HK1199648B

HK1199648B - Ultraviolet light absorbing materials for intraocular lens and uses thereof

Info

Publication number: HK1199648B
Application number: HK15100047.6A
Authority: HK
Inventors: 亚当．勒布耳; 帕特里克．H．宾视
Original assignee: 宾视研发公司
Priority date: 2011-09-16
Filing date: 2012-09-14
Publication date: 2017-09-01

Description

Ultraviolet absorbing material for intraocular lens and use thereof

RELATED APPLICATIONS

Priority of U.S. provisional application serial No. 61/535,849 filed on day 9, 16 of 2011 and U.S. provisional application serial No. 61/599,756 filed on day 2, 16 of 2012, the entire disclosures of each of which are hereby incorporated by reference in their entireties.

Background

Various polymeric compositions for forming intraocular lenses (IOLs) are known. The formation of these polymeric compositions from a variety of monomers of different functionality can significantly affect the performance of the resulting IOLs. Typically, monomers capable of absorbing Ultraviolet (UV) radiation are incorporated into the polymeric composition. The addition of UV-absorbing monomers can alter the overall composition of the polymer and can therefore significantly affect the performance of the resulting IOL. See, for example, U.S. Pat. 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, for examples of IOL materials and methods of preparation. See, additionally, U.S. patent publication nos. 2008/0221235, 2006/0276606, 2006/0199929, 2005/0131183, 2002/0058724, 2002/0058723, and 2002/0027302, each of which is incorporated by reference herein in its entirety.

Many UV absorbing compounds contain aromatic pi-electron systems that inhibit altering the properties, such as refractive index, of the final polymer. Furthermore, increasing the concentration of UV-absorbing monomers can alter the overall hydrophilicity or hydrophobicity of the polymer due to the presence of additional UV-absorbing moieties in the polymer. Thus, the addition of a large number of new components to an IOL polymer composition can result in significant changes to the properties of the compound, which can already establish commercial and/or regulatory significance to existing products.

Existing IOL products containing UV-absorbing moieties, such as those comprising benzophenone moieties, within polymeric compounds may not provide sufficient UV absorption at a particular wavelength without greatly increasing the concentration of the benzophenone moiety from the compositions currently being developed. A large increase in UV absorbing moieties such as benzophenone can alter the physical properties of the resulting compound, thereby requiring reformulation and/or revalidation of commercial compounds. Accordingly, there is a need for the incorporation of UV-absorbing compounds that can be incorporated into polymeric compositions suitable for IOLs in sufficiently low concentrations so as to not significantly alter the characteristics of the IOL other than the transmittance of UV when compared to the same formulation without the new UV-absorbing compound. For these needs, the new compounds should impart UV-absorption so that the formed IOLs can reduce the transmittance of UV radiation at 370nm wavelengths by at least 90%.

Disclosure of Invention

Embodiments described herein include, for example, methods of making and using copolymers, lenses, intraocular lenses, blanks for intraocular lenses that include triaryl-1, 3, 5-triazine moieties to reduce the transmission of radiation without substantially affecting other properties of the copolymers, lenses, intraocular lenses, blanks for intraocular lenses.

For example, one embodiment provides a method of manufacturing an intraocular lens capable of reducing the transmittance of ultraviolet radiation at 370nm, the method comprising: (a) polymerizing a mixture comprising: at least one first monomer and at least one second monomer comprising a triaryl-1, 3, 5-triazine moiety, (b) forming an optical portion from the copolymer, wherein the second monomer is present in an amount sufficient to reduce the transmittance of ultraviolet radiation at 370nm to 10% or less, and wherein the amount of the second monomer does not substantially affect the physical properties of the lens other than the transmittance of ultraviolet radiation.

For example, another embodiment provides a method of making an intraocular lens capable of absorbing 370nm ultraviolet radiation, the method comprising: (a) polymerizing a mixture comprising: at least one first monomer and at least one second monomer comprising a triaryl-1, 3, 5-triazine moiety, (b) forming an optic from the copolymer, wherein the second monomer is present at about 0.10 to about 0.20 wt% of the total dry polymer, and wherein the optic of the intraocular lens exhibits substantially the same refractive index as the optic of the intraocular lens formed from the polymerized mixture of (a) without the second monomer but otherwise under substantially the same conditions.

For example, another embodiment provides a method of preventing the transmission of at least 90% of ultraviolet radiation at 370nm by a foldable intraocular lens, the method comprising, consisting essentially of, or consisting of: (a) incorporating at least one monomer comprising a 4- (4, 6-diphenyl-1, 3, 5-triazin-2-yl) -3-hydroxyphenoxy moiety into at least one polymer, and (b) forming the polymer into a material suitable for use as an intraocular lens, wherein the monomer comprising the 4- (4, 6-diphenyl-1, 3, 5-triazin-2-yl) -3-hydroxyphenoxy moiety comprises from 0.10 to 0.20 wt% of the total dry polymer.

For example, another embodiment provides a foldable intraocular lens or lens blank comprising at least one copolymer comprising at least (a) one first monomer, and (b) one second monomer comprising a 4- (4, 6-diphenyl-1, 3, 5-triazin-2-yl) -3-hydroxyphenoxy moiety present at about 0.05 to about 0.20 percent by weight of the total dry polymer, wherein the foldable intraocular lens or lens blank absorbs at least 90 percent of the transmitted 370nm ultraviolet radiation, and wherein the optic of the intraocular lens exhibits substantially the same refractive index as the optic of an intraocular lens formed from a polymeric mixture of (a) without the second monomer but otherwise of the same composition.

At least one advantage associated with at least one embodiment includes reducing the transmittance of 370nm ultraviolet radiation in an intraocular lens to less than 10% without substantially altering the refractive index of the lens.

