
wherein groups b) and d) can be optionally interrupted by the same groups as in group a) and wherein the aryl rings in groups c) and d) may be further substituted with one or more substituents selected from halogen, C1-C4 alkyl, and C1-C12 perhalo alkyl; said device having a receding contact angle of less than 60°; having absorbed less than about 10 % water in its swollen state; and having a Dk x10-10(mm?ml O2/cm2?sec?mmHg) of at least about 7.
2. The device of claim 1 wherein a is one.
3. The device of claim 1 wherein each D is oxygen.
4. The device of claim 1 wherein each L is -BRB'-, each B and B' is -C(O)NH- wherein the nitrogen atom is bound to R, and R is
5. The device of claim 4 wherein R is
6. The device of claim 1 wherein each R1 and R2 is methyl.
7. The device of claim 1 wherein h and i are each 4.
8. The device of claim 1 wherein v is from about 15 to about 50.
9. The device of claim 6 wherein h is 4; i is 4; and v is from about 15 to about 50.
10. The device of claim 1 wherein (x+y+z) multiplied by q is from about 25 to about 75.
11. The device of claim 1 wherein a) each b, d and f is 1 and R3-R20 are all hydrogen or b) each b, d and f is zero, each R3, R4, R8-R10, R14-R16, and R20 is hydrogen, and each R7, R13 and R19 is methyl.
12. The device of claim 11 wherein (x+y+z) multiplied by q is about 25 to about 75.
13. The device of claim 1, wherein a is one; each D is oxygen each L is -BRB'-; each B and B' is -C(O)NH- with the nitrogen atom bound to R; each R is each R1 and R2 is methyl; h and 1 are each 4; v is from about 15 to about 50; (x+y+z) multiplied by q is about 25 to about 75; and a) each b, d, and f is 1 and R3-R20 are all hydrogen; or b) each b, d, and f is zero; each R3, R4, R8-R10, R14-R16 and R20 is hydrogen; and each R7, R13 and R19 is methyl.
14. A wettable, flexible, oxygen permeable, substantially non-swellable ophthalmic device of claim 1 a) fabricated from a polymer of a crosslinkable monomer having a partial formula Ia, -(D-A-L-S")c- (Ia) wherein each S" is independently a segment of formula I of claim l;
each D, A and L is independently as defined in claim 1; c is 1-10;
and a times c is 1-10;
or b) fabricated from a crosslinkable monomer having a partial formula Ib -(S")c-D-S'-La- (Ib) wherein L is selected from -BRB'- and -BR-; B, R, B' and S' are as defined in claim 1, and wherein S", c, D, A and L are as defined above.
each D, A and L is independently as defined in claim 1; c is 1-10;
and a times c is 1-10;
or b) fabricated from a crosslinkable monomer having a partial formula Ib -(S")c-D-S'-La- (Ib) wherein L is selected from -BRB'- and -BR-; B, R, B' and S' are as defined in claim 1, and wherein S", c, D, A and L are as defined above.
15. The device of claim 14 wherein a is one.
16. The device of claim 14 wherein each D is oxygen.
17. The device of claim 14 wherein each L is -BRB'-, each B and B' is -C(O)NH- wherein the nitrogen atom is bound to R, and R is
18. The device of claim 14 wherein R is
19. The device of claim 14 wherein each R1 and R2 is methyl.
20. The device of claim 14 wherein h and i are each 4.
21. The device of claim 14 wherein v is from about 15 to about 50.
22. The device of claim 14 wherein h is 4; i is 4; and v is from about 15 to about 50.
23. The device of claim 14 wherein (x+y+z) multiplied by q is from about 25 to about 75.
24. The device of claim 14 wherein a) each b, d and f is 1 and R3-R20 are all hydrogen or b) each b, d and f is zero, each R3, R4, R8-R10, R14-R16, and R20 is hydrogen, and each R7, R13 and R19 is methyl.
