Ophthalmic devices comprising light stable mimics of macular pigments and other visible light filters

Abstract

An ophthalmic device containing a visible light filter is described. The present invention provides an ophthalmic device that is the product of a free radical reaction of a reactive mixture comprising: one or more monomers suitable for manufacturing ophthalmic devices; a first visible light filter compound having a maximum visible light absorption between 430 nm and 480 nm and a full width at half maximum (FWHM) of at least 35 nm and at most 150 nm at the maximum visible light absorption, wherein the first visible light filter compound is photostable, and wherein the first visible light filter compound has a concentration of at least 7740 L·mol⁻¹. ‑1 .cm ‑1 The device contains a molar extinction coefficient and a second visible light filter compound having a maximum visible light absorption between 480 nm and 530 nm and a full width at half maximum (FWHM) of at least 50 nm and at most 150 nm. The reactive monomer mixture may also contain a third visible light filter compound. These devices can provide one or more visually beneficial effects, including enhanced macular pigment optical density, improved color perception and color enhancement, and reduced visual artifacts.

Description

Related applications

[0001] This application claims priority to U.S. Patent Application Serial No. 18 / 952,864, filed November 19, 2024, which in turn claims priority to U.S. Provisional Patent Application Serial No. 63 / 608,952, filed December 12, 2023. Technical Field

[0002] This invention relates to ophthalmic devices comprising visible light filters. More specifically, this invention relates to ophthalmic devices containing visible light filtering compounds that substantially mimic the absorption characteristics of macular pigment while maintaining photostability. The ophthalmic device also comprises a secondary visible light filter. Background Technology

[0003] Human eye tissues contain dietary carotenoids lutein (L) and zeaxanthin (Z), collectively known as macular pigments (MPs). Several reports describe the benefits of MPs, such as their use as short-wavelength (blue light) filters and potent antioxidants. MPs are also believed to have a protective effect against age-related macular degeneration (AMD) (Bernstein, PS, Li, B., Vachali, PP, Gorusupudi, A., Shyam, R., Henriksen, BS, Nolan, JM Prog. Retin. Eye Res. 2016, 50, 34-66; Beatty, S., Boulton, M., Koh, HH., Murray, I, J. Br.J. Ophthalmol 1999, 83, 867-877). Further findings revealed that macular pigment was significantly associated with photo-stress recovery time, reduced disabling glare contrast threshold, and reduced visual discomfort (Stringham, JM, Garcia., PV, Smith, PA, McLin, L, N., Foutch, BK IOVS, 2011, 52 (10) 7406-7415).

[0004] The chemical entities associated with macular pigments are carotenoid derivatives, which exhibit a wide range of unsaturations and are highly reactive to olefin isomerization and oxidation upon photoexcitation. The antioxidant protection mechanism provided by carotenoids is essentially sacrificial, where excitation of the pi system leads to the reaction of its excited state with triplet oxygen, thereby protecting / limiting the excitation and reaction of other photosensitive compounds in the ocular environment. See, for example, Ribeiro et al., Food and Chemical Toxicology, Vol. 120, pp. 681-699 (2018); Burton et al., Can.J. Chem., Vol. 92, pp. 305-316 (2014); Ty et al., Journal of Oil Palm Research, Vol. II, No. 1, pp. 62-78 (June 1999); Johnston et al., Plos One, Vol. 9 (10), pp. 1-10 (2014); and Boon et al., Critical Reviews in Food Science and Nutrition, Vol. 50, pp. 515-532 (2010).

[0005] While incorporating macular pigments into products for the purpose of providing eye protection is desirable, the lack of overall stability (thermal stability, oxidative stability, and photochemical stability) of carotenoids presents a significant obstacle to the development of such products. Therefore, developing new stable materials that mimic the light absorption properties of macular pigments would be a major breakthrough. Materials that provide additional visual benefits are also highly anticipated. Summary of the Invention

[0006] This invention relates to ophthalmic devices incorporating a first filtering compound that absorbs light in the wavelength range of 400 nm to 500 nm and has an absorption spectrum that substantially mimics the absorption characteristics of the macular pigment. Such compounds are also photostable, for example, when changes / losses in absorption characteristics are measured under conditions similar to those described in ICH Q1B. Furthermore, the compounds exhibit high extinction coefficients at desired wavelengths in the 400 nm to 500 nm range and can therefore be used at low concentrations to provide their beneficial light absorption effects. In addition, these compounds are thermally stable. Ophthalmic devices incorporating compounds as described herein can enhance the wearer's macular pigment optical density (MPOD). Furthermore, the device can mimic other visually beneficial effects of the macular pigment, such as improved light stimulation recovery time and disabling glare contrast threshold, and reduced visual discomfort.

[0007] In addition to compounds that mimic the light absorption properties of macular pigment, the ophthalmic device described herein also contains a second filtering compound. This second filtering compound filters out other wavelengths in the visible spectrum, thereby providing additional visual benefits to the lens wearer.

[0008] Therefore, the ophthalmic devices described herein may provide the wearer with one or more beneficial effects, including but not limited to: improved MPOD, which may help prevent age-related macular degeneration; improved light stimulation recovery time; improved disability glare contrast threshold; reduced visual discomfort; improved color enhancement; and / or improved color perception.

[0009] Therefore, in one aspect, the present invention provides an ophthalmic device that is a free radical reaction product of a reactive mixture comprising, substantially comprising, or comprising: one or more monomers suitable for manufacturing an ophthalmic device; a first visible light filtering compound having a maximum visible light absorption between 430 nm and 480 nm and a full width at half maximum (FWHM) of at least 35 nm and at most 150 nm at the maximum visible light absorption, wherein the compound is photostable, and wherein the photochemical compound has a concentration of at least 7740 L·mol⁻¹. -1 .cm -1 The mixture of reactive monomers may also contain a third visible light filter compound. The second visible light filter compound has a maximum visible light absorption between 480 nm and 530 nm and a full width at half maximum (FWHM) of at least 50 nm and at most 150 nm.

[0010] In another aspect, the present invention provides an apodization ophthalmic device formed by a method comprising: (a) providing a first reactive composition comprising: (i) a polymerization initiator capable of forming two or more free radical groups upon first activation, at least one of the two or more free radical groups being further activated by subsequent activation; (ii) one or more olefinic unsaturated compounds; and (iii) a crosslinking agent; (b) subjecting the first reactive composition to a first activation step, such that the first reactive composition polymerizes in the first activation step to form a crosslinked substrate network containing a covalently bonded activatable free radical initiator; (c) contacting the crosslinked substrate network with a first graft composition containing a first visible light filtering compound and a second visible light filtering compound, wherein the contact is performed under conditions that allow the first graft composition to penetrate into the crosslinked substrate network; and (d) activating the covalently bonded activatable free radical initiator at one or more selective regions of the crosslinked substrate network, such that the first graft composition polymerizes with the crosslinked substrate network at the selective regions, thereby forming an apodization distribution. The first graft composition may contain a third visible light filtering compound.

[0011] The method may further include: after step (b), extracting the cross-linked substrate network with a solvent while maintaining the covalently bonded activated free radical initiator of the cross-linked substrate network, and optionally hydrating the extracted cross-linked substrate network with an aqueous solution.

[0012] The method may further include, after step (d), contacting a crosslinked substrate network with a second graft composition containing a mixture of a first visible light filtering compound, a second visible light filtering compound, and optionally a third visible light filtering compound, which are different from the first graft composition, and activating the retained covalently bonded activatable free radical initiator, such that the second graft composition polymerizes with the crosslinked substrate network outside the selective region and optionally partially within the selective region.

[0013] The method may further include: after step (d), extracting the cross-linked substrate network with a solvent, hydrating the extracted cross-linked substrate network with an aqueous solution, and autoclaving the ophthalmic device.

[0014] In another aspect, method steps (a) and (b) are performed in a mold assembly consisting of a front mold and a rear mold, which define and close a cavity of ophthalmic device shape between the front mold and the rear mold, and method steps (c) and (d), which include the optional step of grafting a second graft composition, are performed in the mold assembly after the rear mold is removed. The activation in steps (b) and (d) can be photochemical in nature, for example, using a source of photochemical irradiation, such as UV / visible light irradiation, and the source of photochemical irradiation in steps (b) and (d) may include light-emitting diodes and multiple selectively controllable beams of photochemical irradiation controlled by a digital micromirror device according to a predetermined script. The predetermined script can form an apodization distribution by polymerizing a visible light filtering compound in different amounts in selective regions. In this way, an apodization ophthalmic device can be formed, wherein optical design is combined with the apodization distribution to provide the aforementioned visually beneficial effects. Attached Figure Description

[0015] Figure 1 The UV-VIS absorption spectra of 0.1 mM methanol solutions of compounds A and B of the present invention superimposed on the literature spectrum of macular pigment are shown.

[0016] Figure 2 The UV-VIS absorption spectra of 0.2 mM methanol solutions of compounds C and D are shown.

[0017] Figure 3 The UV-VIS absorption spectrum of a 0.2 mM methanol solution of compound E is shown.

[0018] Figure 4 The UV-VIS absorption spectrum of a 0.2 mM methanol solution of compound F is shown.

[0019] Figure 5 The UV-VIS absorption spectrum of a 0.2 mM methanol solution of 1-cyano-2-oxo-1-(9H-thioxanth-9-ylidene)-6,9,12-trioxa-3-azatetradecane-14-yl methacrylate is shown.

[0020] Figure 6 The UV-VIS absorption spectrum of a 0.2 mM methanol solution of compound I is shown.

[0021] Figure 7 The UV-VIS absorption spectrum of a 0.2 mM methanol solution of compound J is shown.

[0022] Figure 8 The UV-VIS absorption spectra of compound K and IMT blue in a 0.2 mM methanol solution are shown.

[0023] Figure 9The UV-VIS transmission spectra of contact lenses prepared from compound A or compound B are shown.

[0024] Figure 10 The UV-VIS transmission spectra of contact lenses prepared from compound B are shown before and after thermal or optical stress treatment.

[0025] Figure 11 The UV-VIS absorption spectra of the contact lens prepared by compound B are shown before and after thermal or optical stress treatment.

[0026] Figure 12 An in-mold fixture for light projection in a digital micromirror device is shown.

[0027] Figure 13 An image of a digital micromirror device, showing a graph of transmittance versus lens radius, is shown for creating apodization distributions within a contact lens.

[0028] Figure 14 An image of a digital micromirror apparatus superimposed on a photomicrograph of the resulting apodization lens is shown.

[0029] Figure 15 The UV-VIS transmission spectrum of the lens of Example 16A and the photomicrograph of the lens of Example 16B are shown.

[0030] Figure 16 The UV-VIS transmission spectra of lenses from Examples 16C to Example E are shown.

[0031] Figure 17 The UV-VIS transmission spectrum of the lens of sterile Example 17A is shown.

[0032] Figure 18 The UV-VIS transmission spectrum of the lens of Example 17C is shown.

[0033] Figure 19 Micrographs of lenses from Examples 17C to Example F are shown.

[0034] Figure 20 The UV-VIS transmission spectrum of the lens of Example 18 is shown.

[0035] Figure 21 The UV-VIS transmission spectrum of Example 21A is shown.

[0036] Figure 22 The UV-VIS transmission spectrum of Example 21C is shown.

[0037] Figure 23 The UV-VIS transmission spectrum of Example 21E is shown.

[0038] Figure 24 Micrographs of the lenses of Examples 21A to 21D are shown. Detailed Implementation

[0039] It should be understood that the present invention is not limited to the details of the construction or process steps set forth in the following description. Using the teachings herein, the present invention can have other embodiments and can be practiced or implemented in various ways.

[0040] The following definitions are provided for the terms used in this disclosure.

[0041] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention pertains. Polymer definitions conform to those published in the Compendium of Polymer Terminology and Nomenclature (IUPAC Recommendations 2008), edited by Richard G. Jones, Jaroslav Kahovec, Robert Stepto, Edward S. Wilks, Michael Hess, Tatsuki Kitayama, and W. ValMetanomski. All publications, patent applications, patents, and other references mentioned herein are incorporated herein by reference.

[0042] As used herein, the term "(methyl)" refers to an optional methyl substitution. Therefore, terms such as "(meth)acrylate" refer to both methacrylate and acrylate.

[0043] Wherever the chemical structure is provided, it should be understood that any combination of the alternatives disclosed for the substituents on the structure is permissible. Therefore, if the structure contains substituents R* and R**, each containing a list of three possible groups, nine combinations are disclosed. The same applies to combinations of properties.

[0044] When the subscript (such as the general formula [***]) is used... n When the "n" in a formula is used to describe the number of repeating units in the chemical formula of a polymer, the formula should be interpreted as representing the number-average molecular weight of the macromolecule.

[0045] The term "individual" includes both humans and vertebrates.

[0046] The term "biomedical device" refers to any article designed for use in or on mammalian tissues or body fluids, and preferably in or on human tissues or body fluids. Examples of such devices include, but are not limited to, wound dressings, sealants, tissue fillers, drug delivery systems, coatings, anti-adhesion barriers, catheters, implants, stents, and ophthalmic devices (such as intraocular lenses and contact lenses). Biomedical devices can be ophthalmic devices, specifically contact lenses, most specifically contact lenses made of silicone hydrogels or conventional hydrogels.

[0047] The term "ocular surface" includes the surface and glandular epithelial cells of the cornea, conjunctiva, lacrimal gland, accessory lacrimal gland, nasolacrimal duct, and meibomian gland, as well as their apical and basal stroma, lacrimal puncta, and adjacent or related structures, including the eyelids, which are connected by the continuity of epithelial cells, nerve innervation, and the endocrine and immune systems to form a functional system.

[0048] The term "ophthalmic device" refers to any optical device relating to the eye, including devices located in or on the eye or any part of the eye, including the ocular surface. These devices can provide optical correction, cosmetic enhancement, improved vision, therapeutic benefits (e.g., as a bandage), or delivery of active ingredients, such as pharmaceutical and nutritional components, or combinations of any of the foregoing functions. Examples of ophthalmic devices include, but are not limited to, lenses, optics, and ocular inserts (including, but not limited to, punctal plugs). "Lens" includes spectacle lenses, sunglasses lenses, soft contact lenses, hard contact lenses, hybrid contact lenses, intraocular lenses, crystalline intraocular lenses, and covering lenses. Ophthalmic devices may include contact lenses.

[0049] The term "contact lens" refers to an ophthalmic device that can be placed on the cornea of ​​an individual's eye. Contact lenses can provide corrective, cosmetic, or therapeutic benefits, including wound healing, drug or nutritional delivery, diagnostic evaluation or monitoring, ultraviolet light absorption, visible light or glare reduction, or any combination thereof. Contact lenses can be made of any suitable material known in the art and can be soft lenses, hard lenses, or hybrid lenses comprising at least two distinct portions with different physical, mechanical, or optical properties such as modulus, water content, light transmission, or combinations thereof.

[0050] Eyeglass lenses or sunglasses lenses may be made of mineral materials (e.g., silicate-based) or organic materials such as polycarbonate; polyamide; polyimide; polysulfone; polyethylene terephthalate / polycarbonate copolymer; and various other materials known in the art.

[0051] As used herein, the term "central area" refers to the central portion of the contact lens and may include the pupil area of ​​the lens. The central area may, for example, have a diameter ranging from about 3 mm to about 12 mm, preferably from about 4 mm to about 11 mm, and more preferably from about 5 mm to about 10 mm. The term "peripheral area" refers to the contact lens area surrounding the central area of ​​the lens. The peripheral area may extend to the edge of the lens. The central area may include an "optical area," which is an area designed (by means of refraction, diffraction, or a combination thereof) to correct refractive errors in the contact lens wearer, such as myopia, hyperopia, presbyopia, astigmatism, etc.

[0052] The biomedical device, ophthalmic device, and lens of the present invention can be made of silicone hydrogel or conventional hydrogel. Silicone hydrogels typically contain at least one hydrophilic monomer and at least one silicone-containing component, which are covalently bonded to each other in a curing device.

[0053] "Target macromolecule" refers to a macromolecule synthesized from a mixture of reactive monomers, including monomers, macromonomers, prepolymers, crosslinking agents, initiators, additives, diluents, etc.

[0054] The term "polymerizable compound" refers to a compound containing one or more polymerizable groups (P). g Compounds. This term encompasses, for example, monomers, macromonomers, oligomers, prepolymers, crosslinking agents, etc.

[0055] A "polymerizable group" is a group capable of undergoing chain-growth polymerization (such as free radical polymerization, anionic polymerization, or cationic polymerization, preferably free radical polymerization), for example, a carbon-carbon double bond capable of polymerization under free radical polymerization initiation conditions. Non-limiting examples of polymerizable groups include (meth)acrylates, styrene groups, (meth)acrylamides, and vinyl groups. Preferably, the polymerizable group is selected from (meth)acrylates, (meth)acrylamides, N-vinyl lactams, N-vinylamides, ethylene carbonates, vinyl ethers, urethane, and styrene functional groups. More preferably, the polymerizable group is selected from (meth)acrylates and (meth)acrylamides. The polymerizable group can be unsubstituted or substituted. For example, in (meth)acrylamides, the nitrogen atom may be bonded to hydrogen, or the hydrogen may be replaced by an alkyl or cycloalkyl group (which itself may be further substituted).

[0056] Any type of free radical polymerization can be used, including but not limited to bulk, solution, suspension and emulsion, as well as any of the controlled free radical polymerization methods, such as stable free radical polymerization, nitro oxygen-mediated living polymerization, atom transfer radical polymerization, reversible addition-fragmentation chain transfer polymerization, organotellurium-mediated living radical polymerization, etc.

[0057] "Monomer" is a monofunctional molecule that can undergo chain-growth polymerization (specifically free radical polymerization) to form a repeating unit in the chemical structure of a target macromolecule. Some monomers have difunctional impurities that can act as crosslinking agents. "Hydrophilic monomer" is also a monomer that produces a clear single-phase solution when mixed with deionized water at a concentration of 5% by weight at 25°C. "Hydrophilic component" is a monomer, macromonomer, prepolymer, initiator, crosslinking agent, additive, or polymer that produces a clear single-phase solution when mixed with deionized water at a concentration of 5% by weight at 25°C. "Hydrophobic component" is a monomer, macromonomer, prepolymer, initiator, crosslinking agent, additive, or polymer that is slightly soluble or insoluble in deionized water at 25°C.

[0058] "Macromolecule" refers to organic compounds with a number average molecular weight greater than 1500 g / mol, and can be reactive or non-reactive.

[0059] A "macromonomer" is a macromolecule having a repeating unit in its chemical structure that can undergo chain-growth polymerization (and specifically free radical polymerization) to form a target macromolecule. Typically, the chemical structure of a macromonomer differs from that of the target macromolecule; in other words, the repeating units of the macromonomer's side groups differ from the repeating units of the target macromolecule or its backbone. The difference between a monomer and a macromonomer lies solely in one of the following: chemical structure, molecular weight, and the molecular weight distribution of the side groups. Therefore, and as used herein, patent literature occasionally defines a monomer as a polymerizable compound with a relatively low molecular weight of about 1,500 Daltons or less, which essentially includes some macromonomers. Specifically, monomethacryloyloxypropyl-terminated mono-n-butyl-terminated polydimethylsiloxanes (mPDMS) with molecular weight = 500 g / mol to 1500 g / mol and mono-(2-hydroxy-3-methacryloyloxypropyl)-propyl ether-terminated mono-n-butyl-terminated polydimethylsiloxanes (OH-mPDMS) can be referred to as monomers or macromonomers. Furthermore, patent literature occasionally defines a macromonomer as having one or more polymerizable groups, thus substantially extending the general definition of a macromonomer to include prepolymers. Therefore, and as used herein, bifunctional and multifunctional macromonomers, prepolymers, and crosslinking agents are used interchangeably.

[0060] "Components containing organosilicon" are monomers, macromonomers, prepolymers, crosslinking agents, initiators, additives or polymers having at least one siloxane bond in a reactive mixture, wherein the at least one siloxane bond is typically in the form of a silanoxy group, a siloxane group, a carbosiloxane group or a mixture thereof.

[0061] Examples of organosilicon-containing components that can be used in this invention are found in U.S. Patents 3,808,178, 4,120,570, 4,136,250, 4,153,641, 4,740,533, 5,034,461, 5,070,215, 5,244,981, 5,314,960, 5,331,067, 5,371,147, 5,760,100, 5,849,811, and 5... No. 962,548, No. 5,965,631, No. 5,998,498, No. 6,367,929, No. 6,822,016, No. 6,943,203, No. 6,951,894, No. 7,052,131, No. 7,247,692, No. 7,396,890, No. 7,461,937, No. 7,468,398, No. 7,538,146, No. 7,553,880, No. 7,572,841, No. 7,666 No. 921, No. 7,691,916, No. 7,786,185, No. 7,825,170, No. 7,915,323, No. 7,994,356, No. 8,022,158, No. 8,163,206, No. 8,273,802, No. 8,399,538, No. 8,415,404, No. 8,420,711, No. 8,450,387, No. 8,487,058, No. 8,568,626, No. 8,937,11 The patents referred to herein are patents 0, 8,937,111, 8,940,812, 8,980,972, 9,056,878, 9,125,808, 9,140,825, 9,156,934, 9,170,349, 9,217,813, 9,244,196, 9,244,197, 9,260,544, 9,297,928, 9,297,929, and European Patent 080539. The entire contents of these patents are incorporated herein by reference.

[0062] A "polymer" is a target macromolecule composed of repeating units of monomers used during polymerization.

[0063] A homopolymer is a polymer made from one monomer; a copolymer is a polymer made from two or more monomers; a terpolymer is a polymer made from three monomers. A block copolymer is composed of blocks or segments with different compositions. A diblock copolymer has two blocks. A triblock copolymer has three blocks. A comb-like or graft copolymer is made from at least one macromonomer.

[0064] A “repeating unit” is the smallest group of atoms in a polymer, which corresponds to the polymerization of a specific monomer or macromonomer.

[0065] An "initiator" is a molecule that can decompose into free radicals, which can then react with monomers to initiate free radical polymerization. Thermal initiators decompose at a rate depending on temperature; typical examples include azo compounds such as 1,1'-azobisisobutyronitrile and 4,4'-azobis(4-cyanopentanoic acid), peroxides such as benzoyl peroxide, tert-butyl peroxide, tert-butyl hydroperoxide, tert-butyl peroxybenzoate, dicumyl peroxide, and lauroyl peroxide, peracids such as peracetic acid and potassium persulfate, and various redox systems. Photoinitiators decompose via photochemical methods; typical examples include benzoyl, benzoin, acetophenone, benzophenone, camphorquinone, and mixtures thereof, as well as various monoacyl and diacylphosphine oxides and their combinations.

[0066] A "crosslinking agent" is a difunctional or polyfunctional monomer or macromonomer that can undergo free radical polymerization at two or more sites on a molecule to form branch points and polymer networks. Common examples include ethylene glycol dimethacrylate, tetraethylene glycol dimethacrylate, trimethylolpropane trimethacrylate, methylenebisacrylamide, and triallyl cyanurate.

[0067] "Prepolymer" is the reaction product of a monomer that contains residual polymerizable groups that can undergo further reactions to form a polymer.

[0068] A "polymer network" is a cross-linked macromolecule that can swell in a solvent but cannot dissolve. A "hydrogel" is a polymer network that swells in water or an aqueous solution, typically absorbing at least 10% by weight of water. An "organosilicon hydrogel" is a hydrogel made from at least one component containing organosilicon and at least one hydrophilic component. The hydrophilic component may also include a non-reactive polymer.

[0069] "Conventional hydrogels" refer to polymer networks made from components that do not contain any siloxy, siloxane, or carbosiloxane groups. Conventional hydrogels are prepared from reactive mixtures containing hydrophilic monomers. Examples include 2-hydroxyethyl methacrylate ("HEMA"), N-vinylpyrrolidone ("NVP"), N,N-dimethylacrylamide ("DMA"), or vinyl acetate. U.S. Patents 4,436,887, 4,495,313, 4,889,664, 5,006,622, 5,039,459, 5,236,969, 5,270,418, 5,298,533, 5,824,719, 6,420,453, 6,423,761, 6,767,979, 7,934,830, 8,138,290, and 8,389,597 disclose the formation of conventional hydrogels. Commercially available conventional hydrogels include, but are not limited to, etafilcon, genfilcon, hilafilcon, lenefilcon, nesofilcon, omafilcon, polymacon, and vifilcon, including all their variations.

[0070] "Organosilicon hydrogel" refers to a polymer network made of at least one hydrophilic component and at least one organosilicon-containing component. Examples of suitable types of hydrophilic components that may be present in the reactive mixture include (meth)acrylates, styrene, vinyl ethers, (meth)acrylamide, N-vinyl lactam, N-vinylamide, N-vinylimide, N-vinylurea, O-vinylcarbamate, O-vinyl carbonate, other hydrophilic vinyl compounds, and mixtures thereof. Organosilicon-containing components are well known and have been extensively described in patent literature. For example, an organosilicon-containing component may contain at least one polymerizable group (e.g., (meth)acrylate, styrene, vinyl ether, (meth)acrylamide, N-vinyl lactam, N-vinylamide, O-vinylcarbamate, O-vinyl carbonate, vinyl group, or mixtures thereof), at least one siloxane group, and one or more linking groups (which may be bonds) connecting one or more polymerizable groups to one or more siloxane groups. An organosilicon-containing component may, for example, contain 1 to 220 repeating siloxane units. An organosilicon-containing component may also contain at least one fluorine atom. Silicone hydrogel lenses may include a coating, and the coating may be made of the same or different material as the substrate.

[0071] Examples of silicone hydrogels include acquafilcon, asmofilcon, balafilcon, comfilcon, delefilcon, lehfilcon, serafilcon, enfilcon, fanfilcon, formofilcon, galyfilcon, lotrafilcon, narafilcon, riofilcon, samfilcon, senofilcon, somofilcon, and stenfilcon, including all their variants, and such as U.S. Patent Nos. 4,659,782, 4,659,783, 5,244,981, 5,314,960, 5,331,067, 5,371,147, 5,998,498, 6,087,415, 5,760,100, 5,776,999, 5,789,461, 5,849,811, 5,965,631, and 6,367,929 Numbers: 6,822,016, 6,867,245, 6,943,203, 7,247,692, 7,249,848, 7,553,880, 7,666,921, 7,786,185, 7,956,131, 8,022,158, 8,273,802, 8,399,538, 8,470,906, 8,450,387, 8,487,058, 8,507,577 Organosilicon hydrogels prepared in Nos. 8,637,621, 8,703,891, 8,937,110, 8,937,111, 8,940,812, 9,056,878, 9,057,821, 9,125,808, 9,140,825, 9,156,934, 9,170,349, 9,244,196, 9,244,197, 9,260,544, 9,297,928, 9,297,929, and WO 03 / 22321, WO 2008 / 061992 and US 2010 / 0048847. These patents are incorporated herein by reference in their entirety.

[0072] An "interpenetrating polymer network" comprises two or more networks that are at least partially interwoven at the molecular scale but not covalently bonded to each other and cannot be separated without hindering chemical bonding. A "semi-interpenetrating polymer network" comprises one or more networks and one or more polymers characterized by some mixing at the molecular level between at least one network and at least one polymer. A mixture of different polymers is a "polymer blend." Technically, a semi-interpenetrating network is a polymer blend, but in some cases, the polymers are entangled together such that they cannot be easily removed.

[0073] "Reactive components" are polymerizable compounds (such as monomers, macromonomers, oligomers, prepolymers, and crosslinking agents) in a reactive mixture (defined below), as well as any other components in the reactive mixture intended to remain substantially in the resulting polymer network after polymerization and all post-processing steps (such as extraction steps) and packaging steps have been completed. Reactive components can remain in the polymer network by covalent bonding, hydrogen bonding, electrostatic interactions, formation of an interpenetrating polymer network, or any other means. Components intended to be released from the polymer network are still considered "reactive components" during use. For example, pharmaceutical or nutritional components in contact lenses intended to be released during wear are considered "reactive components." Components intended to be removed from the polymer network during the manufacturing process (e.g., by extraction), such as diluents, are not "reactive components."

[0074] The terms "reactive mixture" and "reactive monomer mixture" refer to mixtures of components that, when mixed together and subjected to polymerization conditions, result in the formation of polymer networks (such as conventional hydrogels or silicone hydrogels), and biomedical devices, ophthalmic devices, and contact lenses made therefrom. Reactive mixtures may contain reactive components (such as monomers, macromonomers, prepolymers, crosslinking agents, and initiators), additives (such as wetting agents), polymers, dyes, light-absorbing compounds (such as UV absorbers), pigments, photochromic compounds, pharmaceutical compounds, and / or nutrient compounds, any of which may be polymerizable or non-polymerizable but are capable of remaining in the resulting biomedical device (e.g., a contact lens). Reactive mixtures may also contain other components intended to be removed from the device prior to use, such as diluents. It should be understood that a wide range of additives may be added based on the resulting contact lens and its intended use. The concentration of the components in a reactive mixture is expressed as a weight percentage of all reactive components in the reactive mixture (and therefore excluding diluents). When diluents are used, their concentrations are expressed as a percentage by weight based on the amount of all components in the reactive mixture, including the diluent.