At least one advantage associated with at least one embodiment includes reducing the transmittance of ultraviolet radiation at 370nm below 10% in an intraocular lens without substantially altering the water content of the lens.

At least one advantage with respect to at least one embodiment includes reducing the transmittance of ultraviolet radiation at 370nm below 10% in an intraocular lens without substantially altering the glass transition temperature of the lens.

At least one advantage with respect to at least one embodiment includes increasing the water solubility of a particular composition by providing a substituted alkyl linker (linker) in the second monomer as described herein.

Drawings

FIG. 1 is a graph demonstrating the effect of UV absorbers on water content. In embodiments, benzotriazole addition to every 1.0% of the IOL formulation may cause 2.8% water loss. Moving the concentration from 0.2% to 0.6% can reduce the water content change by about 1.1%.

Detailed Description

Introduction to

All documents cited herein are incorporated by reference in their entirety. For the purposes of this application, UV-absorbing material refers to a material by means of which the transmittance of UV rays is reduced. All component amounts are based on% (w/w), ("wt%") unless otherwise indicated. As used herein, substantially affecting a physical property, or substantially changing a physical property, or exhibiting substantially the same property, means not changing a physical property of the polymeric compound, or not changing a physical property of the compound by more than 1.0%, or not changing a physical property of the compound by more than 2.0%, or for refractive index measurements, not changing by more than 0.1% or not changing by more than 0.05%, or for glass transition temperature, not changing by more than 1 ℃.

Commercial specialty intraocular lens materials typically include UV-blocking and/or UV-absorbing compounds incorporated therein. Many factors can influence the level of transmission of UV radiation through the IOL. For example, the concentration of the selected UV-absorbing compound and/or UV-absorbing compound may be such that the transmittance of UV radiation at various wavelengths varies. In addition, the thickness of the IOL can affect the transmittance.

Intraocular lens first compound

The first compounds of the embodiments contained herein are generally monomers that can react at various concentrations or under various conditions to form polymeric compositions suitable for use as foldable IOL materials. Many of the compositions or compounds embodied herein are described in the prior art, for example, U.S. Pat. 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. Also, in U.S. 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. The composition or compound of U.S. provisional patent 61/535,795 entitled hydrophobic intraocular lens, filed on 8.2011 and 16, is incorporated herein by reference in its entirety. It is generally known in the art that monomers can be used for IOL formation, and the first monomer disclosed herein is not meant to be limiting, but merely provides an exemplary compound. In one embodiment, the first compound may be at least one compound comprising an acrylate, methacrylate, acrylamide and/or methacrylamide moiety and at least one further moiety. In some embodiments, the first compound is a hydrophobic molecule comprising acrylate, methacrylate, acrylamide, and/or methacrylamide moieties. In other embodiments, the first compound is a hydrophilic molecule comprising acrylate, methacrylate, acrylamide, and/or methacrylamide moieties. In some embodiments, a plurality of first compounds comprising different functional moieties are polymerized. Embodiments may include other compounds suitable for IOL lenses that include at least one polymerizable moiety, e.g., an acrylate, acrylamide, methacrylamide, and/or methacrylate. For example, some embodiments include at least one hydrophilic molecule comprising acrylate, methacrylate, acrylamide, and/or methacrylamide moieties, and at least one hydrophobic molecule comprising polymerizable moieties, e.g., acrylate, methacrylate, acrylamide, and/or methacrylamide moieties. Other embodiments comprise 2, 3, 4 or more different hydrophilic and/or hydrophobic molecules comprising a polymerizable moiety, e.g., an acrylate, methacrylate, acrylamide and/or methacrylamide moiety. Other embodiments include molecules comprising a polymeric moiety, e.g., acrylate, methacrylate, acrylamide, and/or methacrylamide, which may be considered neither hydrophobic nor hydrophilic. Some embodiments have an alkyl acrylate (alkacrylate) or alkyl acrylamide (alkacryamide) moiety, wherein the alkyl group is a C2-C5 alkyl group. One skilled in the art will recognize that alkyl acrylates and alkyl acrylamides contain an alkyl group covalently bonded to the carbon adjacent to the carbonyl moiety of the alkyl acrylate or alkyl acrylamide. Other embodiments include crosslinking agents and/or other compounds, for example, water, colorants, and/or antioxidants. In one embodiment, the acrylate (a), acrylamide (AA), Methacrylamide (MAA) and/or Methacrylate (MA) moieties are covalently bonded through the O or N atoms of the moieties to additional moieties known in the art to provide monomers suitable for polymerization into foldable IOL compositions. Exemplary, non-limiting monomers include, but are not limited in any way to: 2-hydroxy-3-phenoxypropyl-A, hydroxy-3-phenoxypropyl-AA, hydroxy-3-phenoxypropyl-MA, hydroxy-3-phenoxypropyl-MAA, 2-ethoxyethyl-A, 2-ethoxyethyl-MA, 2-ethoxyethyl-AA, 2-ethoxyethyl-MAA, 2-hydroxyethyl-A, 2-hydroxyethyl-AA, 2-hydroxyethyl-MA, 2-hydroxyethyl-MAA, polyethylene glycol monomethyl ether-A, polyethylene glycol monomethyl ether-MA, polyethylene glycol monomethyl ether-AA, polyethylene glycol monomethyl ether-MAA, 2-hydroxy-3-phenoxypropyl-A, poly (ethylene glycol) methyl ether-MAA, poly (ethylene glycol) methyl ether-AA, poly (ethylene glycol) methyl ether-MAA, poly (ethylene glycol) methyl ether-A, poly (ethylene glycol) methyl ether-MA, 2-hydroxy-3-phenoxypropyl-AA, 2-hydroxy-3-phenoxypropyl-MA, 2-hydroxy-3-phenoxypropyl-MAA, 2-ethoxyethyl-A, 2-ethoxyethyl-AA, 2-ethoxyethyl-MA, 2-ethoxyethyl-MAA, lauryl-A, lauryl-MA, lauryl-AA, lauryl-MAA, glycerol-A, glycerol-MA, glycerol-MAA, glycerol-AA, and additional monomers found in the references cited herein. In addition, other monomers known to those skilled in the art as being capable of forming foldable IOLs may be used in the embodiments herein.