25. The device of claim 24 wherein (x+y+z) multiplied by q is about 25 to about 75.
26. The device of claim 14 or 24 wherein c is 1.
27. The device of claim 14 wherein L is -BRB'-.
28. The device of claim 14 wherein a is one; each D is oxygen; each L is -BRB'-; each B and B' is -C(O)NH- with the nitrogen atom bound to R; each R is each R1 and R2 is methyl; h and i are each 4; v is from about 15 to about 50; (x+y+z) multiplied by q is about 25 to about 75; and a) each b, d, and f is 1 and R3-R20 are all hydrogen; or b) each b, d, and f is zero; each R3, R8, R8-R10, R14-R16 and R20 is hydrogen; and each R7, R13 and R19 is methyl; c is 1; and La is -BRB'-.
29. A wettable, flexible, oxygen permeable, substantially non-swellable ophthalmic device of claim 14 fabricated from a monomer having the formula Ic (Ic) wherein e is zero or 1; S" is of formula -(D-S'-L-D-A-L) as defined in claim 1; each D, A, L, S', a and c is independently as defined in claim 14;
provided that when e ~ 1, the terminal L group (exclusive of L' and L") of formula Ic may also be selected from -BR-;
L' is hydrogen, P'-BRB'-; or P'-RB'-;
L" is -P'; or, in case that e is zero, also D-S'-BR-P' or D-S'-BRB'-P'; and P' is hydrogen, amino, hydroxy, or a moiety containing a crosslinkable group which may be crosslinked when coreacted with a suitable crosslinking agent or when irradiated by actinic radiation.
provided that when e ~ 1, the terminal L group (exclusive of L' and L") of formula Ic may also be selected from -BR-;
L' is hydrogen, P'-BRB'-; or P'-RB'-;
L" is -P'; or, in case that e is zero, also D-S'-BR-P' or D-S'-BRB'-P'; and P' is hydrogen, amino, hydroxy, or a moiety containing a crosslinkable group which may be crosslinked when coreacted with a suitable crosslinking agent or when irradiated by actinic radiation.
30. The device of claim 29 wherein a is one.
31. The device of claim 29 wherein each D is oxygen.
32. The device of claim 29 wherein each L is -BRB'-, each B and B' is -C(O)NH- wherein the nitrogen atom is bound to R, and R is .
33. The device of claim 29 wherein R is
34. The device of claim 29 wherein each R1 and R2 is methyl.
35. The device of claim 29 wherein h and i are 4.
36. The device of claim 29 wherein v is from about 15 to about 50.
37. The device of claim 29 wherein h is 4; i is 4; and v is from about 15 to about 50.
38. The device of claim 29 wherein (x+y+z) multiplied by q is from about 25 to about 75.
39. The device of claim 29 wherein a) each b, d and f is 1 and R3-R20 are all hydrogen or b) each b, d and f is zero, each R3, R4, R8-R10, R14-R16, and R20 is hydrogen, and each R7, R13 and R19 is methyl.
40. The device of claim 39 wherein (x+y+z) multiplied by q is about 25 to about 75.
41. The device of claim 29 wherein c is 1.
42. The device of claim 29 wherein L' is P'-BRB'-.
43. The device of claim 29 wherein L" is -D-S'-BRB'-P'.
44. The device of claim 29 wherein each P' is .
45. The device of claim 29 wherein a is one; each D is oxygen; each L is -BRB'-; each B and B' is -C(O)NH- with the nitrogen atom bound to R; each R is ;
each R1 and R2 is methyl; h and i are each 4; v is from about 15 to about 50; (x+y+z) multiplied by q is about 25 to about 75; and a) each b, d, and f is 1 and R3-R20 are all hydrogen; or b) each b, d, and f is zero; each R3, R4, R8-R10, R14-R16 and R20 is hydrogen; and each R7, R13 and R19 is methyl;
L' is P'-BRB'-; and P' is .
each R1 and R2 is methyl; h and i are each 4; v is from about 15 to about 50; (x+y+z) multiplied by q is about 25 to about 75; and a) each b, d, and f is 1 and R3-R20 are all hydrogen; or b) each b, d, and f is zero; each R3, R4, R8-R10, R14-R16 and R20 is hydrogen; and each R7, R13 and R19 is methyl;
L' is P'-BRB'-; and P' is .
