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    • 专利摘要:
    COMPOSITION INCLUDING AT LEAST ONE COPOLYMER, METHOD FOR PREPARING THE SAME AND INTRAOCULAR LENS THAT CONSISTS OF SUCH COMPOSITION. An intraocular lens (IOL) with excellent non-glossy characteristics comprising at least one copolymer comprising: (a) one or more first monomeric subunits comprising a polymerized acrylate and/or methacrylate group, at least one side group comprising (i) an aryloxy moiety, and (ii) an aliphatic carbon moiety linking the aryloxy moiety with the polymerized acrylate or methacrylate group, wherein the aliphatic carbon moiety comprises at least one hydroxyl substituent, (b) one or more second monomeric subunits different from the first monomeric subunits comprising an acrylate group and/or a polymerized methacrylate, and comprising at least one alkoxyalkyl side group, (c) one or more third monomeric subunits other than the first and second monomeric subunits, the third monomeric subunits comprising a polymerized acrylate and/or methacrylate group, and comprising at least one alkylene oxide side group. o, wherein the first monomeric subunit is present in a greater amount by weight than the second monomeric subunit, and the first and second monomeric subunits together comprise about 75 percent or more of the monomeric subunit composition by weight.
    公开号:BR112014006188B1
    申请号:R112014006188-2
    申请日:2012-09-14
    公开日:2021-06-08
    发明作者:Patrick H. Benz；Adam Reboul
    申请人:Benz Research And Development Corp.；
    IPC主号:
    专利说明:

    FUNDAMENTALS OF THE INVENTION
    [001] Several types of intraocular lenses (IOLs) are known. For example, one-piece intraocular lenses and composite intraocular lenses having multiple pieces are not known. One-piece intraocular lenses are those in which both the optical and non-optical portions are made from a single material. The non-optical portions of IOLs are referred to as haptic portions, and are used for fixation purposes.
    [002] Both hydrophobic and hydrophilic foldable IOLs are described in the prior art, for example, US Patent Nos. 7,947,796, 7,387,642, 7,067,602, 6,517,750, and 6,267,784, each of which is incorporated herein by reference in its entirety. See also, for example, US Patent Publication Nos. 2008/0221235, 2006/0276606, 2006/0199929, 2005/0131183, 2002/0058724, 2002/0058723 and 2002/0027302, each of which is incorporated herein by reference in its entirety.
    [003] Furthermore, lens materials comprising 2-hydroxy-3-phenoxypropyl acrylate monomer are described in the prior art, e.g. WO 2010/128266, WO 2001/018079, WO 2000/079312, WO 96/40303 , and US Patent 5,693,095. The 2-ethoxyethyl methacrylate lens material is also known in the art as a composite with a low glass transition temperature. See, for example, Garcia, F., et al., J. of Polymer Science: Part A: Polymer Chemistry, Vol. 40, 3987-4001 (2002).
    [004] There is a need, however, for better IOL materials including hydrophobic materials, which do not suffer from excessive gloss, can provide an absence of adhesive characteristics after LIOL injection, and can provide for hard-to-reach combinations of properties . SUMMARY OF THE INVENTION
    [005] The modalities described herein include, for example, copolymers, lenses, intraocular lenses, blanks for intraocular lenses, and methods for making and methods of using intraocular compositions and lenses.
    [006] One embodiment provides, for example, an intraocular lens comprising at least one copolymer comprising: (a) one or more first monomeric subunits comprising a polymerized acrylate or methacrylate group, at least one side group comprising (i) an aryloxy moiety , and (ii) an aliphatic carbon moiety linking the aryloxy moiety with the polymerized acrylate or methacrylate group, wherein the aliphatic carbon moiety comprises at least one hydroxyl substituent, and (b) one or more second monomeric subunits different from the first monomeric subunits comprising a polymerized acrylate or methacrylate group, and comprising at least one alkoxyalkyl side group, (c) one or more third monomeric subunits different from the first and second monomeric subunits, the third monomeric subunits comprising a polymerized acrylate or methacrylate group, and comprising at least one alkyl oxide side group. ilene, wherein the first monomeric subunit is present in a greater amount by weight than the second monomeric subunit, and the first and second monomeric subunits together comprise about 75 percent or more of the monomeric subunit composition by weight.
    [007] A composition comprising at least one copolymer comprising: (a) one or more first monomeric subunits comprising a polymerized acrylate or methacrylate group, at least one side group comprising (i) an aryloxy portion, and (ii) a carbon portion aliphatic linking the aryloxy moiety with the polymerized acrylate or methacrylate group, wherein the aliphatic carbon moiety comprises at least one hydroxyl substituent, and (b) one or more second monomeric subunits different from the first monomeric subunits comprising a polymerized acrylate or methacrylate group, and comprising at least one alkoxyalkyl side group, (c) one or more third monomeric subunits other than the first and second monomeric subunits, the third monomeric subunits comprising a polymerized acrylate or methacrylate group, and comprising at least one alkylene oxide side group, where the first monomeric subunit is present in an amount greater by weight than the second monomeric subunit, and the first and second monomeric subunits together comprise about 75 percent or more of the monomeric subunit composition by weight.
    [008] A method for preparing a composition comprising at least one copolymer comprising monomeric subunits comprising: preparing a mixture of comonomers comprising: (a) one or more first monomers comprising a polymerizable acrylate or methacrylate group, at least one side group comprising (i) an aryloxy moiety, and (ii) an aliphatic carbon moiety linking the aryloxy moiety with the polymerizable acrylate or methacrylate group, wherein the aliphatic carbon moiety comprises at least one hydroxyl substituent, and (b) one or more second monomers different from the first monomer(s) comprising a polymerizable acrylate or methacrylate group, and comprising at least one alkoxyalkyl side group, (c) one or more third monomers different from the first and second monomers, the third monomers comprising a polymerizable acrylate or the methacrylate group, and comprising at least one alkylene oxide side group, wherein the first monomer(s) is present in a greater amount by weight than the second monomer(s), and the first and second monomers together comprise about 75 percent or more of the monomers by weight; polymerize the comonomer mixture.
    [009] An intraocular lens comprising at least one copolymer consisting essentially of: (a) one or more first monomeric subunits consisting essentially of a polymerized acrylate or methacrylate group, at least one side group comprising (i) an aryloxy radical, and (ii ) an aliphatic carbon moiety connecting the aryloxy moiety with the polymerized acrylate or methacrylate group, wherein the aliphatic carbon moiety consists essentially of at least one hydroxyl substituent, and (b) one or more second monomeric subunits different from the first monomeric subunits , consisting essentially of a polymerized acrylate or methacrylate group, and consisting essentially of at least one alkoxyalkyl side group, (c) one or more third monomeric subunits different from the first and second monomeric subunits, the third monomeric subunits essentially consisting of an acrylate group, and /or polymerized methacrylate, and consisting of o essentially on at least one alkylene oxide side group, (d) one or more fourth monomeric subunits other than the first, second, and third monomeric subunits which are crosslinked subunits, wherein the first monomeric subunit is present in greater amount by weight than the second monomeric subunit, and the first and second monomeric subunits together essentially consist of about 75 percent or more of the monomeric subunit composition by weight.
    [010] A composition comprising a mixture of comonomers comprising: (a) one or more first monomers comprising a polymerizable acrylate or methacrylate group, at least one side group comprising (i) an aryloxy portion, and (ii) a portion of aliphatic carbon linking the aryloxy moiety with the polymerizable acrylate or methacrylate group, wherein the aliphatic carbon moiety comprises at least one hydroxyl substituent, and (b) one or more second monomers different from the first monomer(s) comprising a acrylate group or a polymerizable methacrylate, and comprising at least one alkoxyalkyl side group, (c) one or more third monomers other than the first and second monomers, the third monomers comprising a polymerizable acrylate or methacrylate group, and comprising at least one side group of alkylene oxide, in which the first monomer(s) is present in an amount greater by weight than the second monomer(s), and The first and second monomers together comprise about 75 percent or more of the monomers by weight.
    [011] At least one advantage for at least one modality includes excellent non-glossy properties for an IOL, in particular, for a hydrophobic IOL.