UV absorbing compounds

The UV-absorbing compounds of the current embodiments include compounds comprising a triaryl-1, 3, 5-triazine moiety, wherein at least one aryl ring has a hydroxyl group ortho to the point of attachment to the triazine ring. In general, the hydroxyl group may refer to a latent hydroxyl group. Generally, such materials are known in the art. See U.S. patent No. 6,365,652 and references therein. Each of which is incorporated herein by reference. The compounds comprising this moiety are incorporated into the polymer for the purpose of stabilizing the material against the effects of actinic radiation and reducing the transmittance of UV radiation by the particular polymer. See U.S. Pat. No. 6,365,652 and JP 1997/028785. The compounds embodied herein generally include an additional moiety added to the triaryl-1, 3, 5-triazine compound that is reactive and can be incorporated into the polymer during polymerization of the other first monomer. In one embodiment, an ether linkage (ether linkage) linking the triaryl-1, 3, 5-triazine and an alkyl linker covalently added to at least one polymerizable moiety, e.g., acrylate, acrylamide, methacrylamide, and/or methacrylate, is included. In other embodiments, at least one polymerizable moiety, e.g., an acrylate (a), acrylamide (AA), Methacrylamide (MAA), and/or Methacrylate (MA) moiety, may be replaced by other moieties capable of polymerization. However, the scope of the present disclosure is not limited to a, AA, MAA, and MA. Even more, for example, other embodiments include further substitution of acrylates and acrylamides, e.g., ethyl acrylate or ethyl acrylamide, and other polymerizable moieties including acrylate and acrylamide functionality (functionality). In some embodiments, the ether linkage may be in the meta position to the triazine. In other embodiments, the ether linkage may be in the para position of the triazine. In other embodiments, the linking agent may include sulfur instead of oxygen.

As used herein, an "alkyl linker" may optionally be composed of 1, 2, 3, or 4 hydroxy groups, (C) halogen, amine, trifluoromethyl₁-C₅) Alkoxy, optionally substituted by 1, 2, 3 or 4 hydroxy, halogen, amine, (C)₁-C₅) Alkoxy-or trifluoromethyl-substituted (C)₁-C₅) Linear or branched alkyl. For example, in one embodiment, the alkyl linker consists of 1, 2, 3, or 4 hydroxyl moietiesAnd (4) substituting.

In some embodiments, the UV absorbing compound comprises a compound of formula (I).

Wherein L is an alkyl linker and A is an acrylate, methacrylate, acrylamide or methacrylamide. In some embodiments, L may be selected from alkyl groups having 1 to 5 carbon atoms, in some embodiments 1, 2, 3, 4, or 5 carbon atoms. Alkyl groups that may be used in accordance with embodiments herein include straight chain alkyl groups including, but not limited to, methyl, ethyl, propyl, butyl, and pentyl. Alkyl groups may also include branched isomers of straight chain alkyl groups, including, but not limited to, the following, which are also provided by way of example only: -CH (CH)₃)₂、–CH(CH₃)(CH₂CH₃)、–CH(CH₂CH₃)₂and-C (CH)₃)₃And the like. The alkyl linker may also be substituted with more than 1 polar moiety. Polar moieties include, for example, hydroxy, halogen, amine, trifluoromethyl, (C)₁-C₅) Alkoxy, optionally substituted by 1, 2, 3 or 4 hydroxy, halogen, amine, (C)₁-C₅) Alkoxy-or trifluoromethyl-substituted (C)₁-C₅) Straight or branched chain alkyl. With respect to L, it will be appreciated that the alkyl linker is bonded to the O of the triaryl-1, 3, 5-triazine-O group and to the O atom or the N atom of the a group. In some embodiments, in the compounds represented by formula I, L is C substituted with 1, 2, 3, or 4 hydroxyl moieties₁-C₅Alkyl and A is acrylate or methacrylate, or L is C substituted with 1 hydroxy moiety₁-C₅Alkyl and A is acrylate or methacrylate, or L is represented by the formula-CH₂CH(OH)CH₂-represents and a is acrylate or methacrylate.

In a preferred embodiment, the UV absorbing monomer may be a compound of formula (II).

Wherein X is H or CH₃。

In another preferred embodiment, the UV absorbing monomer may be a compound of formula (III).

Wherein X is H or CH₃。

Amount of UV absorbing compound

Generally, some of the UV absorbing compounds embodied herein are of a type known in the art. However, the compounds embodied herein are but a subset of the wide variety of compounds known in the art as UV absorbing compounds. In fact, many other compounds are known, for example, those comprising benzophenone moieties absorb UV radiation. In many cases, the compounds embodied in the present embodiments herein have been pre-formulated to meet specific physical characteristics when formed into IOLs. These properties are critical to the function of the lens and include, by way of non-limiting example, refractive index, water content and/or glass transition temperature. Often, many of these compositions include UV absorbing compounds, but in order to meet different UV-blocking or UV-absorbing standards, whether through regulatory rigid regulations or consumer needs, these previously formed compounds may require additional UV absorbing monomers or compounds to achieve the desired UV transmission properties. Frequent addition of additional UV absorbing compounds will result in changes in the properties of the IOL and may result in the need to reformulate the IOL composition. Therefore, a compound capable of blocking or absorbing UV rays while being present in a small concentration is required.