46. The device of claim 29 wherein c is 1 and L" is -D-S'-BRB'-P'.
47. A method of correcting visual defects comprising applying to the eye of a patient in need thereof the device of claim 1.
48. The device of claim 1 wherein each A is of the formula V
(V) wherein n, m and p independently are 1 - 3; and x, y, z and q are as defined in claim 1 provided that each of them is greater than zero; R3 and R20 are alkyl of up to 6 carbon atoms; or of the formula VI
(VI) wherein n, m, p, x, y, z and q are as defined above for formula V
and R14 is alkyl of up to six carbon atoms.
(V) wherein n, m and p independently are 1 - 3; and x, y, z and q are as defined in claim 1 provided that each of them is greater than zero; R3 and R20 are alkyl of up to 6 carbon atoms; or of the formula VI
(VI) wherein n, m, p, x, y, z and q are as defined above for formula V
and R14 is alkyl of up to six carbon atoms.
49. The device of claim 48 wherein in formula V each of n, m and p is one, x, y, z and q are as defined in claim 48, and R8 and R20 are methyl and wherein in formula VI each of n, m and p is one, x, y, z and q are as defined in claim 48, and R14 is methyl.
50. The device of claim 49 wherein q is 1.
51. The device of claim 49 wherein x and 2 within any one A are the same.
52. The device of claim 49 wherein each x and each z has the same value.
53. An optically clear, wettable, flexible, substantially non-swellable, oxygen permeable polymer of a crosslinkable monomer having a segment S" of the formula I, -(D-S'-L-D-A-L)? (I) wherein a is 1 to 10;
each D is independently oxygen or -N(R21)-;
each S' is independently a segment of formula II, (II) each A is independently a segment of formula III, (III) the terminal oxygen within each unit of formula II and III being replaceable by -N(R21)-;
each L is independently -BRB'-, the terminal L group within any one monomer of formula I also being capable of being -BR-;
wherein each b, d and f is independently 0 - 4; q is a number from 1 to 1000; each x, y and z is independently 0 to 100 provided at least one of x, y and z is at least 1; such that (x+y+z) multiplied by q is 4 to 1000;
each h and i is an integer from 1 to 6, v is an integer from 2 to 75;
R1 and R2 are independently alkyl of up to is carbon atoms, or aryl of up to 12 carbon atoms;
each of R3, R4, R7-R10, R13-R16, R19 and R20 is independently selected from the group consisting of hydrogen, halogen, an ali-phatic, aromatic or heterocyclic containing radical selected from unsubstituted C1-C16 alkyl; substituted C1-C16 alkyl; unsubstituted C2-C16 alkenyl; and substituted C2-C16 alkenyl; wherein the alkyl and alkenyl substituents are independently selected from C1-C16 alkoxycarbonyl, C2-C16 alkenyloxycarbonyl, fluoro, aryl of up to 10 carbon atoms, C1-C16 alkoxy, C1-C16 alkanoyloxy, aryloxy of up to 10 carbon atoms, C3-C6 alkenoyloxy, aroyl of up to 10 carbon atoms, aroyloxy of up to 11 carbon atoms, C3-C8 cycloalkyl, C3-C8 cyclo-alkoxy, C3-C8 cycloalkyl-carbonyloxy, C3-C8 cycloalkoxy-carbonyl, oxacycloalkyl of up to 7 carbon atoms, oxacycloalkoxy of up to 7 carbon atoms, oxacycloalkoxy (up to 7 carbon atoms)-carbonyl, oxacycloalkyl (up to 7 carbon atoms)-carbonyloxy, and aryl (of up to 10 carbon atoms)-oxycarbonyl, each of said alkyl and alkenyl substituents being, in turn, optionally substituted by C1-C6 alkyl, fluoro or a C1-C6 alkoxy provided said last mentioned alkoxy is not bound to a carbon atom already singly bound to another oxygen atom;