    [012] At least one additional advantage for at least one modality includes good unfolding properties of an IOL. For example, an IOL incorporated here can unfold in five to ten seconds.
    [013] At least one additional advantage for at least one modality includes an absence of adhesive characteristics after IOL injection (eg, the haptic medium does not adhere to the optics).
    [014] At least one additional advantage for at least one modality includes a refractive index greater than 1.50 in combination with very low brightness.
    [015] Yet another advantage for at least one modality is a high diopter IOL capable of passing through a small orifice injector such as a 1.8mm or Medicel inferior injector. BRIEF DESCRIPTION OF THE FIGURES
    [016] FIG. 1A is a top view of an intraocular lens having a plate-shaped haptic medium.
    [017] FIG. 1B is a side view of the intraocular lens having a haptic in the form of a plate shown in FIG. 1A.
    [018] FIG. 2A is a top view of an intraocular lens having a C-shaped haptic medium.
    [019] FIG. 2B is a side view of the intraocular lens having a C-shaped haptic medium shown in FIG. 2A.
    [020] FIG. 3A is a top view of a universal intraocular lens sketch.
    [021] FIG. 3B is a side view of a universal sketch of the intraocular lens shown in FIG. 3A.
    [022] FIG. 4 shows the stress relaxation of various hydrophilic and hydrophobic IOL materials (25°C) at 1500 Pa, including an embodiment of the present invention, such as HF2. DETAILED DESCRIPTION INTRODUCTION
    [023] All references cited herein are incorporated by reference in their entirety.
    [024] Intraocular lenses are generally known in the art. See, for example, US Patent Nos. 7,947.796; 7,387,642; 7,067,602; 6,517,750; and 6,267,784.
    [025] One embodiment provides an intraocular lens comprising at least one copolymer comprising a series of monomeric subunits including, for example: (a) one or more first monomeric subunits comprising a polymerized acrylate or methacrylate group, at least one side group comprising (i ) an aryloxy moiety, and (ii) an aliphatic carbon moiety linking the aryloxy moiety with the polymerized acrylate or methacrylate group, wherein the aliphatic carbon moiety comprises at least one hydroxyl substituent, and (b) one or more second subunits monomeric subunits other than the first monomeric subunits comprising a polymerized acrylate or methacrylate group, and comprising at least one alkoxyalkyl side group, and (c) one or more third monomeric subunits different from the first and second monomeric subunits, the third monomeric subunits comprising an acrylate group or polymerized methacrylate, and comprising at minus one alkylene oxide side group, wherein the first monomeric subunit is present in greater amount by weight than the second monomeric subunit, and the first and second monomeric subunits together comprise about 75 percent or more of the composition of monomeric subunits by weight. FIRST / PRIMARY MONOMERIC SUBUNIT
    [026] The first monomeric subunit can be the subunit of the monomer present in the greatest amount, as measured in percentage by weight of the copolymer. This subunit comprises a polymerizable moiety such as acrylate, methacrylate, acrylamide and/or methacrylamide. The subunit also comprises an aliphatic spacer comprising one or more hydroxyl moieties. Finally, the first monomeric subunit comprises an optionally substituted aryl or aryloxy moiety. In another embodiment, the one or more first monomeric subunits comprising a polymerized acrylate or methacrylate group may instead comprise a polymerized acrylamide or methacrylamide group which is optionally substituted on the nitrogen atom by a hydrogen atom or C1 to C5 alkyl.
    [027] For example, aryloxyalkyl methacrylate monomers can be represented by the formula Ar-O-R1-MA, wherein Ar is an optionally substituted aryl compound, such as, for example, an optionally substituted phenyl group, R1 is a spacer aliphatic, such as a divalent alkyl group and "MA" is methacrylate. Alternatively, aryloxyalkyl acrylate monomers can be represented by the formula Ar-O-R2-A, wherein Ar is an optionally substituted aryl compound, such as, for example, an optionally substituted phenyl, R2 is an aliphatic spacer, such as a bivalent alkyl group and "A" is acrylate. Likewise, aryloxyalkyl acrylamide monomers can be represented by the formula Ar-O-R3-AA, where Ar is an optionally substituted aryl compound, such as, for example, an optionally substituted phenyl group, R3 is an aliphatic spacer such as a divalent alkyl group and "AA" is acrylamide. Furthermore, aryloxyalkyl methacrylamide monomers can be represented by the formula Ar-O-R4-MAA, where Ar is an optionally substituted aryl compound such as, for example, an optionally substituted phenyl group, R4 is an aliphatic spacer such as a group bivalent alkyl and "MAA" is methacrylamide. The bivalent group R1, R2, R3, and R4 can be further substituted by at least one hydroxy group. The AA or MAA monomers can be optionally substituted on the nitrogen by a hydrogen atom or a C1 to C5 alkyl. Examples of C1 to C5 include methyl, ethyl, propyl, butyl, pentyl and their isomers.
    [028] Both hydroxy substituted aryloxyalkyl methacrylates and hydroxy substituted aryloxyalkyl acrylates are composed of ester-containing monomers, as will be recognized by those skilled in the art. Likewise, those skilled in the art will recognize hydroxy substituted aryloxyalkyl acrylamides and hydroxy substituted aryloxyalkyl methacrylamides as amide containing monomer compounds. In some embodiments, R 1 , R 2 , R 3 , and R 4 can be independently selected from hydroxy-substituted alkyl groups having 1 to 5 carbon atoms and, in some embodiments, 1, 2, 3, 4 or 5 carbon atoms. carbon, the alkyl group is substituted by one or more hydroxy groups. With respect to R 1 , it will be understood that the hydroxy substituted alkyl group is bonded to the O of the Ar-O group and is also bonded to the atom of the MA group. Likewise, with respect to R2, it should be understood that the hydroxy substituted alkyl group is bonded to the O of the Ar-O group and is also bonded to the O atom of the A group. With respect to R3 it is to be understood that the hydroxy substituted alkyl group is bonded to the O of the Ar-O group and is also bonded to the N atom of the AA group. Likewise, with respect to R4, it will be understood that the hydroxy substituted alkyl group is bonded to the O of the Ar-O group and is also bonded to the N atom of the MAA group. The hydroxy group can be substituted on any carbon in the alkyl group. Hydroxy-substituted alkyl groups that can be used in accordance with the modalities herein include straight-chain alkyl groups, including, but not limited to, methyl, ethyl, propyl, butyl, pentyl groups, wherein at least one CH is replaced by C -Oh. Alkyl groups may also include the branched-chain isomers of straight-chain alkyl groups, including, but not limited to, the following, which are given by way of example only: -CH(CH3)2, -CH(CH3) (CH2CH3), -CH(CH2CH3)2, -C(CH3)3, and the like, wherein at least one CH is replaced by C-OH. In some embodiments, the hydroxy substituted aryloxyalkyl methacrylate or hydroxy substituted aryloxyalkyl acrylate is selected where R 1 and R 2 have 1, 2, 3, or 4 carbon atoms. Specific modalities of R1, R2, R3 and R4 are by way of non-limiting example, propyl 1-hydroxy, propyl 2-hydroxy, propyl 3-hydroxy, butyl 2-hydroxy, butyl 3-hydroxy, butyl 2,3-dihydroxy and similar. The AA or MAA monomers optionally being substituted on the nitrogen by a hydrogen or a C1 to C5 alkyl.
    [029] Aryloxy groups that will be recognized by those skilled in the art to include an aryl compound attached to the oxygen atom. In some embodiments, the aryl group comprises optionally substituted phenyl or naphthyl. In some embodiments, the aryl group can contain one or more heteroatoms, such as, by way of non-limiting example, nitrogen or sulfur. The aryl moiety can be optionally substituted by one or more alkyl groups including, but not limited to, methyl, ethyl, propyl, butyl, and pentyl. Alkyl groups can be the branched-chain isomers of straight-chain alkyl groups. The aryl moiety may optionally be substituted by one or more alkoxy groups comprising an alkyl group attached to an oxygen, the alkyl group comprising, but not limited to, methyl, ethyl, propyl, butyl, and/or pentyl groups. Alkyl groups can be the branched-chain isomers of straight-chain alkyl groups. Furthermore, the aryl moiety can be substituted by one or more halogen groups, for example, F, Cl, Br, and/or I.