The UV absorbing monomers of the present embodiment are used herein at a low percentage of the total dry monomers used to form the polymer suitable for an IOL. In some embodiments, the UV absorbing monomer is 0.001 to 0.30 weight percent of the total dry monomers used to form the polymer suitable for an IOL. In other embodiments, the UV absorbing monomer is 0.05 to 0.20 weight percent of the total dry monomers used to form the polymer suitable for an IOL. In a more preferred embodiment, the UV absorbing monomer is 0.10 to 0.15% by weight of the total dry monomers used to form the polymer suitable for an IOL. It is to be understood that these ranges are non-limiting and that preferred embodiments may be, for example, 0.08 to 0.18 wt% or any other suitable range within 0.05 to 0.25 wt% of the total dry monomers used to form the polymer suitable for the IOL. In a preferred embodiment, the UV absorbing monomer is present at about 0.13% to 0.17% by weight of the total dry monomers used to form the polymer suitable for the IOL.

In some embodiments, the UV absorbing monomer will be present in an amount sufficient to provide 5,6, 7, 8, 9, or 10% transmittance of UV radiation at 368, 369, 370, 371, and/or 372nm wavelengths in the formed IOL. In a preferred embodiment, the UV-absorbing monomer will be present in an amount sufficient to provide a transmission of 5,6, 7, 8, 9 or 10% to UV radiation at 370nm in the formed IOL. The transmittance for this 370nm UV radiation may be 5,6, 7, 8, 9 or 10% in IOLs of thicknesses known in the art, for example, 300 to 1000 μm. In other embodiments, the UV absorbing monomer will be present in an amount sufficient to have a diopter of 0 to 35 or 10 to 30m^-1Is present in an amount providing a transmittance of 5,6, 7, 8, 9 or 10% for UV radiation at 370 nm. In another embodiment, the IOL or IOL blank comprises a material having a molar extinction coefficient greater than 3000M at 370nm^-1cm^-1The UV absorbing monomer of (1). Formation of Polymer compositions

As used herein, the term "polymer" refers to a composition formed by polymerizing one monomer or two or more (different) monomers. Thus, the term "polymer" includes "homopolymers" formed from only one monomer, "copolymers" formed from two or more different monomers, "terpolymers" formed from at least three different monomers, and any polymer formed from at least one monomer and which may be formed from 1, 2, 3, 4 or more different monomers. The polymers may also be formed from oligomers as embodied herein, including oligomeric monomers.

In the polymer, the total amount of more than one first monomer may make up the majority of the polymer, as measured by weight. The second monomer comprising a triaryl-1, 3, 5-triazine moiety may be present at less than 0.20 wt% of the total polymer.

The polymers of the embodiments herein may be prepared using conventional polymerization techniques known to those in the polymer chemistry art. In addition, the formulations of polymers suitable for IOLs are described in detail in the references cited and incorporated herein. Typically, the first polymer and the UV absorbing monomer will polymerize under the conditions disclosed herein and in the references incorporated by reference. Crosslinking agents, also known as crosslinking agents, may be employed in the polymerization reaction. For example, any suitable crosslinking di-functional, multi-functional monomer, or combination of these may be used in an amount effective to achieve the desired crosslink density. For example, in a concentration range of 0.4 to about 4%, such as from about 0.4 to about 3%, or in some embodiments from 0.5 to 1.5% by weight, based on the weight of the polymer. Examples of suitable crosslinkers include diolefinic compounds such as Ethylene Glycol Dimethacrylate (EGDMA) and tetraethylene glycol dimethacrylate (TEGDMA) and other crosslinkers comprising more than three olefinic polymeric functionalities such as trimethylolpropane trimethacrylate (TMPTMA). Generally, the crosslinking agent helps to enhance the dimensional stability of the resulting polymer.

Further, an initiator may be used in the polymerization, if necessary. Any initiator commonly used in the art may be used, such as azo derivatives like 2, 2-azobis (2, 4-dimethylvaleronitrile) and 2,2 '-azobis-2-methyl-propionitrile (propanentirle, 2-methyl,2, 2' -azobis), or UV initiators. The initiator is used in an amount effective for initiating purposes and is typically present in about 0.01 to 1.0 weight percent based on the weight of the polymer.

When the polymer is considered to include monomers such as 2-methyl-, 2- [4- (4, 6-diphenyl-1, 3, 5-triazin-2-yl) -3-hydroxyphenoxy ] ethyl-2-propenoate, it will be understood that this means that 2-methyl-, 2- [4- (4, 6-diphenyl-1, 3, 5-triazin-2-yl) -3-hydroxyphenoxy ] ethyl-2-propenoate monomers have been reflected and incorporated into the polymer.

Properties of the composition

The polymers can be designed to have a wide range of physical properties. In addition to UV transmittance, the polymer typically has substantially similar physical properties to the same polymer lacking the UV absorbing compound embodied herein. By way of non-limiting example, tables 1 and 2 show the physical properties of hydrophobic and hydrophilic lenses with and without the embodied triazine UV absorbers. It will be appreciated that this embodiment discloses the weight percent of the UV absorbing compound relative to all dry monomers making up the mixture suitable for polymerization, and for the purposes of this embodiment herein, when a polymer comprising the UV absorbing compound is compared to the same polymer lacking the UV absorbing compound, it will be appreciated that the lacking percent of UV absorption can be replaced by more than one other co-monomer compound. As described herein, substantially similar physical properties refer to properties such as water content, refractive index, and/or glass transition temperature.