[0075] The term “residue” used in conjunction with compounds or monomers refers to portions of such compounds or monomers that have been incorporated into at least a portion of the polymeric network structure after the polymerization of a reactive monomer mixture.

[0076] The term "silicone hydrogel contact lens" refers to a hydrogel contact lens made from at least one compound containing organosilicon. Compared to conventional hydrogels, silicone hydrogel contact lenses typically have improved oxygen permeability. Silicone hydrogel contact lenses utilize both their water and polymer contents to deliver oxygen to the eye.

[0077] The term "multifunctional" refers to a component having two or more polymerizable groups. The term "monofunctional" refers to a component having only one polymerizable group.

[0078] The term "halogen" or "halogenated group" refers to fluorine, chlorine, bromine, and iodine.

[0079] "alkyl" means a straight-chain or branched alkyl group containing a specified number of carbon atoms with optional substitutions. If no number is specified, the alkyl group (including any optional substituents on the alkyl group) may contain 1 to 16 carbon atoms. Preferably, the alkyl group contains 1 to 10 carbon atoms, alternatively 1 to 8 carbon atoms, alternatively 1 to 6 carbon atoms, or alternatively 1 to 4 carbon atoms. Examples of alkyl groups include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl and tert-butyl, pentyl, hexyl, heptyl, 3-ethylbutyl, etc. Examples of substituents on the alkyl group include one, two, or three groups independently selected from: hydroxyl, amino, amide, oxa, carboxyl, alkylcarboxyl, carbonyl, alkoxy, alkylthio, carbamate, carbonate, halogen, phenyl, benzyl, and combinations thereof. "Alkylene" refers to divalent alkyl groups, such as -CH2-, -CH2CH2-, -CH2CH2CH2-, -CH2CH(CH)3CH2-, and -CH2CH2CH2CH2-.

[0080] "Haloalkyl" refers to an alkyl group as defined above, substituted with one or more halogen atoms, wherein each halogen is independently F, Cl, Br, or I. The preferred halogen is F. Preferred haloalkyl groups contain 1 to 6 carbons, more preferably 1 to 4 carbons, and even more preferably 1 to 2 carbons. "Haloalkyl" includes perhaloalkyl groups, such as -CF3- or -CF2CF3-. "Haloalkylene" means a divalent haloalkyl group, such as -CH2CF2-.

[0081] “Cycloalkyl” refers to a cyclic hydrocarbon with optional substitutions containing a specified number of cyclic carbon atoms. If no number is specified, a cycloalkyl group may contain 3 to 12 cyclic carbon atoms. Preferred are C3-C8 cycloalkyl groups, C3-C7 cycloalkyl groups, more preferably C4-C7 cycloalkyl groups, and even more preferably C5-C6 cycloalkyl groups. Examples of cycloalkyl groups include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, and cyclooctyl. Examples of substituents on a cycloalkyl group include one, two, or three groups independently selected from: alkyl, hydroxyl, amino, amide, oxa, carbonyl, alkoxy, alkylthio, amide, carbamate, carbonate, halogen, phenyl, benzyl, and combinations thereof. “Cycloalkylene” means a divalent cycloalkyl group, such as 1,2-cyclohexylene, 1,3-cyclohexylene, or 1,4-cyclohexylene.

[0082] "Heterocyclic alkyl" refers to a cycloalkyl ring or ring system as defined above, in which at least one ring carbon has been replaced by a heteroatom selected from nitrogen, oxygen, and sulfur. The heterocyclic alkyl ring may optionally be fused to or otherwise connected to other heterocyclic alkyl rings and / or non-aromatic hydrocarbon rings and / or benzene rings. Preferred heterocyclic alkyl groups have 5 to 7 members. More preferably, they have 5 or 6 members. Heterocyclic alkylene refers to a divalent heterocyclic alkyl group.

[0083] "Aryl" refers to an optionally substituted aromatic hydrocarbon ring system containing at least one aromatic ring. An aryl group contains a specified number of ring carbon atoms. If no number is indicated, an aryl group may contain 6 to 14 ring carbon atoms. The aromatic ring may optionally be fused or otherwise attached to other aromatic or non-aromatic hydrocarbon rings. Examples of aryl groups include phenyl, naphthyl, and biphenyl. Preferred examples of aryl groups include phenyl. Examples of substituents on the aryl group include one, two, or three groups independently selected from: alkyl, hydroxyl, amino, amide, oxa, carboxyl, alkylcarboxyl, carbonyl, alkoxy, alkylthio, carbamate, carbonate, halogroup, phenyl, benzyl, and combinations thereof. "Arylene" means a divalent aryl group, such as 1,2-phenylene, 1,3-phenylene, or 1,4-phenylene.

[0084] "Heteroaryl" refers to an aryl ring or ring system as defined above, in which at least one ring carbon atom has been replaced by a heteroatom selected from nitrogen, oxygen, and sulfur. Heteroaryl rings may be fused or otherwise attached to one or more heteroaryl rings, aromatic or non-aromatic hydrocarbon rings, or heterocyclic alkyl rings. Examples of heteroaryl groups include pyridinyl, furanyl, and thiopheneyl. "Heteroarylene" refers to a divalent heteroaryl group.

[0085] "Alkoxy" refers to an alkyl group that is connected to the parent molecule via an oxygen bridge. Examples of alkoxy groups include, for example, methoxy, ethoxy, propoxy, and isopropoxy. "Alkthio" refers to an alkyl group that is connected to the parent molecule via a sulfur bridge. Examples of alkthio groups include, for example, methylthio, ethylthio, n-propylthio, and isopropylthio. "Aryloxy" refers to an aryl group that is connected to the parent molecule via an oxygen bridge. Examples include phenoxy. "Cycloalkoxy" refers to a cycloalkyl group that is connected to the parent molecule via an oxygen bridge.

[0086] "Alkylamine" refers to an alkyl group that is attached to the parent molecule via a -NH bridge. Alkylene amines refer to divalent alkylamine groups, such as -CH2CH2NH-.

[0087] "Siloxane" refers to a structure having at least one Si-O-Si bond. Therefore, for example, a siloxane group means a group having at least one Si-O-Si group (i.e., a siloxane group), and a siloxane compound means a compound having at least one Si-O-Si group. "Siloxane" encompasses monomers (e.g., Si-O-Si) as well as oligomeric / polymeric structures (e.g., -[Si-O)). n - where n is 2 or greater). Each silicon atom in the siloxane group is independently selected by R. A Group substitution (where R) A As defined in options (b) to (i) of equation A, to complete its valence.

[0088] "Silyl" refers to the structure of formula R3Si-, and "siloxy" refers to the structure of formula R3Si-O-, wherein each R in silyl or siloxy is independently selected from trimethylsiloxy, C1-C8 alkyl (preferably C1-C3 alkyl, more preferably ethyl or methyl) and C3-C8 cycloalkyl.

[0089] "Alkyloxy group" refers to a compound with the general formula -(alkylene-O-). p - or -(O-alkylene) p -A group, wherein the alkylene group is as defined above, and p is 1 to 200, or 1 to 100, or 1 to 50, or 1 to 25, or 1 to 20, or 1 to 10, wherein each alkylene group is independently and optionally substituted by one or more groups independently selected from hydroxyl, halogroup (e.g., fluorine), amino, amide, ether, carbonyl, carboxyl, and combinations thereof. If p is greater than 1, each alkylene group may be the same or different, and the alkene oxygen group may be block or random. When the alkene oxygen group forms a terminal group in the molecule, the terminal of the alkene oxygen group may be, for example, a hydroxyl or alkoxy group (e.g., HO-[CH2CH2O)). p -or CH3O-[CH2CH2O] pExamples of alkene oxides include poly(ethylene oxide), poly(propylene oxide), poly(butylene oxide), and poly(ethylene oxide-co-propylene oxide).

[0090] "Oxyalkylene" refers to an alkylene group as defined above, wherein one or more non-adjacent CH2 groups have been replaced by an oxygen atom, such as -CH2CH2OCH(CH3)CH2-. "Thioalkylene" refers to an alkylene group as defined above, wherein one or more non-adjacent CH2 groups have been replaced by a sulfur atom, such as -CH2CH2SCH(CH3)CH2-.

[0091] The term "linking group" refers to the portion that connects a polymerizable group to a parent molecule. The linking group can be any portion compatible with the compound, which is part of the compound and does not undesirably interfere with the polymerization of the compound, and is stable under polymerization conditions and under conditions used for processing and storing the final product. For example, the linking group can be a bond, or it can include one or more alkylene groups, haloalkylene groups, amides, amines, alkylamines, carbamates, esters (-CO2-), arylenes, heteroarylenes, cycloalkylenes, heterocycloalkylenes, alkoxy groups, oxaalkylenes, thiaalkylenes, haloalkoxy groups (alkoxy groups substituted with one or more halogroups, such as -OCF2-, -OCF2CF2-, -OCF2CH2-), siloxanes, siloxanes, or combinations thereof. The linking group may optionally be substituted with one or more substituent groups. Suitable substituent groups may include those independently selected from alkyl, halogen (e.g., fluorine), hydroxyl, HO-alkeneoxy, MeO-alkeneoxy, siloxane, silanoxy, silanoxy-alkeneoxy-, silanoxy-alkyl-alkeneoxy- (wherein more than one alkeneoxy group may be present, and where each methylene group in the alkylene and alkeneoxy groups is independently and optionally substituted with a hydroxyl group), ether, amine, carbonyl, urethane, and combinations thereof. Linking groups may also be replaced by polymerizable groups such as (meth)acrylates (in addition to the polymerizable groups to which the linking group is attached).

[0092] Preferred linking groups include C1-C8 alkylene (preferably C2-C6 alkylene), C1-C8 oxaalkylene (preferably C2-C6 oxaalkylene), and ethoxide (preferably (CH2CH2O)). p (where p=1-6), C1-C8 thiazide, C1-C8 alkylene-carboxylate-C1-C8 alkylene, C1-C8 alkylene-amide-C1-C8 alkylene, and C1-C8 alkylene-amine-C1-C8 alkylene, each of which is optionally substituted by one or two groups independently selected from hydroxyl and silanoxy.

[0093] When the linking group is composed of a combination of moieties as described above (e.g., alkylene and cycloalkylene), the moieties can be present in any order. For example, if in formula A below, L indicates -alkylene-cycloalkyl-, then P g -L can be P g -alkylene-cycloalkylene-, or P g -cycloalkylene-alkylene-. Nevertheless, the order listed indicates the terminal polymerizable groups (P) attached from the linking group. g The preferred order in which the moieties begin to appear in the compound. For example, if in formula A, L indicates -alkylene-cycloalkylene-, then P g -L is preferably P g -alkylene-cycloalkylene-.

[0094] The term "electron-withdrawing group" (EWG) refers to a chemical group that withdraws electrons from the atom or group of atoms to which it is attached. Examples of EWGs include, but are not limited to, cyano, amide, ester, ketone, or aldehyde groups. A preferred EWG is a cyano (CN).

[0095] The term "visible light absorbing compound" refers to a chemical material that absorbs light within the visible spectrum (e.g., in the range of 380 nm to 760 nm). "High-energy radiation absorber," "UV / HEV absorber," or "high-energy light absorbing compound" refers to a chemical material that absorbs various wavelengths of ultraviolet light, high-energy visible light, or both. A material's ability to absorb certain wavelengths of light can be determined by measuring its ultraviolet / visible transmission or absorption spectrum.

[0096] As used herein, if the transmittance of a device or material is expressed as a percentage over a specific wavelength range, it should be understood that the device or material exhibits that percentage of transmittance at all wavelengths within that range.

[0097] When the compounds described herein contain an alkene double bond or other geometrically asymmetric center, and unless otherwise specified, the compounds are intended to include cis, trans, Z-, and E-configurations. Likewise, all tautomers and salt forms are intended to be included.

[0098] The term "optional substituent" means that the hydrogen atom in the following portion is optionally replaced by a substituent. Any substituent that is sterically useful at the substitution site and synthetically feasible can be used. The identification of suitable optional substituents is entirely within the capabilities of a person skilled in the art. Examples of "optional substituents" include, but are not limited to, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 thioalkyl, C3-C7 cycloalkyl, aryl, haloyl, hydroxyl, amino, and NR. 4 R 5 Benzyl, SO3H, SO3Na or -YP g , where R4 and R 5 Independently, it is H or C1-C6 alkyl, Y is a linking group; and P g These are polymerizable groups. The aforementioned substituents may optionally be replaced by other substituents (unless otherwise specified, they are preferably not further substituted). For example, alkyl groups may be replaced by halogenated groups (e.g., to produce CF3).

[0099] "Visible light absorption maximum" refers to one or more wavelengths within the visible light range (380 nm to 760 nm) where an absorption peak exists. Materials can exhibit multiple absorption peaks within the visible light range, in which case the material has multiple visible light absorption maximums. For materials exhibiting multiple visible light absorption maximums, the peak displaying the highest absorbance among these maximums is called the "visible light absorption maximum." This definition also covers materials that exhibit an overall absorption maximum outside the visible light range (such as in the UV region).

[0100] The terms "photostable," "photostability," or similar expressions mean that a compound (which, when measured, may optionally be embedded in an ophthalmic device, such as a hydrogel contact lens, and optionally measured inside or outside a blister pack or vial) exhibits a loss of absorbance of no more than 20% at the maximum absorbance of visible light after exposure to light under conditions such as those described in the "Q1B Photostability Test for New Drug Substances and Products" of the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) Guidelines published in November 1996. Preferably, under the ICH Photostability Guidelines, an Option 2 light source is used, preferably in a photostable chamber controlled at 25°C / Amb RH, at a concentration of 1.5192 × 10⁻⁶. 6 Estimated light exposure in Lux hours (168.8 hours of exposure time) and 259.4 watt-hours / m² 2 The estimated ultraviolet (UV) irradiation exposure (16.2 hours) was performed. After exposure, the UV / Vis spectra of the samples were collected and compared with the spectra of the samples before exposure. The change in the maximum visible light absorption of the lens relative to the value observed before exposure was calculated. For example, if the absorbance at the maximum visible light absorption was 4 absorbance units before exposure and 2 absorbance units after exposure, the absorbance loss is 50%. In this invention, the absorbance loss after light exposure is preferably no more than 15%, or no more than 10%, or no more than 7%, or no more than 5%, or no more than 4%, or no more than 3%, or no more than 2%, or no more than 1%, or no more than 0.5%, or no more than 0.1%.

[0101] The term “more photostable than macular pigment” or similar expression means that a compound (which, when tested, may optionally be embedded in an ophthalmic device, such as a hydrogel contact lens, and may optionally be measured inside or outside a blister pack) exhibits less loss of absorbance at the maximum visible light absorption than that observed with macular pigment after exposure to light, for example, in accordance with the ICH photostable guidelines described above.

[0102] The term full width at half maximum (FWHM) refers to the width (in nanometers) of an absorption peak at half its maximum intensity.

[0103] The terms "thermally stable," "thermally stable," or similar expressions mean that a compound (which, when measured, may optionally be embedded in an ophthalmic device, such as a hydrogel contact lens, and optionally measured inside or outside a blister pack or vial) exhibits an absorbance loss of no more than 20% at the maximum visible absorption after one month of exposure in a stability chamber at 89°C, as described in the following example. After exposure, the UV / Vis spectra of the sample are collected and compared with the spectra of the sample before exposure. The change in the maximum visible absorption of the lens relative to the value observed before exposure is calculated. By way of example, if the absorbance at the maximum visible absorption was 4 absorbance units before exposure and 2 absorbance units after exposure, the absorbance loss is 50%. In this invention, the absorbance loss after thermal exposure is preferably no more than 20%, or no more than 15%, or no more than 12%, or no more than 10%, or no more than 5%, or no more than 4%, or no more than 3%, or no more than 2%, or no more than 1%, or no more than 0.5%, or no more than 0.1%.

[0104] The term “more thermally stable than macular pigment” or similar expression means that a compound (which, when tested, may optionally be embedded in an ophthalmic device, such as a hydrogel contact lens, and may optionally be measured inside or outside a blister pack) exhibits less loss of absorbance at the maximum visible light absorption after thermal exposure as described above than that observed with macular pigment.

[0105] Unless otherwise specified, ratios, percentages, parts, etc. are by weight.

[0106] Unless otherwise specified, numerical ranges, such as "2 to 10" or "

[0107] ophthalmic devices

[0108] In one aspect, the present invention provides an ophthalmic device that is a free radical reaction product of a reactive mixture comprising, substantially comprising, or comprising: one or more monomers suitable for manufacturing an ophthalmic device; a first visible light filtering compound having a maximum visible light absorption between 430 nm and 480 nm and a full width at half maximum (FWHM) of at least 35 nm and at most 150 nm at the maximum visible light absorption, wherein the compound is photostable, and wherein the photochemical compound has a concentration of at least 7740 L·mol⁻¹. -1 .cm -1 The mixture of reactive monomers may also contain a third visible light filter compound. The second visible light filter compound has a maximum visible light absorption between 480 nm and 530 nm and a full width at half maximum (FWHM) of at least 50 nm and at most 150 nm.

[0109] As described above, in one aspect, the present invention provides an ophthalmic device comprising a free radical reaction product containing a first visible light filtering compound and a second visible light filtering compound. The first visible light filtering compound used in the present invention substantially mimics the visible light absorption characteristics of macular pigment. However, the first visible light filtering compound is more photostable than macular pigment, and therefore, unlike macular pigment, it can be used to manufacture ophthalmic devices. The first visible light filtering compound may also be more thermally stable than macular pigment.

[0110] Therefore, the first visible light filtering compound of the present invention may have a maximum visible light absorption between 430 nm and 480 nm and a full width at half maximum (FWHM) of at least 35 nm and at most 150 nm. The compound may be photostable (e.g., when measured according to ICH Guideline Q1B). The compound may be more photostable than macular pigment.

[0111] The first visible light filter compound may have a maximum visible light absorption value between 430 nm and 480 nm, or between 440 nm and 470 nm, or between 450 nm and 470 nm, or between 460 nm and 470 nm.

[0112] The first visible light filtering compound may exhibit a visible light absorption maximum (FWHM) of at least 35 nm, or at least 40 nm, or at least 45 nm, or at least 55 nm, or at least 60 nm. The first visible light filtering compound may exhibit an FWHM of at most 150 nm, or at most 125 nm, or at most 100 nm, or at most 95 nm, or at most 90 nm, or at most 85 nm, or at most 80 nm, or at most 75 nm, or at most 70 nm. The FWHM of the first visible light filtering compound at the visible light absorption maximum may be in the range of 35 nm to 150 nm, or 35 nm to 100 nm, or 40 nm to 95 nm, or 45 nm to 90 nm, or 55 nm to 80 nm, or 60 nm to 75 nm, or 60 nm to 70 nm, or 62 nm to 67 nm.

[0113] The first visible light filtering compound of the present invention exhibits a molar extinction coefficient at the maximum visible light absorption of at least 5000, or at least 5500, or at least 6000, or at least 6500, or at least 7000, or at least 7500, or at least 7740, or at least 7800, or at least 8000, or at least 9000, or at least 10,000, or at least 11,000, or at least 12,000, or at least 12,500. The molar extinction coefficient is an inherent property of the material and can be calculated from absorbance data using the Beer-Lambert law. The molar extinction coefficient is typically expressed in L.mol. -1 .cm -1 The unit is indicated.

[0114] The first visible light filtering compound of the present invention may be a compound of formula I:

[0115]

[0116] Where m and n are independently 0, 1, 2, 3, or 4; T is a bond, O, or NR. 6 , where R 6 It is H, C1-C6 alkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, or YP g R is H, C1-C8 alkyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; Y is a linking group; P g It is a polymerizable group; R 1 and R 2 When present, it is independently C1-C6 alkyl, C1-C6 alkoxy, C1-C6 thioalkyl, C3-C7 cycloalkyl, aryl (preferably unsubstituted phenyl or phenyl substituted with alkyl or halogroup), halogroup, hydroxyl, amino, NR 3 R 4, benzyl, SO3H, or SO3M (M is a monovalent cation, such as sodium or potassium ion), where R 3 and R 4 Independently H or C1-C6 alkyl, or two adjacent R 1 Or R 2 The groups combine with the carbon atoms to which they are attached to form cycloalkyl or aryl rings; and EWG is an electron-withdrawing group.

[0117] The compound of formula I preferably contains one or two YP. g More preferably, the compound contains a YP group. g Group.

[0118] Compounds of Formula I may include compounds of Formula I-1, wherein m and n are independently 0 or 1, or alternatively both 0.

[0119] Compounds of formula I and I-1 may include compounds of formula I-2, wherein the compounds of formula I-2 are compounds of formula I or I-1 in which n is 0 and m is 1.

[0120] Compounds of Formula I, Formula I-1, and Formula I-2 may include compounds of Formula I-3, wherein n is 0, m is 1, and R 1 Compounds of formula I, I-1 or I-2 that are C1-C6 alkyl or C1-C6 alkoxy.

[0121] Compounds of Formula I, I-1, I-2, and I-3 may include compounds of Formula I-4, which are compounds of Formula I, I-1, I-2, or I-3 wherein R is H or a C1-C8 alkyl group. Preferably, R is a C1-C6 alkyl group.

[0122] Compounds of Formula I, Formula I-1, Formula I-2, Formula I-3, and Formula I-4 may include compounds of Formula I-5, wherein T is NR. 6 And R 6 Compounds of formula I, I-1, I-2, I-3, or I-4 that are H or C1-C6 alkyl groups. Preferably, R 6 For H.

[0123] Compounds of Formula I, Formula I-1, Formula I-2, Formula I-3, Formula I-4, and Formula I-5 may include compounds of Formula I-6, wherein P is a compound of Formula I-6. gThe polymerizable group, each time appearing independently, is a compound of formula I, I-1, I-2, I-3, I-4, or I-5, consisting of styrene, vinyl carbonate, vinyl ether, vinyl carbamate, N-vinyl lactam, N-vinylamide, (meth)acrylate, or (meth)acrylamide. The polymerizable group allows the compounds of the present invention to form covalent bonds when reacting with monomers, crosslinking agents, and other components commonly used in the manufacture of polymer devices. The compatibility of the compound with reactive mixtures can be controlled by selecting the polymerizable group (and linking group). Preferred polymerizable groups include (meth)acrylate or (meth)acrylamide. More preferably, the polymerizable group is methacrylate.

[0124] Compounds of formulas I, I-1, I-2, I-3, I-4, I-5, and I-6 may include compounds of formula I-7, which are compounds of formulas I, I-1, I-2, I-3, I-4, I-5, and I-6 wherein Y (the linking group) is an alkylene, cycloalkylene, heterocycloalkylene, aryl (e.g., phenylene), heteroaryl, oxaalkylene, alkylene-amide-alkylene, alkylene-amine-alkylene, or a combination of any of the above groups. Preferred linking groups include C1-C8 alkylene (e.g., ethylene or propyleneene), C1-C8 oxaalkylene, C1-C8 alkylene-amide-C1-C8 alkylene, and C1-C8 alkylene-amine-C1-C8 alkylene. C1-C8 alkylene, especially ethylene (-CH2CH2-), is particularly preferred. When T is O in the compound of formula I, it is preferable to have a carbon atom that hinders the linking group to which O is attached. For example, if T is O and Y is an alkylene group, then the preferred alkylene group is -C(R). H )2(CH2) x -, where R H Independently C1-C6 alkyl (preferably independently methyl or ethyl) and x is 1 to 5.

[0125] Compounds of formulas I, I-1, I-2, I-3, I-4, I-5, I-6, and I-7 may include compounds of formula I-8, wherein T is a bond or NR. 6 (Preferably NH) compounds of formula I, I-1, I-2, I-3, I-4, I-5, I-6 or I-7.

[0126] Compounds of Formula I, I-1, I-2, I-3, I-4, I-5, I-6, I-7, and I-8 may include compounds of Formula I-9, which are compounds of Formula I, I-1, I-2, I-3, I-4, I-5, I-6, I-7, or I-8 wherein the EWG is a cyano, amide, ester, ketone, or aldehyde. Preferably, the EWG is a cyano.

[0127] The first visible light filtering compound of the present invention may have formula IA:

[0128]

[0129] in:

[0130] T represents a bond, O, or NR. 6 , where R 6 It can be H, C1-C6 alkyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl;

[0131] R is H, C1-C8 alkyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl;

[0132] Y is a linking group;

[0133] P g It is a polymerizable group;

[0134] R 7 H, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 thioalkyl, C3-C7 cycloalkyl, aryl (preferably unsubstituted phenyl or phenyl substituted with alkyl or halogen), halogen, hydroxyl, amino, NR 3 R 4 , benzyl, SO3H or SO3M (M is a monovalent cation, such as sodium ion or potassium ion), where R 3 and R 4 Independently H or C1-C6 alkyl; and

[0135] EWG is an electron-withdrawing group.

[0136] Compounds of formula IA may include compounds of formula IA-1, wherein R is a compound of formula IA-1. 7 Compounds of formula IA with H.

[0137] Compounds of formula IA may include compounds of formula IA-2, wherein R is a compound of formula IA-2. 7 Compounds of formula IA that are C1-C6 alkyl, C1-C6 alkoxy, or C1-C6 thioalkyl.

[0138] Compounds of formula IA and IA-2 may include compounds of formula IA-3, wherein R is a compound of formula IA-3. 7 Compounds of formula IA or IA-2 that are C1-C6 alkoxy groups (such as ethoxy or methoxy, preferably methoxy).

[0139] Compounds of formula IA, IA-1, IA-2, and IA-3 may include compounds of formula IA-4, which are compounds of formula IA, IA-1, IA-2, or IA-3 wherein R is H or a C1-C8 alkyl group. Preferably, R is a C1-C6 alkyl group, such as methyl, ethyl, n-propyl, isopropyl, n-butyl, tert-butyl, or sec-butyl. Preferably, R is n-propyl or n-butyl.

[0140] Compounds of formula IA, IA-1, IA-2, IA-3, and IA-4 may include compounds of formula IA-5, wherein T is NR. 6 And R 6 Compounds of formula IA, IA-1, IA-2, IA-3, or IA-4 that are H or C1-C6 alkyl groups. Preferably, R 6 For H.

[0141] Compounds of formulas IA, IA-1, IA-2, IA-3, IA-4, and IA-5 may include compounds of formula IA-6, wherein P is a compound of formula IA-6. g The polymerizable group, each time it appears, independently includes compounds of formula IA, IA-1, IA-2, IA-3, IA-4, or IA-5 of styrene, vinyl carbonate, vinyl ether, vinyl carbamate, N-vinyl lactam, N-vinylamide, (meth)acrylate, or (meth)acrylamide. Preferred polymerizable groups include (meth)acrylate or (meth)acrylamide. More preferably, the polymerizable group is methacrylate.

[0142] Compounds of formulas IA, IA-1, IA-2, IA-3, IA-4, IA-5, and IA-6 may include compounds of formula IA-7, which are compounds of formulas IA, IA-1, IA-2, IA-3, IA-4, IA-5, and IA-6 wherein Y (the linking group) is an alkylene, cycloalkylene, heterocycloalkylene, aryl (e.g., phenylene), heteroaryl, oxaalkylene, alkylene-amide-alkylene, alkylene-amine-alkylene, or any combination thereof. Preferred linking groups include C1-C8 alkylene (e.g., ethylene or propyleneene), C1-C8 oxaalkylene, C1-C8 alkylene-amide-C1-C8 alkylene, and C1-C8 alkylene-amine-C1-C8 alkylene. Particularly preferred are C1-C8 alkylene, especially ethylene (-CH2CH2-). When T is O in a compound of formula IA, it is preferable to have a carbon atom that hinders the linking group to which O is attached. For example, if T is O and Y is an alkylene group, then the preferred alkylene group is -C(R). H )2(CH2) x -, where R H Independently C1-C6 alkyl (preferably independently methyl or ethyl) and x is 1 to 5.

[0143] Compounds of formulas IA, IA-1, IA-2, IA-3, IA-4, IA-5, IA-6, and IA-7 may include compounds of formula IA-8, wherein T is a bond or NR. 6 (Preferably NH) compounds of the formula IA, IA-1, IA-2, IA-3, IA-4, IA-5, IA-6 or IA-7.

[0144] Compounds of formula IA, IA-1, IA-2, IA-3, IA-4, IA-5, IA-6, IA-7, and IA-8 may include compounds of formula IA-9, which are compounds of formula IA, IA-1, IA-2, IA-3, IA-4, IA-5, IA-6, IA-7, or IA-8 wherein the EWG is a cyano group, amide, ester, ketone group, or aldehyde. Preferably, the EWG is a cyano group.

[0145] Specific examples of the first visible light filtering compound of the present invention are shown in Table A.