    [030] Specific examples of any of the hydroxy substituted aryloxyalkyl methacrylate, hydroxy substituted aryloxyalkyl acrylate, hydroxy substituted aryloxyalkyl methacrylamide and hydroxy substituted aryloxyalkyl acrylamide monomers useful to form the copolymers, but are not limited to, 2-hydroxy-3-phenoxypropyl acrylate, 2-hydroxy-3-phenoxypropyl methacrylate, 2-hydroxy-3-phenoxypropyl acrylamide, and/or 2-hydroxy-3-phenoxypropyl methacrylamide.
    [031] In some embodiments, the present copolymers may also include a first monomer that is represented by the general formula (I), where R' is hydrogen or methyl, Y is O or -NR", X is H, Cl, - CH3, or -OCH3, n is 1 to 6, R" is hydrogen or a C1 to C5 alkyl.

    [032] In other embodiments, n is 1 or 2 and X is hydrogen and Y is O.
    [033] Thus, a preferred embodiment provides an intraocular lens, wherein the first monomeric subunits comprise a polymerized acrylate group. In another embodiment, the aryloxy group comprises a phenoxy group. In yet another embodiment, the aryloxy group comprises an unsubstituted phenoxy group. In another embodiment, the aliphatic carbon portion of the first monomeric subunit is replaced with a hydroxyl group. In another embodiment, the aliphatic carbon portion of the first monomeric subunit is a C3 portion. In another embodiment, the aliphatic carbon portion of the first monomeric subunit is represented by -CH2-CHOH-CH2-. Finally, the side group of the first monomeric subunit, in one embodiment, comprises -CH2-CHOH-CH2-OPh, where OPh is a substituted phenoxy group. SECOND MONOMERIC SUBUNIT
    [034] The present copolymers can also include one or more hydrophobic monomeric subunits that can be formed from a second monomer different from the first monomer. Examples of such hydrophobic monomers used to prepare the monomeric subunits include alkoxyalkyl methacrylate and/or alkoxyalkyl acrylate monomers. Alkoxyalkyl methacrylate monomers can be represented by the formula R5-O-R6-MA, where R5 and R6 are alkyl groups and "MA" is a methacrylate. Alkoxyalkyl acrylate monomers can be represented by the formula R7-O-R8-A, where R7 and R8 are alkyl groups and "A" is acrylate. Both alkoxyalkyl methacrylates and alkoxyalkyl acrylates are composed of ester-containing monomers, as will be recognized by those skilled in the art. In some embodiments, R 5 to R 8 can be independently selected from alkyl groups having 1 to 5 carbon atoms and in some embodiments 1, 2, 3, 4 or 5 carbon atoms. With respect to R6 it should be understood that the alkyl group is bonded to the O of the R5-O group and is also bonded to the O atom of the MA group. Likewise, with respect to R8, it should be understood that the alkyl group is bonded to the O of the R7-O group and is also bonded to the O atom of the A group. embodiments herein include straight chain alkyl groups, including, but not limited to, methyl, ethyl, propyl, butyl, and pentyl groups. Alkyl groups may also include the branched-chain isomers of straight-chain alkyl groups, including, but not limited to the following, which are given by way of example only: -CH(CH3)2, -CH(CH3)(CH2CH3 ), -CH(CH2CH3)2, -C(CH3)3, and so on. In some embodiments, the alkoxyalkyl methacrylate or alkoxyalkyl acrylate is selected where R5 through R8 have 1, 2, 3, or 4 carbon atoms. Specific examples of any of the alkoxyalkyl methacrylate and alkoxyalkyl acrylate monomers useful to form the copolymers of the embodiments herein include, but are not limited to, methoxyethyl methacrylate, ethoxyethyl methacrylate, propoxyethyl methacrylate, butoxymethyl methacrylate, methoxypropyl methacrylate , ethoxypropyl methacrylate, propoxypropyl methacrylate, butoxypropyl methacrylate, methoxybutyl methacrylate, ethoxybutyl methacrylate, propoxybutyl methacrylate, butoxybutyl methacrylate, methoxyethyl acrylate, ethoxyethyl acrylate, propoxyethyl acrylate, butoxymethyl acrylate, methoxy acrylate of ethoxypropyl, propoxypropyl acrylate, butoxypropyl acrylate, methoxybutyl acrylate, ethoxybutyl acrylate, propoxybutyl acrylate, and butoxybutyl acrylate. In some preferred embodiments, the copolymer includes ethoxyethyl methacrylate (EOEMA).
    [035] Thus, a particularly preferred embodiment provides an intraocular lens, wherein the alkoxyalkyl group is a C3 to C12 group. In one embodiment, the alkoxyalkyl group comprises a single oxygen atom. In a specific embodiment, the alkoxyalkyl group is 2-ethoxyethyl.
    [036] In some embodiments, a hydrophobic monomer that is not mentioned above but known to be a suitable monomer for collapsible IOLs may be incorporated. Examples of an additional hydrophobic monomer include, but are not limited to alkoxyalkoxyalkyl methacrylates, such as, but not limited to, ethoxyethoxyethyl methacrylate; alkoxyalkoxyalkyl acrylates such as but not limited to ethoxyethoxyethyl acrylate; alkyl methacrylate monomers; and combinations thereof, with specific examples of alkyl methacrylate monomers being C1 to C15 alkyl methacrylate monomers, such as, but not limited to, methyl methacrylate, ethyl methacrylate, propyl methacrylate, butyl methacrylate, hexyl methacrylate , lauryl methacrylate, and combinations thereof. THIRD MONOMERIC SUBUNITS
    [037] A third monomeric subunit may be present which is different from the first and second monomeric subunits. The present copolymers can also include, for example, one or more polyalkylene glycol alkyl ether acrylate and/or polyalkylene glycol alkyl ether methacrylate monomers including the higher molecular weight. Examples of polyalkylene glycol alkyl ether acrylate and/or polyalkylene glycol alkyl ether methacrylate include, for example, polyethylene glycol monomethyl ether methacrylate monomers of varying molecular weight. In some embodiments, the third monomer can be polyethylene glycol monomethyl ether methacrylate (200 PEG MW) or polyethylene glycol monomethyl ether methacrylate (PEG 400 MW). In another embodiment, polyethylene glycol monomethyl ether methacrylate of other molecular weights can be used. Other polyethylene glycol monomethyl ether methacrylate compositions can be used.
    [038] Thus, a particularly preferred embodiment provides an intraocular lens or an IOL blank, wherein the alkylene oxide side group is a poly(alkylene oxide) side group. In one embodiment, the alkylene oxide side group has a molecular weight of 100 g/mol to 2000 g/mol. In another embodiment, the alkylene oxide side group has a molecular weight of 100 g/mol to 1000 g/mol. In yet another embodiment, the alkylene oxide side group has a molecular weight of 100 g/mol to 500 g/mol. In one embodiment, the alkylene oxide side group is a poly(ethylene oxide) side group. In one embodiment, the third monomeric subunit consists of polymerized polyethylene glycol monomethyl ether methacrylate with a polyethylene glycol molecular weight of about 150 to 250. In another embodiment, the third monomeric subunit consists of polymerized polyethylene glycol monomethyl ether methacrylate with a polyethylene glycol molecular weight of about 350 to 450. RETICULATOR (FOURTH MONOMER)
    [039] Intraocular lenses can comprise a copolymer that further comprises fourth monomeric subunits that are crosslinked subunits. In particular, tri-functional crosslinking agents can be used to form the crosslinked subunits. However, other di- or multifunctional crosslinking agents known in the art can also be employed.
    [040] Copolymers can be prepared using conventional polymerization techniques known in the field of polymer chemistry. Crosslinkers can be used in the polymerization reaction. For example, any crosslinking or difunctional monomer can be used in amounts effective to obtain the desired crosslink density. For example, in a concentration range of 0 to about 10 percent, such as about 0.01 to about 4 percent, or in some embodiments from 0.5 to 3 percent by weight based on the weight of the polymer. Examples of suitable crosslinking agents include di-olefinic functional component or ethylene glycol dimethacrylate (EGDMA). Generally, crosslinkers help to improve the dimensional stability of the resulting copolymer.