In some embodiments, the polymer will have a transmission of 3, 4, 5,6, 7, 8, 9, or 10% of UV radiation at 365, 366, 367, 368, 369, 370, 371, 372, 373, 374 and/or 375nm wavelengths in the formed IOL or IOL blank. In a preferred embodiment, the UV absorbing monomer will be present in an amount sufficient to provide a transmission of less than 10% to UV radiation at 370nm in the formed IOL or IOL blank. In other preferred embodiments, the UV absorbing monomer will be present in an amount sufficient to provide 10, 9, 8, 7,6, 5, 4, 3, 2, 1% or less transmittance to UV radiation at 370nm in the formed IOL or IOL blank. The thickness of the lens will affect the amount of UV absorption by the lens. At one endIn one embodiment, the UV absorbing monomer will be present in an amount sufficient to provide a transmittance of UV radiation of 370nm of 10% or less in the formed IOL or IOL blank having a hydrated thickness of about 300 μm to about 1000 μm. In another embodiment, the UV absorbing monomer will be present in an amount sufficient to provide a transmittance of UV radiation of 370nm of 10% or less in the formed IOL or IOL blank having a hydrated thickness of about 400 μm to about 900 μm. In other embodiments, the UV absorbing monomer will be formed to have a diopter of 0 to 35 or 10 to 30m^-1Is present in an amount sufficient to provide a transmittance of 5,6, 7, 8, 9 or 10% of UV radiation at 370 nm. In another embodiment, the UV absorbing monomer will be present in an amount sufficient to provide a molar extinction coefficient greater than 3000 at 370 nm.

Since the polymers have been designed for use as intraocular lenses, they also typically have a high refractive index, which is generally higher than about 1.40. Some of the polymers may have a refractive index of 1.48 or more. In one embodiment, the polymer will have a refractive index substantially similar to the refractive index of the same polymer lacking the UV absorbing compound embodied herein. In another embodiment, the refractive index of the polymer will be from about 0.0001% to about 0.1% higher or lower than the same polymer in the absence of the UV absorbing compound. In yet another embodiment, the refractive index of the polymer will be from about 0.0001% to about 0.05% higher or lower than the same polymer in the absence of the UV absorbing compound.

Since the polymer has been designed for use as a foldable intraocular lens, the polymeric material also typically has a relatively low glass transition temperature (Tg) when the water content is relatively low, i.e., in a hydrophobic lens, the polymer can also be designed to have a glass transition temperature of less than about 35 ℃ or about 35 ℃, less than about 30 ℃ or about 30 ℃, less than about 25 ℃ or about 25 ℃, e.g., from about-25 ℃ to about 35 ℃, 30 ℃ or 25 ℃, from about-5 ℃ to about 15 ℃, 20 ℃, or about 25 ℃, or from about 0 ℃ to about 15 ℃. The preferred range is from about-5 ℃ to about 15 ℃. In one embodiment, the polymerization will have a Tg substantially similar to the Tg of the same polymer in the absence of the UV absorbing compound. In another embodiment, the Tg of the polymer will be 1 ℃ higher or lower than the same polymer lacking the UV absorbing compound. The glass transition temperature referred to herein can be measured at the half-width value at a temperature change rate of 10 deg.c/minute.

The polymers optionally include hydrophobic polymers wherein the polymer has a water content of 5.0% or less, and hydrophilic polymers wherein the water content is typically 20% to 30%. Other polymers having water contents between that of the hydrophobic and hydrophilic monomers are also contemplated. In one embodiment, the polymer will have a water content that is substantially similar to the water content of the same polymer lacking the UV absorbing compound. In another embodiment, the water content of the polymer will be from 0.01% higher or lower to 2.0% of the same polymer lacking the UV absorbing compound. In yet another embodiment, the water content of the polymer will be from 0.1% higher or lower to 1.0% of the same polymer lacking the UV absorbing compound.

Intraocular lens formation

The present embodiments herein also provide intraocular lenses made at least in part from the polymers of the present invention. The intraocular lens comprises an optic portion and one or more haptic portions. Typically, the polymers of the embodiments herein will make up part or the entire optic of an intraocular lens. In some embodiments, the optic of the lens will have a core made of one polymer of the invention surrounded by a different polymer or material. A lens in which the optic is made at least in part of one of the polymers of the invention will also typically have haptics. The contacts may also be made from the polymers of the embodiments herein, or may be made from different materials, such as other polymers.

In some embodiments, the intraocular lenses of the invention are one-piece lenses having a soft, foldable central optical zone and a peripheral zone (haptic zone), wherein both zones are made of the same polymer. In other embodiments, the optical zone and the contact zone can be formed from different types of polymers or materials, if desired. Some lenses may also have haptics composed of a different material, for example, where one or more haptics are made of the same material as the optic and other haptics are made of a material other than the polymers of the embodiments herein. Multicomponent lenses can be made by embedding one material in another, by a simultaneous extrusion process, by curing the hard material around the soft material, or by forming an interpenetrating network of the rigid component in a preformed hydrophobic core. In instances where one or more of the haptics are made of a different material than the optic of the lens, the haptics may be attached to the optic in any manner known in the art, such as by drilling a hole or holes in the optic and embedding the haptics. In additional embodiments, the polymer may be formed into a universal billet as known in the art.

The polymers of the present embodiments herein are designed such that they can be folded so that the intraocular lens can be inserted into an individual's eye through a small incision. The haptics of the lens provide the support required for the lens within the eye after insertion or deployment of the lens and tend to help stabilize the position of the inserted lens and the closure of the incision. The shape of the contact design is not particularly limited and may be of any desired configuration, for example, a plate or a spiral filament of graduated thickness, also known as a C-loop design.

Component not provided for by the polymer

In one embodiment, the polymer composition does not include a first monomer comprising methyl methacrylate and ethylene glycol dimethacrylate. In one embodiment, the polymer composition does not include a first monomer consisting of methyl methacrylate and ethylene glycol dimethacrylate.