R3, R4, R7-R10, R13-R16, R19 and R20 being further independently selected from aryl of up to 10 carbon atoms, C3-C8 cycloalkyl, and oxacycloalkyl of up to 7 carbon atoms, each of which may be unsub-stituted or further substituted with a substituent selected from the group of substituents for said R3 alkyl set forth above;
R5, R6, R11, R12, R17 and R13 are selected from the same group set forth above for R3; and R5, R6, R11, R12, R17 and R15 are further independently selected from C1-C16 alkoxycarbonyl, C3-C16 alkenoyl-oxy, C2-C16 alkenyloxycarbonyl, and C1-C16 alkanoyloxy, each of which may be further substituted by fluoro, aryl of up to 10 carbon atoms, or C1-C16 alkoxy, and R5, R6, R11, R12, R17 and R18 are still further independently selected from aryloxy of up to 10 carbon atoms, cycloalkoxy of up to 8 carbon atoms, cycloalkyl (of up to 8 carbon atoms)-carbonyloxy, cycloalkoxy (of up to 8 carbon atoms)-carbonyl, aroyloxy of up to 11 carbon atoms, oxacycloalkoxy of up to 7 carbon atoms, oxacycloalkenyloxy of up to 7 carbon atoms, oxa-cycloalkoxy (of up to 7 carbon atoms)-carbonyl, oxacycloalkyl (of up to 7 carbon atoms)-carbonyloxy, and aryloxy (of up to 10 carbon atoms)-carbonyl, each of which may be further substituted by fluoro, C1-C6 alkyl or C1-C6 alkoxy, provided that any substituent having a singly bound oxygen atom as its link to the rest of the molecule may not be a substituent on the same carbon atom which is singly bonded to another oxygen atom; or 2 adjacent groups, selected from R3-R20, together with the atoms to which they are attached may form a 5 - 8 membered cycloalkyl, oxacycloalkyl or bicycloalkyl ring; R21 is independently selected from hydrogen, C1-C4 alkyl and phenyl; and wherein each B and B' is selected from -?-, -?-O-; and -?NH-with the carbonyl group being bound to A, S' or D;
each R is independently a divalent linking group selected from a) a divalent aliphatic group of up to 25 carbon atoms which may be interrupted by oxy, carbonyloxy, amino, aminocarbonyl, oxy-carbonyl, ureido, oxycarbonylamino, or carbonylamino;
b) a divalent 5 - 7 membered cycloaliphatic group having 5 - 25 car-bon atoms;
c) a divalent arylene group having 6 - 25 carbon atoms; and d) a divalent-aralkyl or alkaryl group having 7 to 25 carbon atoms;
wherein groups b) and d) can be optionally interrupted by the same groups as in group a) and wherein the aryl rings in groups c) and d) may be further substituted with one or more substituents selected from halogen, C1-C4 alkyl, and C1-C12 perhalo alkyl; said polymer having a receding contact angle of less than 60°; having absorbed less than about 10 % water in its swollen state; and having a Dk x10-10 (mm?ml O2/cm2?sec?mmHg) of at least about 7.