    [041] In some embodiments, the compositions include one or more crosslinking agents with three or more polymerizable functionalities (a multifunctional crosslinking agent). An example of a multifunctional crosslinking agent includes, but is not limited to trimethylol propane trimethacrylate (TMPTMA). Analog acrylate crosslinking agents, for example trimethylol propane triacrylate, can also be used in place of any of its methacrylate analogs or in combination with the methacrylate analogs. Some embodiments include two or more trifunctional crosslinking agents or a multifunctional crosslinking agent and a difunctional crosslinking agent known in the art or incorporated herein by reference, such as, for example, EGDMA. Therefore, in some embodiments, copolymer compositions include EGDMA and TMPTMA. In some such embodiments, the amount of EGDMA ranges from about 0.05 to about 0.5 or about 0.4 percent by weight based on the weight of dry copolymer and the amount of TMPTMA ranges from about 0 .3 to about 1.5 weight percent based on dry polymer weight. In some such embodiments, the amount of EGDMA ranges from about 0.08 to about 0.25 weight percent based on the weight of dry copolymer and the amount of TMPTMA ranges from about 0.45 to about 1 .2 percent by weight based on dry polymer weight. In still other such embodiments, the amount of EGDMA ranges from about 0.1 to about 0.2 percent by weight based on the weight of dry copolymer and the amount of TMPTMA ranges from about 0.5 to about 1.0 weight percent based on dry polymer weight.
    [042] In one embodiment, the only crosslinker used is a trifunctional crosslinker such as a trifunctional methacrylate crosslinker.
    [043] Examples of specific copolymers useful in the present embodiments will be discussed in the examples where all weights are given in grams. COMPOSITIONS/QUANTITIES
    [044] The copolymers described herein may include the first monomers, for example the hydroxy substituted aryloxyalkyl methacrylate monomers or hydroxy substituted aryloxyalkyl acrylate monomers as the main component and the second and third monomers as the smallest component measured by weight .
    [045] In the present copolymers, the total amount of one or more of the first monomer may constitute the majority of the polymer, as measured by weight. For example, in some embodiments, the total amount of the combined amounts of any of the hydroxy substituted aryloxyalkyl methacrylate, hydroxy substituted aryloxyalkyl acrylate, hydroxy substituted aryloxyalkyl methacrylamide, or hydroxy substituted aryloxyalkyl acrylamide monomers can be about 50 percent to about 80 percent by weight based on the total weight of the polymer. Alternatively, the first monomer can comprise about 60 percent to about 65 percent by weight of the polymer. While the present claims are not limited by theory, the presence of the hydroxy substituted aryloxyalkyl moiety can provide a hydrophobic copolymer subject to less gloss based on hydroxyl functionality, which can provide a hydrogen bond donor/receptor site for enhancement compatibility with water.
    [046] In the present copolymers, the total amount of one or more of the second monomer will constitute a minority of the polymer when measured by weight. For example, in some embodiments, the total amount of the combined amounts of the second monomer can be from about 20 percent to about 35 percent by weight of the total polymer weight. Alternatively, the second monomer can comprise from about 27 percent to about 32 percent by weight of the polymer. The second monomer is a hydrophobic monomer providing a low glass transition temperature such as, for example, EEOMA.
    [047] In the present copolymers, the total amount of one or more of the third monomer will constitute a minority of the polymer. For example, in some embodiments, the total amount of the combined amounts of the third monomer can be from about 5 percent to about 15 percent by weight of the polymer. Alternatively, the third monomer can comprise about 7 percent to about 10 percent by weight of the polymer. The third monomer has a higher molecular weight and therefore can provide gloss reduction by using a smaller number of molecules, while also not substantially increasing the Tg of the final polymeric material.
    [048] In the present copolymers, the total amount of one or more of the crosslinking monomers will constitute a minority of the polymer. For example, in some embodiments, the total amount of combined amounts of incorporated crosslinking monomer ranges from 0.3 percent to 1.5 percent, and in some embodiments from 0.45 percent to 1.2 percent or from 0.5 to 1.0 percent, based on the total weight of dry copolymer of the optical portion.
    [049] When a polymer or copolymer is said to include or contain a monomer such as ethoxyethyl methacrylate, it should be understood that this means that the ethoxyethyl methacrylate monomer has been reacted and incorporated into the polymer. A monomer of the claimed compounds can also be in the form of an oligomer which can be polymerized to the incorporated polymeric compounds.
    [050] An exemplary polymeric composition contains about 50 percent to about 70 percent of a polymerized hydroxy substituted aryloxyalkyl methacrylate and/or polymerized hydroxy substituted aryloxyalkyl acrylate, about 20 percent to about 35 percent of a polymerized alkoxyalkyl methacrylate and/or polymerized alkoxyalkyl acrylate and about 5 percent to about 15 percent of a polymerized polyethylene glycol monomethyl ether methacrylate, with the balance of the copolymer consisting of other components, such as absorbers UV agents, initiating agents and/or crosslinking agents. Another exemplary composition contains about 60 percent to about 65 percent of a polymerized hydroxy substituted aryloxyalkyl methacrylate and/or polymerized hydroxy substituted aryloxyalkyl acrylate, about 27 percent to about 32 percent of a polymerized methacrylate polymerized alkoxyalkyl and/or polymerized alkoxyalkyl acrylate and about 7 percent to about 10 percent of a polymerized polyethylene glycol monomethyl ether methacrylate with the balance of the copolymer again consisting of other components. Another exemplary composition contains about 65 percent to about 70 percent of a polymerized hydroxy substituted aryloxyalkyl methacrylate and/or polymerized hydroxy substituted aryloxyalkyl acrylate, about 20 percent to about 30 percent of a polymerized methacrylate polymerized alkoxyalkyl and/or polymerized alkoxyalkyl acrylate and about 5 percent to about 15 percent of a polymerized polyethylene glycol monomethyl ether methacrylate, with the balance of the copolymer again being made up of other components. Another exemplary composition contains about 50 percent to about 70 percent polymerized 2-hydroxy-3-phenoxypropyl acrylate, about 20 percent to about 35 percent of a polymerized alkoxyalkyl methacrylate, and/or alkoxyalkyl acrylate polymerized and about 5 percent to about 15 percent of a polymerized polyethylene glycol monomethyl ether methacrylate, with the balance of the copolymer again being made up of other components. In some of these compositions, the polymerized hydroxy substituted aryloxyalkyl acrylate and/or polymerized hydroxy substituted aryloxyalkyl methacrylate may be polymerized 2-hydroxy-3-phenoxypropyl acrylate. In still other such compositions, the polymerized alkoxyalkyl methacrylate and/or polymerized alkoxyalkyl acrylate is polymerized 2-ethoxyethyl methacrylate. In still other such compositions, the polymerized polyethylene glycol monomethyl ether methacrylate monomer has a molecular weight of about 200 to about 400. As can be seen from these exemplary compositions, the present intraocular lens can have a range of material components and still have the desired characteristics.
    [051] In another embodiment, the compositions of the preceding paragraph comprise polymerized hydroxy substituted aryloxyalkyl methacrylamide and/or polymerized hydroxy substituted aryloxyalkyl acrylamide as a first monomer instead of polymerized hydroxy substituted aryloxyalkyl methacrylate and/or aryloxyalkyl acrylate replaced by polymerized hydroxy.
    [052] In some of the embodiments, the copolymer compositions of the present embodiments consist of or consist essentially of a copolymer formed from a hydroxy substituted aryloxyalkyl acrylate, an alkoxyalkyl methacrylate, polyalkylene glycol alkyl ether methacrylate and one or more crosslinking agents.
    [053] In some of such embodiments, the copolymer is formed from monomers consisting of 2-hydroxy-3-phenoxypropyl acrylate, 2-ethoxyethyl methacrylate, polyethylene glycol monomethyl ether methacrylate, and TMPTMA.