[0146] Table A

[0147]

[0148] Compounds of Formula I can be prepared as described in the pre-authorization disclosure US20220194944A1. For example, the compounds can be prepared from N-substituted acridinones using triphenylphosphine dibromide. Triphenylphosphine dibromide can be generated "in situ" by adding bromine to triphenylphosphine in a suitable solvent. The addition of the N-substituted acridinone after complete consumption of bromine avoids the potential oxidation of the N-substituted acridinone and forms the desired product in high yield while significantly reducing the formation of byproducts. An exemplary synthesis of compounds of Formula I is shown in Scheme A.

[0149]

[0150] The reactive mixture used to prepare the ophthalmic device of the present invention contains, in addition to the first visible light filtering compound, a second visible light filtering compound having a maximum visible light absorption value between 480 nm and 530 nm or between 490 nm and 520 nm, and a full width at half maximum (FWHM) of at least 50 nm and at most 150 nm, or at least 70 nm and at most 130 nm, or at least 80 nm and at most 120 nm.

[0151] The second visible light filtering compound of the present invention may be a compound of formula II:

[0152]

[0153] (II)

[0154] Where Y is a linking group, and P g It is a polymerizable group.

[0155] Preferred linking groups in the second visible light filtering compound of Formula II include alkylene, oxaalkylene, alkoxide, or combinations thereof. More preferred linking groups are alkylene and oxaalkylene segments having five to ten carbon atoms, as well as ethylene oxygen segments (CH2CH2O). p Where p is three to six. These preferred linking groups provide good solubility of the second visible light filtering compound of Formula II in reactive monomer mixtures and acceptable photochemical, thermal, and hydrolytic stability for ophthalmic devices. Preferred polymerizable groups in the second visible light filtering compound of Formula II include styrene, vinyl carbonate, vinyl ether, vinyl carbamate, N-vinyl lactam, N-vinylamide, (meth)acrylate, or (meth)acrylamide. More preferably, p g It consists of (meth)acrylates and (meth)acrylamide. The most preferred P... g It is (meth)acrylate.

[0156] Specific examples of the second visible light filtering compound of the present invention are shown in Table B-1. A preferred second visible light filtering compound is 2-(2-(2-((9,10-dioxo-9,10-dihydroanthracene-1-yl)amino)ethoxy)ethoxy)ethyl methacrylate.

[0157] Table B-1

[0158]

[0159] The reactive mixture used to prepare the ophthalmic device of the present invention may contain a third visible light filtering compound in addition to the first and second visible light filtering compounds, the third visible light filtering compound having one or more visible light absorption maximum values ​​between 550 nm and 660 nm. The third visible light filtering compound may be added to alter the ultraviolet-visible absorption or transmission spectrum of the ophthalmic device.

[0160] The third visible light filtering compound can be a compound of formula III:

[0161]

[0162] (III)

[0163] Where Y is an independent linking group each time it appears and P g It is an independent polymerizable group each time it appears.

[0164] Compounds of Formula III may include compounds of Formula III-1, which are compounds of Formula III, wherein Y, each time it appears, is independently alkylene, cycloalkylene, heterocycloalkylene, aryl, heteroaryl, oxaalkylene, alkylene-amide-alkylene, alkylene-amine-alkylene, or a combination thereof.

[0165] Compounds of formula III and III-1 may include compounds of formula III-2, which are compounds of formula III or III-1, wherein P g Each occurrence independently includes styrene, vinyl carbonate, vinyl ether, vinyl carbamate, N-vinyl lactam, N-vinylamide, (meth)acrylate, or (meth)acrylamide. Preferably, P g Each occurrence contains (meth)acrylate, more preferably methacrylate.

[0166] The third visible light filtering compound of Formula III may include 1,4-bis[2-methacryloyloxyethylamino]-9,10-anthraquinone or ((9,10-dioxo-9,10-dihydroanthracene-1,4-diyl)bis(azadiyl))bis(ethane-2,1-diyl)bis(methyl 2-acrylate) (RB247), (((9,10-dioxo-9,10-dihydroanthracene-1,4-diyl)bis(azadiyl))bis(4,1-phenylene))bis(ethane-2,1-diyl)bis(2-methacrylate) (RB246), (9, 10-Dioxo-9,10-dihydroanthracene-1,4-diyl)bis(azadiyl))bis(ethane-2,1-diyl))bis(oxy))bis(ethane-2,1-diyl))bis(oxy))bis(ethane-2,1-diyl)bis(methyl 2-acrylate) or N,N'-(((((((9,10-dioxo-9,10-dihydroanthracene-1,4-diyl)bis(azadiyl))bis(ethane-2,1-diyl))bis(oxy))bis(ethane-2,1-diyl))bis(oxy))bis(ethane-2,1-diyl))bis(oxy))bis(ethane-2,1-diyl))diacrylamide. Some third visible light filtering compounds of Formula III are commercially available and / or can be readily prepared by those skilled in the art, for example as described in US4997897, the entire text of which is incorporated herein by reference.

[0167] The third visible light filtering compound may alternatively be a compound having the chemical structure of Formula IV:

[0168]

[0169] (IV)

[0170] Where R 1 It is H, methyl or Br and R 2 Each time it appears independently, it is C1-C6 alkyl, C1-C6 alkoxy, C1-C6 thioalkyl, C3-C7 cycloalkyl, aryl (preferably unsubstituted phenyl or phenyl substituted with alkyl or halogroup), benzyl, halogroup, hydroxyl, amino, NR 3 R 4 SO3H or SO3M (M is a monovalent cation, such as sodium or potassium ion), where R 3 and R 4 Independently H or C1-C6 alkyl, or two adjacent R 2 The groups combine with the carbon atoms to which they are attached to form cycloalkyl or aryl rings.

[0171] The third visible light filtering compound of Formula IV includes sodium 1-amino-4-((4-(2-bromoacrylamido)-2-sulfonylphenyl)amino)-9,10-dioxo-9,10-dihydroanthracene-2-sulfonate (IMT Blue), sodium 4-((4-acrylamidophenyl)amino)-1-amino-9,10-dioxo-9,10-dihydroanthracene-2-sulfonate, sodium 1-amino-4-((4-methylacrylamidophenyl)amino)-9,10-dioxo-9,10-dihydroanthracene-2-sulfonate, or combinations thereof. A preferred third visible light filtering compound is sodium 1-amino-4-((4-(2-bromoacrylamido)-2-sulfonylphenyl)amino)-9,10-dioxo-9,10-dihydroanthracene-2-sulfonate having the following chemical structure:

[0172]

[0173] The third visible light filtering compound may optionally (or otherwise) contain a high-energy visible light filter that limits the transmittance of the device in the 400 nm to 409 nm wavelength range to between 0% and 70%, or between 0.2% and 70%, or between 0.5% and 70%, or between 1% and 70%. The high-energy visible light filter may limit the transmittance of the device in the 400 nm to 409 nm wavelength range to 0%, or at least 0.2%, or at least 0.5%, or at least 1%, or at least 2%, or at least 3%, or at least 4% and at most 60%, or at most 50%, or at most 40%, or at most 30%, or at most 20%, or at most 15%, or at most 10%. High-energy visible light filters can limit the transmittance of a device in the wavelength range of 400nm to 409nm to between 0% and 40%, or between 0.2% and 35%, or between 2% and 30%, or between 4% and 25%, or between 5% and 20%, or between 0.2% and 20%.

[0174] High-energy visible light filters may contain at least one polymerizable group.

[0175] High-energy visible light filters can be compounds of formula V:

[0176]

[0177] (V)

[0178] in:

[0179] m and n are independently 0, 1, 2, 3 or 4;

[0180] T represents a bond, O, or NR;

[0181] Y is a linking group;

[0182] P gIt is a polymerizable group;

[0183] R is independently H, C1-C6 alkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, or YP each time it appears. g ;and

[0184] R 1 and R 2 When present, it is independently C1-C6 alkyl, C1-C6 alkoxy, C1-C6 thioalkyl, C3-C7 cycloalkyl, aryl (preferably unsubstituted phenyl or phenyl substituted with alkyl or halogroup), halogroup, hydroxyl, amino, NR 3 R 4 , or benzyl, wherein R 3 and R 4 Independently H or C1-C6 alkyl, or two adjacent R 1 Or R 2 The groups, together with the carbon atoms they are attached to, combine to form cycloalkyl or aryl rings. Compounds of formula V preferably contain one or two YP groups. g More preferably, the compound contains a YP group. g Group.

[0185] Compounds of formula V may include compounds of formula V-1, wherein m and n are independently 0 or 1 or alternatively both 0.

[0186] Compounds of formulas V and V-1 may include compounds of formula V-2, wherein m is 1 and R 1 Compounds of formula V or V-1 that are C1-C6 alkyl, preferably ethyl or methyl.

[0187] Compounds of formulas V, V-1, and V-2 may include compounds of formula V-3, wherein n is 1 and R 2 Compounds of formula V, V-1 or V-2 that are C1-C6 alkyl, preferably ethyl or methyl.

[0188] Compounds of formulas V, V-1, V-2, and V-3 may include compounds of formula V-4, which are compounds of formulas V, V-1, V-2, or V-3 wherein R is H or a C1-C6 alkyl group. Preferably, R in group T is H.

[0189] Compounds of formulas V, V-1, V-2, V-3, and V-4 may include compounds of formula V-5, wherein P is a compound of formula V-5. gThe polymerizable group, each time it appears, independently includes compounds of formula V, V-1, V-2, V-3, or V-4, consisting of styrene, vinyl carbonate, vinyl ether, vinyl carbamate, N-vinyl lactam, N-vinylamide, (meth)acrylate, or (meth)acrylamide. The polymerizable group allows the compounds of the present invention to form covalent bonds when reacting with monomers, crosslinking agents, and other components commonly used in the manufacture of contact lenses. The compatibility of the compound with reactive mixtures can be controlled by selecting the polymerizable group (and linking group). Preferred polymerizable groups include (meth)acrylate or (meth)acrylamide. More preferably, the polymerizable group is methacrylate.

[0190] Compounds of formulas V, V-1, V-2, V-3, V-4, and V-5 may include compounds of formula V-6, which are compounds of formulas V, V-1, V-2, V-3, V-4, or V-5 in which Y (the linking group) is an alkylene, cycloalkylene, heterocycloalkylene, aryl (e.g., phenylene), heteroaryl, oxaalkylene, alkylene-amide-alkylene, alkylene-amine-alkylene, or a combination of any of the above groups. Preferred linking groups include C1-C8 alkylene (e.g., ethylene or propyleneene), C1-C8 oxaalkylene, C1-C8 alkylene-amide-C1-C8 alkylene, and C1-C8 alkylene-amine-C1-C8 alkylene. C1-C8 alkylene is particularly preferred, especially ethylene (-CH2CH2-). When T in a compound of formula V is O, it is preferred to have a carbon atom that hinders the linking group to which O is attached. For example, if T is O and Y is an alkylene group, then the preferred alkylene group is -C(R). H )2(CH2) x -, where R H Independently C1-C6 alkyl (preferably independently methyl or ethyl) and x is 1 to 5.

[0191] Compounds of formulas V, V-1, V-2, V-3, V-4, V-5, and V-6 may include compounds of formula V-7, which are compounds of formulas V, V-1, V-2, V-3, V-4, V-5, or V-6 in which T is a bond or NR (preferably NH).

[0192] Compounds of formula V may include compounds of formula VA:

[0193]

[0194] (VA)

[0195] in:

[0196] m and n are independently 0, 1, 2, 3 or 4;

[0197] Y is a linking group;

[0198] P g It is a polymerizable group;

[0199] R is independently H, C1-C6 alkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, or YP each time it appears. g ;and

[0200] R 1 and R 2 When present, it is independently C1-C6 alkyl, C1-C6 alkoxy, C1-C6 thioalkyl, C3-C7 cycloalkyl, aryl (preferably unsubstituted phenyl or phenyl substituted with alkyl or halogroup), halogroup, hydroxyl, amino, NR 3 R 4 , or benzyl, wherein R 3 and R 4 Independently H or C1-C6 alkyl, or two adjacent R 1 Or R 2 The groups, together with the carbon atoms they are attached to, combine to form cycloalkyl or aryl rings. Compounds of formula VA preferably contain one or two YP groups. g More preferably, the compound contains a YP group. g Group.

[0201] Compounds of formula VA may include compounds of formula VA-1, wherein m and n are independently 0 or 1, or alternatively both 0.

[0202] Compounds of formula VA and VA-1 may include compounds of formula VA-2, wherein m is 1 and R 1 Compounds of the formula VA or VA-1, which are C1-C6 alkyl, preferably ethyl or methyl.

[0203] Compounds of formula VA, VA-1, and VA-2 may include compounds of formula VA-3, wherein n is 1 and R 2 Compounds of the formula VA, VA-1 or VA-2 that are C1-C6 alkyl, preferably ethyl or methyl.

[0204] Compounds of formula VA, VA-1, VA-2, and VA-3 may include compounds of formula VA-4, which are compounds of formula VA, VA-1, VA-2, or VA-3 in which R is independently H or a C1-C6 alkyl group each time it appears. Preferably, R is H each time it appears. Preferably, R in group T is H.

[0205] Compounds of formula VA, VA-1, VA-2, VA-3, and VA-4 may include compounds of formula VA-5, wherein P is a compound of formula VA-5. g The polymerizable group, each time it appears, independently includes compounds of formula VA, VA-1, VA-2, VA-3, or VA-4, consisting of styrene, vinyl carbonate, vinyl ether, vinyl carbamate, N-vinyl lactam, N-vinylamide, (meth)acrylate, or (meth)acrylamide. The polymerizable group allows the compounds of the present invention to form covalent bonds when reacting with monomers, crosslinking agents, and other components commonly used in the manufacture of polymer devices. The compatibility of the compound with reactive mixtures can be controlled by selecting the polymerizable group (and linking group). Preferred polymerizable groups include (meth)acrylate or (meth)acrylamide. More preferably, the polymerizable group is methacrylate.

[0206] Compounds of formulas VA, VA-1, VA-2, VA-3, VA-4, and VA-5 may include compounds of formula VA-6, which are compounds of formulas VA, VA-1, VA-2, VA-3, VA-4, or VA-5 in which Y (the linking group) is an alkylene, cycloalkylene, heterocycloalkylene, aryl (e.g., phenylene), heteroaryl, oxaalkylene, alkylene-amide-alkylene, alkylene-amine-alkylene, or a combination of any of the above groups. Preferred linking groups include C1-C8 alkylene (e.g., ethylene or propyleneene), C1-C8 oxaalkylene, C1-C8 alkylene-amide-C1-C8 alkylene, and C1-C8 alkylene-amine-C1-C8 alkylene. Particularly preferred are C1-C8 alkylene, especially ethylene (-CH2CH2-).

[0207] Specific examples of compounds of formula V include, but are not limited to, the compounds shown in Table B-2.

[0208] Table B-2

[0209]

[0210]

[0211]

[0212] Compounds of formula V can be readily prepared by those skilled in the art, for example as described in US20210061934, which is incorporated herein by reference in its entirety.

[0213] The third visible light filtering compound can be a high-energy visible light filter having a chemical structure according to Formula VI:

[0214] .

[0215] (VI)

[0216] Where m and n are independently 0, 1, 2, 3, or 4; R 1 and R 2 Each occurrence is independently of H, optional substituents, or -YP. g Or two adjacent R 1 Or R 2 Groups and the atoms they are attached to combine to form optionally -YP g Substituted cycloalkyl or aryl rings; and EWG is an electron-withdrawing group independently each time it appears. P g Each occurrence of Y is an independent polymerizable group; each occurrence of Y is an independent linking group; wherein the compound of formula VI contains at least one P g Group.

[0217] Compounds of formula VI may include compounds of formula VI-1, which are compounds of formula IV-1 in which m and n are independently 0 or 1, or alternatively one is 0 and the other is 1.

[0218] Compounds of formula VI and VI-1 may include compounds of formula VI-2, which are compounds of formula VI or VI-1, wherein R 1 It is H, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 thioalkyl, C3-C7 cycloalkyl, aryl, halogroup, hydroxyl, amino, NR 4 R 5 , benzyl, SO3H, or SO3Na, wherein R 4 and R 5 It is independently H or C1-C6 alkyl.

[0219] Compounds of formula VI, VI-1 and VI-2 may include compounds of formula VI-3, wherein R is... 2 For -YP g Compounds of formula VI, formula VI-1, or formula VI-2.

[0220] Compounds of formulas VI, VI-1, VI-2, and VI-3 may include compounds of formula VI-4, wherein the compound of formula IV-4 is wherein P gThe polymerizable group, each time appearing independently, comprises compounds of formula VI, VI-1, VI-2, or VI-3 of styrene, ethylene carbonate, vinyl ether, vinyl carbamate, N-vinyl lactam, N-vinylamide, (meth)acrylate, or (meth)acrylamide. The polymerizable group allows the compounds of the present invention to form covalent bonds when reacting with monomers, crosslinking agents, and other components that can be used to manufacture polymer devices. The compatibility of the compound with reactive mixtures can be controlled by selecting the polymerizable group (and linking group). Preferred polymerizable groups include (meth)acrylate or (meth)acrylamide. More preferably, the polymerizable group is methacrylate.

[0221] Compounds of formulas VI, VI-1, VI-2, VI-3, and VI-4 may include compounds of formula VI-5, which are compounds of formulas VI, VI-1, VI-2, VI-3, or VI-4 wherein Y (the linking group) is an alkylene, cycloalkylene, heterocycloalkylene, aryl (e.g., phenylene), heteroaryl, oxaalkylene, alkylene-amide-alkylene, alkylene-amine-alkylene, or a combination of any of the above groups. Preferred linking groups include C1-C8 alkylene (e.g., ethylene or propyleneene), C1-C8 oxaalkylene, C1-C8 alkylene-amide-C1-C8 alkylene, and C1-C8 alkylene-amine-C1-C8 alkylene. Particularly preferred are oxa-C1-C8 alkylene, especially oxa-propylene (-O-CH2CH2CH2-).

[0222] Compounds of formulas VI, VI-1, VI-2, VI-3, VI-4, and VI-5 may include compounds of formula VI-6, which are compounds of formulas VI, VI-1, VI-2, VI-3, VI-4, or VI-5 in which the EWG is independently a cyano, amide, ester, ketone, or aldehyde in each occurrence. Preferably, the EWG is a cyano in each occurrence.

[0223] Compounds of formulas VI, VI-1, VI-2, VI-3, VI-4, VI-5, and VI-6 may include compounds of formula VI-7, wherein the compound contains a YP. g Compounds of the formula VI, VI-1, VI-2, VI-3, VI-4, VI-5 or VI-6.

[0224] Compounds of formulas VI, VI-1, VI-2, VI-3, VI-4, VI-5, VI-6, and VI-7 may include compounds of formula VI-8, wherein m is 0 and R 2 For -YP gCompounds of formula VI, VI-1, VI-2, VI-3, VI-4, VI-5, VI-6 or VI-7.

[0225] Specific examples of compounds of formula VI are included, but are not limited to, those listed in Table C:

[0226] Table C

[0227]

[0228]

[0229] Compounds of Formula VI may exhibit a molar extinction coefficient of at least 5000, or at least 7500, or at least 10,000, or at least 12,500, or at least 15,000, or at least 17,500, or at least 19,000 at the maximum visible light absorption. The molar extinction coefficient is an intrinsic property of the material and can be calculated from absorbance data using the Beer-Lambert law. The unit of molar extinction coefficient is typically L·mol⁻¹. -1 .cm -1 .

[0230] The compounds of formula VI can be readily prepared by those skilled in the art, for example as described in US20200407324 and U.S. Provisional Patent Application No. 63 / 265,706, filed December 20, 2021, each of which is incorporated herein by reference in its entirety.

[0231] The high-energy visible light (HEV) absorbing filters used in this invention, including those of formulas V and VI, are preferably photostable. Therefore, the devices of this invention, such as contact lenses containing a high-energy visible light filter as a third visible light filtering compound, preferably exhibit a change in their average transmittance of 20% or less, or 15% or less, or 10% or less, or 7% or less, or 5% or less, or 2% or less in the wavelength range of 380 nm to 450 nm after exposure to ICH Q1B conditions.

[0232] As described above, the reactive mixture used to prepare the ophthalmic device of the present invention may contain a third visible light filtering compound in addition to the first and second visible light filtering compounds. The third filtering compound may comprise a mixture of visible light filters (such as those represented by formulas III and IV) and high-energy visible light filters (such as those represented by formulas V and VI), as described above.

[0233] Other light-absorbing compounds may be included in the reactive mixture used to prepare the ophthalmic device of the present invention to provide additional desired absorption properties. For example, a preferred reactive mixture may contain a first visible light filtering compound, a second visible light filtering compound, and a third visible light filtering compound as described above, as well as a UV-absorbing compound. Suitable UV-absorbing compounds are known in the art and fall into several classes, including but not limited to benzophenone, benzotriazole, triazine, substituted acrylonitrile, salicylic acid derivatives, benzoic acid derivatives, cinnamic acid derivatives, chalcone derivatives, diphenyl ethyl ketone derivatives, crotonic acid derivatives, or any mixture thereof. One preferred class of UV-absorbing compounds is benzotriazole, such as (2-(2'-hydroxy-5-methacryloyloxyethylphenyl)-2H-benzotriazole) known as Norbloc.

[0234] The ophthalmic device of the present invention is preferably light-stable. For example, the device, such as a contact lens, preferably exhibits a change in average transmittance of 20% or less, or 15% or less, or 10% or less, or 7% or less, or 5% or less, or 2% or less in the wavelength range of 400 nm to 660 nm after exposure to ICH Q1B conditions.

[0235] Various ophthalmic devices can be fabricated, including spectacle lenses, sunglasses lenses, rigid contact lenses, soft contact lenses, corneal inlays, corneal embeddings, intraocular lenses, lenticule intraocular lenses, or covering lenses. Preferably, the ophthalmic device is an intraocular lens or a soft contact lens. Soft contact lenses can be made from conventional (non-silicone) hydrogels or from silicone hydrogels.

[0236] The reactive monomer mixture of the present invention may contain a first visible light filtering compound of formula I, based on a weight percentage of 0.01 wt% to 10 wt%, preferably 0.01 wt% to 5 wt%, or 0.01 wt% to 3 wt%, and most preferably 0.01 wt% to 1 wt% of all components in the reactive mixture (excluding diluents). The reactive monomer mixture of the present invention may contain a second visible light filtering compound of formula II, based on a weight percentage of 0.01 wt% to 10 wt%, preferably 0.01 wt% to 5 wt%, or 0.01 wt% to 3 wt%, and most preferably 0.01 wt% to 2 wt% of all components in the reactive mixture (excluding diluents). The reactive monomer mixture of the present invention may contain a third visible light filtering compound of formulas III-VI, based on a weight percentage of 0.01 wt% to 10 wt%, preferably 0.01 wt% to 7 wt%, or 0.01 wt% to 5 wt%, and most preferably 0.01 wt% to 3 wt%, or 0.01 wt% to 1 wt% of all components in the reactive mixture (excluding diluents). The absorption or transmission spectrum of the ophthalmic device can be altered by varying the concentrations of the first, second, and third visible light filtering compounds and the thickness of the device. Typical thicknesses of ophthalmic devices range from 60 to 300 micrometers, or 70 to 250 micrometers, or 80 to 200 micrometers, or 90 to 110 micrometers.

[0237] For example, the ophthalmic device of the present invention may have a transmittance distribution of (a) between 1% and 50% in the wavelength range of 480 nm to 660 nm and (b) between 20% and 70% in the wavelength range of 375 nm to 425 nm, or alternatively (a) between 10% and 40% in the wavelength range of 480 nm to 660 nm and (b) between 30% and 60% in the wavelength range of 375 nm to 425 nm. In some aspects, the transmittance in the wavelength range of 480 nm to 660 nm differs from the average transmittance by 15% or less, 10% or less, 7.5% or less, or 5% or less, wherein the average transmittance is between 20% and 40%.

[0238] The ophthalmic device of the present invention may include the free radical reaction product of a reactive mixture containing one or more monomers suitable for manufacturing the desired ophthalmic device (also referred to herein as device-forming monomers or hydrogel-forming monomers) and optional components. Upon polymerization, the reactive mixture results in the formation of a polymeric network, which the ophthalmic device may include. The polymeric network may be, for example, a hydrogel (e.g., a conventional hydrogel or a silicone hydrogel).

[0239] The visible light filtering compound of the present invention can be copolymerized with other components in a reactive mixture, in which case the reactive mixture may contain one or more of the visible light filtering compound in addition to one or more monomers (and any optional components) suitable for manufacturing the desired ophthalmic device.

[0240] Non-limiting examples of polymer networks in which visible light filtering compounds (e.g., as monomers) may be incorporated are as described above, and include, for example, etafenac, genifelcon, hilafilcon, linifelcon, nesofilcon, omafilcon, polymacon, vificon, acquafilcon, asmofilcon, balafilcon, comfilcon, delefilcon, lehfilcon, serafilcon, enfilcon, fanfilcon, formofilcon, galyfilcon, lotrafilcon, narafilcon, riofilcon, samfilcon, senofilcon, somofilcon, and stenfilcon, including all their variants.

[0241] By another example, the polymer network can be made from a reactive mixture comprising one or more of the following: a hydrophilic component, a hydrophobic component, an organosilicon-containing component, a wetting agent (such as polyamide), a crosslinking agent, and other components (such as diluents and initiators). As mentioned above, the reactive mixture also contains one or more first and second visible light filtering compounds.

[0242] hydrophilic components

[0243] Examples of suitable types of hydrophilic monomers that may be present in reactive mixtures include (meth)acrylates, styrene, vinyl ethers, (meth)acrylamide, N-vinyl lactam, N-vinylamide, N-vinylimide, N-vinyl urea, O-vinyl carbamate, O-vinyl carbonate, other hydrophilic vinyl compounds, and mixtures thereof.

[0244] Non-limiting examples of hydrophilic (meth)acrylates and (meth)acrylamide monomers include: acrylamide, N-isopropylacrylamide, N,N-dimethylaminopropyl (meth)acrylamide, N,N-dimethylacrylamide (DMA), 2-hydroxyethyl methacrylate (HEMA), 2-hydroxypropyl (meth)acrylate, 3-hydroxypropyl (meth)acrylate, 2,3-dihydroxypropyl (meth)acrylate, 2-hydroxybutyl (meth)acrylate, 3-hydroxybutyl (meth)acrylate, 4-hydroxybutyl (meth)acrylate, N-(2-hydroxyethyl)(meth)acrylamide, N,N-bis(2-hydroxyethyl)(meth)acrylamide, N-(2-hydroxypropyl)(meth)acrylamide, N,N-bis(2-hydroxypropyl)(meth)acrylamide, N-(3-hydroxypropyl)... (Methacrylamide), N-(2-hydroxybutyl)methacrylamide, N-(3-hydroxybutyl)methacrylamide, N-(4-hydroxybutyl)methacrylamide, 2-aminoethyl (meth)acrylate, 3-aminopropyl (meth)acrylate, 2-aminopropyl (meth)acrylate, N-2-aminoethyl (meth)acrylamide, N-3-aminopropyl (meth)acrylamide, N-2-aminopropyl (meth)acrylamide, N,N-bis-2-aminoethyl (meth)acrylamide, N,N-bis-3-aminopropyl (meth)acrylamide, N,N-bis-2-aminopropyl (meth)acrylamide, glyceryl methacrylate, polyethylene glycol monomethacrylate, (meth)acrylic acid, vinyl acetate, acrylonitrile, and mixtures thereof.

[0245] Hydrophilic monomers can also be ionic, including anionic, cationic, amphoteric, betaine, and mixtures thereof. Non-limiting examples of such charged monomers include (meth)acrylic acid, N-[(ethoxy)carbonyl]-β-alanine (VINAL), 3-acrylamidopropionic acid (ACA1), 5-acrylamidovalerate (ACA2), 3-acrylamido-3-methylbutyric acid (AMBA), 2-(methacryloyloxy)ethyltrimethylammonium chloride (Q salt or METAC), 2-acrylamido-2-methylpropanesulfonic acid (AMPS), N-(2-carboxyethyl)-N,N-dimethyl-3-[(1-oxo-2-propen-1-yl)amino]-1-propaneammonium inner salt (CBT), N,N-dimethyl-N-[3-[(1-oxo-2-propen-1-yl)amino]propyl]-3-sulfo-1-propaneammonium inner salt (SBT), 4-hydroxy-N,N,N- Trimethyl-9-oxo-4-oxide 3,5-dioxa-8-aza-4-phospha-undeca-10-en-1-ammonium inner salt (9CI) (PBT), 2-methacryloyloxyethyl phosphocholine, 3-(dimethyl(4-vinylbenzyl)ammonium)propane-1-sulfonate (DMVBAPS), 3-((3-acrylamidopropyl)dimethylammonium)propane-1-sulfonate (AMPDAPS), 3-((3-methacrylamidopropyl)dimethylammonium)propane-1-sulfonate (MAMPDAPS), 3-((3-(acryloyloxy)propyl)dimethylammonium)propane-1-sulfonate (APDAPS), and 3-((3-(methacryloyloxy)propyl)dimethylammonium)propane-1-sulfonate (MAPDAPS).