Working examples

EOEMA refers to 2-ethoxyethyl methacrylate

HEMA refers to 2-hydroxyethyl methacrylate

LMA means lauryl methacrylate

GMA means glycerol methacrylate

HEA is 2-hydroxyethyl acrylate

TMPTMA refers to trimethylolpropane trimethacrylate

DI refers to deionized water

HPTZ is 2-methyl-2- [4- (4, 6-diphenyl-1, 3, 5-triazin-2-yl) -3-hydroxyphenoxy ] ethyl 2-propenoate

Example 1: synthesis of HPTZ

A solution of 10.8g (31.7mmol)2- (2, 4-dihydroxyphenyl) -4, 6-diphenyl-1, 3, 5-triazine, 5.8g (39.1mmol) 2-chloroethyl methacrylate and 5.8g (42.0mmol) anhydrous potassium carbonate in 200ml DMSO was heated in an oil bath preheated to 82 ℃ for 17.5 hours. The final bath temperature was 87 ℃. In two systems (silica gel, hexane: acetone:: 3:1(v/v) and CH₂Cl₂) A thick slurry was first obtained, thinning on each water addition, a noticeable exotherm was observed on the first two water additions, but minimal exotherm on the third addition, the contents of the flask were transferred to a 1L separatory funnel using 100ml DI water for flushing the flask, the aqueous suspension was 2 × 200ml CH 200ml₂Cl₂And finally 100ml of CH₂Cl₂The extraction and the combined organic extracts were concentrated in vacuo to give 69.1g of a wet beige solid which was refluxed with 3 × 100ml of CH₂Cl₂And (6) processing. The suspension was observed until the last aliquot of CH was added₂Cl₂At this point a clear, very dark solution was obtained. After cooling to room temperature, the solution was stored in a freezer at-20 ℃ 72And (4) hours. The product began to crystallize after-1 hour. After 3 days, the cold slurry was filtered and the solids were treated with CH₂Cl₂(precooled to-20 ℃) to give the product as gold crystals. The crystals were dried in vacuo to constant weight to give 8.6g (60%) of product. By TLC (CH)₂Cl₂) And NMR (CDCl)₃) The material is pure.

Example 2: hydrophobic polymers 1 suitable for IOLs

35.0g of EOEMA was mixed with 2.0g of HEA, 2.0g of LMA, 1.0g of GMA, 0.040g of HPTZ, 0.021g of 2,2 '-azobis (2, 4-dimethylvaleronitrile), 0.08g of 2,2' -azobis (2-methylbutyronitrile) and 1.1g of TMPTMA. The mixture was degassed while applying vigorous stirring. The mixture was dispensed into a mold, polymerized at 70 ℃ for 8 hours, and post-cured at 95 ℃ for 10 hours. The mold was allowed to cool to room temperature. The mold was opened and the polymeric disc was removed and inspected.

Example 3: hydrophobic polymers 2 suitable for use in IOLs

35.0g of EOEMA was mixed with 2.0g of HEA, 2.0g of LMA, 1.0g of GMA, 0.050g of HPTZ, 0.021g of 2,2 '-azobis (2, 4-dimethylvaleronitrile), 0.08g of 2,2' -azobis (2-methylbutyronitrile) and 1.1g of TMPTMA. The mixture was degassed while applying vigorous stirring. The mixture was dispensed into a mold, polymerized at 70 ℃ for 8 hours, and post-cured at 95 ℃ for 10 hours. The mold was allowed to cool to room temperature. The mold was opened and the polymeric disc was removed and inspected.

Example 4: hydrophobic polymers 3 suitable for IOLs

35.0g of EOEMA was mixed with 2.0g of HEA, 2.0g of LMA, 1.0g of GMA, 0.060g of HPTZ, 0.021g of 2,2 '-azobis (2, 4-dimethylvaleronitrile), 0.08g of 2,2' -azobis (2-methylbutyronitrile) and 1.1g of TMPTMA. The mixture was degassed while applying vigorous stirring. The mixture was dispensed into a mold, polymerized at 70 ℃ for 8 hours, and post-cured at 95 ℃ for 10 hours. The mold was allowed to cool to room temperature. The mold was opened and the polymeric disc was removed and inspected.

Example 5: hydrophilic polymers 1 suitable for IOLs

30.0g HEMA was combined with 10.0g EOEMA, 0.4g DI, 0.060g HPTZ, 0.022g2,2 '-azobis (2, 4-dimethylvaleronitrile), 0.088g2,2' -azobis (2-methylbutyronitrile) and 0.6g TMPTMA. The mixture was degassed while applying vigorous stirring. The mixture was dispensed into a mold, polymerized at 70 ℃ for 8 hours, and post-cured at 95 ℃ for 10 hours. The mold was allowed to cool to room temperature. The mold was opened and the polymeric disc was removed and inspected.

Example 6: hydrophilic polymers 2 suitable for IOLs

30.0g HEMA was mixed with 10.0g EOEMA, 0.4g DI, 0.050g HPTZ, 0.022g2,2 '-azobis (2, 4-dimethylvaleronitrile), 0.088g2,2' -azobis (2-methylbutyronitrile) and 0.6g TMPTMA. The mixture was degassed while applying vigorous stirring. The mixture was dispensed into a mold, polymerized at 70 ℃ for 8 hours, and post-cured at 95 ℃ for 10 hours. The mold was allowed to cool to room temperature. The mold was opened and the polymeric disc was removed and inspected.

Example 7: hydrophilic polymers 3 suitable for IOLs

30.0g HEMA was combined with 10.0g EOEMA, 0.4g DI, 0.040g HPTZ, 0.022g2,2 '-azobis (2, 4-dimethylvaleronitrile), 0.088g2,2' -azobis (2-methylbutyronitrile) and 0.6g TMPTMA. The mixture was degassed while applying vigorous stirring. The mixture was dispensed into a mold, polymerized at 70 ℃ for 8 hours, and post-cured at 95 ℃ for 10 hours. The mold was allowed to cool to room temperature. The mold was opened and the polymeric disc was removed and inspected.