    [054] In some embodiments, a copolymer comprises, consists essentially of, or consists of: (a) An incorporated hydroxy-substituted aryloxyalkyl acrylate, such as 2-hydroxy-3-phenoxypropyl acrylate in an amount of 50 to 80 per hundred; (b) an incorporated alkoxyalkyl methacrylate and/or alkoxyalkyl acrylate, such as 2-ethoxyethyl methacrylate, in an amount of 20 to 35 percent; (c) A polyethylene glycol monomethyl ether methacrylate incorporated as PEG200M or PEG400M in an amount from 5 to 15 percent; (d) An incorporated functional methacrylate or acrylate crosslinking agent such as TMPTMA in an amount ranging from 0.4 to 1 percent; and (e) optionally, one or more other optional ingredients, such as water, one or more UV absorbing compounds or monomers, a colorant, and an antioxidant.
    [055] In one embodiment, the first and second monomeric subunits together comprise about 70, 75, 80, 85 and/or 90 percent or more of the monomeric subunit composition by weight. COMPOSITION PROPERTIES
    [056] Copolymers can have a water content of less than or about 5 percent, or less than about 3 percent based on the weight of the copolymer after it is fully balanced in water. In some embodiments, the copolymers have an equilibrium water content ranging from at or about 1 percent to at or about 5 percent based on the weight of the copolymer after it is fully balanced in water. In other embodiments, the water content ranges from about 2 percent to about 4 percent by weight of the copolymer after it is fully balanced with water.
    [057] Copolymers can possess superior mechanical and optical properties over other materials used to make IOLs. Often, because hydrophobic IOLs are incompatible with water, they form sheen caused by water droplets in voids in the material. It is the Applicant's belief that hydroxyl functionality adjacent to aryloxy functionality may provide a hydrogen bond donor/recipient site to enhance compatibility with water. Combining a monomer such as hydroxy substituted aryloxyalkyl acrylate with a hydrophobic monomer such as alkoxyalkyl methacrylate with a low Tg can provide materials with a higher refractive index relative to the prior art, which also remain bendable. Furthermore, the additional PEG 200 or PEG 400 can provide hydrogen bonding receptors which can also provide a plasticizing effect so the Tg remains low. Components of the present embodiments can provide a hydrophobic lens with low Tg, reduced glare and reduced adhesion to provide an IOL with desirable and reliable unfold times while maintaining a high refractive index.
    [058] Copolymers can be designed to have a wide range of physical characteristics. In some cases, the present copolymers can be designed to have glass transition temperatures below or about 35°C, below or about 30°C, below or about 25°C, such as at or about -25°C to at or about 35°C, 30°C, or 25°C, from about -5°C to about 5°C, 10°C, 15°C, 20°C, or about 25°C or from at or about 0°C to at or about 15°C. In preferred embodiments, the glass transition temperature will be from about -5°C to about 5°C. The glass transition temperatures referred to herein can be measured half-width at a temperature change rate of 10°C/minute, or other methods known in the art. As the present copolymers have been designed to be used as intraocular lenses, they also typically have a high refractive index, which is generally above about 1.40. Some of the present copolymers may have a refractive index of 1.48 or greater. Some of the present copolymers may have a refractive index of 1.50 or greater. Because the present copolymers are hydrophobic, they can also have equilibrium water contents, which are about 5 percent or less, eg, 4 percent, 3 percent, 2 percent, 1 percent or less. Due to their low water contents, the present copolymers are generally not considered hydrogels and can be considered hydrophobic. Generally, the present lenses also have advantageous properties compared to previous lenses because they have a refractive index comparable to or greater than lenses containing silicone or p-hydroxyethyl methacrylate and are more flexible, eg, bendable, than hydrophobic lenses that include aromatic monomers to increase the refractive index of the resulting polymer. LENSES
    [059] The present embodiment also provides intraocular lenses made from at least partially the present copolymers. Such intraocular lenses include an optical portion and one or more haptic media portions. Typically, the copolymers of the modalities will make up a part or all of the optical portion of the intraocular lens. In some embodiments, the optical portion of the lens will have a core made of a copolymer of the present surrounded by different polymers or materials. Lenses in which the optical portion is comprised of at least partially one of the present copolymers will generally also have a haptic portion. The haptic portion can also be made from the copolymer of the modalities or it can be made from a different material, for example, another polymer.
    [060] In some embodiments, the present intraocular lens is a one-piece lens having a soft, central foldable optical region and an outer peripheral region (haptic region) in which both regions are made of the same polymer. In other embodiments, optical and haptic regions can be formed from different types of polymers or materials, if desired. Some lenses may also have haptic portions that are made of different materials, for example, when one or more haptic portions is made from the same material as the optical portion and other haptic portions are made of materials other than a polymer of the modalities. Multicomponent lenses can be made by incorporating one material into the other, extrusion processes simultaneously, solidifying the hard material onto the soft material, or forming an interpenetrating network of the rigid component into a preformed hydrophobic core. In cases where one or more haptic portions are produced from a material other than the optical portion of the lens, the haptic portion may be attached to the optical portion in any manner known in the art, such as by drilling a hole or holes in the optic portion and inserting the haptic portion.
    [061] The copolymers of the present embodiments can be designed so that they are likely to be bent so that the intraocular lens can be inserted into an individual's eye through a small incision. The haptic portion of the lens provides the necessary support for the lens in the eye after lens insertion and deployment and tends to help stabilize the lens position after incision insertion and closure. The shape of the design of the haptic portion is not particularly limited and can be of any desired configuration, for example, or a type of plate or spiral filaments of graduated thickness, also known as a C-cycle design.
    [062] FIGS. 1A, 1B, 2A, 2B, 3A and 3B illustrate examples of intraocular lenses in accordance with the present embodiments. The figures are for illustrative purposes only and do not limit the scope of the modalities. For example, the intraocular lens can be any type of intraocular lens. In Figures 1 and 2, 1 is the optical portion of the lens, 2 is the haptic portion, and 3 is a positioning hole. Figure 3 provides a universal design that provides an out-of-mold shaped lens, and requires only minimal cutting and/or molding from the molded polymer to be a finished IOL. One skilled in the art of intraocular lenses understands the functions of these portions of intraocular lenses.
    [063] The optical portion 1 can be about 6 mm in diameter before hydration. The 6mm diameter is quite conventional in the art, and is generally chosen to cover the pupil in its fully dilated state under naturally occurring conditions. However, other sizes are possible and the present embodiments are not limited to any particular diameter or size of intraocular lens. Furthermore, it is not necessary for the optical portion of the lens to be circular; it can also be oval, square, or any other shape as desired.
    [064] The intraocular lens may further include one or more non-optical haptic components 2 extending outward from the outer peripheral surface of the optic portion. The haptic components can be of any desired shape, for example graduated spiral filaments or flat plate sections, and are used to support the lens within the posterior chamber of the eye. Lenses having any desired design configuration can be fabricated. Also, although two types of haptic designs are shown in the figures, haptics may have configurations other than those illustrated. If the intraocular lens includes components other than the optical and haptic portions, such other portions may be made of a polymer such as the haptic and optical portions, or if desired, another material.
    [065] Modalities intraocular lenses can be inserted into the eye in known ways. For example, the intraocular lens can be bent before insertion into the eye by a small, thin forceps of the type commonly used by ophthalmic surgeons. After the lens is at the target location, it is released to unfold. As is well known in the art, generally, the lens being replaced is removed prior to insertion of the intraocular lens. The intraocular lens of the present embodiments can be made of a soft, generally physiologically inert polymeric material that is capable of providing a transparent, clear, and refracting lens body, even after folding and unfolding. In some embodiments, the collapsible intraocular lens of the present embodiments can be inserted into either eye by injection where the mechanically compatible material is folded and forced through a small tube, such as a 1mm to 3mm inner diameter tube. mm. In one embodiment, the small tube has an inside diameter of about 2.0 or 1.9 or 1.8 or 1.7 or 1.6 or 1.5 mm or less. In one embodiment, the inner diameter is approximately 1.4 to 2.0 mm. In one modality, the inner diameter is approximately 1.8 mm, in the other it is 1.6 mm. In one embodiment, the finished IOL lens is microinjectable (eg, capable of being injected through a small tube that has an inside diameter of about 1.8 mm or 1.6 mm). PREPARATION COMPOSITION METHODS
    [066] The copolymers of the embodiments of this invention can be prepared using conventional polymerization techniques known in the field of polymer chemistry. Crosslinkers, also referred to as crosslinking agents, can be employed in the polymerization reaction. For example, any suitable difunctional crosslinking, multifunctional monomer, or combination thereof can be used in amounts effective to obtain the desired crosslink density. For example, in a concentration range of 0.4 to about 4 percent, such as about 0.4 to about 3 percent, or in some embodiments from 0.5 to 1.5 percent by weight, based on polymer weight. Examples of suitable crosslinking agents include di-olefin compounds such as ethylene glycol dimethacrylate (EGDMA) and tetraethylene glycol dimethacrylate (TEGDMA) and other crosslinking agents such as trimethylol propane trimethacrylate (TMPTMA) which include three or more olefinic polymerizable functionalities. Crosslinkers generally help to improve the dimensional stability of the resulting polymer.