[0246] Non-limiting examples of hydrophilic N-vinyl lactams and N-vinylamide monomers include: N-vinylpyrrolidone (NVP), N-vinyl-2-piperidinone, N-vinyl-2-caprolactam, N-vinyl-3-methyl-2-caprolactam, N-vinyl-3-methyl-2-piperidinone, N-vinyl-4-methyl-2-piperidinone, N-vinyl-4-methyl-2-caprolactam, N-vinyl-3-ethyl-2-pyrrolidone, N-vinyl-4,5-dimethyl-2-pyrrolidone, N-vinylacetamide (NVA), N-vinyl-N-methylacetamide (VMA), N-vinyl-N-ethylacetamide, N-vinyl-N-ethylformamide, N-vinylformamide, N-vinyl-N-methylpropionamide, N-vinyl-N-methyl-2-methylpropionamide, N-vinyl... N-2-methylpropionamide, N-vinyl-N,N'-dimethylurea, 1-methyl-3-methylene-2-pyrrolidone, 1-methyl-5-methylene-2-pyrrolidone, 5-methyl-3-methylene-2-pyrrolidone; 1-ethyl-5-methylene-2-pyrrolidone, N-methyl-3-methylene-2-pyrrolidone, 5-ethyl-3-methylene-2-pyrrolidone, 1-N-propyl-3-methylene-2-pyrrolidone, 1-N-propyl-5-methylene-2-pyrrolidone, 1-isopropyl-3-methylene-2-pyrrolidone, 1-isopropyl-5-methylene-2-pyrrolidone, N-vinyl-N-ethylacetamide, N-vinyl-N-ethylformamide, N-vinylformamide, N-vinylisopropylamide, N-vinylcaprolactam, N-vinylimidazolium, and mixtures thereof.

[0247] Non-limiting examples of hydrophilic O-vinylcarbamate and O-vinyl carbonate monomers include N-2-hydroxyethylvinylcarbamate and N-carboxy-β-alanine N-vinyl ester. Further examples of hydrophilic ethylene carbonate or vinyl carbamate monomers are disclosed in U.S. Patent No. 5,070,215. Hydrophilic azole monomers are disclosed in U.S. Patent No. 4,910,277.

[0248] Other hydrophilic vinyl compounds include ethylene glycol vinyl ether (EGVE), di(ethylene glycol) vinyl ether (DEGVE), allyl alcohol, and 2-ethyloxazoline.

[0249] The hydrophilic monomers can also be linear or branched macromonomers or prepolymers of poly(ethylene glycol) and poly(propylene glycol), or statistically random or block copolymers of ethylene oxide and propylene oxide, having polymerizable portions such as (meth)acrylates, styrene, vinyl ethers, (meth)acrylamide, N-vinylamide, etc. These polyether macromonomers have one polymerizable group; prepolymers may have two or more polymerizable groups.

[0250] Preferred hydrophilic monomers of the present invention are DMA, NVP, HEMA, VMA, NVA, and mixtures thereof. Preferred hydrophilic monomers include mixtures of DMA and HEMA. Other suitable hydrophilic monomers will be apparent to those skilled in the art.

[0251] Generally, there are no particular limitations on the amount of hydrophilic monomers present in the reactive monomer mixture. The amount of hydrophilic monomers can be selected based on the desired characteristics of the resulting hydrogel, including water content, transmittance, wettability, protein uptake, etc. Wettability can be measured by the contact angle, and the desired contact angle is less than about 100º, less than about 80º, and less than about 60º. Based on the total weight of the reactive components in the reactive monomer mixture, the hydrophilic monomers can be present, for example, in the range of about 0.1 wt% to about 100 wt%, alternatively in the range of about 1 wt% to about 80 wt%, alternatively in the range of about 5 wt% to about 65 wt%, alternatively in the range of about 40 wt% to about 60 wt%, or alternatively in the range of about 55 wt% to about 60 wt%.

[0252] Components containing organosilicon

[0253] The organosilicon-containing components applicable to the present invention comprise one or more polymerizable compounds, wherein each compound independently comprises at least one polymerizable group, at least one siloxane group, and one or more linking groups connecting the one or more polymerizable groups to the one or more siloxane groups. The organosilicon-containing components may, for example, contain 1 to 220 repeating siloxane units, such as groups as defined below. The organosilicon-containing components may also contain at least one fluorine atom.

[0254] The organosilicon-containing component may comprise: one or more polymerizable groups as defined above; one or more optionally repeating siloxane units; and one or more linking groups that connect the polymerizable group to the siloxane unit. The organosilicon-containing component may comprise: one or more polymerizable groups, which are independently (meth)acrylates, styrene, vinyl ethers, (meth)acrylamide, N-vinyl lactam, N-vinylamide, O-vinylcarbamate, O-vinyl carbonate, vinyl groups, or mixtures thereof; one or more optionally repeating siloxane units; and one or more linking groups that connect the polymerizable group to the siloxane unit.

[0255] The component containing organosilicon may include: one or more polymerizable groups, which are independently (meth)acrylate, (meth)acrylamide, N-vinyl lactam, N-vinylamide, styrene, or a mixture of the foregoing; one or more optionally repeating siloxane units; and one or more linking groups that connect the polymerizable groups to the siloxane units.

[0256] The component containing organosilicon may include: one or more polymerizable groups, which are independently (meth)acrylate, (meth)acrylamide, or a mixture of the foregoing; one or more optionally repeating siloxane units; and one or more linking groups that connect the polymerizable groups to the siloxane units.

[0257] The component containing organosilicon may include one or more polymerizable compounds of formula A:

[0258]

[0259] Formula A

[0260] Where: at least one R A For formula P g -L- groups, where P g L is a polymerizable group, and L is a linking group, and the remaining R... A Each independently is: P g -L-; C1-C optionally substituted with one or more hydroxyl, amino, amide, oxo, carboxyl, alkylcarboxyl, carbonyl, alkoxy, amide, carbamate, carbonate, halogroup, phenyl, benzyl, or combinations thereof. 16 Alkyl group; C3-C column optionally substituted with one or more alkyl, hydroxyl, amino, amide, oxo, carbonyl, alkoxy, amide, carbamate, carbonate, halogroup, phenyl, benzyl, or combinations thereof. 12 Cycloalkyl; C6-C substituted with one or more alkyl, hydroxyl, amino, amide, oxa, carboxyl, alkylcarboxyl, carbonyl, alkoxy, amide, carbamate, carbonate, halogroup, phenyl, benzyl, or combinations thereof. 14A monovalent siloxane chain comprising 1 to 100 repeating siloxane units, substituted with alkyl, alkoxy, alkoxy, cycloalkoxy, or aryloxy; silyloxy; alkyleneoxy-alkyl or alkoxy-alkyleneoxy-alkyl (such as polyvinyloxyalkyl, polyacryloxyalkyl, or poly(vinyloxy-co-propyleneoxyalkyl)); or optionally substituted with alkyl, alkoxy, hydroxy, amino, oxa, carboxyl, alkylcarboxyl, alkoxy, amide, carbamate, halogen, or combinations thereof; and n is 0 to 500, or 0 to 200, or 0 to 100, or 0 to 20, wherein it should be understood that when n is not 0, n is a distribution with a mode equal to the specified value. When n is 2 or greater, the SiO unit may have the same or different R A Substituents, and if different R are present A If a substituent is present, the n-group can be random or block.

[0261] In equation A, the three R's A Each may contain a polymerizable group, and two additional R groups may be selected. A Each may contain a polymerizable group, or alternatively, an R A It may contain polymerizable groups.

[0262] Examples of organosilicon-containing components suitable for use in this invention include, but are not limited to, the compounds listed in Table D. The compounds in Table D contain polysiloxane groups, and unless otherwise specified, the number of SiO repeating units in such compounds is preferably 3 to 100, more preferably 3 to 40, or even more preferably 3 to 20.

[0263] Table D

[0264]

[0265]

[0266] Additional non-limiting examples of suitable organosilicon-containing components are listed in Table E. Unless otherwise specified, j2 is preferably 1 to 100, more preferably 3 to 40, or even more preferably 3 to 15, where applicable. In compounds containing j1 and j2, the sum of j1 and j2 is preferably 2 to 100, more preferably 3 to 40, or even more preferably 3 to 15.

[0267] Table E

[0268]

[0269]

[0270] Mixtures containing organosilicon components may be used. Suitable mixtures may include, but are not limited to: mixtures of mono-(2-hydroxy-3-methacryloxypropoxy)-propyl-terminated mono-n-butyl-terminated polydimethylsiloxanes (OH-mPDMS) with different molecular weights, such as mixtures of OH-mPDMS containing 4 and 15 SiO repeating units; mixtures of OH-mPDMS with different molecular weights (e.g., containing 4 and 15 repeating SiO repeating units) with organosilicon-based crosslinking agents (such as bis-3-acryloxy-2-hydroxypropoxypropyl polydimethylsiloxane (ac-PDMS)); and mixtures of 2-hydroxy-3-[3-methyl-3,3-di(trimethylsiloxy)silylpropoxy]-propyl methacrylate (SiMAA) and mono-methacryloxypropyl-terminated mono-n-butyl-terminated polydimethylsiloxanes (mPDMS) (such as mPDMS 1000).

[0271] The organosilicon-containing components used in this invention may have an average molecular weight of about 400 Daltons to about 4000 Daltons.

[0272] Based on all reactive components of the reactive mixture (excluding diluents), one or more organosilicon-containing components may be present in an amount of up to about 95% by weight, or about 10% by weight to about 80% by weight, or about 20% by weight to about 70% by weight.

[0273] polyamide

[0274] The reactive mixture may contain at least one polyamide. As used herein, the term "polyamide" refers to polymers and copolymers comprising repeating units containing amide groups. Polyamides may include cyclic amide groups, acyclic amide groups, and combinations thereof, and may be any polyamide known to those skilled in the art. Acyclic polyamides contain acyclic amide side groups and are capable of bonding with hydroxyl groups. Cyclic polyamides contain cyclic amide groups and are capable of bonding with hydroxyl groups.

[0275] Examples of suitable acyclic polyamides include polymers and copolymers containing repeating units of formula B1 and B2:

[0276]

[0277] Formula B1

[0278]

[0279] Formula B2

[0280] Where X is a direct bond, -(CO)- or -(CONHR)- 44 )-, where R 44It is a C1 to C3 alkyl group; R 40 Selected from H, straight-chain or branched substituted or unsubstituted C1 to C4 alkyl groups; R 41 Selected from H, straight-chain or branched substituted or unsubstituted C1 to C4 alkyl groups, amino groups having up to two carbon atoms, amide groups having up to four carbon atoms, and alkoxy groups having up to two carbon atoms; R 42 Selected from H, straight-chain or branched substituted or unsubstituted C1 to C4 alkyl groups; or methyl, ethoxy, hydroxyethyl and hydroxymethyl; R 43 Selected from H, straight-chain or branched substituted or unsubstituted C1 to C4 alkyl groups; or methyl, ethoxy, hydroxyethyl and hydroxymethyl; wherein R 40 and R 41 The total number of carbon atoms in the [element name] is 8 or less, including 7, 6, 5, 4, 3 or less; and R [element name] is [element name]. 42 and R 43 The total number of carbon atoms in R is 8 or less, including 7, 6, 5, 4, 3 or less. 40 and R 41 The total number of carbon atoms in R can be 6 or less, or 4 or less. 42 and R 43 The total number of carbon atoms in the alkyl group can be 6 or less. As used herein, substituted alkyl groups include alkyl groups substituted with amine, amide, ether, hydroxyl, carbonyl, or carboxyl groups or combinations thereof.

[0281] R 40 and R 41 It can be independently selected from H, substituted or unsubstituted C1 to C2 alkyl groups. X can be a direct bond, and R 40 and R 41 It can be independently selected from H, substituted or unsubstituted C1 to C2 alkyl groups. R 42 and R 43 It can be independently selected from H, substituted or unsubstituted C1 to C2 alkyl groups, methyl, ethoxy, hydroxyethyl and hydroxymethyl.

[0282] The acyclic polyamides of the present invention may comprise a majority of repeating units of formula B1 or B2, or the acyclic polyamides may comprise at least 50 mol% (including at least 70 mol% and at least 80 mol%) of repeating units of formula B1 or B2. Specific examples of repeating units of formula B1 and B2 include repeating units derived from the following monomers: N-vinyl-N-methylacetamide, N-vinylacetamide, N-vinyl-N-methylpropionamide, N-vinyl-N-methyl-2-methylpropionamide, N-vinyl-2-methylpropionamide, N-vinyl-N,N'-dimethylurea, N,N-dimethylacrylamide and methacrylamide, as well as acyclic amide monomers of formulas B3 and B4.

[0283]

[0284] Formula B3

[0285]

[0286] Formula B4

[0287] Examples of suitable cyclic amides that can be used to form cyclic polyamides include α-lactams, β-lactams, γ-lactams, δ-lactams, and ε-lactams. Examples of suitable cyclic polyamides include polymers and copolymers containing repeating units of formula B5.

[0288]

[0289] Formula B5

[0290] Where R 45 It is a hydrogen atom or a methyl group; where f is a number from 1 to 10; where X is a direct bond, -(CO)- or -(CONHR)-. 46 )-, where R 46 It is a C1 to C3 alkyl group. In formula LIX, f can be 8 or less, including 7, 6, 5, 4, 3, 2 or 1. In formula G4, f can be 6 or less, including 5, 4, 3, 2 or 1. In formula G4, f can be 2 to 8, including 2, 3, 4, 5, 6, 7 or 8. In formula LIX, f can be 2 or 3. When X is a direct bond, f can be 2. In such cases, the cyclic polyamide can be polyvinylpyrrolidone (PVP).

[0291] The cyclic polyamide of the present invention may contain 50 mol% or more of repeating units of formula B5, or the cyclic polyamide may contain at least 50 mol% (including at least 70 mol% and at least 80 mol%) of repeating units of formula B5.

[0292] Polyamides can also be copolymers comprising repeating units of both cyclic and acyclic amides. Additional repeating units can be formed from monomers selected from: hydroxyalkyl (meth)acrylates, alkyl (meth)acrylates, other hydrophilic monomers, and siloxane-substituted (meth)acrylates. Any of the monomers (listed as suitable hydrophilic monomers) can be used as comonomers to form additional repeating units. Specific examples of additional monomers that can be used to form polyamides include 2-hydroxyethyl (meth)acrylate, vinyl acetate, acrylonitrile, hydroxypropyl (meth)acrylate, methyl (meth)acrylate and hydroxybutyl (meth)acrylate, dihydroxypropyl (meth)acrylate, polyethylene glycol mono(meth)acrylate, and mixtures thereof. Ionic monomers may also be included. Examples of ionic monomers include (meth)acrylic acid, N-[(ethoxy)carbonyl]-β-alanine (VINAL, CAS #148969-96-4), 3-acrylamidopropionic acid (ACA1), 5-acrylamidovalerate (ACA2), 3-acrylamido-3-methylbutyric acid (AMBA), 2-(methacryloyloxy)ethyltrimethylammonium chloride (Q salt or METAC), 2-acrylamido-2-methylpropanesulfonic acid (AMPS), N-(2-carboxyethyl)-N,N-dimethyl-3-[(1-oxo-2-propen-1-yl)amino]-1-propaneammonium inner salt (CBT, carboxybetaine; CAS 79704-35-1), N,N-dimethyl-N-[3-[(1-oxo-2-propen-1-yl)amino]propyl]-3-sulfo-1-propaneammonium inner salt (SBT, sulfobetaine, CAS 79704-35-1). 80293-60-3), 4-hydroxy-N,N,N-trimethyl-9-oxo-4-oxide 3,5-dioxa-8-aza-4-phospha-undecan-10-ene-1-ammonium inner salt (9CI) (PBT, phosphate betaine, CAS 163674-35-9), 2-methacryloyloxyethyl phosphate choline, 3-(dimethyl(4-vinylbenzyl)ammonium)propane-1-sulfonate (DMVBAPS), 3-((3-acrylamidopropyl)dimethylammonium)propane-1-sulfonate (AMPDAPS), 3-((3-methacrylamidopropyl)dimethylammonium)propane-1-sulfonate (MAMPDAPS), 3-((3-(acryloyloxy)propyl)dimethylammonium)propane-1-sulfonate (APDAPS), methacryloyloxy)propyl)dimethylammonium)propane-1-sulfonate (MAPDAPS).

[0293] The reactive monomer mixture may comprise both acyclic polyamides and cyclic polyamides, or copolymers thereof. The acyclic polyamide may be any of the acyclic polyamides described herein or copolymers thereof, and the cyclic polyamide may be any of the cyclic polyamides described herein or copolymers thereof. The polyamide may be selected from polyvinylpyrrolidone (PVP), polyvinylmethylacetamide (PVMA), polydimethylacrylamide (PDMA), polyvinylacetamide (PNVA), poly(hydroxyethyl(meth)acrylamide), polyacrylamide, and copolymers and mixtures thereof. The polyamide may be PVP (e.g., PVP K90) and PVMA (e.g., M... having about 570 kDa). w A mixture of ).

[0294] In all cases, based on the total weight of the reactive components (excluding diluents) in the reactive monomer mixture, the total amount of all polyamides in the reactive mixture may be in the range of about 1% by weight to about 35% by weight, including the range of about 1% by weight to about 15% by weight and the range of about 5% by weight to about 15% by weight.

[0295] Unwilling to be bound by theory, when used with silicone hydrogels, the polyamide acts as an internal wetting agent. The polyamide of the present invention can be non-polymerizable and, in this case, incorporated into the silicone hydrogel as a semi-interpenetrating network. The polyamide is trapped or physically retained within the silicone hydrogel. Alternatively, the polyamide of the present invention is polymerizable, for example, as a polyamide macromonomer or prepolymer, and in this case, covalently introduced into the silicone hydrogel. Mixtures of polymerizable and non-polymerizable polyamides can also be used.

[0296] When polyamides are incorporated into a mixture of reactive monomers, their weight-average molecular weights can be at least 100,000 Daltons; greater than about 150,000; about 150,000 to about 2,000,000 Daltons; or about 300,000 Daltons to about 1,800,000 Daltons. Higher molecular weight polyamides may be used if they are compatible with the reactive monomer mixture.

[0297] Crosslinking agent

[0298] It is generally desirable to add one or more crosslinking agents (also known as crosslinking monomers, multifunctional macromonomers, and prepolymers) to reactive mixtures. Crosslinking agents can be selected from bifunctional, trifunctional, tetrafunctional, and mixtures thereof, including silicone-containing and silicone-free crosslinking agents. Silicone-free crosslinking agents include ethylene glycol dimethacrylate (EGDMA), tetraethylene glycol dimethacrylate (TEGDMA), trimethylolpropane trimethacrylate (TMPTMA), triallyl cyanurate (TAC), glyceryl trimethacrylate, oxyethyl vinyl methacrylate (HEMAVc), allyl methacrylate, methylenebisacrylamide (MBA), and polyethylene glycol dimethacrylate (wherein the polyethylene glycol has a molecular weight of up to about 5000 Daltons). Crosslinking agents are used in reactive mixtures in conventional amounts (e.g., about 0.000415 mol to about 0.0156 mol per 100 g of reactive formula). Alternatively, if the hydrophilic monomer and / or the organosilicon-containing component is multifunctional due to molecular design or impurities, it is optional to add a crosslinking agent to the reactive mixture. Examples of hydrophilic monomers and macromonomers that can act as crosslinking agents and (when present) do not require the addition of additional crosslinking agents to the reactive mixture include (meth)acrylate and (meth)acrylamide-terminated polyethers. Other crosslinking agents will be known to those skilled in the art and can be used to prepare the organosilicon hydrogels of the present invention.

[0299] It may be desirable to select one or more crosslinking agents with similar reactivity to other reactive components in the formulation. In some cases, it may be desirable to select a mixture of crosslinking agents with different reactivity to control some physical, mechanical, or biological properties of the resulting silicone hydrogel. The structure and morphology of the silicone hydrogel can also be affected by one or more diluents used and the curing conditions.

[0300] Multifunctional organosilicon-containing components (including macromonomers, crosslinking agents, and prepolymers) may also be included to further increase modulus and maintain tensile strength. Organosilicon-containing crosslinking agents can be used alone or in combination with other crosslinking agents. Examples of organosilicon-containing components that can act as crosslinking agents and (when present) do not require the addition of crosslinking monomers to the reactive mixture include α,ω-bis(methacryloyloxypropyl)polydimethylsiloxane. Another example is bis-3-acryloyloxy-2-hydroxypropoxypropyl)polydimethylsiloxane (ac-PDMS).

[0301] Crosslinking agents having a rigid chemical structure and polymerizable groups that undergo free radical polymerization can also be used. Non-limiting examples of suitable rigid structures include crosslinking agents comprising phenyl and benzyl rings, such as 1,4-phenylene diacrylate, 1,4-phenylene dimethacrylate, 2,2-bis(4-methacryloyloxyphenyl)-propane, 2,2-bis[4-(2-acryloyloxyethoxy)phenyl]propane, 2,2-bis[4-(2-hydroxy-3-methacryloyloxypropoxy)-phenyl]propane, and 4-vinylbenzyl methacrylate, and combinations thereof. Based on the total weight of all reactive components, the rigid crosslinking agent can be included in amounts between about 0.5 and about 15, or 2 to 10, or 3 to 7. By adjusting the components in the reactive mixture, the physical and mechanical properties of the silicone hydrogel of the present invention can be optimized for specific applications.

[0302] Non-limiting examples of organosilicon crosslinking agents also include the multifunctional organosilicon-containing components listed in Table C.

[0303] Other components

[0304] Reactive mixtures may contain additional components, such as, but not limited to, diluents, initiators, UV absorbers, visible light absorbers, photochromic compounds, pharmaceuticals, nutritional preparations, antimicrobial substances, toners, pigments, copolymerizable dyes, non-polymerizable dyes, release agents, visible hues, and combinations thereof.

[0305] The categories of diluents suitable for reactive silicone hydrogel mixtures include alcohols having 2 to 20 carbon atoms, amides derived from primary amines having 10 to 20 carbon atoms, and carboxylic acids having 8 to 20 carbon atoms. Diluents can be primary, secondary, and tertiary alcohols.

[0306] Generally, reactive components are mixed in a diluent to form a reactive mixture. Suitable diluents are known in the art. Diluents suitable for silicone hydrogels are disclosed in WO 03 / 022321 and US 6020445, the disclosures of which are incorporated herein by reference.

[0307] Suitable diluents for reactive silicone hydrogel mixtures include alcohols having 2 to 20 carbon atoms, amides derived from primary amines having 10 to 20 carbon atoms, and carboxylic acids having 8 to 20 carbon atoms. Primary and tertiary alcohols can be used. Preferred categories include alcohols having 5 to 20 carbon atoms and carboxylic acids having 10 to 20 carbon atoms.

[0308] Specific diluents that can be used include 1-ethoxy-2-propanol, diisopropylaminoethanol, isopropanol, 3,7-dimethyl-3-octanol, 1-decanol, 1-dodecanol, 1-octanol, 1-pentanol, 2-pentanol, 1-hexanol, 2-hexanol, 2-octanol, 3-methyl-3-pentanol, tert-pentanol, tert-butanol, 2-butanol, 1-butanol, 2-methyl-2-pentanol, 2-propanol, 1-propanol, ethanol, 2-ethyl-1-butanol, (3-acetoxy-2-hydroxypropoxy)propylbis(trimethylsilyloxy)methylsilane, 1-tert-butoxy-2-propanol, 3,3-dimethyl-2-butanol, tert-butoxyethanol, 2-octyl-1-dodecanol, decanoic acid, octanoic acid, dodecanoic acid, 2-(diisopropylamino)ethanol, mixtures thereof, etc. Examples of amide diluents include N,N-dimethylpropionamide and dimethylacetamide.

[0309] Preferred diluents include 3,7-dimethyl-3-octanol, 1-dodecanol, 1-decanol, 1-octanol, 1-pentanol, 1-hexanol, 2-hexanol, 2-octanol, 3-methyl-3-pentanol, 2-pentanol, tert-pentanol, tert-butanol, 2-butanol, 1-butanol, 2-methyl-2-pentanol, 2-ethyl-1-butanol, ethanol, 3,3-dimethyl-2-butanol, 2-octyl-1-dodecanol, decanoic acid, octanoic acid, dodecanoic acid, and mixtures thereof.

[0310] More preferred diluents include 3,7-dimethyl-3-octanol, 1-dodecanol, 1-decanol, 1-octanol, 1-pentanol, 1-hexanol, 2-hexanol, 2-octanol, 1-dodecanol, 3-methyl-3-pentanol, 1-pentanol, 2-pentanol, tert-pentanol, tert-butanol, 2-butanol, 1-butanol, 2-methyl-2-pentanol, 2-ethyl-1-butanol, 3,3-dimethyl-2-butanol, 2-octyl-1-dodecanol, and mixtures thereof.

[0311] If a diluent is present, there is generally no particular limitation on the amount of diluent present. When a diluent is used, it may be present in an amount ranging from about 2% to about 70% by weight (including from about 5% to about 50% by weight and from about 15% to about 40% by weight) based on the total weight of the reactive mixture (including reactive and non-reactive chemical formulas). Mixtures of diluents may be used.

[0312] Polymerization initiators can be used in reactive mixtures. Polymerization initiators may include at least one of lauroyl peroxide, benzoyl peroxide, isopropyl percarbonate, azobisisobutyronitrile, etc., which generate free radicals at moderately high temperatures; and photoinitiator systems such as aromatic α-hydroxy ketones, alkoxyoxobenzoin, acetophenone, acylphosphine oxides, diacylphosphine oxides, and tertiary amine-diketones, mixtures thereof, etc. Exemplary examples of photoinitiators are compositions of 1-hydroxycyclohexylphenyl ketone, 2-hydroxy-2-methyl-1-phenylpropane-1-one, bis(2,6-dimethoxybenzoyl)-2,4-4-trimethylpentylphosphine oxide (DMBAPO), bis(2,4,6-trimethylbenzoyl)-phenylphosphine oxide (Irgacure 819), 2,4,6-trimethylbenzyl diphenylphosphine oxide and 2,4,6-trimethylbenzoyl diphenylphosphine oxide, benzoin methyl ester, and camphorquinone and ethyl 4-(N,N-dimethylamino)benzoate.

[0313] Commercially available visible light initiator systems (from IGM Resins BV, The Netherlands) include Irgacure. ® 819, Irgacure ® 1700, Irgacure ® 1800, Irgacure ® 819, Irgacure ® 1850 and Lucrin ® TPO initiators. Commercially available UV photoinitiators (from IGM Resins BV) include Darocur. ® 1173 and Darocur ®2959. These and other photoinitiators that may be used are disclosed in Volume III, Photoinitiators for Free Radical Cationic & Anionic Photopolymerization, 2nd ed., by J.V. Crivello & K. Dietliker; edited by G. Bradley; John Wiley and Sons; New York; 1998. The initiator is used in the reactive mixture in an effective amount for initiating the photopolymerization of the reactive mixture (e.g., about 0.1 parts by weight to about 2 parts by weight per 100 parts of the reactive monomer mixture). The polymerization of the reactive mixture can be initiated by heat or visible or ultraviolet light or other methods of appropriate selection, depending on the polymerization initiator used. Alternatively, initiation can be carried out using an electron beam without a photoinitiator. However, when a photoinitiator is used, the preferred initiator is a diacylphosphine oxide, such as bis(2,4,6-trimethylbenzoyl)-phenylphosphine oxide (Irgacure). ® 819) or a combination of 1-hydroxycyclohexylphenyl ketone and bis(2,6-dimethoxybenzoyl)-2,4-4-trimethylpentylphosphine oxide (DMBAPO). Thermally initiated polymerization can be carried out, for example, as described in US20200399429, the entire text of which is incorporated herein by reference. A combination of photocuring and thermal curing can be used.

[0314] The reactive mixture used to manufacture the ophthalmic device of the present invention may contain, in addition to the first visible light filtering compound, the second visible light filtering compound, and optionally the third visible light filtering compound, any of the polymerizable compounds and optional components described above.

[0315] The reactive mixture may contain: a first visible light filtering compound, a second visible light filtering compound, and optionally a third visible light filtering compound, as well as a hydrophilic component.

[0316] The reactive mixture may comprise: a first visible light filtering compound, a second visible light filtering compound, and optionally a third visible light filtering compound, as well as a hydrophilic component selected from DMA, NVP, HEMA, VMA, NVA, methacrylic acid, and mixtures thereof. A mixture of HEMA and methacrylic acid is preferred.

[0317] The reactive mixture may include: a first visible light filtering compound, a second visible light filtering compound, and optionally a third visible light filtering compound, a hydrophilic component, and a component containing organosilicon.