Comparative data for hydrophilic lenses

A generic lens blank was prepared according to the disclosed method to compare refractive index and water content to lens blanks currently sold by Benz Research and development. Universal lens blanks were prepared according to the formulation traded under BENZ IOL25(UV Clear) except 0.15 wt% HPTZ was added to the formulation. The lens blank exhibited the characteristics shown in table 1. Furthermore, the loss of water content based on the percentage of UV absorber is shown in figure 1.

TABLE 1 comparative hydrophilic lens data

Deviation (589nm)

1.460 +/-0.002 at 20 deg.c

1.460 +/-0.002 at 35 deg.c

Deviation (546nm)

1.462 +/-0.002 at 20 deg.c

1.462 +/-0.002 at 35 deg.c

Comparative data for hydrophobic lenses

A generic lens blank was prepared according to the disclosed method to compare the refractive index with the lens blanks currently sold by Benz Research and development. Universal lens blanks were prepared according to the formulation traded under BENZ HF1, except 0.15 wt% HPTZ was added to the formulation. The lens blank exhibited the characteristics shown in table 2.

TABLE 2 data comparing hydrophobic lenses

Deviation (589nm)

1.485 +/-0.002 at 20 deg.c

1.483 +/-0.002 at 35 deg.C

Deviation (546nm)

1.487 +/-0.002 at 20 deg.C

1.485 +/-0.002 at 35 deg.c

Example 8: synthesis of a second monomer with a hydroxy-substituted alkyl linker

A suspension of 9.6g (28.2mmol)1, 4.8ml (36.3mmol) GMA and 0.40g tetraethylammonium bromide (TEAB) in 100ml anhydrous EtOH was refluxed overnight (22 hours). The reaction mixture was then decanted while still hot into a new container, leaving a small amount of brown solid adhering to the walls of the flask. The decanted slurry was cooled to room temperature and placed in an ice bath for 1.5 hours. The slurry was then filtered and washed with-100 ml of anhydrous EtOH (pre-cooled to-20 ℃). TLC analysis at this point (silica gel, hexane: AcCH)₃3:1(v/v)) shows that the filtered solid consists of 3 and 2 and negligible 1; EtOH filtrate was discarded. The filtered solid was then dried in vacuo to give 9.3g of crude material, which was in 400ml of CH₂Cl₂Stirred overnight.

The slurry was filtered and the recovered solid was dried to give 3.4g of 2(TLC) with a trace of 3 present; CH (CH)₂Cl₂The filtrate contains 3 with a small amount of impurities. Is prepared in CH₂Cl₂275g of silica gel (70-230 mesh) column, and the filtrate was charged into the column, followed by hexane: AcCH₃3:1(v/v) elution. The purified product was concentrated in vacuo and the contents were slurried in hexane and filtered. The product was dried in vacuo to reveal by NMR analysis 2.6g of pure 3.

Claims

1. A method of making a foldable intraocular lens capable of reducing the transmittance of ultraviolet radiation at 370nm, the method comprising:

(a) polymerizing a mixture comprising:

at least one first monomer and

at least one second monomer comprising a triaryl-1, 3, 5-triazine moiety,

(b) the optical portion is formed from the copolymer,

wherein the second monomer is present in an amount sufficient to reduce the transmittance of ultraviolet radiation at 370nm to 10% or less with an optical portion having a thickness of 300 to 1000 μm after hydration, and wherein the amount of the second monomer does not substantially affect the physical properties of the lens other than the transmittance of ultraviolet radiation, and is represented by formula (I),

wherein L is C substituted by 1, 2, 3 or 4 hydroxy groups₁-C₅An alkyl group, a carboxyl group,

a is acrylate, methacrylate, acrylamide or methacrylamide, and L is covalently bonded to A through an oxygen atom or a nitrogen atom in A.

2. The method of claim 1, wherein the substantially unaffected physical property is refractive index.

3. The method of claim 1, wherein the substantially unaffected physical property is water content.

4. The method of claim 1, wherein the substantially unaffected physical property is glass transition temperature.

5. The method of claim 1, wherein step (a) comprises at least two different first monomers.

6. The method of claim 1, wherein the first monomer in step (a) does not consist of methyl methacrylate and ethylene glycol dimethacrylate.

7. The method of claim 1, wherein the second monomer is present at 0.10 to 0.20 weight percent of the total dry mixture polymerized in step (a).

8. The method of claim 1, wherein the mixture in step (a) contains at least two first monomers, wherein the resulting polymer has a water content of 5% or less.

9. The process of claim 1, wherein the mixture in step (a) contains at least two first monomers, wherein the resulting polymer has a water content of 20% to 30%.

10. A method of making a foldable intraocular lens capable of absorbing ultraviolet radiation at 370nm, the method comprising:

(a) polymerizing a mixture comprising:

at least one first monomer and

at least one second monomer comprising a triaryl-1, 3, 5-triazine moiety,

(b) the optical portion is formed from the copolymer,

wherein the second monomer is present at 0.10 to 0.20% by weight of the total polymer and wherein the optic of the intraocular lens exhibits substantially the same refractive index as the optic of the intraocular lens formed from the polymerized mixture of (a) without the second monomer, but otherwise under substantially the same conditions, the second monomer being represented by formula (I),

11. The method of claim 10, wherein step (a) comprises at least two first monomers.

12. The method of claim 10, wherein the first monomer in step (a) comprises an acrylate or methacrylate moiety and at least one additional moiety covalently bonded to the O of the acrylate or methacrylate moiety.

13. The method of claim 10 wherein the optic of the intraocular lens exhibits substantially the same water content as the optic of the intraocular lens formed from the polymerized mixture of (a) without the second monomer but otherwise under the same conditions.

14. The method of claim 10, wherein the intraocular lens has a transmittance of ultraviolet radiation at a wavelength of 370nm of 10% or less.