    [067] Furthermore, if desired an initiator can be used in the polymerization. Any initiator commonly used in the art such as azo derivatives such as 2,2-azobis(2,4-dimethylvaleronitrile) and propanenitrile, 2-methyl, 2,2'-azobis can be used. The initiator may also be a UV initiator or other type of mimic as recognized by one skilled in the art. The initiator is used in an effective amount for priming purposes, and is generally present from about 0.01 to 1.0 percent by weight based on the weight of the polymer.
    [068] The copolymers of the present embodiments may also include additional monomers, such as, but not limited to, monomers that impart ultraviolet (UV) absorption to the polymer. UV absorbing monomers are typically aromatic compounds with olefin functionality. Advantageous UV absorbing compounds can be added prior to polymerization for incorporation into the resulting polymer, as is well known in the art. The UV absorber should preferably be capable of polymerization into the lens matrix so as to be stable under physiological conditions. Any monomer copolymerizable with the described monomers may optionally be used, provided such monomers do not materially or adversely affect the basic characteristics of the intraocular lens. Examples of additional useful monomers that can be used are described in US Patent 5,326,506, incorporated herein by reference, directed to a composite intraocular lens. In addition, aryl substituted triazole compounds, such as, for example, the tris-aryl triazole compounds described in US Patent No. 6,365,652 can be used in low concentrations to achieve the desired UV absorbing properties. These optional additional monomers preferably are present in a total amount of no more than 10 percent by weight, generally less than 5 percent by weight, based on the total weight of the polymer.
    [069] As described above, it may be useful to add crosslinking agents such as EGDMA, TEGDMA, or TMPTA, for example, to improve the dimensional stability of the resulting polymer. It may also be advantageous to add UV absorbing compounds with the lens monomers prior to polymerization for incorporation into the resulting polymer. The UV absorber should preferably be capable of polymerization into the lens matrix so as to resist extraction under physiological conditions. The UV absorbing monomer can be present in an amount effective to obtain the desired UV absorbing properties, generally less than 4 percent by weight of the polymer, such as from 0.01 to about 1 percent by weight. polymer weight.
    [070] Examples of specific copolymers useful in the present embodiments are included in Table 1, which are also discussed in the examples where all weights used in polymerization are shown in grams with the percentage of monomers in the polymer shown in parentheses, based on the total of all monomers and crosslinking agents and assuming the incorporation of all monomers and crosslinking agents in the copolymers. INTRAOCULAR LENS FORMATION
    [071] The intraocular lenses of the present embodiments can be formed by methods known in the art. For example, in an exemplary process, the monomers that form the copolymer are polymerized on a polymer rod, polymer blanks or disks are formed from the stem, and then the blanks are cut, for example, by a lathe mechanic for the intraocular lens. Stems can be made by a procedure that begins with polymerization, in a mold, such as a tubular or cylindrical mold, a mixture of monomers and initiator, to form an optically smooth and clear lens body. As discussed above, it may be desirable to incorporate crosslinking materials and ultraviolet absorbing compounds during polymerization or in the resulting polymer matrix. In some embodiments, the polymer rods are then cut and milled, or otherwise milled, into sketches of the desired diameter and lathe cut thickness, and milled by milling at temperatures below the Tg in an intraocular lens.
    [072] Generally, the composite material rod is lathe cut or milled to a diameter 0.5 to 2.0 mm thicker than the required distance from the center of the lens body to the farthest edge of the lens. members or haptics. This rod is then cut into sketches of uniform thickness. The blanks are milled and bent to a diameter and thickness suitable for lathe cutting and milled in the mill in the conventional manner for the intraocular lens of the present embodiments. Because the present copolymers may have low glass transition temperatures, the shank or blanks may require cooling below Tg, before and/or during cutting, turning and/or milling.
    [073] A general description of a multi-step process for forming the outlines in intraocular lenses is presented in the flowchart below. An expert having skill in the field of intraocular lens fabrication, from an analysis of this report can make intraocular lenses using general knowledge in the art in intraocular lens fabrication and the cryogenic machining process.
    [074] Intraocular lenses can also be made by molding the present copolymer to form all or part of the optical portion of the lenses. For example, the present copolymer can be polymerized in a mold by a liquid blend of monomers and additional components to form an optically smooth and clear lens body. These shaping methods may involve shaping the optics in half of the lens, such as the front or back portion, or shaping the lens completely. When only half of the optical portion of the lens is formed in the mold, then the second optical side can be milled, for example, as discussed above. In either of these modalities, additional material can be molded to allow milling of various haptic designs. The copolymer can optionally be molded into a preformed lens shape, as is known in the art as a universal blank. POLYMERS DO NOT INCLUDE COMPONENTS
    [075] In one embodiment, the copolymer composition does not comprise a third monomer, which is a hydrophilic low molecular weight monomer having a molecular weight of less than about 150 g/mol, or less than about 100 g/mol .
    [076] For example, in one embodiment, the copolymer composition does not comprise polymerized hydroxyethylacrylate (HEA). In one embodiment, the copolymer composition does not comprise polymerized glycidyl methacrylate (GMA). In one embodiment, the copolymer composition does not comprise the combination of HEA and GMA. APPLICATIONS
    [077] One application is lens, including lenses adapted for the human eye, including IOLs.