[0318] The reactive mixture may comprise: a first visible light filtering compound, a second visible light filtering compound, and optionally a third visible light filtering compound; a hydrophilic component selected from DMA, HEMA, and mixtures thereof; an organosilicon-containing component selected from 2-hydroxy-3-[3-methyl-3,3-di(trimethylsiloxy)silylpropoxy]-propyl methacrylate (SiMAA), mono-methacryloxypropyl-terminated mono-n-butyl-terminated polydimethylsiloxane (mPDMS), mono-(2-hydroxy-3-methacryloxypropyl)-propyl ether-terminated mono-n-butyl-terminated polydimethylsiloxane (OH-mPDMS), and mixtures thereof; and a wetting agent (preferably PVP or PVMA). For the hydrophilic component, a mixture of DMA and HEMA is preferred. For the organosilicon-containing component, a mixture of SiMAA and mPDMS is preferred.

[0319] The reactive mixture may comprise: a first visible light filtering compound, a second visible light filtering compound, and optionally a third visible light filtering compound; a hydrophilic component comprising a mixture of DMA and HEMA; and an organosilicon-containing component comprising a mixture of OH-mPDMS having 2 to 20 repeating units (preferably a mixture of 4 and 15 repeating units). Preferably, the reactive mixture further comprises an organosilicon-containing crosslinking agent, such as ac-PDMS. Even more preferably, the reactive mixture contains a wetting agent (preferably DMA, PVP, PVMA, or a mixture thereof).

[0320] The reactive mixture may comprise: a first visible light filtering compound, a second visible light filtering compound, and optionally a third visible light filtering compound; at least one polyamide (e.g., acyclic polyamide, cyclic polyamide, or mixtures thereof) between about 1% and about 15% by weight; at least one first monofunctional hydroxyl-substituted poly(disubstituted siloxane) having 4 to 8 siloxane repeating units (e.g., OH-mPDMS, where n is 4 to 8, preferably n is 4); at least one second hydroxyl-substituted poly(disubstituted siloxane) having 10 to 8 hydroxyl repeating units. 200, or 10 to 100, or 10 to 50, or 10 to 20 siloxane repeating units of a monofunctional hydroxyl-substituted poly(disubstituted siloxane) (e.g., OH-mPDMS, where n is 10 to 200, or 10 to 100, or 10 to 50, or 10 to 20, preferably n is 15); about 5% to about 35% by weight of at least one hydrophilic monomer; and optionally a polyfunctional hydroxyl-substituted poly(disubstituted siloxane) having 10 to 200 or 10 to 100 siloxane repeating units (e.g., ac-PDMS). Preferably, the first monofunctional hydroxyl-substituted poly(disubstituted siloxane) and the second hydroxyl-substituted poly(disubstituted siloxane) are present at a concentration such that the weight percentage of the first monofunctional hydroxyl-substituted poly(disubstituted siloxane) to the weight percentage of the second hydroxyl-substituted poly(disubstituted siloxane) is 0.4 to 1.3 or 0.4 to 1.0.

[0321] The aforementioned reactive mixture may contain optional components, such as, but not limited to, one or more initiators, internal wetting agents, crosslinking agents, other UV or HEV absorbers, and diluents.

[0322] The curing of hydrogels and the manufacturing of lenses

[0323] Reactive mixtures can be formed by any of the methods known in the art, such as vibration or agitation, and by known methods used to form articles or apparatus of polymers. Reactive components are mixed together with or without a diluent to form a reactive mixture.

[0324] For example, an ophthalmic device can be prepared by mixing a reactive component and optionally one or more diluents with a polymerization initiator, curing it under appropriate conditions to form a product, which can then be shaped into a suitable form by machining, cutting, etc. Alternatively, the reactive mixture can be placed in a mold and subsequently cured into a suitable article.

[0325] A method for manufacturing molded ophthalmic devices such as silicone hydrogel contact lenses may include: preparing a reactive monomer mixture; transferring the reactive monomer mixture onto a first mold; placing a second mold on top of the first mold filled with the reactive monomer mixture; and curing the reactive monomer mixture by free radical copolymerization to form a silicone hydrogel in the shape of a contact lens.

[0326] The reactive mixture can be cured via any known process (including spin casting and static casting) used for molding the reactive mixture during the production of contact lenses. Spin casting methods are disclosed in U.S. Patent Nos. 3,408,429 and 3,660,545, and static casting methods are disclosed in U.S. Patent Nos. 4,113,224 and 4,197,266. The contact lenses of the present invention can be formed by directly molding the hydrogel, a method that is both economical and allows for precise control over the final shape of the hydrated lens. In this method, the reactive mixture is placed in a mold having the final desired shape of the hydrogel, and the reactive mixture is subjected to conditions that cause the monomers to polymerize, thereby producing a polymer having the general shape of the final desired product.

[0327] After curing, the lens can be extracted to remove unreacted components and detach the lens from the lens mold. Extraction can be performed using conventional extraction solutions (organic solvents such as alcohols) or aqueous solutions.

[0328] The aqueous solution is a solution containing water. The aqueous solution of the present invention may contain at least about 20% by weight of water, or at least about 50% by weight of water, or at least about 70% by weight of water, or at least about 95% by weight of water. The aqueous solution may also contain additional water-soluble components, such as inorganic salts or release agents, wetting agents, slip agents, pharmaceutical and nutritional formulations, combinations thereof, etc. Release agents are compounds or mixtures of compounds that, when combined with water, reduce the time required to remove the contact lens from the mold compared to using an aqueous solution without a release agent. The aqueous solution may not require special treatment, such as purification, recycling, or special disposal processes.

[0329] Extraction can be achieved, for example, by immersing the lens in an aqueous solution or exposing it to a flowing aqueous solution. Extraction may also include, for example, one or more of the following: heating the aqueous solution; stirring the aqueous solution; increasing the content of a release agent in the aqueous solution to a level sufficient to detach the lens; mechanically or ultrasonically stirring the lens; and incorporating at least one filtration or extraction agent into the aqueous solution until it reaches a level sufficient to promote adequate removal of unreacted components from the lens. The above operations can be performed in batches or continuously, with heating, stirring, or both, or without any of these steps.

[0330] Physical agitation may be desired to facilitate extraction and demolding. For example, the lens mold component with the lens attached can be vibrated or moved back and forth in an aqueous solution. Other methods may include ultrasound through an aqueous solution.

[0331] Lenses can be sterilized by known methods, such as, but not limited to, autoclaving.

[0332] As described above, the preferred ophthalmic device is a contact lens, more preferably a soft hydrogel contact lens. The transmission wavelengths and percentages described herein can be measured for lenses of various thicknesses using methods such as those described in the examples. By way of example, a preferred center thickness for measuring the transmission spectrum in a soft contact lens can be 80 to 100 micrometers, or 80 to 95 micrometers, or 85 to 95 micrometers. Typically, measurements can be taken at the center of the lens using an instrument slit width of, for example, 4 nm on a UV-VIS spectrophotometer.

[0333] When the ophthalmic device of the present invention is a silicone hydrogel contact lens, the lens preferably exhibits the following properties. All values ​​are preceded by "about", and the lens may have any combination of the listed properties. These properties can be determined by methods known to those skilled in the art, such as those described in U.S. pre-grant publication US20180037690, which is incorporated herein by reference.

[0334] • Water content (by weight): at least 20% by weight, or at least 25% by weight and at most 80% by weight, or at most 70% by weight.

[0335] • Haze: 30% or lower, or 10% or lower

[0336] • Forward dynamic contact angle (Wilhelmy plate method, degrees) or Sessile Drop: 100° or less, or 80° or less; or 50° or less

[0337] • Tensile modulus (psi): 120 or lower, or 80 to 120

[0338] • Edge-corrected oxygen permeability (EC D) k (Bahrain): at least 50, or at least 60, or at least 80, or at least 100, or at least 120

[0339] • Elongation at break: at least 100%

[0340] • For ionic silica hydrogels, the following properties may also be preferred (in addition to those mentioned above):

[0341] • Lysozyme absorption rate (µg / lens): at least 100, or at least 150, or at least 500, or at least 700

[0342] • Polyquaternium 1 (PQ1) intake (%): 15 or less, or 10 or less, or 5 or less

[0343] Besides ophthalmic devices, the visible light filtering compounds described herein can also be used with other products. For example, the compounds can be used in windows (e.g., vehicle or building windows) or optical devices such as binoculars and cameras. In such applications, the compounds can be coated, for example, onto the surface of the device. To facilitate coating, the compounds can be dissolved in a solvent.

[0344] The first, second, and optional third visible light filtering compounds in the final ophthalmic device can be uniformly distributed, for example, in an edge-to-edge tinted contact lens, or independently distributed in the central and peripheral regions of the contact lens, such that the central and peripheral regions have different visible light absorption characteristics, or are more concentrated in the central region than in the peripheral region (or vice versa). A preferred configuration is a tinted or apomorphized central region contact lens, sometimes referred to as a pupil-only or optical-area-only contact lens. However, this configuration is useful for other ophthalmic devices, particularly intraocular lenses. Because these visible light filtering compounds absorb visible light, giving the lens its color, concentration variations within the ophthalmic device can vary depending on their concentration. Alternatively, UV-VIS spectroscopy can be used, whereby, based on Beer's law, a higher absorbance of any particular visible light filtering compound or mixture generally indicates a higher concentration.

[0345] There are manufacturing methods for producing ophthalmic devices in which a first visible light filtering compound, a second visible light filtering compound, and optionally a third visible light filtering compound are concentrated in a central region of a lens, and include, for example, the method described in US8697770, the entire contents of which are incorporated herein by reference. This curing technique uses a multi-dose mixture of reactive monomers introduced into a lens mold, wherein a first, higher viscosity mixture containing the first, second, and optionally third visible light filtering compounds is added in doses to the central region of the mold, and a lower viscosity reactive mixture not containing the first, second, and optionally third visible light filtering compounds is added at a dose higher than or approximately the first dose. The half-molds are then joined together, and subsequently the reactive monomer mixture is cured. In this way, the visible light filtering formulation is concentrated in the central region of the lens. Alternatively, the lower viscosity reactive mixture may also contain only a different amount of the first, second, and optionally third visible light filtering compounds than the higher viscosity reactive mixture.

[0346] Other techniques can also be used to manufacture such apodization ophthalmic devices, such as contact lenses, for example, the methods described in US11034789, US11780953, and US Application 18 / 457455, which are incorporated herein by reference in their entirety and relate to the selective grafting of a first visible light filter compound, a second visible light filter compound, and optionally a third visible light filter compound into the ophthalmic device by projecting light onto specific areas within a preformed device or lens using a computer-controlled digital micromirror device. This selective grafting occurs where the molar concentrations of the first, second, and optional third visible light filter compounds can be independently distributed in the central and peripheral regions, or where the first visible light... The molar concentrations of the first, second, and optional third visible light filter compounds may be independently greater in the central region than in the peripheral region (or vice versa), or the molar concentrations of the first, second, and optional third visible light filter compounds may be independently distributed only in the central region, or the molar concentrations of the first, second, and optional third visible light filter compounds may be independently spatially varied to form an apodization distribution in the contact lens, or the molar concentrations of the first, second, and optional third visible light filter compounds may be independently varied radially, circumferentially, or in combination thereof to form an apodization distribution. The apodization distribution can vary according to mathematical functions such as linear functions, polynomial functions, Gaussian functions, Lorentz functions, logarithmic functions, exponential functions, numerical equations, or combinations thereof. The apodization distribution may also include a transparent region located at the center of a contact lens of any shape or size. In some applications, the transparent area is circular, with a diameter between 0.1 mm and 5 mm, or between 1 mm and 4 mm. Examples of this type of apodization distribution are shown in... Figure 12 and Figure 13 As shown in the figure. Finally, the contact lens of the present invention may include a central region having an optical region therein for correcting refractive errors selected from the group consisting of myopia, hyperopia, presbyopia and astigmatism.

[0347] In another aspect, the present invention provides an apodization ophthalmic device, such as a contact lens, formed by: (a) providing a first reactive composition comprising: (i) a polymerization initiator capable of forming two or more free radical groups upon first activation, at least one of the two or more free radical groups being further activated by subsequent activation; (ii) one or more olefinic unsaturated compounds; and (iii) a crosslinking agent; (b) subjecting the first reactive composition to a first activation step, such that the first reactive composition polymerizes in the first activation step to form a crosslinked substrate network containing a covalently bonded activatable free radical initiator; (c) contacting the crosslinked substrate network with a first graft composition containing a first visible light filtering compound and a second visible light filtering compound, wherein the contact is performed under conditions that allow the first graft composition to penetrate into the crosslinked substrate network; and (d) activating the covalently bonded activatable free radical initiator at one or more selective regions of the crosslinked substrate network, such that the first graft composition polymerizes with the crosslinked substrate network at the selective regions, thereby forming an apodization distribution.

[0348] The first reactive composition may comprise one or more olefinically unsaturated compounds having one or more polymerizable groups independently selected from the group consisting of: (meth)acrylate, (meth)acrylamide, styrene, vinyl, N-vinyl lactam, N-vinylamide, O-vinyl ether, O-vinyl carbonate, O-vinyl carbamate, C 2-12 alkenyl, C 2-12 alkenylphenyl, C 2-12 alkenylnaphthalene, and C 2-6 alkenylphenyl-C 1-6Alkyl groups. Preferred polymerizable groups are (meth)acrylates and (meth)acrylamide. The first reactive composition may contain a hydrophilic reactive component, an organosilicon-containing component, or a combination thereof. The first reactive composition contains a polymerization initiator selected from the group consisting of: bis(acylphosphine oxide), bis(acylphosphine oxide), diazo compounds, dieperoxide compounds, azobis(monoacylphosphine oxide), azobis(monoacylphosphine oxide), peroxybis(monoacylphosphine oxide), peroxybis(monoacylphosphine oxide), azobis(α-hydroxy ketone), peroxybis(α-hydroxy ketone), azobis(1,2-dione), peroxybis(1,2-dione), germanium compounds, tert-butyl 7-methyl-7-(tert-butylazo)peroxyoctanoate, or a combination thereof. A preferred initiator is bis(acylphosphine oxide), which generates monoacylphosphine oxide as a covalently bonded, activatable free radical initiator in the crosslinked substrate network. In this case, the preferred first activation is irradiation using a wavelength between 400 nm and 450 nm or between 420 nm and 450 nm, and the preferred second activation is irradiation using a wavelength between 365 nm and 420 nm.

[0349] The first grafting composition may comprise a hydrophilic reactive component, an organosilicon-containing component or a combination thereof, a crosslinking agent, or a third visible light filtering compound. The first grafting composition comprises a first visible light filtering compound having the chemical structure of formula (I) and a second visible light filtering compound having the chemical structure of formula (II). The first grafting composition may also comprise a third visible light filtering compound having the chemical structures of formulas (III), (IV), (V), and (VI), or a combination thereof. The first grafting composition may be dissolved in a suitable diluent that swells the crosslinked substrate network, thereby impregnating the first, second, and optionally third visible light filtering compounds into the crosslinked substrate network. The diluent may be used to control the swelling time to incorporate the visible light filtering compounds into an ophthalmic device made from the crosslinked substrate network prior to grafting. Any organic solvent, aqueous organic solvent, and aqueous solution may be used as a diluent, such as, but not limited to, dimethylformamide, acetonitrile, dimethyl sulfoxide, and aliphatic alcohols. Preferred diluents are primary alcohols, secondary alcohols, and tertiary alcohols, as well as aqueous solutions thereof (see the list above). More preferred diluents are aqueous solutions of 1-propanol, 2-propanol, or mixtures thereof.

[0350] The method may be combined with several additional steps, including, but not limited to, after step (b), solvent extraction of the crosslinked substrate network while maintaining the covalently bound activatable free radical initiator of the crosslinked substrate network, and optionally hydration of the extracted crosslinked substrate network with an aqueous solution; and / or after step (d), contacting the crosslinked substrate network with a second graft composition containing a mixture of a first visible light filter compound, a second visible light filter compound, and optionally a third visible light filter compound different from the first graft composition, and activating the retained covalently bound activatable free radical initiator, such that the second graft composition polymerizes with the crosslinked substrate network outside the selective region and optionally partially within the selective region; and / or after step (d), solvent extraction of the crosslinked substrate network, hydration of the extracted crosslinked substrate network with an aqueous solution, and autoclaving of the ophthalmic device.

[0351] Furthermore, steps (a) and (b) can be performed in a mold assembly consisting of a front mold and a rear mold, which define and close a cavity shaped like an ophthalmic device (such as a contact lens) between the front mold and the rear mold, and steps (c) and (d) are performed in the mold assembly after the rear mold is removed. Activation in steps (b) and (d) can be achieved via a source of photochemical irradiation (such as UV / visible light irradiation) using multiple selectively controllable beams of photochemical irradiation controlled by the digital micromirror device according to a predetermined script. The predetermined script directs the selectively controllable beams of photochemical irradiation to one or more surfaces or locations within the cavity, thereby determining the amount of irradiation exposed to any location or volumetric element within the cavity. In this way, in step (d), the grafting amounts of a first visible light filter compound, a second visible light filter compound, and optionally a third visible light filter compound can be controlled. Step (b) is typically performed using a light-emitting diode lamp of a specific wavelength. Preferred digital micromirror devices include an illumination source that also contains at least one light-emitting diode.

[0352] As previously mentioned, the preferred initiator is bisacylphosphine oxide, which generates monoacylphosphine oxide (MAPO) as a covalently bonded, activatable free radical initiator in the crosslinked substrate network. The amount of visible light filtering compound grafted at any location within the MAPO substrate lens is controlled by: varying the exposure time using light of a fixed intensity and wavelength, or varying the intensity or wavelength of photochemical irradiation using a fixed exposure time, or adjusting the concentration of the visible light filtering compound in the first or second grafting composition, and / or changing the diluent that can affect swelling and penetration (without affecting adhesion to the FC mold) into the MAPO substrate lens, including adding monomers that promote the copolymerization of the first, second, and optionally third visible light filtering compounds.

[0353] This method can be used to prepare ophthalmic devices, such as contact lenses, intraocular lenses, crystalline intraocular lenses, punctal plugs, and ocular inserts. These ophthalmic devices can be made of hydrogel or silicone hydrogel. These ophthalmic devices may also have a central region and a peripheral region, wherein the apodization distribution varies across the central region, or across the peripheral region, or across both the central and peripheral regions. The apodization distribution can vary according to a mathematical function, for example, a linear function, a polynomial function, a Gaussian function, a Lorentz function, a logarithmic function, an exponential function, a numerical function, or a combination thereof. The apodization distribution may also include a transparent region located at the center of the ophthalmic device, wherein the transparent region is circular with a diameter between 0.1 mm and 5 mm or between 1 mm and 4 mm. The central region may also include an optical region for correcting refractive errors selected from the group consisting of myopia, hyperopia, presbyopia, and astigmatism.

[0354] More generally, the present invention also provides an ophthalmic device, such as a contact lens, comprising one or more visible light absorbing compounds concentrated in a central region of the lens. Such an ophthalmic device can be formed by a method comprising: (a) providing a first reactive composition comprising: (i) a polymerization initiator capable of forming two or more free radical groups upon first activation, at least one of the two or more free radical groups being further activated by subsequent activation; (ii) one or more olefinically unsaturated compounds; and (iii) a crosslinking agent; (b) subjecting the first reactive composition to a first activation step, such that the first reactive composition polymerizes in the first activation step to form a crosslinked substrate network containing a covalently bonded, activatable free radical initiator; (c) contacting the crosslinked substrate network with a first graft composition containing one or more polymerizable visible light absorbing compounds, wherein the contact is performed under conditions that allow the first graft composition to penetrate into the crosslinked substrate network; and (d) in selective regions of the crosslinked substrate network... The method involves activating a covalently bonded, activatable free radical initiator in a selective region corresponding to the central region of an ophthalmic device, causing a first grafted composition to polymerize with a crosslinked substrate network at the selective region, thereby forming an ophthalmic device having one or more light-absorbing compounds concentrated in its central region. Steps (a) and (b) are performed in a mold assembly consisting of a front mold and a rear mold, which define and close a cavity shaped like an ophthalmic device (such as a contact lens) between the front and rear molds. Steps (c) and (d) are performed in the mold assembly after the rear mold is removed. The activation in steps (b) and (d) is performed via a photochemical irradiation source and includes multiple selectively controllable beams of photochemical irradiation controlled by a digital micromirror device according to a predetermined script that guides the selectively controllable beams of photochemical irradiation to the selective region of the crosslinked substrate network within the cavity. In this way, the grafting amount of one or more visible light-absorbing compounds can be controlled in step (d). Step (b) can be performed using a light-emitting diode lamp of a specific wavelength. A preferred digital micromirror device includes an illumination source that also contains at least one light-emitting diode.

[0355] In another aspect, the present invention provides 1-(10-butyl-2-methoxyacryl-9(10H)-ylidene)-1-cyano-2-oxo-6,9,12,15,18-pentaoxa-3-aza-20-yl methacrylate.

[0356] The present invention also provides 2-(2-(2-((9,10-dioxo-9,10-dihydroanthracene-1-yl)amino)ethoxy)ethoxy)ethyl methacrylate.

[0357] The present invention also provides 5-((9,10-dioxo-9,10-dihydroanthracene-1-yl)amino)pentyl methacrylate.

[0358] The present invention also provides 17-((9-(dicyanomethylene)-9H-xanthon-3-yl)oxy)-3,6,9,12,15-pentaheptadecyl methacrylate.

[0359] Terms and Conditions

[0360] The following provisions set forth non-restrictive embodiments of this disclosure:

[0361] Clause 1. An ophthalmic device, said ophthalmic device being a free radical reaction product of a mixture of reactive monomers, said reactive monomer mixture comprising:

[0362] (a) One or more monomers, said one or more monomers being suitable for manufacturing the ophthalmic device;

[0363] (b) A first visible light filtering compound having a maximum visible light absorption between 430 nm and 480 nm and a full width at half maximum (FWHM) of at least 35 nm and at most 150 nm at the maximum visible light absorption, wherein the first visible light filtering compound is photostable, and wherein the first visible light filtering compound has a content of at least 7740 L·mol⁻¹. -1 .cm -1 The molar extinction coefficient; and

[0364] (c) A second visible light filtering compound having a maximum visible light absorption between 480 nm and 530 nm and a full width at half maximum (FWHM) of at least 50 nm and at most 150 nm.

[0365] Clause 2. The ophthalmic device according to Clause 1, wherein the maximum visible light absorption of the first visible light filtering compound is between 440 nm and 470 nm.

[0366] Clause 3. The ophthalmic device according to Clause 1, wherein the maximum visible light absorption of the second visible light filter compound is between 490 nm and 520 nm.

[0367] Clause 4. The ophthalmic device according to any one of the preceding clauses, wherein the full width at half maximum (FWHM) of the first visible light filtering compound at the maximum visible light absorption is at least 40 nanometers and at most 95 nanometers.

[0368] Clause 5. The ophthalmic device according to any one of the preceding clauses, wherein the full width at half maximum (FWHM) of the second visible light filtering compound at the maximum visible light absorption is at least 70 nm and at most 130 nm.

[0369] Clause 6. The ophthalmic device according to any one of the preceding clauses, wherein photostability includes a loss of absorbance of no more than 20% at the maximum visible light absorption.

[0370] Clause 7. The ophthalmic device according to any one of the preceding clauses, wherein the light stability includes: being more light stable than macular pigment.

[0371] Clause 8. The ophthalmic device according to any one of the preceding clauses, wherein the first visible light filtering compound is thermally stable.

[0372] Clause 9. The ophthalmic device according to any one of the preceding clauses, wherein the first visible light filtering compound is more thermally stable than macular pigment.

[0373] Clause 10. The ophthalmic device according to any one of the preceding clauses, wherein the first visible light filtering compound and the second visible light filtering compound independently comprise at least one polymerizable group.

[0374] Clause 11. The ophthalmic device according to any one of Clauses 1 to 10, wherein the first visible light filtering compound has Formula I:

[0375]

[0376] (I)

[0377] Where m and n are independently 0, 1, 2, 3, or 4; T is a bond, O, or NR. 6 , where R 6 It is H, C1-C6 alkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, or YP g R is H, C1-C8 alkyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; Y is a linking group; P g It is a polymerizable group; R 1 and R 2 When present, it is independently C1-C6 alkyl, C1-C6 alkoxy, C1-C6 thioalkyl, C3-C7 cycloalkyl, aryl (preferably unsubstituted phenyl or phenyl substituted with alkyl or halogroup), halogroup, hydroxyl, amino, NR 3 R 4 , benzyl, SO3H or SO3M (M is a monovalent cation, such as sodium ion or potassium ion), where R 3 and R 4Independently H or C1-C6 alkyl, or two adjacent R 1 Or R 2 The groups combine with the carbon atoms to which they are attached to form cycloalkyl or aryl rings; and EWG is an electron-withdrawing group.

[0378] Clause 12. The ophthalmic device as described in Clause 11, wherein m and n are each independently 0 or 1.

[0379] Clause 13. An ophthalmic device according to any one of Clauses 11 to 12, wherein Y, in each occurrence, is independently alkylene, cycloalkylene, heterocycloalkylene, aryl, heteroaryl, oxaalkylene, alkylene-amide-alkylene, alkylene-amine-alkylene, or a combination thereof.

[0380] Clause 14. The ophthalmic device according to any one of Clauses 11 to 13, wherein P g Including styrene, vinyl carbonate, vinyl ether, vinyl carbamate, N-vinyl lactam, N-vinylamide, (meth)acrylate, or (meth)acrylamide.

[0381] Clause 15. An ophthalmic device according to any one of Clauses 11 to 14, wherein the EWG is cyano, amide, ester, ketone, or aldehyde.

[0382] Clause 16. The ophthalmic device as described in Clause 15, wherein the EWG is cyano.

[0383] Clause 17. The ophthalmic device according to Clause 11, wherein the first visible light filtering compound comprises: ethyl 2-(2-cyano-2-(2-methoxy-10-propylacridin-9(10H)-ylidene)acetamido), ethyl 2-(2-cyano-2-(2-methoxy-10-butylacridin-9(10H)-ylidene)acetamido), ethyl 1-(10-butyl-2-methoxyacridin-9(10H)-ylidene)-1-cyano-2-oxo-6,9,12,15,18-pentaoxa-3-azaeicosaecan-20-yl ester, or a mixture thereof.

[0384] Clause 18. The ophthalmic device according to Clause 17, wherein the first visible light filtering compound is ethyl methacrylate 2-(2-cyano-2-(2-methoxy-10-butylacridin-9(10H)-ylidene)acetamido)methacrylate having the following chemical structure:

[0385]

[0386] Clause 19. The ophthalmic device according to any one of Clauses 1 to 18, wherein the second visible light filtering compound comprises a visible light filter of Formula II:

[0387]

[0388] (II)

[0389] Where Y is a linking group, and P g It is a polymerizable group.

[0390] Clause 20. The ophthalmic device according to Clause 19, wherein Y is an alkylene, oxaalkylene, alkoxide, or a combination thereof.

[0391] Clause 21. The ophthalmic device according to any one of Clauses 19 to 20, wherein P g Including styrene, vinyl carbonate, vinyl ether, vinyl carbamate, N-vinyl lactam, N-vinylamide, (meth)acrylate, or (meth)acrylamide.

[0392] Clause 22. The ophthalmic device according to Clause 21, wherein the second visible light filtering compound comprises 2-(2-(2-((9,10-dioxo-9,10-dihydroanthracene-1-yl)amino)ethoxy)ethoxy)ethyl methacrylate, 5-((9,10-dioxo-9,10-dihydroanthracene-1-yl)amino)pentyl methacrylate, 2-((9,10-dioxo-9,10-dihydroanthracene-1-yl)amino)ethyl methacrylate, and combinations thereof.

[0393] Clause 23. The ophthalmic device according to Clause 22, wherein the second visible light filtering compound is 2-(2-(2-((9,10-dioxo-9,10-dihydroanthracene-1-yl)amino)ethoxy)ethoxy)ethyl methacrylate having the following chemical structure:

[0394]

[0395] Clause 24. An ophthalmic device according to any one of Clauses 1 to 23, wherein the ophthalmic device further comprises a third light-filtering compound.

[0396] Clause 25. The ophthalmic device according to Clause 24, wherein the third visible light filtering compound exhibits one or more maximum visible light absorption values ​​between 550 nm and 660 nm.

[0397] Clause 26. The ophthalmic device according to any one of Clauses 24 to 25, wherein the third visible light filtering compound comprises a visible light filter of formula III:

[0398]

[0399] (III)

[0400] Where Y is an independent linking group each time it appears and P g It is an independent polymerizable group each time it appears.

[0401] Clause 27. The ophthalmic device according to Clause 26, wherein Y, each time it appears, is independently alkylene, oxaalkylene, alkyleneoxy, cycloalkylene, heterocycloalkylene, aryl, heteroaryl, alkylene-amide-alkylene, alkylene-amine-alkylene, or a combination thereof.