15. The method of claim 10, wherein the intraocular lens has a transmittance of ultraviolet radiation at a wavelength of 370nm of 6% or less.

16. The method of claim 10, wherein the second monomer is present at 0.13 to 0.17 weight percent of the total polymer.

17. The method of claim 10, wherein the first monomer does not consist of methyl methacrylate and ethylene glycol dimethacrylate.

18. The method of claim 10, wherein (b) comprises cutting, grinding or both cutting and grinding the intraocular lens blank into an optic.

19. A method of altering an individual's vision comprising inserting an intraocular lens prepared by comprising the method of claim 1 into an eye of a subject.

20. The method of claim 19, further comprising folding the intraocular lens prior to inserting the intraocular lens into an eye and unfolding the intraocular lens after inserting the intraocular lens into an eye.

21. A method of increasing the extinction coefficient of a copolymer of ultraviolet radiation at 370nm through a foldable intraocular lens, the method comprising:

(a) introducing a monomer comprising a 4- (4, 6-diphenyl-1, 3, 5-triazin-2-yl) -3-hydroxyphenoxy moiety into at least one polymer, and

(b) the polymer is formed into a material suitable for use as an intraocular lens,

wherein the monomer comprising a 4- (4, 6-diphenyl-1, 3, 5-triazin-2-yl) -3-hydroxyphenoxy moiety comprises from 0.10 to 0.15 wt.% of the total dry polymer, and the monomer comprising a 4- (4, 6-diphenyl-1, 3, 5-triazin-2-yl) -3-hydroxyphenoxy moiety is represented by formula (I):

wherein L is C substituted by 1, 2, 3 or 4 hydroxy groups₁-C₅An alkyl group;

22. A method of preventing the transmission of at least 90% of ultraviolet radiation at 370nm through a foldable intraocular lens, the method comprising:

23. The method of claim 22, wherein the foldable intraocular lens has a transmittance of ultraviolet radiation at a wavelength of 370nm of 9% or less.

24. The method of claim 22, wherein the foldable intraocular lens has a transmittance of ultraviolet radiation at a wavelength of 370nm of 6% or less.

25. The method of claim 22, wherein the polymer does not consist of methyl methacrylate and ethylene glycol dimethacrylate.

26. The method of claim 22, wherein the polymer has a refractive index substantially the same as a polymer that does not have a monomer comprising a 4- (4, 6-diphenyl-1, 3, 5-triazin-2-yl) -3-hydroxyphenoxy moiety but is otherwise of the same composition.

27. The method of claim 22, wherein the polymer has substantially the same water content as a polymer that does not have monomers comprising 4- (4, 6-diphenyl-1, 3, 5-triazin-2-yl) -3-hydroxyphenoxy moieties but is otherwise of the same composition.

28. A foldable intraocular lens or lens blank comprising at least one copolymer comprising at least (a) a first monomer, and

(b) a second monomer comprising a 4- (4, 6-diphenyl-1, 3, 5-triazin-2-yl) -3-hydroxyphenoxy moiety present at 0.05 to 0.20% by weight of the total dry polymer,

wherein the foldable intraocular lens or lens blank absorbs at least 90% of the transmitted 370nm ultraviolet radiation and wherein the optic of the intraocular lens exhibits substantially the same refractive index as the optic of an intraocular lens formed from a polymeric mixture of (a) without the second monomer but otherwise of the same composition, the monomer comprising a 4- (4, 6-diphenyl-1, 3, 5-triazin-2-yl) -3-hydroxyphenoxy moiety being represented by formula (I):

29. The foldable intraocular lens or lens blank according to claim 28, wherein the second monomer is present at 0.13 to 0.17 wt% of the total dry polymer.

30. The foldable intraocular lens or lens blank of claim 28, wherein the second monomer has at least 3000M^-1cm^-1The extinction coefficient to 370nm radiation.

31. The foldable intraocular lens or lens blank according to claim 28, wherein the lens has a transmittance of ultraviolet radiation at 370nm wavelength of 9% or less.

32. The foldable intraocular lens or lens blank according to claim 28, wherein the lens has a transmittance of ultraviolet radiation at 370nm wavelength of 6% or less.

33. The method of claim 1, wherein L is C substituted with 1, 2, 3, or 4 hydroxyl moieties₁-C₅Alkyl and A are acrylate or methacrylate.

34. The method of claim 1, wherein L is C substituted with 1 hydroxyl moiety₁-C₅Alkyl and A are acrylate or methacrylate.

35. The method of claim 1, wherein L is C substituted with 1 hydroxyl moiety₃Alkyl and A are acrylate or methacrylate.

36. The method of claim 1, wherein L is of the formula-CH₂CH(OH)CH₂-represents and a is acrylate or methacrylate.

37. The method of claim 10, wherein the second monomer is represented by formula (III):

wherein X is H or CH₃。

38. The method of claim 22, wherein L is C substituted with 1, 2, 3, or 4 hydroxyl moieties₁-C₅Alkyl and A are acrylate or methacrylate.

39. The method of claim 22, wherein L is C substituted with 1 hydroxyl moiety₁-C₅Alkyl and A are acrylate or methacrylate.

40. The method of claim 22, wherein L is represented by the formula-CH₂CH(OH)CH₂-represents and a is acrylate or methacrylate.

41. The foldable intraocular lens or lens blank according to claim 28, wherein L is C substituted with 1, 2, 3 or 4 hydroxyl moieties₁-C₅Alkyl and A are acrylate or methacrylate.

42. The foldable intraocular lens or lens blank according to claim 28, wherein L is C substituted with 1 hydroxyl moiety₁-C₅Alkyl and A are acrylate or methacrylate.

43. The foldable intraocular lens or lens blank of claim 28, wherein L is represented by the formula-CH₂CH(OH)CH₂-represents and a is acrylate or methacrylate.