    [078] Additional modalities are provided in the following non-limiting working examples and contrasted with the comparative examples. WORKING EXAMPLES HPPA refers to 2-hydroxy-3-phenoxypropyl acrylate EOEMA refers to 2-ethoxyethyl methacrylate PEG200M refers to polyethylene glycol monomethyl ether methacrylate (200 PEG MW) PEG400M refers to monomethyl methacrylate polyethylene glycol ether (400 PEG MW) TMPTMA refers to trimethylol propane trimethacrylate Example 1:
    [079] 24.8 grams of HPPA were mixed with 12.2 grams of EOEMA, 3.0 grams of PEG200M, and 1.1 grams of TMPTMA. The mixture was degassed during application of vigorous stirring. The mixture was dispensed into molds and polymerized at 70°C for eight hours, and post-cured at 95°C for 10 hours. The molds were allowed to cool to room temperature. The molds were opened and the polymer disk removed and inspected. The polymer exhibited the properties summarized in Table 1. Example 2:
    [080] 26.0 grams of HPPA were mixed with 11.0 grams of EOEMA, 3.0 grams of PEG200M, and 1.1 grams of TMPTMA. The mixture was degassed during application of vigorous stirring. The mixture was dispensed into molds, polymerized at 70°C for eight hours, and post-cured at 95°C for 10 hours. The molds were allowed to cool to room temperature. The molds were opened and the polymer disk removed and inspected. The polymer exhibited the properties summarized in Table 1. Example 3:
    [081] 26.0 grams of HPPA were mixed with 10.0 grams of EOEMA, 4.0 grams of PEG200M and 1.1 grams of TMPTMA. The mixture was degassed during application of vigorous stirring. The mixture was dispensed into molds, polymerized at 70°C for eight hours, and post-cured at 95°C for 10 hours. The molds were allowed to cool to room temperature. The molds were opened and the polymer disk removed and inspected. The polymer exhibited the properties summarized in Table 1. Example 4:
    [082] 24.8 grams of HPPA were mixed with 9.2 grams of EOEMA, 6.0 grams of PEG200M, and 1.1 grams of TMPTMA. The mixture was degassed during application of vigorous stirring. The mixture was dispensed into molds, polymerized at 70°C for eight hours, and post-cured at 95°C for 10 hours. The molds were allowed to cool to room temperature. The molds were opened and the polymer disk removed and inspected. The polymer exhibited the properties summarized in Table 1. Example 5:
    [083] 24.8 grams of HPPA were mixed with 9.2 grams of EOEMA, 6.0 grams of PEG400M, and 1.1 grams of TMPTMA. The mixture was degassed during application of vigorous stirring. The mixture was dispensed into molds, polymerized at 70°C for eight hours, and post-cured at 95°C for 10 hours. The molds were allowed to cool to room temperature. The molds were opened and the polymer disk removed and inspected. The polymer exhibited the properties summarized in Table 1. Table 1: Properties of Working Examples

    Example 5: Shear force measurements
    [084] Using a Precision Rheometer with a liquid thermostat cell maintained at 25°C, two commonly used hydrophilic IOL materials (HEMA/EOEMA hydrophilic copolymer “LIO 25” (water content = 25%) and hydrophilic HEMA/MMA copolymer and “Benz Flex” (water content = 26%)) were examined. 1500 Pa of shear force was applied for 60 seconds at a normal holding force of 5 Newtons. The results are summarized in Figure 4. The data shows that the IOL 25 material can absorb more than twice the shear force (by elastic deformation), and release it more quickly than the Benz Flex material. A used hydrophobic IOL material (hydrophobic EOEMA-based copolymer “HF1.2” (Tg = 4°C)) has been subjected to similar conditions and can absorb only half the force and relax more slowly. HF1.2 is injectable via a 2.4-2.8 mm syringe and has an opening time of approximately 25-30 seconds. The ability to recover from deformation is affected by these properties. The hydrophobic aromatic copolymer incorporated herein, such as the IOL material of Example 1 ("HF2" (Tg = 5°C)) more closely resembles IOL 25 and releases almost as quickly (see Figure 4). COMPARATIVE EXAMPLES HPPA refers to 2-hydroxy-3-phenoxypropyl acrylate EOEMA refers to 2-ethoxyethyl methacrylate EOEA refers to 2-ethoxyethyl acrylate TMPTMA refers to trimethylol propane trimethacrylate HEA refers to acrylate of 2-hydroxyethyl GMA refers to glycerol methacrylate SI refers to the Trattler severity index of gloss. Comparative Example 1:
    [085] 24.8 grams of HPPA were mixed with 12.4 grams of EOEMA, 2.8 grams of HEA, and 1.1 grams of TMPTMA. The mixture was degassed during application of vigorous stirring. The mixture was dispensed into molds and polymerized at 70°C for eight hours, and post-cured at 95°C for 10 hours. The molds were allowed to cool to room temperature. The molds were opened and the polymer disk removed and inspected. The polymer exhibited a gloss level of SI = 862 on the Trattler Severity Index. Comparative Example 2:
    [086] 30.0 grams of HPPA were mixed with 7.0 grams of EOEA, 2.0 grams of HEA, 1.0 gram of GMA and 1.1 gram of TMPTMA. The mixture was degassed during application of vigorous stirring. The mixture was dispensed into molds and polymerized at 70°C for eight hours, and post-cured at 95°C for 10 hours. The molds were allowed to cool to room temperature. The molds were opened and the polymer disk removed and inspected. The polymer exhibited a gloss level of SI = 826 on the Trattler Severity Index. Comparative Example 3:
    [087] 18.5 grams of HPPA were mixed with 18.5 grams of EOEMA, 1.0 g of HEA, 2.0 grams of GMA and 1.1 grams of TMPTMA. The mixture was degassed during application of vigorous stirring. The mixture was dispensed into molds and polymerized at 70°C for eight hours, and post-cured at 95°C for 10 hours. The molds were allowed to cool to room temperature. The molds were opened and the polymer disk removed and inspected. The polymer exhibited a gloss level of SI = 850 on the Trattler Severity Index. Comparative example 4:
    [088] 26.0 grams of HPPA were mixed with 14 grams of EOEMA, and 1.1 grams of TMPTMA. The mixture was degassed during application of vigorous stirring. The mixture was dispensed into molds and polymerized at 70°C for eight hours, and post-cured at 95°C for 10 hours. The molds were allowed to cool to room temperature. The molds were opened and the polymer disk removed and inspected. The polymer exhibited a brightness level of SI = 801 on the Trattler Severity Index. Refractive Index Measures
    [089] The refractive index can be measured by methods known in the art. The values given here were determined by the following method.
    [090] Measurements were obtained using an Atago Multiwavelength Abbe refractometer at test temperatures of 20°C ± 2 and 35°C ± 2. To the prism of the refractometer a drop of 1-bromonaphthalene was applied and the flat polymer was placed in it. and allowed to equilibrate for 10 minutes. RI values were recorded over three to five additional discs with the same formula to achieve an average value of dry measurements.
    [091] Wet readings were then performed by hydrating the discs at 20°C±2 for a minimum period of 24 hours. The disc is placed in the refractometer and allowed to equilibrate at 20°C±2 for ten minutes. Measurements are repeated at 35°C±2. water content measurements
    [092] A set of five discs from the same batch of polymeric material were weighed and placed in an oven at 110°C±10 for at least 1.5 hours. Discs were dried, then weighed. The discs were then hydrated in saline for 48 hours. Then, the discs were removed from the solution, blotted dry and weighed again. The change in weight was indicative of the water content of the IOL. Opening time measurements
    [093] A universal IOL sketch or a finished lens was folded with tweezers and placed in physiological saline at 20°C. The sample was then released and the amount of time it took the IOL to return to its original shape was recorded. The procedure was repeated at 35°C. Severity Index Measurement
    [094] A universal IOL sketch was placed in saline at room temperature for 12 hours. The fully immersed IOL was then inspected under 20x magnification, at an angle of 30 to 55 degrees (can be adjusted for maximum vacuole visibility). The number, size and density of the glows were calculated through visual inspection.
    [095] As will be understood by one of skill in the art, for any and all purposes, particularly in terms of providing a written description, all tracks disclosed herein also encompass any and all possible sub-bands and sub-band combinations thereof. Any track listed can be easily recognized as sufficiently describing and allowing the same track to be divided into at least equal halves, thirds, quarters, fifths, tenths, etc. As a non-limiting example, each range discussed here can be readily divided into a lower third, middle third and an upper third, etc. As will also be understood by a person skilled in the art all language such as "up to", "at least", "higher", "lower", "more than" and the like include the number recited and refer to tracks that can be subsequently divided into subbands, as discussed above. Likewise, all reasons disclosed herein also include all sub-reasons covered by the broader reason.
    [096] One skilled in the art will also readily recognize that when members are grouped together in a common way, such as in a Markush group, the present modalities encompass not only the entire listed group as a whole, but each member of the group individually and all possible subgroups of the main group. Thus, for all intents and purposes, the present modalities cover not only the main group, but also the main group absent one or more of the group members. The present modalities also provide for the explicit exclusion of one or more of any of the members of the group from the claimed modalities.
    [097] All references, patents, and publications disclosed herein are specifically incorporated by reference in their entirety and for all intents and purposes as if presented in their entirety. Unless otherwise stated, “one” or “an” means “one or more”.
    [098] Although the preferred embodiments have been illustrated and described, it is to be understood that changes and modifications may be made in accordance with the person skilled in the art without departing from the embodiments in their broader aspects as defined in the following claims.
    权利要求:
    Claims (25)
    [0001]
    1. Intraocular lens characterized in that it comprises at least one copolymer comprising: (a) a first monomeric subunit comprising a polymerized 2-hydroxy-3-phenoxypropyl acrylate, (b) a second monomeric subunit comprising a 2-ethoxyethyl methacrylate polymerized, (c) a third monomeric subunit comprising a polymerized polyethylene glycol monomethyl ether methacrylate having a polyethylene glycol molecular weight of 200 to 400, and (d) a trimethacrylate crosslinking subunit, wherein the 2-hydroxy acrylate Polymerized 3-phenoxypropyl is from 50% to 70% by weight of the copolymer, and polymerized 2-ethoxyethyl methacrylate is from 20% to 35% by weight of the copolymer, and polymerized polyethylene glycol monomethyl ether methacrylate with a molecular weight of 200 to 400 polyethylene glycol is from 5% to 15% by weight of the copolymer, and the trimethacrylate crosslinker is from 0.5 to 3% by weight of the copolymer, wherein the intraocular lens when hydrated has a m SI value less than 800.