each D is independently oxygen or -N(R21)-;
each S' is independently a segment of formula II, (II) each A is independently a segment of formula III, (III) the terminal oxygen within each unit of formula II and III being replaceable by -N(R21)-;
each L is independently -BRB'-, the terminal L group within any one monomer of formula I also being capable of being -BR-;
wherein each b, d and f is independently 0 - 4; q is a number from 1 to 1000; each x, y and z is independently 0 to 100 provided at least one of x, y and z is at least 1; such that (x+y+z) multiplied by q is 4 to 1000;
each h and i is an integer from 1 to 6, v is an integer from 2 to 75;
R1 and R2 are independently alkyl of up to is carbon atoms, or aryl of up to 12 carbon atoms;
each of R3, R4, R7-R10, R13-R16, R19 and R20 is independently selected from the group consisting of hydrogen, halogen, an ali-phatic, aromatic or heterocyclic containing radical selected from unsubstituted C1-C16 alkyl; substituted C1-C16 alkyl; unsubstituted C2-C16 alkenyl; and substituted C2-C16 alkenyl; wherein the alkyl and alkenyl substituents are independently selected from C1-C16 alkoxycarbonyl, C2-C16 alkenyloxycarbonyl, fluoro, aryl of up to 10 carbon atoms, C1-C16 alkoxy, C1-C16 alkanoyloxy, aryloxy of up to 10 carbon atoms, C3-C6 alkenoyloxy, aroyl of up to 10 carbon atoms, aroyloxy of up to 11 carbon atoms, C3-C8 cycloalkyl, C3-C8 cyclo-alkoxy, C3-C8 cycloalkyl-carbonyloxy, C3-C8 cycloalkoxy-carbonyl, oxacycloalkyl of up to 7 carbon atoms, oxacycloalkoxy of up to 7 carbon atoms, oxacycloalkoxy (up to 7 carbon atoms)-carbonyl, oxacycloalkyl (up to 7 carbon atoms)-carbonyloxy, and aryl (of up to 10 carbon atoms)-oxycarbonyl, each of said alkyl and alkenyl substituents being, in turn, optionally substituted by C1-C6 alkyl, fluoro or a C1-C6 alkoxy provided said last mentioned alkoxy is not bound to a carbon atom already singly bound to another oxygen atom;
R3, R4, R7-R10, R13-R16, R19 and R20 being further independently selected from aryl of up to 10 carbon atoms, C3-C8 cycloalkyl, and oxacycloalkyl of up to 7 carbon atoms, each of which may be unsub-stituted or further substituted with a substituent selected from the group of substituents for said R3 alkyl set forth above;
R5, R6, R11, R12, R17 and R13 are selected from the same group set forth above for R3; and R5, R6, R11, R12, R17 and R15 are further independently selected from C1-C16 alkoxycarbonyl, C3-C16 alkenoyl-oxy, C2-C16 alkenyloxycarbonyl, and C1-C16 alkanoyloxy, each of which may be further substituted by fluoro, aryl of up to 10 carbon atoms, or C1-C16 alkoxy, and R5, R6, R11, R12, R17 and R18 are still further independently selected from aryloxy of up to 10 carbon atoms, cycloalkoxy of up to 8 carbon atoms, cycloalkyl (of up to 8 carbon atoms)-carbonyloxy, cycloalkoxy (of up to 8 carbon atoms)-carbonyl, aroyloxy of up to 11 carbon atoms, oxacycloalkoxy of up to 7 carbon atoms, oxacycloalkenyloxy of up to 7 carbon atoms, oxa-cycloalkoxy (of up to 7 carbon atoms)-carbonyl, oxacycloalkyl (of up to 7 carbon atoms)-carbonyloxy, and aryloxy (of up to 10 carbon atoms)-carbonyl, each of which may be further substituted by fluoro, C1-C6 alkyl or C1-C6 alkoxy, provided that any substituent having a singly bound oxygen atom as its link to the rest of the molecule may not be a substituent on the same carbon atom which is singly bonded to another oxygen atom; or 2 adjacent groups, selected from R3-R20, together with the atoms to which they are attached may form a 5 - 8 membered cycloalkyl, oxacycloalkyl or bicycloalkyl ring; R21 is independently selected from hydrogen, C1-C4 alkyl and phenyl; and wherein each B and B' is selected from -?-, -?-O-; and -?NH-with the carbonyl group being bound to A, S' or D;
each R is independently a divalent linking group selected from a) a divalent aliphatic group of up to 25 carbon atoms which may be interrupted by oxy, carbonyloxy, amino, aminocarbonyl, oxy-carbonyl, ureido, oxycarbonylamino, or carbonylamino;
b) a divalent 5 - 7 membered cycloaliphatic group having 5 - 25 car-bon atoms;
c) a divalent arylene group having 6 - 25 carbon atoms; and d) a divalent-aralkyl or alkaryl group having 7 to 25 carbon atoms;
wherein groups b) and d) can be optionally interrupted by the same groups as in group a) and wherein the aryl rings in groups c) and d) may be further substituted with one or more substituents selected from halogen, C1-C4 alkyl, and C1-C12 perhalo alkyl; said polymer having a receding contact angle of less than 60°; having absorbed less than about 10 % water in its swollen state; and having a Dk x10-10 (mm?ml O2/cm2?sec?mmHg) of at least about 7.