[0402] Clause 28. An ophthalmic device according to any one of Clauses 26 to 27, wherein P g Each time it appears, it independently includes styrene, vinyl carbonate, vinyl ether, vinyl carbamate, N-vinyl lactam, N-vinylamide, (meth)acrylate, or (meth)acrylamide.

[0403] Clause 29. The ophthalmic device according to Clause 28, wherein the third visible light filtering compound comprises 1,4-bis[2-methacryloyloxyethylamino]-9,10-anthraquinone, (9,10-dioxo-9,10-dihydroanthracene-1,4-diyl)bis(azadiyl))bis(ethane-2,1-diyl))bis(oxy))bis(ethane-2,1-diyl))bis(oxy))bis(ethane-2,1-diyl)bis(methyl 2-acrylate), or N,N'-((((((9,10-dioxo-9,10-dihydroanthracene-1,4-diyl)bis(azadiyl))bis(ethane-2,1-diyl))bis(oxy))bis(ethane-2,1-diyl))bis(oxy))bis(ethane-2,1-diyl))bisacrylamide.

[0404] Clause 30. The ophthalmic device according to Clause 29, wherein the third visible light filtering compound is (9,10-dioxo-9,10-dihydroanthracene-1,4-diyl)bis(azadiyl))bis(ethane-2,1-diyl))bis(oxy))bis(ethane-2,1-diyl))bis(oxy))bis(ethane-2,1-diyl))bis(methyl 2-acrylate):

[0405]

[0406] Clause 31. The ophthalmic device according to any one of Clauses 24 to 25, wherein the third visible light filtering compound comprises a visible light filter of formula IV:

[0407]

[0408] (IV)

[0409] Where R 1 It is H, methyl or Br and R 2 Each time it appears independently, it is C1-C6 alkyl, C1-C6 alkoxy, C1-C6 thioalkyl, C3-C7 cycloalkyl, aryl (preferably unsubstituted phenyl or phenyl substituted with alkyl or halogroup), benzyl, halogroup, hydroxyl, amino, NR 3 R 4 SO3H or SO3M (M is a monovalent cation, such as sodium or potassium ion), where R 3 and R 4 Independently H or C1-C6 alkyl, or two adjacent R 2 The groups combine with the carbon atoms to which they are attached to form cycloalkyl or aryl rings.

[0410] Clause 32. The ophthalmic device according to Clause 31, wherein the third visible light filtering compound is 1-amino-4-((4-(2-bromoacrylamido)-2-sulfonylphenyl)amino)-9,10-dioxo-9,10-dihydroanthracene-2-sulfonate, 4-((4-acrylamidophenyl)amino)-1-amino-9,10-dioxo-9,10-dihydroanthracene-2-sulfonate, 1-amino-4-((4-methacrylamidophenyl)amino)-9,10-dioxo-9,10-dihydroanthracene-2-sulfonate, or a combination thereof.

[0411] Clause 33. The ophthalmic device according to Clause 32, wherein the third visible light filtering compound is sodium 1-amino-4-((4-(2-bromoacrylamido)-2-sulfonylphenyl)amino)-9,10-dioxo-9,10-dihydroanthracene-2-sulfonate having the following chemical structure:

[0412]

[0413] Clause 34. The ophthalmic device according to Clause 24, wherein the third visible light filtering compound comprises a visible light filter of formula V:

[0414]

[0415] (V)

[0416] in:

[0417] m and n are independently 0, 1, 2, 3, or 4; T is a bond, O, or NR; Y is a linking group; P gIt is a polymerizable group; R is independently H, C1-C6 alkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, or YP each time it appears. g And R 1 and R 2 When present, it is independently C1-C6 alkyl, C1-C6 alkoxy, C1-C6 thioalkyl, C3-C7 cycloalkyl, aryl (preferably unsubstituted phenyl or phenyl substituted with alkyl or halogroup), halogroup, hydroxyl, amino, NR 3 R 4 , or benzyl, wherein R 3 and R 4 Independently H or C1-C6 alkyl, or two adjacent R 1 Or R 2 The groups combine with the carbon atoms to which they are attached to form cycloalkyl or aryl rings.

[0418] Clause 35. An ophthalmic device as described in Clause 34, wherein m and n are each independently 0 or 1.

[0419] Clause 36. An ophthalmic device according to any one of Clauses 34 to 35, wherein Y, in each occurrence, is independently alkylene, oxaalkylene, alkyleneoxy, cycloalkylene, heterocycloalkylene, aryl, heteroaryl, alkylene-amide-alkylene, alkylene-amine-alkylene, or a combination thereof.

[0420] Clause 37. An ophthalmic device according to any one of Clauses 34 to 35, wherein P g Including styrene, vinyl carbonate, vinyl ether, vinyl carbamate, N-vinyl lactam, N-vinylamide, (meth)acrylate, or (meth)acrylamide.

[0421] Clause 38. The ophthalmic device according to Clause 37, wherein the third visible light filtering compound comprises: 2-(2-cyano-2-(9H-thiosol-9-ylidene)acetamido)ethyl methacrylate; 2-(2-cyano-2-(9H-thiosol-9-ylidene)acetamido)ethyl acrylate; N-(2-(2-cyano-2-(9H-thiosol-9-ylidene)acetamido)ethyl)methacrylamide; N-(2-(2-cyano-2-(9H-thiosol-9-ylidene)acetamido)ethyl)acrylamide; 2-(2-cyano-N-methyl-2-(9H-thiosol-9-ylidene)acetamido)ethyl methacrylate; 2-cyano-2-(9H-thiosol-9-ylidene)-N-(2-(N-vinylacetamido)ethyl)acetamide; 2-(2-cyano-2-(9H-thiosol-9-ylidene)methacrylate 2-(2-cyano-2-(2,4-dichloro-9H-thiosol-9-ylidene)acetamido)ethyl methacrylate; 2-(2-(2-chloro-9H-thiosol-9-ylidene)-2-cyanoacetamido)ethyl methacrylate; 2-(2-cyano-2-(2-isopropyl-9H-thiosol-9-ylidene)acetamido)ethyl methacrylate; 2-(2-cyano-2-(2-isopropyl-9H-thiosol-9-ylidene)acetamido)ethyl methacrylate; -(2-cyano-2-(4-isopropyl-9H-thioxanthoxy-9-ylidene)acetamido)ethyl ester; 2-(2-cyano-2-(9H-thioxanthoxy-9-ylidene)acetoxy)ethyl ester of methacrylate; 1-cyano-2-oxo-1-(9H-thioxanthoxy-9-ylidene)-6,9,12,15,18-pentaoxa-3-aza-20-yl ester of methacrylate; or mixtures of two or more thereof.

[0422] Clause 39. The ophthalmic device according to Clause 38, wherein the third visible light filtering compound is ethyl 2-(2-cyano-2-(9H-thioxanthoxy-9-ylidene)acetamido)methacrylate having the following chemical structure:

[0423]

[0424] Clause 40. The ophthalmic device according to Clause 24, wherein the third visible light filtering compound comprises a visible light filter of formula VI:

[0425]

[0426] (VI)

[0427] Where m and n are independently 0, 1, 2, 3, or 4; R 1 and R 2 Each occurrence is independently of H, optional substituents, or -YP. g Or two adjacent R 1 Or R2 Groups and the atoms they are attached to combine to form optionally -YP g Substituted cycloalkyl or aryl rings; EWG is an electron-withdrawing group independently each time it appears; P g Each occurrence of Y is independently a polymerizable group; and each occurrence of Y is independently a linking group; wherein the compound of formula VI contains at least one P g Group.

[0428] Clause 41. An ophthalmic device as described in Clause 40, wherein m and n are independently 0 or 1.

[0429] Clause 42. The ophthalmic device according to any one of Clauses 40 to 41, wherein R 1 H, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 thioalkyl, C3-C7 cycloalkyl, aryl, halogroup, hydroxyl, amino, NR 4 R 5 , benzyl, SO3H, or SO3Na, wherein R 4 and R 5 It is independently H or C1-C6 alkyl.

[0430] Clause 43. The ophthalmic device according to any one of Clauses 40 to 42, wherein R 2 For -YP g .

[0431] Clause 44. An ophthalmic device according to any one of Clauses 40 to 43, wherein P g Each time it appears, it independently includes styrene, vinyl carbonate, vinyl ether, vinyl carbamate, N-vinyl lactam, N-vinylamide, (meth)acrylate, or (meth)acrylamide.

[0432] Clause 45. An ophthalmic device according to any one of Clauses 40 to 44, wherein Y, in each occurrence, is independently an alkylene group, an oxaalkylene group, an alkyleneoxy group, a cycloalkylene group, a heterocycloalkylene group, an aryl group, a heteroaryl group, an alkylene-amide-alkylene group, an alkylene-amine-alkylene group, or a combination of any one of the foregoing groups.

[0433] Clause 46. An ophthalmic device according to any one of Clauses 40 to 45, wherein the EWG is independently cyano, amide, ester, ketone, or aldehyde in each occurrence.

[0434] Clause 47. An ophthalmic device according to any one of Clauses 40 to 46, wherein said compound contains a YP g Group.

[0435] Clause 48. The ophthalmic device according to Clause 47, wherein the third visible light filtering compound comprises:

[0436] (a) 3-((9-(dicyanomethylene)-9H-xanthon-3-yl)oxy)propyl methacrylate;

[0437] (b) 3-((9-(dicyanomethylene)-9H-xanthon-2-yl)oxy)propyl methacrylate;

[0438] (c) 1-((9-(dicyanomethylene)-9H-xanthon-3-yl)oxy)propyl-2-yl methacrylate;

[0439] (d) 4-((9-(dicyanomethylene)-9H-xanthon-3-yl)oxy)butyl methacrylate;

[0440] (e) 3-((9-(dicyanomethylene)-9H-xanthon-3-yl)oxy)propyl acrylate;

[0441] (f) 1-((9-(dicyanomethylene)-9H-xanthon-3-yl)oxy)propyl-2-yl acrylate;

[0442] (g) 4-((9-(dicyanomethylene)-9H-xanthan-3-yl)oxy)butyl acrylate;

[0443] (h)N-(3-((9-(dicyanomethylene)-9H-xanthon-3-yl)oxy)propyl)methacrylamide;

[0444] (i)N-(3-((9-(dicyanomethylene)-9H-xanthon-3-yl)oxy)propyl)acrylamide;

[0445] (j) 3-((9-(dicyanomethylene)-9H-xanthon-3-yl)amino)propyl methacrylate;

[0446] (k) 17-((9-(dicyanomethylene)-9H-xanthon-3-yl)oxy)-3,6,9,12,15-pentaoxetane ester;

[0447] (l) or a mixture of two or more of them.

[0448] Clause 49. The ophthalmic device according to Clause 48, wherein the third visible light filtering compound is 3-((9-(dicyanomethylene)-9H-xanthon-3-yl)oxy)propyl methacrylate having the following chemical structure:

[0449]

[0450] Clause 50. The ophthalmic device according to any one of the preceding clauses, wherein the reactive mixture further comprises an ultraviolet-absorbing compound, wherein the ultraviolet-absorbing compound comprises benzophenone, benzotriazole, triazine, substituted acrylonitrile, salicylic acid derivative, benzoic acid derivative, cinnamic acid derivative, chalcone derivative, diphenyl ethyl ketone derivative, crotonic acid derivative, or mixtures thereof.

[0451] Clause 51. The ophthalmic device according to Clause 50, wherein the ultraviolet-absorbing compound is (2-(2'-hydroxy-5-methacryloyloxyethylphenyl)-2H-benzotriazole).

[0452] Clause 52. The ophthalmic device according to any one of the preceding clauses, wherein the ophthalmic device has the following transmittance:

[0453] (a) Between 1% and 50% in the wavelength range of 480 nm to 660 nm; and

[0454] (b) Between 20% and 70% in the wavelength range of 375 nm to 425 nm.

[0455] Clause 53. The ophthalmic device according to Clause 52, wherein the ophthalmic device has the following transmittance:

[0456] (a) Between 10% and 40% in the wavelength range of 480 nm to 660 nm; and

[0457] (b) Between 30% and 60% in the wavelength range of 375 nm to 425 nm.

[0458] Clause 54. An ophthalmic device according to any one of Clauses 52 to 53, wherein the transmittance between 480 nm and 660 nm differs from the average transmittance by 15% or less.

[0459] Clause 55. An ophthalmic device according to any one of Clauses 52 to 53, wherein the transmittance between 480 nm and 660 nm differs from the average transmittance by 10% or less.

[0460] Clause 56. An ophthalmic device according to any one of Clauses 52 to 53, wherein the transmittance between 480 nm and 660 nm differs from the average transmittance by 7.5% or less.

[0461] Clause 57. An ophthalmic device according to any one of Clauses 52 to 53, wherein the transmittance between 480 nm and 660 nm differs from the average transmittance by 5% or less.

[0462] Clause 58. An ophthalmic device according to any one of Clauses 54 to 57, wherein the average transmittance is between 20% and 50%.

[0463] Clause 59. An ophthalmic device according to any one of Clauses 52 to 58, wherein the transmittance is normalized using Formula 1 or Formula 2:

[0464] T N = [T - T min ] ÷ [T max - T min ]

[0465] Formula 1

[0466] or

[0467] %T N = 100 × { [T - T min ] ÷ [T max - T min ]}

[0468] Formula 2

[0469] Where T N T is the normalized transmittance calculated from the measured transmittance T. min The minimum transmittance value is between 300 nm and 800 nm, and T max The maximum transmittance value is between 300 nm and 800 nm.

[0470] Clause 60. An ophthalmic device according to any one of Clauses 1 to 59, wherein the ophthalmic device is formed by photocuring of the reactive mixture.

[0471] Clause 61. An ophthalmic device according to any one of Clauses 1 to 59, wherein the ophthalmic device is formed by thermosetting the reactive mixture.

[0472] Clause 62. An ophthalmic device according to any one of Clauses 1 to 59, wherein the ophthalmic device is formed by a combination of photocuring and thermocuring of the reactive mixture.

[0473] Clause 63. The ophthalmic device according to any one of the preceding clauses, wherein the ophthalmic device is selected from the group consisting of contact lenses, intraocular lenses, crystalline intraocular lenses, punctal plugs, and ocular inserts.

[0474] Clause 64. An ophthalmic device according to any one of the preceding clauses, wherein the ophthalmic device is a contact lens having a central region and a peripheral region.

[0475] Clause 65. The ophthalmic device according to Clause 64, wherein the molar concentrations of the first visible light filtering compound, the second visible light filtering compound, and the third visible light filtering compound are independently distributed in the central region and the peripheral region.

[0476] Clause 66. The ophthalmic device according to Clause 64, wherein the molar concentrations of the first visible light filtering compound, the second visible light filtering compound, and the third visible light filtering compound are independently greater in the central region than in the peripheral region.

[0477] Clause 67. The ophthalmic device according to Clause 64, wherein the molar concentrations of the first visible light filtering compound, the second visible light filtering compound, and the third visible light filtering compound are independently distributed only in the central region.

[0478] Clause 68. An ophthalmic device according to any one of Clauses 63 to 67, wherein the molar concentrations of the first visible light filtering compound, the second visible light filtering compound, and the third visible light filtering compound vary spatially independently to form an apodization distribution.

[0479] Clause 69. The ophthalmic device according to Clause 68, wherein the molar concentrations of the first visible light filtering compound, the second visible light filtering compound, and the third visible light filtering compound vary independently in the radial, circumferential, or combinations thereof to form the apodization distribution.

[0480] Clause 70. The ophthalmic device according to any one of Clauses 68 to 69, wherein the apodization distribution varies according to a mathematical function.

[0481] Clause 71. The ophthalmic device according to Clause 70, wherein the mathematical function is a linear function, a polynomial function, a Gaussian function, a Lorentz function, a logarithmic function, an exponential function, a numerical function, or a combination thereof.

[0482] Clause 72. The ophthalmic device according to any one of Clauses 68 to 71, wherein the apodization distribution further comprises a transparent region located at the center of the contact lens.

[0483] Clause 73. The ophthalmic device according to Clause 72, wherein the transparent region is shaped as a circle having a diameter between 0.1 mm and 5 mm.

[0484] Clause 74. The ophthalmic device according to Clause 73, wherein the transparent region has a diameter between 1 mm and 4 mm.

[0485] Clause 75. An ophthalmic device according to any one of Clauses 68 to 74, wherein the central region includes an optical region for correcting refractive errors selected from the group consisting of myopia, hyperopia, presbyopia and astigmatism.

[0486] Clause 76. The ophthalmic device according to any one of the preceding clauses, wherein the reactive monomer mixture comprises a hydrophilic component, an organosilicon-containing component, or a mixture thereof.

[0487] Clause 77. An ophthalmic device according to any one of the preceding clauses, wherein the device is a silicone hydrogel contact lens having a contact angle of about 100° or less, a water content of at least 25% by weight, and an oxygen permeability of at least 60 bar (edge-corrected).

[0488] Clause 78. An azooscopy device, said azooscopy device being formed by a method comprising:

[0489] (a) Providing a first reactive composition comprising: (i) a polymerization initiator capable of forming two or more free radical groups upon first activation, at least one of the two or more free radical groups being further activated by subsequent activation; (ii) one or more olefinic unsaturated compounds; and (iii) a crosslinking agent;

[0490] (b) subjecting the first reactive composition to a first activation step, wherein the first reactive composition polymerizes in the first activation step to form a crosslinked substrate network containing a covalently bonded, activatable free radical initiator;

[0491] (c) Contacting the crosslinked substrate network with a first grafted composition containing a first visible light filtering compound and a second visible light filtering compound, wherein the contact is performed under conditions that allow the first grafted composition to penetrate into the crosslinked substrate network; and

[0492] (d) The covalently bonded activatable free radical initiator is activated at one or more selective regions of the crosslinked substrate network, such that the first graft composition polymerizes with the crosslinked substrate network at the selective regions to form an apodization distribution.

[0493] Clause 79. The ophthalmic device according to Clause 78 further comprises: a third visible light filtering compound in the first grafting composition.

[0494] Clause 80. The ophthalmic device according to Clauses 78 to 79, wherein the first grafting composition of step (c) contains a crosslinking agent.

[0495] Clause 81. The ophthalmic device according to Clauses 78 to 79, wherein the first grafting composition in step (c) is free of crosslinking agent.

[0496] Clause 82. An ophthalmic device according to any one of Clauses 78 to 81, wherein the one or more olefinically unsaturated compounds of step (a) comprise one or more polymerizable groups independently selected from: (meth)acrylate, (meth)acrylamide, styrene, vinyl, N-vinyl lactam, N-vinylamide, O-vinyl ether, O-vinyl carbonate, O-vinyl carbamate, C 2-12 alkenyl, C 2-12 alkenylphenyl, C 2-12 alkenylnaphthalene, and C 2-6 alkenylphenyl-C 1-6 alkyl.

[0497] Clause 83. An ophthalmic device according to any one of Clauses 78 to 82, wherein the first reactive composition comprises a hydrophilic reactive component, an organosilicon-containing component, or a combination thereof.

[0498] Clause 84. An ophthalmic device according to any one of Clauses 78 to 83, wherein the first visible light filtering compound of the first grafted composition in step (c) comprises a compound having a chemical structure of formula (I).

[0499] Clause 85. An ophthalmic device according to any one of Clauses 78 to 84, wherein the second visible light filtering compound of the first grafted composition in step (c) comprises a compound having the chemical structure of formula (II).

[0500] Clause 86. An ophthalmic device according to any one of Clauses 78 to 85, wherein the third visible light filtering compound of the first grafted composition in step (c) comprises a compound having a chemical structure of formula (III), formula (IV), formula (V), formula (VI), or a combination thereof.

[0501] Clause 87. The ophthalmic device according to any one of Clauses 78 to 86, wherein the polymerization initiator is a bis(acylphosphine oxide), a bis(acylphosphine oxide), a diazo compound, a peroxide compound, azobis(acylphosphine oxide), azobis(acylphosphine oxide), peroxybis(acylphosphine oxide), peroxybis(acylphosphine oxide), azobis(α-hydroxy ketone), peroxybis(α-hydroxy ketone), azobis(1,2-dione), peroxybis(1,2-dione), germanium-based compound, tert-butyl 7-methyl-7-(tert-butylazo)peroxyoctanoate, or a combination thereof.

[0502] Clause 88. The ophthalmic device according to Clause 87, wherein the polymerization initiator is bisacylphosphine oxide.

[0503] Clause 89. The ophthalmic device according to Clause 88, wherein the first activation is irradiation using a wavelength between 400 nanometers and 450 nanometers.

[0504] Clause 90. The ophthalmic device according to Clause 89, wherein the first activation is irradiation using a wavelength between 420 nanometers and 450 nanometers.

[0505] Clause 91. The ophthalmic device according to any one of claims 89 to 90, wherein the second activation is irradiation using a wavelength between 365 nm and 420 nm.

[0506] Clause 92. An ophthalmic device according to any one of Clauses 78 to 91, wherein the method further comprises: after step (b), extracting the crosslinked substrate network with a solvent while maintaining the covalently bound activatable free radical initiator of the crosslinked substrate network, and optionally hydrating the extracted crosslinked substrate network with an aqueous solution.

[0507] Clause 93. An ophthalmic device according to any one of Clauses 78 to 92, wherein the method further comprises: after step (d), contacting the crosslinked substrate network with a second grafted composition comprising a mixture of a first visible light filtering compound, a second visible light filtering compound, and optionally a third visible light filtering compound different from the first grafted composition, and activating the retained covalently bound activatable free radical initiator such that the second grafted composition polymerizes with the crosslinked substrate network outside the selective region and optionally partially within the selective region.

[0508] Clause 94. An ophthalmic device according to any one of Clauses 78 to 93, wherein the method further comprises: after step (d), extracting the cross-linked substrate network with a solvent, hydrating the extracted cross-linked substrate network with an aqueous solution, and autoclaving the ophthalmic device.

[0509] Clause 95. An ophthalmic device according to any one of Clauses 78 to 94, wherein method steps (a) and (b) are performed in a mold assembly consisting of a front mold and a rear mold defining and closing a cavity of the shape of the ophthalmic device between the front mold and the rear mold, and method steps (c) and (d) are performed in the mold assembly after the rear mold has been removed.

[0510] Clause 96. An ophthalmic device according to any one of Clauses 78 to 95, wherein the activation in steps (b) and (d) is performed via a source of photochemical irradiation, and said source comprises a plurality of selectively controllable beams of said photochemical irradiation controlled by a digital micromirror device according to a predetermined script.

[0511] Clause 97. The ophthalmic device according to Clause 96, wherein the plurality of selectively controllable beams of light irradiated by the digital micromirror device according to a predetermined script are guided onto one or more surfaces of the ophthalmic device.

[0512] Clause 98. An ophthalmic device according to any one of Clauses 96 to 97, wherein the digital micromirror device includes an illumination source comprising at least one light-emitting diode.

[0513] Clause 99. An ophthalmic device according to any one of Clauses 78 to 98, wherein the predetermined script forms the apodization distribution.

[0514] Clause 100. An ophthalmic device according to any one of Clauses 78 to 99, wherein the ophthalmic device is selected from the group consisting of contact lenses, intraocular lenses, crystalline intraocular lenses, punctal plugs, and ocular inserts.

[0515] Clause 101. An ophthalmic device according to any one of Clauses 78 to 100, wherein the ophthalmic device is a hydrogel.

[0516] Clause 102. An ophthalmic device according to any one of Clauses 78 to 101, wherein the ophthalmic device has a central region and a peripheral region.

[0517] Clause 103. The ophthalmic device according to Clause 102, wherein the apodization distribution varies across the central region.

[0518] Clause 104. The ophthalmic device according to Clause 102, wherein the apodization distribution varies across the peripheral region.

[0519] Clause 105. The ophthalmic device according to Clause 102, wherein the apodization distribution varies across the central region and the peripheral region.

[0520] Clause 106. The ophthalmic device according to any one of Clauses 78 to 105, wherein the apodization distribution varies according to a mathematical function.

[0521] Clause 107. The ophthalmic device according to Clause 106, wherein the mathematical function is a linear function, a polynomial function, a Gaussian function, a Lorentz function, a logarithmic function, an exponential function, a numerical function, or a combination thereof.

[0522] Clause 108. The ophthalmic device according to any one of Clauses 78 to 107, wherein the apodization distribution further comprises a transparent region located at the center of the ophthalmic device.

[0523] Clause 109. The ophthalmic device according to Clause 108, wherein the transparent region is shaped as a circle having a diameter between 0.1 mm and 5 mm.

[0524] Clause 110. The ophthalmic device according to Clause 109, wherein the transparent region has a diameter between 1 mm and 4 mm.

[0525] Clause 111. An ophthalmic device according to any one of Clauses 78 to 110, wherein the central region includes an optical region for correcting refractive errors selected from the group consisting of myopia, hyperopia, presbyopia and astigmatism.

[0526] Clause 112. A method of manufacturing an azooscopy device, the method comprising:

[0527] (a) Providing a first reactive composition comprising: (i) a polymerization initiator capable of forming two or more free radical groups upon first activation, at least one of the two or more free radical groups being further activated by subsequent activation; (ii) one or more olefinic unsaturated compounds; and (iii) a crosslinking agent;

[0528] (b) subjecting the first reactive composition to a first activation step, wherein the first reactive composition polymerizes in the first activation step to form a crosslinked substrate network containing a covalently bonded, activatable free radical initiator;

[0529] (c) Contacting the crosslinked substrate network with a first grafted composition containing a first visible light filtering compound and a second visible light filtering compound, wherein the contact is performed under conditions that allow the first grafted composition to penetrate into the crosslinked substrate network; and

[0530] (d) The covalently bonded activatable free radical initiator is activated at one or more selective regions of the crosslinked substrate network, such that the first graft composition polymerizes with the crosslinked substrate network at the selective regions to form an apodization distribution.

[0531] Clause 113. The method according to Clause 112 further includes a third visible light filtering compound in the first grafting composition.

[0532] Clause 114. The method according to Clauses 112 to 113, wherein the first grafting composition of step (c) contains a crosslinking agent.

[0533] Clause 115. The method according to Clauses 112 to 113, wherein the first grafting composition of step (c) is free of crosslinking agent.

[0534] Clause 116. The method according to any one of Clauses 112 to 115, wherein the one or more olefinically unsaturated compounds of step (a) comprise one or more polymerizable groups independently selected from: (meth)acrylate, (meth)acrylamide, styrene, vinyl, N-vinyl lactam, N-vinylamide, O-vinyl ether, O-vinyl carbonate, O-vinyl carbamate, C 2-12 alkenyl, C 2-12 alkenylphenyl, C 2-12 alkenylnaphthalene, and C 2-6 alkenylphenyl-C 1-6 alkyl.

[0535] Clause 117. The method according to any one of Clauses 112 to 116, wherein the first reactive composition comprises a hydrophilic reactive component, an organosilicon-containing component, or a combination thereof.

[0536] Clause 118. The method according to any one of Clauses 112 to 117, wherein the first visible light filtering compound of the first grafted composition in step (c) comprises a compound having the chemical structure of formula (I).

[0537] Clause 119. The method according to any one of Clauses 112 to 118, wherein the second visible light filtering compound of the first grafted composition in step (c) comprises a compound having the chemical structure of formula (II).

[0538] Clause 120. The method according to any one of Clauses 112 to 119, wherein the third visible light filtering compound of the first grafted composition in step (c) comprises a compound having a chemical structure of formula (III), formula (IV), formula (V), formula (VI) or a combination thereof.

[0539] Clause 121. The method according to any one of Clauses 112 to 120, wherein the polymerization initiator is a bis(acylphosphine oxide), a bis(acylphosphine oxide), a diazo compound, a dieperoxide compound, azobis(acylphosphine oxide), azobis(acylphosphine oxide), peroxybis(acylphosphine oxide), peroxybis(acylphosphine oxide), azobis(α-hydroxy ketone), peroxybis(α-hydroxy ketone), azobis(1,2-dione), peroxybis(1,2-dione), germanium-based compound, tert-butyl 7-methyl-7-(tert-butylazo)peroxyoctanoate, or a combination thereof.

[0540] Clause 122. The method according to Clause 121, wherein the polymerization initiator is bisacylphosphine oxide.

[0541] Clause 123. The method according to Clause 122, wherein the first activation is irradiation using a wavelength between 400 nm and 450 nm.

[0542] Clause 124. The method according to Clause 123, wherein the first activation is irradiation using a wavelength between 420 nm and 450 nm.

[0543] Clause 125. The method of any one of claims 123 to 124, wherein the second activation is irradiation using a wavelength between 365 nm and 420 nm.

[0544] Clause 126. The method according to any one of Clauses 112 to 125, wherein the method further comprises: after step (b), extracting the crosslinked substrate network with a solvent while maintaining the covalently bound activatable free radical initiator of the crosslinked substrate network, and optionally hydrating the extracted crosslinked substrate network with an aqueous solution.