    [0002]
    2. Intraocular lens according to claim 1, characterized in that the copolymer has a glass transition temperature below 35°C.
    [0003]
    3. Intraocular lens according to claim 1, characterized in that the copolymer has a glass transition temperature of -5°C to 5°C.
    [0004]
    4. Intraocular lens according to claim 1, characterized in that the copolymer has an equilibrium water content of 5% by weight or less.
    [0005]
    5. Intraocular lens according to claim 1, characterized in that the copolymer has an equilibrium water content of 4% by weight or less.
    [0006]
    6. Intraocular lens according to claim 1, characterized in that the lens has a central thickness of up to 1 mm, and unfolds in less than or 1 minute when placed in a saline solution at a temperature of 36 °C.
    [0007]
    7. Intraocular lens according to claim 1, characterized in that the lens has a central thickness of up to 1 mm and unfolds in 5 to 10 seconds.
    [0008]
    8. Intraocular lens according to claim 1, characterized in that the SI value is less than 750.
    [0009]
    9. Composition characterized in that it comprises at least one copolymer comprising: (a) a first monomeric subunit comprising a polymerized 2-hydroxy-3-phenoxypropyl acrylate, (b) a second monomeric subunit comprising a polymerized 2-ethoxyethyl methacrylate , (c) a third monomeric subunit comprising a polymerized polyethylene glycol monomethyl ether methacrylate having a polyethylene glycol molecular weight of 200 to 400, and (d) a fourth monomeric subunit comprising a polymerized trimethacrylate crosslinker, wherein the acrylate is Polymerized 2-hydroxy-3-phenoxypropyl is from 50% to 70% by weight of the copolymer, and polymerized 2-ethoxyethyl methacrylate is from 20% to 35% by weight of the copolymer, and polymerized polyethylene glycol monomethyl ether methacrylate with a polyethylene glycol molecular weight of 200 to 400 is from 5% to 15% by weight of the copolymer, and the trimethacrylate crosslinker is from 0.5 to 3% by weight of the copolymer.
    [0010]
    10. Composition according to claim 9, characterized in that the copolymer has a glass transition temperature lower than 35°C.
    [0011]
    11. Composition according to claim 9, characterized in that the copolymer has a glass transition temperature of -5°C to 5°C.
    [0012]
    12. Composition according to claim 9, characterized in that the copolymer has an equilibrium water content of 5% by weight or less.
    [0013]
    13. Composition according to claim 9, characterized in that the hydrated intraocular lens made from the composition has an SI value of less than 800.
    [0014]
    14. Method for preparing a composition comprising at least one copolymer comprising monomeric subunits characterized in that it comprises: preparing a comonomer mixture comprising: (a) a first 2-hydroxy-3-phenoxypropyl acrylate monomer, (b) a second 2-ethoxyethyl methacrylate monomer, (c) a third monomer comprising polyethylene glycol monomethyl ether methacrylate having a polyethylene glycol molecular weight of 200 to 400, and (d) a fourth monomer which is a trimethacrylate crosslinker, wherein the first monomer is from 50% to 70% by weight of the comonomer mixture, and the second monomer is from 20% to 35% by weight of the comonomer mixture, and the polyethylene glycol monomethyl ether methacrylate with a polyethylene glycol molecular weight of 200 to 400 is from 5% to 15% by weight of the comonomer mixture, and the fourth monomer is from 0.5 to 3% by weight of the comonomer mixture; polymerize the comonomer mixture.
    [0015]
    15. Intraocular lens characterized in that it comprises at least one copolymer consisting essentially of: (a) a first monomeric subunit comprising a polymerized 2-hydroxy-3-phenoxypropyl acrylate, (b) a second monomeric subunit comprising a 2 methacrylate polymerized ethoxyethyl, (c) a third monomeric subunit comprising a polymerized polyethylene glycol monomethyl ether methacrylate having a polyethylene glycol molecular weight of 200 to 400, and (d) one or more fourth monomeric subunits which is a trimethacrylate crosslinker, wherein the first monomeric subunit is present in a greater amount by weight than the second monomeric subunit, and the first and second monomeric subunits together essentially consist of 75 percent or more of the monomeric subunits by weight, wherein the acrylate is Polymerized 2-hydroxy-3-phenoxypropyl is from 50% to 70% by weight of the copolymer, and 2-ethoxyethylpol methacrylate immersed is from 20% to 35% by weight of the copolymer, and polymerized polyethylene glycol monomethyl ether methacrylate with a polyethylene glycol molecular weight of 200 to 400 is from 5% to 15% by weight of the copolymer, and the crosslinker of trimethacrylate is from 0.5 to 3% by weight of the copolymer.
    [0016]
    16. Intraocular lens according to claim 1, characterized in that the polymerized 2-hydroxy-3-phenoxypropyl acrylate is from 60% to 65% by weight of the copolymer; polymerized 2-ethoxyethyl methacrylate is from 27% to 32% by weight of the copolymer; and polymerized polyethylene glycol monomethyl ether methacrylate having a polyethylene glycol molecular weight of 200 to 400 is 7% to 10% by weight of the copolymer.
    [0017]
    17. Intraocular lens according to claim 1, characterized in that the polymerized 2-ethoxyethyl methacrylate is from 27% to 32% by weight of the copolymer.
    [0018]
    18. Intraocular lens according to claim 1, characterized in that the polymerized polyethylene glycol monomethyl ether methacrylate with a polyethylene glycol molecular weight of 200 to 400 is 7% to 10% by weight of the copolymer.
    [0019]
    19. Intraocular lens according to claim 1, characterized in that the polyethylene glycol monomethyl ether methacrylate polymerized with a polyethylene glycol has a molecular weight of 200.
    [0020]
    20. Intraocular lens according to claim 1, characterized in that the polyethylene glycol monomethyl ether methacrylate polymerized with a polyethylene glycol has a molecular weight of 400.
    [0021]
    21. Intraocular lens according to claim 16, characterized in that the polyethylene glycol monomethyl ether methacrylate polymerized with a polyethylene glycol has a molecular weight of 200.
    [0022]
    22. Intraocular lens according to claim 16, characterized in that the polyethylene glycol monomethyl ether methacrylate polymerized with a polyethylene glycol has a molecular weight of 400.
    [0023]
    23. Intraocular lens according to claim 17, characterized in that the polyethylene glycol monomethyl ether methacrylate polymerized with a polyethylene glycol has a molecular weight of 200.
    [0024]
    24. Intraocular lens according to claim 17, characterized in that the polyethylene glycol monomethyl ether methacrylate polymerized with a polyethylene glycol has a molecular weight of 400.
    [0025]
    25. Intraocular lens according to claim 18, characterized in that the polyethylene glycol monomethyl ether methacrylate polymerized with a polyethylene glycol has a molecular weight of 200.
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    同族专利:
    公开号 | 公开日
    TW201317262A|2013-05-01|
    CN103946251A|2014-07-23|
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    法律状态:
    2018-03-27| B06F| Objections, documents and/or translations needed after an examination request according [chapter 6.6 patent gazette]|
    2019-09-10| B06U| Preliminary requirement: requests with searches performed by other patent offices: procedure suspended [chapter 6.21 patent gazette]|
    2020-06-30| B06A| Patent application procedure suspended [chapter 6.1 patent gazette]|
    2020-11-17| B06A| Patent application procedure suspended [chapter 6.1 patent gazette]|
    2021-03-23| B09A| Decision: intention to grant [chapter 9.1 patent gazette]|
    2021-06-08| B16A| Patent or certificate of addition of invention granted [chapter 16.1 patent gazette]|Free format text: PRAZO DE VALIDADE: 20 (VINTE) ANOS CONTADOS A PARTIR DE 14/09/2012, OBSERVADAS AS CONDICOES LEGAIS. |
    优先权:
    申请号 | 申请日 | 专利标题
    US201161535795P| true| 2011-09-16|2011-09-16|
    US61/535,795|2011-09-16|
    PCT/US2012/055540|WO2013040434A1|2011-09-16|2012-09-14|Hydrophobic intraocular lens|
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