54. A wettable, flexible, oxygen permeable, substantially non-swellable polymer of claim 53 a) fabricated from a crosslinkable monomer having a partial formula Ia, -(S")c-D-S'-La- (Ia) wherein each S" is independently a segment of formula I of claim 53;
each D, A and L is independently as defined in claim 53; c is 1-10;
and a times c is 1-10;
or b) fabricated from a crosslinkable monomer having a partial formula Ib (Ib) wherein L is selected from -BRB'- and -BR-; B, R, B' and S' are as defined in claim 53, and wherein S", c, D, A and L are as defined above.
each D, A and L is independently as defined in claim 53; c is 1-10;
and a times c is 1-10;
or b) fabricated from a crosslinkable monomer having a partial formula Ib (Ib) wherein L is selected from -BRB'- and -BR-; B, R, B' and S' are as defined in claim 53, and wherein S", c, D, A and L are as defined above.
55. A wettable, flexible, oxygen permeable, substantially non-swellable polymer of claim 54 fabricated from a monomer having the formula Ic (Ic) wherein e is zero or 1; S" is of formula -(D-S'-L-D-A-L) as defined in claim 54; each D, A, L, S', a and c is independently as defined in claim 53;
provided that when e = 1, the terminal L group (exclusive of L' and L") of formula Ic may also be selected from -BR-;
L' is hydrogen, P'-BRB'-; or P'-RB'-;
L" is -P'; or, in case that e is zero, also D-S'-BR-P' or D-S'-BRB'-P'; and P' is hydrogen, amino, hydroxy, or a moiety containing a crosslinkable group which may be crosslinked when coreacted with a suitable crosslinking agent or when irradiated by actinic radiation.
provided that when e = 1, the terminal L group (exclusive of L' and L") of formula Ic may also be selected from -BR-;
L' is hydrogen, P'-BRB'-; or P'-RB'-;
L" is -P'; or, in case that e is zero, also D-S'-BR-P' or D-S'-BRB'-P'; and P' is hydrogen, amino, hydroxy, or a moiety containing a crosslinkable group which may be crosslinked when coreacted with a suitable crosslinking agent or when irradiated by actinic radiation.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CA000551005A CA1293082C (en) | 1987-11-04 | 1987-11-04 | Substantially non-swellable contact lens containing block copolymer polysiloxane-polyoxyalkylene backbone units |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CA000551005A CA1293082C (en) | 1987-11-04 | 1987-11-04 | Substantially non-swellable contact lens containing block copolymer polysiloxane-polyoxyalkylene backbone units |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1293082C true CA1293082C (en) | 1991-12-10 |
Family
ID=4136784
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA000551005A Expired - Lifetime CA1293082C (en) | 1987-11-04 | 1987-11-04 | Substantially non-swellable contact lens containing block copolymer polysiloxane-polyoxyalkylene backbone units |
Country Status (1)
| Country | Link |
|---|---|
| CA (1) | CA1293082C (en) |
-
1987
- 1987-11-04 CA CA000551005A patent/CA1293082C/en not_active Expired - Lifetime
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