[0545] Clause 127. The method according to any one of Clauses 112 to 126, wherein the method further comprises: after step (d), contacting the crosslinked substrate network with a second grafted composition containing a mixture of a first visible light filtering compound, a second visible light filtering compound, and optionally a third visible light filtering compound different from the first grafted composition, and activating the retained covalently bound activatable free radical initiator such that the second grafted composition polymerizes with the crosslinked substrate network outside the selective region and optionally partially within the selective region.

[0546] Clause 128. The method according to any one of Clauses 112 to 127, wherein the method further comprises: after step (d), extracting the cross-linked substrate network with a solvent, hydrating the extracted cross-linked substrate network with an aqueous solution, and autoclaving the ophthalmic device.

[0547] Clause 129. The method according to any one of Clauses 112 to 128, wherein method steps (a) and (b) are performed in a mold assembly consisting of a front mold and a rear mold defining and closing a cavity of the shape of the ophthalmic device between the front mold and the rear mold, and method steps (c) and (d) are performed in the mold assembly after the rear mold has been removed.

[0548] Clause 130. The method according to any one of Clauses 112 to 129, wherein the activation in steps (b) and (d) is performed via a source of photochemical irradiation, the source comprising a plurality of selectively controllable beams of the photochemical irradiation controlled by a digital micromirror device according to a predetermined script.

[0549] Clause 131. The method according to Clause 130, wherein the plurality of selectively controllable beams of light irradiated by the digital micromirror device according to a predetermined script are directed onto one or more surfaces of the ophthalmic device.

[0550] Clause 132. The method according to any one of Clauses 112 to 131, wherein the digital micromirror device includes an illumination source containing at least one light-emitting diode.

[0551] Clause 133. The method according to any one of Clauses 112 to 132, wherein the predetermined script forms the apodization distribution.

[0552] Clause 134. The method according to any one of Clauses 112 to 133, wherein the ophthalmic device is selected from the group consisting of contact lenses, intraocular lenses, crystalline intraocular lenses, punctal plugs, and ocular inserts.

[0553] Clause 135. The method according to any one of Clauses 112 to 134, wherein the ophthalmic device is a hydrogel.

[0554] Clause 136. The method according to any one of Clauses 112 to 135, wherein the ophthalmic device has a central region and a peripheral region.

[0555] Clause 137. The method according to Clause 136, wherein the apodization distribution varies across the central region.

[0556] Clause 138. The method according to Clause 136, wherein the apodization distribution varies across the peripheral region.

[0557] Clause 139. The method according to Clause 136, wherein the apodization distribution varies across the central region and the peripheral region.

[0558] Clause 140. The method according to any one of Clauses 112 to 139, wherein the apodization distribution varies according to a mathematical function.

[0559] Clause 141. The method described in accordance with Clause 140, wherein the mathematical function is a linear function, a polynomial function, a Gaussian function, a Lorentz function, a logarithmic function, an exponential function, a numerical function, or a combination thereof.

[0560] Clause 142. The method according to any one of Clauses 112 to 141, wherein the apodization distribution further comprises a transparent region located at the center of the method.

[0561] Clause 143. The method according to Clause 142, wherein the transparent area is shaped as a circle having a diameter between 0.1 mm and 5 mm.

[0562] Clause 144. The method according to Clause 143, wherein the transparent region has a diameter between 1 mm and 4 mm.

[0563] Clause 145. The method according to any one of Clauses 136 to 144, wherein the central region includes an optical region for correcting refractive errors selected from the group consisting of myopia, hyperopia, presbyopia and astigmatism.

[0564] Clause 146. A compound having a chemical structure described by Formula II:

[0565]

[0566] (II)

[0567] Where Y is a linking group, and P g It is a polymerizable group.

[0568] Clause 147. The compound described in Clause 146, wherein Y is an alkylene, oxaalkylene, alkeneoxy, or a combination thereof.

[0569] Clause 148. The compound according to any one of Clauses 146 to 147, wherein the alkylene group has five to ten carbon atoms.

[0570] Clause 149. The compound according to any one of Clauses 146 to 147, wherein the oxaalkylene has five to ten carbon atoms.

[0571] Clause 150. The compound according to any one of Clauses 146 to 147, wherein the alkeneoxy group is an ethylideneoxy group (CH2CH2O). p And p is between three and six.

[0572] Clause 151. The compound according to any one of Clauses 146 to 150, wherein P g Including styrene, vinyl carbonate, vinyl ether, vinyl carbamate, N-vinyl lactam, N-vinylamide, (meth)acrylate, or (meth)acrylamide.

[0573] Clause 152. The compound according to Clause 151, wherein the compound comprises 2-(2-(2-((9,10-dioxo-9,10-dihydroanthracene-1-yl)amino)ethoxy)ethoxy)ethyl methacrylate, 5-((9,10-dioxo-9,10-dihydroanthracene-1-yl)amino)pentyl methacrylate, or 2-((9,10-dioxo-9,10-dihydroanthracene-1-yl)amino)ethyl methacrylate.

[0574] Clause 153. A compound having a chemical structure described by formula VII:

[0575]

[0576] (VII)

[0577] Where R 1 It is H or methyl, and R is wherein 2 Each time it appears independently, it is C1-C6 alkyl, C1-C6 alkoxy, C1-C6 thioalkyl, C3-C7 cycloalkyl, aryl (preferably unsubstituted phenyl or phenyl substituted with alkyl or halogroup), benzyl, halogroup, hydroxyl, amino, NR 3 R 4 , where R 3 and R 4 Independently H or C1-C6 alkyl, or two adjacent R 1 Or R 2 The groups combine with the carbon atoms to which they are attached to form cycloalkyl or aryl rings.

[0578] Clause 154. The compound according to Clause 153, wherein the compound is sodium 4-((4-acrylamidophenyl)amino)-1-amino-9,10-dioxo-9,10-dihydroanthracene-2-sulfonate or sodium 1-amino-4-((4-methacrylamidophenyl)amino)-9,10-dioxo-9,10-dihydroanthracene-2-sulfonate.

[0579] Clause 155. A composition prepared by free radical polymerization of a mixture of reactive monomers comprising any one of the compounds described in Clauses 146 to 154.

[0580] Clause 156. The composition according to Clause 155, wherein the composition is a homopolymer, copolymer, block copolymer, graft copolymer, or polymer network.

[0581] Clause 157. The composition according to any one of Clauses 155 to 156, wherein the reactive monomer mixture further comprises a hydrophilic component, an organosilicon-containing component, a crosslinking agent, an initiator, or a mixture thereof.

[0582] Clause 158. The composition according to Clause 157 further comprises a visible light filtering compound selected from the group consisting of formulas (I), (III), (V), (VI) and combinations thereof.

[0583] Clause 159. The composition according to Clause 158, wherein the composition is a hydrogel.

[0584] Clause 160. An ophthalmic device comprising any one of the compositions described in Clauses 155 to 159.

[0585] Clause 161. The ophthalmic device according to Clause 160, wherein the ophthalmic device is selected from the group consisting of intraocular lenses, crystalline intraocular lenses, contact lenses, corneal inlays, corneal exophthalmic inlays, or corneal inserts.

[0586] Clause 162. An ophthalmic device as described in Clause 161, wherein the ophthalmic device is a contact lens.

[0587] Some embodiments of the present invention will now be described in detail in the following examples.

[0588] Test methods

[0589] Measure the UV-Vis spectra of compounds in solution on a Perkin Elmer Lambda 45, Agilent Cary 6000i, or Ocean Optics QE65 PRO (DH-2000-BAL light source) UV-VIS scanning spectrometer. Allow the instrument to thermally equilibrate for at least 30 minutes before use. For the Perkin Elmer instrument, use a scan range of 200 nm to 800 nm; a scan rate of 960 nm / min; a slit width of 4 nm; and the mode should be set to transmittance or absorbance, with baseline correction selected. For the Cary instrument, use a scan range of 200 nm to 800 nm; a scan rate of 600 nm / min; a slit width of 2 nm; and the mode should be set to transmittance or absorbance, with baseline correction selected. For the Ocean Optics instrument, use a scan range of 200 nm to 800 nm; a slit width of 10 µm; and the mode should be set to transmittance or absorbance, with baseline correction selected. Perform baseline correction before analyzing the sample using the automatic zeroing function.

[0590] Using a wetting solution, measure the UV-Vis spectrum of contact lenses partially formed from the claimed composition on a Perkin Elmer Lambda 45 UV / VIS, Agilent Cary 6000i, or Ocean Optics UV-VIS scanning spectrometer. Allow the instrument to thermally equilibrate for at least thirty minutes before use. Baseline correction is performed using cuvettes comprising a plastic two-piece lens holder and the same solvent. These two-piece contact lens holders are designed to hold the sample in the quartz cuvette at the point where the incident beam passes. A reference cuvette also includes a two-piece holder. To ensure a constant sample thickness, all lenses are made using the same mold. If necessary, measure the center thickness of the contact lenses using an electronic thickness gauge, and obtain the percentage of transmission spectrum by averaging the data from three individual lenses.

[0591] It is important to ensure that the outer surface of the cuvette is completely clean and dry, and that there are no air bubbles inside the cuvette. Measurement repeatability can be improved by keeping the reference cuvette and its lens holder constant, and by using the same sample cuvette and its lens holder for all samples, thus ensuring that both cuvettes are correctly inserted into the instrument.

[0592] To address some instrument and testing method errors in various apodized contact lenses, a normalized UV-VIS transmission spectrum (“normalized %T” or “%T”) is generated from the measured UV-VIS transmission spectrum by applying the following normalization factor or formula to the measured transmittance, expressed in “T”, for each wavelength between 200 and 800 nm. N ), to calculate as shown in Formula 1, expressed as "T". N Normalized transmittance of “”:

[0593] T N = [T - T min ] ÷ [T max - T min ]

[0594] Formula 1

[0595] Where T min The minimum transmittance value between 300 nm and 800 nm, and T max The maximum transmittance values ​​are between 300 nm and 800 nm. UV-VIS spectra are typically plotted as a percentage of transmittance versus wavelength, as shown in Equation 2:

[0596] %T N = 100 × { [T - T min ] ÷ [T max - T min ]}

[0597] Formula 2

[0598] Before creating a spectrum or spectrum, it is easiest to apply a normalization factor to a spectral data table in Microsoft Excel.

[0599] The refractive index (“RI”) of the contact lens was measured using a Leica ARIAS 500 Abbe refractometer in manual mode or a Reichert ARIAS 500 Abbe refractometer in automatic mode with a prism gap distance of 100 micrometers. The instrument was calibrated with deionized water at 20°C (± 0.2°C). The prism assembly was opened and the test lens was placed on the lower prism between the magnetic points closest to the light source. If the prism was dry, a few drops of saline solution were applied to the bottom prism. The front curved surface of the lens was then placed against the bottom prism. The prism assembly was then closed. The control was adjusted so that the terminator appeared behind the crosshair area, and the refractive index was measured. RI measurements were performed on five test lenses. The average RI calculated from the five measurements was recorded as the refractive index and its standard deviation.

[0600] Water content was determined using gravimetric analysis. Lenses were allowed to equilibrate in the wetting solution for 24 hours. Each of the three test lenses was removed from the wetting solution using a cotton swab and placed on an absorbent towel moistened with the wetting solution. Both sides of the lens were in contact with the absorbent towel. The test lens was placed into the weighing pan using tweezers and weighed. Two more samples were prepared and weighed. All weight measurements were performed in triplicate, and the average of those values ​​was used for calculation. The wet weight was defined as the total weight of the pan and the wet lens minus the weight of the weighing pan alone.

[0601] Measure the dry weight by placing the sample pan in a vacuum oven preheated to 60°C for 30 minutes. Apply a vacuum until the pressure reaches at least 1 inch of mercury (Hg); lower pressures are permissible. Close the vacuum valve and pump, and allow the lenses to dry for at least 12 hours, typically overnight. Open the vent valve to allow dry air or dry nitrogen to enter. Bring the oven to atmospheric pressure. Remove the pan and weigh it. The dry weight is defined as the total weight of the pan and the dried lens minus the weight of the weighing pan alone. Calculate the water content of the test lens as follows: Water content % = (Wet weight - Dry weight) / Wet weight × 100.

[0602] Calculate the average and standard deviation of the water content, and report the average as the water content of the test lens.

[0603] Oxygen permeability (“D”) is determined by polarographic methods broadly described in ISO 9913-1:1996 and ISO 18369-4:2006, but with the following variations. kMeasurements were performed in an environment containing 2.1% oxygen, created by equipping the test chamber with nitrogen and air inputs set at an appropriate ratio, such as 1800 mL / min of nitrogen and 200 mL / min of air. The adjusted oxygen concentration was used to calculate t / D. k Borate buffer solution was used. Dark current was measured using a humidified pure nitrogen environment without applying MMA lenses. The lenses were not dried before measurement. Four lenses were stacked instead of using lenses with different thicknesses (t) measured in centimeters. A curved sensor was used instead of a flat sensor; the radius was 7.8 mm. Calculations for a 7.8 mm radius sensor and a 10% (v / v) airflow are as follows:

[0604] D k / t = (Measured current - Dark current) × (2.97 × 10⁻⁸ mL O₂ / (µA - sec - cm⁻¹)) 2 -mm Hg)

[0605] Edge correction and material D k related.

[0606] For all D values ​​less than 90 lbler k value:

[0607] t / D k (Edge Correction) = (1 + (5.88×t))×(t / D) k )

[0608] For D between 90 and 300 lbs k value:

[0609] t / D k (Edge Correction) = (1 + (3.56×t))×(t / D) k )

[0610] For D greater than 300 lblers k value:

[0611] t / D k (Edge Correction) = (1 + (3.16×t))×(t / D) k )

[0612] The uncorrected D is calculated based on the reciprocal of the slope obtained from the linear regression analysis of the data. k Where x is the center thickness in centimeters and y is t / D k The value. On the other hand, the marginal correction D is calculated based on the reciprocal of the slope obtained from the linear regression analysis of the data. k (EC D) k”, where x is the center thickness in centimeters and y is the t / D of the edge correction. k Value. The obtained D k Values ​​are reported in Palestinian units.

[0613] The wettability of the lens was determined using a calibrated Kruss K100 tensiometer at room temperature (23±4°C) via a modified Wilhelmy plate method, with a surfactant-free borate-buffered saline solution as the probe solution. All equipment had to be clean and dry; vibration around the instruments had to be minimized during testing. Wettability was typically reported as the advancing contact angle (“Kruss DCA”). The tensiometer was equipped with a humidity generator, and a temperature and hygrometer were placed in the tensiometer chamber. Relative humidity was maintained at 70±5%. The experiment was conducted by immersing a lens specimen of known circumference in a wetting solution with known surface tension, while simultaneously measuring the forces exerted on the sample due to wetting using a sensitive balance. The advancing contact angle of the packaging solution on the lens was determined based on the force data collected during sample immersion. The receding contact angle was determined from the force data while the sample was removed from the liquid. The Wilhelmy plate method is based on the following equation: Fg = γρcosθ - B, where F = wetting force between the liquid and the lens (mg), and g = gravitational acceleration (980.665 cm / sec). 2 γ = surface tension of the probe liquid (dyne / cm), ρ = circumference of the contact lens at the liquid / lens meniscus (cm), θ = dynamic contact angle (degrees), and B = buoyancy (mg). B is zero when the immersion depth is zero. Typically, test strips are cut from the center region of the contact lens. Each strip is approximately 5 mm wide and 14 mm long, attached to a metal clamp using plastic tweezers, pierced with a metal wire hook, and equilibrated in the wetting solution for at least 3 hours. Each sample is then cycled four times, and the results are averaged to obtain the advance and retreat contact angles of the lens. A typical measurement speed is 12 mm / min. The sample is kept completely immersed in the wetting solution during data acquisition and analysis without contacting the metal clamp. The values ​​of five individual lenses are averaged to obtain the reported advance and retreat contact angles of the experimental lens.

[0614] Using a Kruss K100™ instrument at room temperature and deionized water as the probe solution (Sessile Drop), determine lens wettability using the suspension drop technique. Rinse the lens to be tested in deionized water to remove residual wetting solution. Place each test lens on a lint-free absorbent towel moistened with the wetting solution. Ensure both sides of the lens are in contact with the absorbent towel to remove surface moisture without drying the lens. To ensure proper flattening, place the lens "cup-side down" on the convex surface of the contact lens mold. Place the mold and lens on the suspension drop instrument holder, ensuring the syringe is correctly centered. Using DSA 100-Drop Shape Analysis software, form a 3-4 μL droplet of deionized water at the syringe tip, ensuring the droplet is suspended from the lens. Smoothly release the droplet onto the lens surface by lowering the needle. Immediately withdraw the needle after dispensing the droplet. Allow the droplet to equilibrate on the lens for 5-10 seconds and measure the contact angle between the droplet image and the lens surface. Typically, evaluate three to five lenses and report the average contact angle. The contact angle is measured on both the front and rear surfaces of the lens, as shown in the table for the front surface (“FC”) and the base surface (“BC”).

[0615] The mechanical properties of the contact lens were measured using a tensile testing machine, such as the Instron Model 1122 or 5542 equipped with a force sensor and pneumatic grip control. Negative-power lenses are preferred due to their uniform thickness distribution at the center. A dog-bone shaped sample slice from a negative-power spherical lens, with a length of 0.522 inches, an "ear" width of 0.276 inches, and a "neck" width of 0.213 inches, was placed in a fixture and stretched at a constant strain rate of 2 inches / minute until it broke. The center thickness of the dog-bone sample was measured using an electronic thickness gauge prior to testing. The initial measurement length (L) of the sample was measured. o ) and the length at fracture (L) f ). Measure at least five specimens for each composition and calculate the percentage elongation at break using the average value: Elongation percentage = [(L f - L o ) / L o ×100. Tensile modulus is calculated as the slope of the initial linear portion of the stress-strain curve; the unit of modulus is pounds per square inch (psi). Tensile strength is calculated from the peak load and the initial cross-sectional area: Tensile strength = peak load divided by the initial cross-sectional area; the unit of tensile strength is psi. Toughness is calculated from the fracture energy and the initial sample volume: Toughness = fracture energy divided by the initial sample volume; the unit of toughness is in-lbs / in. 3 .

[0616] Contact lens parameters in a wetting solution were measured using a calibrated double interferometry method. These parameters included the equivalent spherical power (diopter or D) at multiple openings, the cylindrical power (diopter or D) at multiple openings, the diameter (mm), the central thickness (mm or mm), the sagittal height (mm or mm), and the root mean square (RMS) optical path wavefront deviation from the lens design target (in micrometers (μm)). Where, for measurements using a 6.5 mm opening, spherical / cylindrical power and coma were removed. The instrument consisted of a custom propionic interferometer for measuring wavefront parameters and a Lumetrics OptiGauge for measuring the dimensional parameters of sagittal height and central thickness. ® The system consists of two low-coherence interferometers. The two individual instruments in the combination are similar to those in the Lumetrics Clearwave. ™ Plus, and the software is similar to Lumetrics OptiGaugeControl Center v7.0 or later. Utilizing Clearwave. ™ Additionally, a camera is used to locate the lens edge and then calculate the lens center, which is then used to align a 1310 nm interferometer probe at the lens center for measuring sagittal height and central thickness. Transmitted wavefronts are also collected using wavefront sensors (shack-Hartmann sensors) in series. Several parameters from the transmitted wavefront in contact with the lens are measured, and other parameters are calculated from those measurements.

[0617] Based on the collected data, difference terms are calculated by comparing the measured values ​​with the target. These include, for example, the root mean square optical path wavefront deviation from the lens design target in μm (spherical power / cylindrical power and coma are removed) (RMS_65) measured using a 6.5 mm opening; the second equivalent spherical power deviation from the lens design target in diopters (D) measured using a 5 mm opening; the deviation from the lens design target diameter in mm (DMD); the deviation from the lens design target base curvature radius in mm calculated from the sagittal height measured according to ISO 18369-3 and the target lens diameter (BCD); and the deviation from the lens design target center thickness in mm (CTD).

[0618] The following abbreviations will be used throughout the embodiments and figures, and have the following meanings:

[0619] L: Rise

[0620] mL: milliliters

[0621] Equiv. or eq.: equivalent

[0622] kg: kilogram

[0623] g: grams

[0624] mg: milligram

[0625] mol: mole

[0626] mmol: millimole

[0627] M: Moore

[0628] mM: millimoles

[0629] Da: Daltons or g / moles

[0630] kDa: A unit of atomic mass equal to 1,000 Daltons.

[0631] min: minutes

[0632] sec: seconds

[0633] mm: millimeter

[0634] cm: centimeter

[0635] µm: micrometer

[0636] nm: nanometer

[0637] λ: wavelength

[0638] wt.%: weight %

[0639] Cmpd: compound

[0640] TLC: Thin-layer chromatography

[0641] 1 H NMR: Proton nuclear magnetic resonance spectrum

[0642] UV-VIS: Ultraviolet-Visible Spectrum

[0643] HEV: High Energy Visible (Light)

[0644] LED: Light Emitting Diode

[0645] mW: milliwatt

[0646] AU: Absorbance unit

[0647] %T: Percentage of transmission

[0648] BC: Base Curved Surface Plastic Mold

[0649] FC: Front Curved Surface Plastic Mold

[0650] PP: Polypropylene, a homopolymer of propylene.

[0651] TT: Tuftec, which stands for hydrogenated styrene-butadiene block copolymer (Asahi Kasei Chemicals).

[0652] Z: Zeonor, which is a polycyclic olefin thermoplastic polymer (Nippon Zeon Co Ltd).

[0653] RMM: Reactive Monomer Mixture

[0654] DMA: N,N-dimethylacrylamide (Jarchem)

[0655] HEMA: 2-Hydroxyethyl Methacrylate (Bimax)

[0656] PVP K90: Poly(N-vinylpyrrolidone) (ISP Ashland)

[0657] EGDMA: Ethylene dimethacrylate (Esstech)

[0658] TEGDMA: Tetraethylene dimethacrylate (Esstech)

[0659] Tegomer MA: Bis-3-methacryloyloxy-2-hydroxypropyloxypropyl polydimethylsiloxane (M n =2000 g / mol, n=20 (Shin Etsu)

[0660]

[0661] Omnirad 1870: Blend of bis(2,6-dimethoxybenzoyl)-2,4,4-trimethylpentylphosphine oxide with 1-hydroxycyclohexylphenyl ketone (IGM Resins, BASF, or Ciba Specialty Chemicals)

[0662] AIBN: Azobisisobutyronitrile [CAS 78-67-1]

[0663] mPDMS: Mono-n-butyl-terminated monomethacryloyloxypropyl-terminated polydimethylsiloxane (M... n =800 Daltons - 1500 Daltons (Gelest)

[0664] HO-mPDMS: Mono-n-butyl-terminated mono(2-hydroxy-3-methacryloyloxypropoxy)-propyl-terminated polydimethylsiloxane (M n = 400 to 1400 grams per mole (Ortec or DSM-Polymer Technology Group)

[0665] OH-mPDMS (n=4):

[0666]

[0667] OH-mPDMS (n=15) is an oligomeric macromonomer with a number-average degree of polymerization (DP) of 15.

[0668]

[0669] SiMAA: 2-Acrylic acid, 2-methyl-2-hydroxy-3-[3-[1,3,3,3-tetramethyl-1-[(trimethylsilyl)oxy]disiloxyl]propoxy]propyl ester (Toray) or 3-(3-(1,1,1,3,5,5,5-heptamethyltrisiloxane-3-yl)propoxy)-2-hydroxypropyl methacrylate

[0670] Norbloc: 2-(2'-hydroxy-5-methacryloyloxyethylphenyl)-2H-benzotriazole (Janssen)

[0671] IMT Blue: Sodium 1-amino-4-((4-(2-bromoacrylamido)-2-sulfonylphenyl)amino)-9,10-dioxo-9,10-dihydroanthracene-2-sulfonate

[0672]

[0673] RB246: (((9,10-dioxo-9,10-dihydroanthracene-1,4-diyl)bis(azadiyl))bis(4,1-phenylene))bis(ethane-2,1-diyl)bis(methyl 2-acrylate)

[0674]

[0675] RB247: 1,4-bis[2-methacryloyloxyethylamino]-9,10-anthraquinone

[0676]

[0677] Compound B: 2-(2-cyano-2-(2-methoxy-10-butylacridin-9(10H)-ylidene)acetamido)ethyl methacrylate

[0678]

[0679] Compound C: 2-(2-cyano-2-(9H-thioxanth-9-ylidene)acetamido)ethyl methacrylate (prepared as described in US20210061934)

[0680]

[0681] Compound D: 3-((9-(dicyanomethylene)-9H-xanthon-3-yl)oxy)propyl methacrylate

[0682]

[0683] D3O: 3,7-Dimethyl-3-octanol (Vigon)

[0684] DIW: Deionized Water

[0685] NPA: n-Propanol or 1-Propanol or 1-Propyl alcohol

[0686] IPA: Isopropyl alcohol

[0687] PG: 1,2-Propanediol or 1,2-Propanediol

[0688] DMF: Dimethylformamide

[0689] CDCl3: Deuterated chloroform

[0690] HCl: hydrochloric acid

[0691] PS: Borate buffer wetting solution: Dissolve 18.52 g (300 mmol) of boric acid, 3.7 g (9.7 mmol) of sodium borate decahydrate and 28 g (197 mmol) of sodium sulfate in enough deionized water to fill a 2-liter volumetric flask.

[0692] Example 1—2-(2-cyano-2-(2-methoxy-10-propylacridine-9(10H)-ylidene) as shown in Scheme 1 Synthesis of ethyl methacrylate (compound A)

[0693]

[0694] Option 1

[0695] 12.40 g of 2-iodobenzoic acid (approximately 0.05 mol), 12.32 g of 4-methoxyaniline (approximately 2 equivalents), 6.91 g of anhydrous potassium carbonate (approximately 0.05 mol), and 300 mg of copper powder (4.76 mmol) were placed in a 100 mL three-necked round-bottom flask equipped with a magnetic stir bar and a reflux condenser. 30 mL of deionized water was added to the solid mixture, and the system was heated under reflux for 6 hours with constant stirring. The mixture solidified upon cooling to room temperature. The system was diluted with deionized water and gradually poured into a 1 equivalent of hydrochloric acid aqueous solution with stirring. The mixture was stirred at room temperature for 30 minutes, then filtered through a sintered glass funnel and dried in a vacuum oven at 60 °C. The remaining 2-((4-methoxyphenyl)amino)benzoic acid was washed with 3 × 100 mL of deionized water and used “as is” for intramolecular cyclization. 1H NMR (CDCl3) -δ 3.81 (3H, s), 6.66 (1H, t), 6.89-6.93 (3H, m), 7.16 (2H, d), 7.27 (1H, t), 7.99 (1H, d), 9.12 (1H, bs)

[0696] 12.5 g of 2-((4-methoxyphenyl)amino)benzoic acid and 100 mL of Eaton's acid (a 10 wt% methanesulfonic acid solution of P₂O₅) were added to a 250 mL round-bottom flask equipped with a magnetic stir bar and a reflux condenser. The mixture was heated at 90 °C (hood temperature) for 5 hours with constant stirring, while the process was monitored by TLC. After cooling to room temperature, the reaction mixture was poured onto ice, stirred for 30 minutes, and filtered through a sintered glass funnel. The residue 2-methoxyacridin-9(10H)-one was washed with 3 × 100 mL of deionized water, then washed with acetonitrile, and dried in a vacuum oven at 60 °C. 1 H NMR(DMSO d6) -δ 3.86 (3H, s), 7.23 (1H, t), 7.41 (1H, dd), 7.52 (1H, d), 7.53 (1H,d), 7.63 (1H, d), 7.70 (1H, dt), 8.23 ​​(1H, d)

[0697] 5.4 g of 2-methoxyacridin-9(10H)-one (0.0244 mol) and 12.9 g of cesium carbonate (approximately 1.5 equivalents) were charged into a 250 mL round-bottom flask equipped with a magnetic stir bar and a reflux condenser. The solids were dried under vacuum at 80 °C, and then the system was placed under a nitrogen atmosphere and 80 mL of anhydrous N,N-dimethylformamide was added to the flask. 6.0 g of 1-bromopropane (approximately 2 equivalents) was added to the flask, and the mixture was heated at 50 °C (hood temperature) for 36 hours. TLC showed the presence of two compounds (O-alkylated and N-alkylated). The organic matter was poured into 200 mL of deionized water and extracted into approximately 150 mL of ethyl acetate. The organic matter was then washed with 3 × 100 mL of water, followed by washing with 3 × 100 mL of dilute HCl aqueous solution to remove the O-alkylated acridine byproduct, and finally washed with deionized water. TLC of the organic matter indicated the presence of a single compound, 2-methoxy-10-propylacridin-9(10H)-one, which was dried under reduced pressure and used for subsequent conversion. 1H NMR (CDCl3) -δ 1.12 (3H,t), 1.93 (2H, m), 4.28 (2H, dd), 7.25 (1H, ddd), 7.35 (1H, dd), 7.45 (1H, dd), 7.66(1H, m), 7.96 (1H, d), 7.57 (1H, dd).

[0698] 4.5 g of 2-methoxy-10-propylacridin-9(10H)-one (0.017 mol) and 6.4 g of N-2-methacryloyloxyethyl-2-cyanoacetamide (0.033 mol) were added to a 250 mL three-necked round-bottom flask equipped with a magnetic stir bar and a reflux condenser. The system was placed under a nitrogen atmosphere, and 20 mL of dichloromethane was added to the mixture, stirring until homogeneous. After cooling the system in an ice bath, titanium tetrachloride (4.5 mL, 7.78 g, 0.041 mol) was added dropwise to the mixture, and stirring was continued for another 15 minutes. 5 mL of pyridine (4.9 g, 0.06 mol) was added to the mixture, and the mixture was heated to ambient temperature and then refluxed for 8 hours. After cooling the mixture to room temperature, it was poured onto a dilute aqueous HCl solution, and the product mixture was extracted into dichloromethane. The evaporation was carried out under reduced pressure, and product compound A was purified by rapid chromatography. 1 ¹H NMR (CDCl₃)-δ 1.07 (3H, t), 1.87 (3H, s), 1.91 (2H, m), 3.58 (2H, dd), 3.85 (3H, s), 4.07 (2H, dd), 4.18 (2H, t), 5.5 (1H, dd), 6.03 (1H, ss), 6.07 (1H, t), 7.07 (1H, t), 7.14 (1H, dd), 7.23 (2H, two doublets), 7.48 (1H, m), 7.92 (1H, bs).

[0699] Example 2—2-(2-cyano-2-(2-methoxy-10-butylacridin-9(10H)-ylidene) as shown in Scheme 2 Synthesis of ethyl methacrylate (compound B)

[0700]

[0701] Option 2

[0702] 10.0 g of 2-methoxyacridin-9(10H)-one (0.044 mol) and 19.6 g of cesium carbonate (approximately 1.25 equivalents) were charged into a 200 mL round-bottom flask equipped with a magnetic stir bar and a reflux condenser. The solids were dried under vacuum at 80 °C, and then the system was placed under a nitrogen atmosphere and 60 mL of anhydrous DMSO was added to the flask. 7.55 g of 1-bromobutane (approximately 1.25 equivalents) was added to the flask, and the mixture was heated at 110 °C (hood temperature) for 6 hours. The two products were observed by TLC and showed very similar retention factors and were inseparable by chromatography. The cooled suspension was poured into 500 mL of deionized water, and the mixture was stirred at room temperature for 30 minutes. The organic matter was extracted into ethyl acetate and washed with 3 × 200 mL of deionized water. NMR analysis of the organic compound revealed the presence of an O-alkylated acridine derivative in addition to the desired compound, 2-methoxy-10-butylacridin-9(10H)-one. This material can be used "as is" for Knoevenagel condensation. Preferably, the crude product is washed with a dilute aqueous HCl solution to remove the O-alkylated acridine derivative, thereby yielding pure 2-methoxy-10-butylacridin-9(10H)-one. 1 HNMR (CDCl3) - δ 1.05 (3H, t), 1.55 (2H, m), 1.82 (2H, m), 4.31 (2H, dd), 7.25(1H, ddd), 7.34 (1H, dd), 7.45 (1H, dd), 7.68 (1H, m), 7.96 (1H, d), 8.56 (1H,dd).

[0703] 10.0 g of a crude product mixture containing 2-methoxy-10-butylacridin-9(10H)-one and 15 g of N-2-methacryloyloxyethyl-2-cyanoacetamide were added to a 250 mL three-necked round-bottom flask equipped with a magnetic stir bar and a reflux condenser. The system was placed under a nitrogen atmosphere, and 150 mL of dichloromethane was added to the mixture, stirring until homogeneous. After cooling the system in an ice bath, titanium tetrachloride (10 mL, 17.3 g, 1.092 mol) was added dropwise to the mixture, and stirring was continued for another 15 minutes. 10 mL of pyridine (9.82 g, 0.12 mol) was added to the mixture, and the mixture was heated to ambient temperature and then refluxed for 8 hours.

[0704] TLC revealed the presence of several compounds, including unreacted O-alkylated derivatives present in the starting material mixture. The major product—compound B—was a slightly more polar, dark brown-orange species. This major product was isolated after quenching the system in a dilute aqueous HCl solution, followed by water extraction and chromatographic analysis. 1¹H NMR (CDCl₃) -δ 1.04 (3H,t), 1.51 (2H, m), 1.87 (3H, s, 2H, m), 3.58 (2H, dd), 3.84 (3H, s), 4.12 (2H, dd), 4.19 (2H, t), 5.55 (1H, dd), 6.03 (1H, bs), 6.07 (1H, t), 7.07 (1H, t), 7.15 (1H, dd), 7.25 (2H, two doublets), 7.48 (1H, t), 7.75 (1H, bs), 7.92 (1H, bs).

[0705] Alternative synthesis of compound B is shown in scheme 3.

[0706]

[0707] Option 3

[0708] Synthesis of ethyl 2-(2-(10-butyl-2-methoxyacridin-9(10H)-ylidene)-2-cyanoacetamido)methacrylate or compound B when R is n-butyl: 9.43 g of triphenylphosphine (36 mmol) and 120 mL of anhydrous dichloromethane were added to a 500 mL RBF container equipped with a magnetic stir bar and a reflux condenser. Bromine (5.76 g, 33 mmol) was added dropwise to the solution, and the mixture was stirred at room temperature for 30 minutes. Then, 10-butyl-2-methoxyacridin-9(10H)-one (8.43 g, 30 mmol) was added to the mixture, and the mixture was heated under reflux for 18 hours. Ethyl 2-(2-cyanoacetamido)methacrylate (8.23 g, 36 mmol, 1.4 equivalents) was added to the reaction mixture, and the reaction mixture was heated and stirred for 8 hours. At this point, very little starting material was observed by TLC, and an orange-brown compound was observed at the baseline. The mixture was cooled to room temperature, and 150 mL of aqueous sodium carbonate solution (approximately 10.6 g, 100 mmol dissolved Na₂CO₃) was added. The mixture was stirred for 30 minutes. Treatment with alkali yielded the desired compound. The aqueous layer was extracted with an additional dichloromethane. Organic matter was removed under reduced pressure, and the product was purified by chromatography. The raw material was first washed with dichloromethane and ethyl acetate through silica gel to remove polar components. Then, after loading the material with a minimal amount of dichloromethane, a second pass was performed with ethyl acetate / hexane or diethyl ether / hexane to give the desired product in >80% yield.

[0709] Table 1 shows the selected absorption characteristics of compounds A and B.

[0710]

[0711] exist Figure 1 The UV-VIS absorption spectra of 0.1 mM methanol solutions of compounds A and B are shown and superimposed on the literature spectra of macular pigments.

[0712] Example 3—Synthesis of 2-(2-cyanoacetamido)ethyl methacrylate (A) and methacrylate as shown in Scheme 4 2-(2-cyano-2-(9H-thioxanthoxy-9-ylidene)acetamido)ethyl ester

[0713]

[0714] Option 4

[0715] In a nitrogen atmosphere, methyl cyanoacetate (40 g, 0.4037 mol) and 25 mL dichloromethane were stirred in a 500 mL three-necked round-bottom flask equipped with a reflux condenser. 2-Aminoethanol (23.8 g, 0.3897 mol, approximately 0.97 eq.) was added to the solution via a feeding funnel, after which the temperature was raised and methylene chloride began to reflux. After the exothermic reaction ceased, external heat was applied to continue the gentle reflux for a total of two hours. Ethanolamine was then not observed by thin-layer chromatography.

[0716] The reaction can also be carried out at room temperature and is completed within a few hours.

[0717] The mixture was cooled to room temperature, and all methylene chloride was evaporated under reduced pressure. The remaining oil was washed three times with 50 mL of ethyl acetate to remove unreacted starting material and nonpolar impurities. The remaining ethyl acetate was then removed under reduced pressure, and the resulting oil was used for acylation without any further purification.

[0718] In a three-necked round-bottom flask equipped with a reflux condenser, a feeding funnel, and a magnetic stir bar, crude N-2-hydroxyethylacetamide derivative was dissolved in 150 mL of dichloromethane containing 40 g of pyridine (approximately 0.5 mol). The flask was immersed in an ice bath and cooled to approximately 0 °C. Methacrylamide chloride (45.76 g, approximately 0.44 mol) was added dropwise through the feeding funnel, and the resulting reaction mixture was warmed to room temperature while continuously stirring. Methanol (20 mL) was added to the flask to quench any unreacted methacryloyl chloride. Volatile components were removed by rotary evaporation under reduced pressure, and the crude product was dissolved in 800 mL of diluted HCl aqueous solution. The resulting aqueous solution was extracted three times with 100 mL of hexane in a separatory funnel to remove any nonpolar impurities. The organic layer was discarded. Sodium chloride was added to the aqueous layer, which was then extracted three times with 300 mL of ethyl acetate. Approximately 50 mg of BHT was added as an inhibitor to the combined organic fractions, and ethyl acetate was removed by rotary evaporation under reduced pressure. During solvent removal, the crude product crystallized from the solution. When approximately 100 mL of ethyl acetate remained in the flask, 250 mL of hexane was added, and the crude product was separated by vacuum filtration using a sintered glass funnel. Thin-layer chromatography indicated the presence of a single compound. The filter cake was washed twice with 150 mL of hexane and then dried under vacuum at 40 °C to give 53 g (approximately 70% yield) of 2-(2-cyanoacetamido)ethyl methacrylate (A). 1 ¹H NMR (500MHz, CDCl₃) δ 1.93 (3H, s, CH₃), 3.36 (2H, s, CNCH₂), 3.60 (2H, dd, CH₂NH), 4.26 (2H, t, CH₂OC=O), 5.59 (1H, m, ethylene), 6.11 (1H, bs, ethylene), 6.52 (1H, bs, NH).

[0719] Under a nitrogen atmosphere, a mixture of 9H-thioxanth-9-one (2.12 g, 0.01 mol) and thionyl chloride (5 mL, 8.2 g, about 0.07 mol) was refluxed in a 50 mL round-bottom flask with constant stirring. After two hours, the red solution was evaporated to dryness to ensure that all unreacted thionyl chloride was removed from the system. Ethyl 2-(2-cyanoacetamido)methacrylate (A) (2.3 g, 0.0117 mol, about 1.17 eq.) and 15 mL of dichloromethane were added, and the resulting reaction mixture was heated to reflux under nitrogen. The reaction was monitored by thin-layer chromatography. After two hours, no change was observed in the chromatogram, so the reactive mixture was cooled to room temperature. 2-(2-cyano-2-(9H-thioxanthoxy-9-ylidene)acetamido)ethyl methacrylate (B) was isolated as yellow crystals (3.2 g, yield 82%) after passing through a short silica gel column (CH2Cl2, followed by 8 wt% EtOAc in CH2Cl2). The UV-VIS transmission spectrum of a 0.2 mM methanol solution of compound B was obtained in [the following section is missing from the original text]. Figure 1 As shown in the image. 1 ¹H NMR (500MHz, CDCl₃) δ 1.84 (3H, s, CH₃), 3.47 (2H, m, CH₂NH), 4.01 (2H, t, CH₂OC=O), 5.55 (1H, m, ethylene), 5.91 (1H, bs, NH), 5.98 (1H, bs, ethylene), 7.24 (1H, t, Ar-H), 7.31 (1H, t, Ar-H), 7.39 (2H, m, Ar-H), 7.49 (1H, d, Ar-H), 7.55 (1H, m, Ar-H), 7.61 (1H, d, Ar-H), 8.04 (1H, m, Ar-H).

[0720] Example 4. Methacrylic acid 3-((9-(dicyanomethylene)-9H-xanthon-3-yl)oxy as shown in Scheme 5 Synthesis of propyl methyl ester (compound D) .

[0721]

[0722] Option 5

[0723] Synthesis of 3-((9-oxo-9H-xanthon-3-yl)oxy)propyl acetate :

[0724] A suspension of 42.4 g (0.2 mol) of 3-hydroxy-9H-xanthon-9-one, 70.0 g (0.2 mol) of Cs₂CO₃, and sodium iodide (catalytic amount 200 mg) was dried under vacuum in a 500 mL round-bottom flask with a magnetic stir bar. Anhydrous DMSO (250 mL) was added, followed by 2-chloroethyl methacrylate (30.0 g, 0.2 mol). The reaction mixture was heated overnight at 70 °C. TLC monitoring indicated complete consumption of the hydroxyxanthonone, with the formation of a less polar derivative. The reaction mixture was cooled to room temperature and slowly poured into a dilute aqueous hydrochloric acid solution with continuous stirring. After stirring for 30 minutes, the off-white solid was separated by vacuum filtration through a sintered glass funnel. The filter cake was washed with deionized water, followed by two washes with 200 mL of hexane. 3-((9-oxo-9H-xanthon-3-yl)oxy)propyl acetate was dried under vacuum at 60 °C to constant weight.

[0725] Synthesis of 3-((9-oxo-9H-xanthon-3-yl)oxy)propanol :

[0726] 27 g of 3-((9-oxo-9H-xanthon-3-yl)oxy)propyl acetate was stirred in approximately 700 mL of methanol at room temperature. During this process, 20 mL of 10 N sodium hydroxide aqueous solution was added to the mixture, followed by approximately 30 mL of deionized water. TLC monitoring showed that the hydrolysis reaction was completed within a few minutes. The mixture was slowly acidified by adding dilute hydrochloric acid aqueous solution, followed by the addition of 150 mL of deionized water while continuously stirring the system. 3-((9-oxo-9H-xanthon-3-yl)oxy)propanol was separated by vacuum filtration using a sintered glass funnel, washed with an additional amount of water, and finally dried in a vacuum oven at 60 °C.

[0727] Synthesis of 3-((9-oxo-9H-xanthon-3-yl)oxy)propyl methacrylate :

[0728] In a 1-liter three-necked round-bottom flask equipped with a magnetic stir bar and a reflux condenser, 25 g of 3-((9-oxo-9H-xanthon-3-yl)oxy)propanol and 15 mL (10.89 g) of triethylamine were stirred in 300 mL of anhydrous acetonitrile. Methacryl chloride (9.9 g) was added dropwise to the flask, and the mixture was stirred for one hour. The volatile components were evaporated under reduced pressure, and the resulting solid was washed and filtered through a sintered glass funnel, followed by rinsing with deionized water. The residue was further washed with dilute hydrochloric acid solution, then with deionized water, and finally with hexane. 3-((9-oxo-9H-xanthon-3-yl)oxy)propyl methacrylate was then dried in a rotary evaporator at a bath temperature maintained below 20°C.

[0729] Synthesis of 3-((9-(dicyanomethylene)-9H-xanthon-3-yl)oxy)propyl methacrylate (compound D) :

[0730] In a round-bottom flask equipped with a magnetic stir bar and a reflux condenser, 6.76 g of 3-((9-oxo-9H-xanthon-3-yl)oxy)propyl methacrylate and 15 mL of thionyl chloride were heated at 65 °C (covered temperature) for 2 hours. The mixture was cooled to room temperature, and excess thionyl chloride was evaporated under reduced pressure while keeping the bath temperature below 20 °C. 3.96 g of malononitrile was added to the flask, followed by 25 mL of anhydrous dichloromethane, and the mixture was stirred and heated under gentle reflux for two hours. The mixture was cooled to room temperature, then rinsed through a short silicone stopper and eluted with dichloromethane. The volatile components were evaporated under reduced pressure while keeping the temperature below 20 °C, and the solids were then suspended in cold methanol (100 mL) and stirred for 20 minutes. The crude product was separated by vacuum filtration, and the filter cake was washed with additional cold methanol. 3-((9-(dicyanomethylene)-9H-xanthon-3-yl)oxy)propyl methacrylate was further purified by silica gel column elution with dichloromethane. 1 ¹H NMR (500MHz, CDCl₃) -δ 1.95 (3H, CH₃), 2.25 (2H, m, CH₂), 4.20 (2H, t, CH₂benzyl), 4.37 (2H, t, CH₂O ester), 5.59 (1H, m, vinyl), 6.12 (1H, m, vinyl), 6.90 (1H, dAr-H), 6.97 (1H, dd, Ar-H), 7.40 (1H, ddd, Ar-H), 7.45 (1H, dd, Ar-H), 7.68 (1H, ddd, Ar-H), 8.50 (1H, d, Ar-H), 8.57 (1H, dd, Ar-H). Figure 2 The UV-VIS absorption spectra of 0.2 mM methanol solutions of compounds C and D are shown. Compound D exhibits an absorption of 19,341 L·mol⁻¹. -1 •cm -1 The molar extinction coefficient, such as in λ 最大值 = Calculated at 396 nm in 0.2 mM dichloromethane.

[0731] Example 5. (9,10-dioxo-9,10-dihydroanthracene-1,4-diyl)bis(azadiyl) as shown in Scheme 6. bis(ethane-2,1-diyl) bis(oxy) bis(ethane-2,1-diyl) bis(oxy) bis(ethane-2,1-diyl) bis(2- Synthesis of methyl acrylate .

[0732]

[0733] Option 6

[0734] Anthracene-1,4,9,10-tetraol (75 g, 0.3096 mol), 2-ethoxyethanol (225 mL), 2-(2-(2-aminoethoxy)ethoxy)ethanol-1-ol (161.58 g, 1.083 mol), and sodium dithionite (107.81 g, 0.6192 mol) were added to an autoclave under a nitrogen atmosphere and ambient temperature. The reaction mixture was vigorously stirred at 85 °C under 5 kg nitrogen pressure for 16 hours. The reaction progress was monitored by thin-layer chromatography (5% methanol in dichloromethane solution). Upon completion of the reaction, the reaction mixture was cooled to ambient temperature. Dichloromethane (2000 mL) and deionized water (1000 mL) were added, and the reaction mixture was stirred for 5–7 minutes. The organic layers were separated, and the aqueous layer was extracted with dichloromethane (500 mL). The combined organic extracts were washed with water (2 × 1000 mL) and brine (2 × 1000 mL). Activated carbon (75 g) was added to the organic layer and stirred overnight at room temperature. The activated carbon was removed by diatomaceous earth filtration and washed with dichloromethane (3000 mL). The filtrate was dried over sodium sulfate and filtered. The solvent was removed under reduced pressure to give the crude product 1,4-bis((2-(2-(2-hydroxyethoxy)ethoxy)ethyl)amino)anthracene-9,10-dione (126 g). The crude product was stirred in ethyl acetate (1000 mL) at 60 °C for one hour, followed by stirring at ambient temperature for 14–16 hours. The solid was filtered and washed with ethyl acetate (300 mL). The residue was air-dried at 45 °C for 14–16 hours to give 1,4-bis((2-(2-(2-hydroxyethoxy)ethoxy)ethyl)amino)anthracene-9,10-dione (100.0 g; yield = 64%) as a blue solid. 1 H-NMR (DMSO-d) 6 , 400MHz): ẟ 3.70-3.45 (m, 24H), 7.51 (s, 2H), 7.78 (m, 2H), 8.25 (m, 2H), 10.89 (br s, 2H).

[0735] At room temperature, triethylamine (302.1 g, 414.97 mL, 2.9866 mol) was added to a solution of 1,4-bis((2-(2-(2-hydroxyethoxy)ethoxy)ethyl)amino)anthracene-9,10-dione (75.0 g, 0.1493 mol) in tetrahydrofuran (1500 mL). After stirring for 15 minutes, a solution of methacrylamide chloride (62.43 g, 58.35 mL, 0.5973 mol) in tetrahydrofuran (150 mL) was added dropwise while maintaining the reaction temperature between 0 °C and -5 °C. The reaction mixture was stirred at 0 °C to -5 °C for 1 hour, and the reaction progress was monitored by thin-layer chromatography (5% methanol in dichloromethane solution). When the reaction was complete, ethyl acetate (3000 mL) and deionized water (2000 mL) were added at 10 °C–15 °C, and the reaction mixture was stirred for 8–10 minutes. The organic layer was separated and the aqueous layer was extracted with ethyl acetate (3 × 1000 mL). The combined organic layers were washed with deionized water (4 × 2000 mL) and brine (1000 mL), dried over sodium sulfate, and filtered. The solvent was removed under reduced pressure to give a crude product (86 g), which was then purified by column chromatography on 230-400 mesh silica gel (2.8 kg) by elution with a 0.1%-0.5% methanol-dichloromethane solution to give (9,10-dioxo-9,10-dihydroanthracene-1,4-diyl)bis(azadiyl))bis(ethane-2,1-diyl))bis(oxy))bis(ethane-2,1-diyl))bis(oxy))bis(ethane-2,1-diyl)bis(methyl 2-acrylate) or compound E, as a blue solid (22 g; yield = 23%). 1 H-NMR (DMSO-d) 6 , 400MHz): ẟ 1.83 (s, 6H), 4.20-4.16 (m, 20H), 4.21 (m, 4H), 5.62 (s, 2H), 5.98 (s, 2H), 7.5 (s, 2H), 7.77 (m, 2H), 8.23 (m, 2H), 10.87 (t, 2H, J = 5.2, 5.6Hz). Figure 3 The UV-VIS absorption spectra of (9,10-dioxo-9,10-dihydroanthracene-1,4-diyl)bis(azadiyl)bis(ethane-2,1-diyl)bis(oxy)bis(ethane-2,1-diyl)bis(oxy)bis(ethane-2,1-diyl)bis(methyl 2-acrylate) labeled as compound E and 1,4-bis[2-methacryloyloxyethylamino]-9,10-anthraquinone designated as RB247 in 0.2 mM methanol solution are shown.

[0736] Example 6. N,N'-((((((9,10-dioxo-9,10-dihydroanthracene-1,4-diyl)bis as shown in Scheme 7 (azadiyl))bis(ethane-2,1-diyl))bis(oxy))bis(ethane-2,1-diyl))bis(oxy))bis(ethane-2,1- Synthesis of Diacrylamide .

[0737]

[0738] Option 7

[0739] Anthracene-1,4,9,10-tetraol (10.0 g, 0.042 mol), 2,2'-(ethane-1,2-diylbis(oxy))bis(ethane-1-amine) (61.17 g, 0.413 mol), and sodium bisulfite (10.0 g, 0.058 mol) were added to a tube at ambient temperature and then sealed. The reaction mixture was stirred at 85 °C for 16 hours. The reaction progress was monitored by thin-layer chromatography (20% methanol in dichloromethane solution). After the reaction was complete, the reaction mixture was cooled to room temperature and deionized water (250 mL) and dichloromethane (250 mL) were added. The aqueous layer was re-extracted with dichloromethane (250 mL). The combined organic extracts were washed with deionized water (250 mL) and brine (250 mL). The organic phase was then dried over anhydrous sodium sulfate, filtered, and evaporated under reduced pressure to give a crude product (23 g), which was used in the next step without further purification.

[0740] At room temperature, triethylamine (46.5 g, 64 mL, 0.46 mol) was slowly added to a solution of 1,4-bis((2-(2-(2-aminoethoxy)ethoxy)ethyl)amino)anthracene-9,10-dione (23.0 g, 0.046 mol) in dichloromethane (690 mL), followed by dropwise addition of a solution of acryloyl chloride (12.4 g, 10.8 mL, 0.1379 mol) in dichloromethane (46 mL), while maintaining the reaction temperature between 0 °C and 5 °C. The mixture was then stirred for two hours. The reaction progress was monitored by thin-layer chromatography (5% methanol in dichloromethane). At the completion of the reaction, a saturated sodium bicarbonate solution (300 mL) was added to the reaction mixture at 0–5 °C. The organic layer was separated, and the aqueous layer was extracted again with dichloromethane (2 × 230 mL). The combined organic extracts were washed with deionized water (460 mL) and brine (460 mL), dried over sodium sulfate, filtered, and evaporated under reduced pressure at 30 °C to give N,N'-(((((((9,10-dioxo-9,10-dihydroanthracene-1,4-diyl)bis(azadiyl))bis(ethane-2,1-diyl))bis(oxy))bis(ethane-2,1-diyl))bis(oxy))bis(ethane-2,1-diyl))diacrylamide (27 g). The crude product was then purified by column chromatography using 100-200 mesh silica gel, eluted with 0.2%-0.6% methanol / dichloromethane, to give a blue solid (65% yield). 1 H-NMR (DMSO-d) 6, 400MHz): ẟ 3.71-3.28 (m, 24H), 5.56 (s, J = 10.8Hz, 2H), 6.09 (d, J = 16.8Hz, 2H), 6.24 (m, 2H), 7.47 (s, 2H), 7.85 (m, 2H), 8.24-8.15 (m, 4H), 10.86 (br s, 2H). Figure 4 The UV-VIS absorption spectra of N,N'-((((((9,10-dioxo-9,10-dihydroanthracene-1,4-diyl)bis(azadiyl))bis(ethane-2,1-diyl))bis(oxy))bis(ethane-2,1-diyl))bis(oxy))bis(ethane-2,1-diyl))bis(oxy))bis(ethane-2,1-diyl))diacrylamide or compound F in 0.2 mM methanol solution are shown.

[0741] Example 7—1-cyano-2-oxo-1-(9H-thioxanth-9-ylidene)-6,9-methacrylic acid as shown in Scheme 8 Synthesis of 12-trioxa-3-azatetradecane-14-yl ester

[0742]

[0743] Option 8

[0744] Synthesis of 2-cyano-N-(2-(2-(2-(2-(2-hydroxyethoxy)ethoxy)ethoxy)ethyl)acetamide

[0745] Under nitrogen atmosphere, a solution of 0.98 equivalents of 2-(2-(2-(2-aminoethoxy)ethoxy)ethoxy)ethanol-1-ol in 25 mL of dichloromethane was added to a solution of methyl cyanoacetate (1.0 equivalent) in 50 mL of chloromethane in a 100 mL three-necked round-bottom flask equipped with a reflux condenser. As the reaction temperature increased, the reaction mixture began to reflux. After the exothermic reaction ceased, external heat was applied to continue reflux for a total of two hours, after which 2-(2-(2-(2-aminoethoxy)ethoxy)ethoxy)ethanol-1-ol was not observed by thin-layer chromatography. The reaction can also be carried out at room temperature, but this would require several hours. The mixture was cooled to room temperature, and dichloromethane was removed by rotary evaporation under reduced pressure. The residual oil was washed three times with 50 mL of ethyl acetate to remove unreacted starting material and nonpolar impurities. The residual ethyl acetate was then removed by rotary evaporation under reduced pressure, and the resulting oil, 2-cyano-N-(2-(2-(2-(2-(2-hydroxyethoxy)ethoxy)ethoxy)ethyl)acetamide (compound G), was used for subsequent acylation without any further purification.

[0746] Synthesis of 1-cyano-2-oxo-6,9,12-trioxa-3-azatetradecane-14-yl methacrylate

[0747] In a three-necked round-bottom flask equipped with a reflux condenser, a feeding funnel, and a magnetic stir bar, compound G was dissolved in 150 mL of dichloromethane containing pyridine (2.5 equivalents). The flask was immersed in an ice bath and cooled to 0°C, and methacryloyl chloride (1.5 equivalents) was added dropwise through the feeding funnel. The resulting reaction mixture was heated to room temperature while continuously stirring. Then, methanol (20 mL) was added to the flask to quench any unreacted methacryloyl chloride. Volatile components were removed by rotary evaporation under reduced pressure, and the crude product was dissolved in 800 mL of diluted hydrochloric acid solution. The resulting aqueous solution was extracted three times with 100 mL of hexane in a separatory funnel to remove any nonpolar impurities. The organic layer was discarded. Sodium chloride was added to the aqueous layer, which was then extracted three times with 300 mL of ethyl acetate. Approximately 50 mg of butylated hydroxytoluene (BHT) or 2,6-di-tert-butyl-4-methylphenol was added as an inhibitor to the combined organic fractions, and ethyl acetate was removed by rotary evaporation under reduced pressure. During solvent removal, the crude product crystallized out of solution. When approximately 100 mL of ethyl acetate remained in the flask, 250 mL of hexane was added, and the crude product was separated by vacuum filtration using a sintered glass funnel. The filter cake was washed twice with 150 mL of hexane and then dried under vacuum at 40 °C to give 1-cyano-2-oxo-6,9,12-trioxa-3-azatetradecane-14-yl methacrylate (compound H).

[0748] 1-Cyano-2-oxo-1-(9H-thioxanth-9-ylidene)-6,9,12-trioxa-3-azatetradecanoic acid Synthesis of alkyl-14-yl esters

[0749] Under a nitrogen atmosphere, a mixture of 9H-thioxanth-9-one (1.0 equivalent) and thionyl chloride (7.0 equivalent) was refluxed in a 100 mL round-bottom flask with constant stirring. After two hours, the red solution was evaporated to dryness to remove excess thionyl chloride from the system. Compound H (1.05 equivalent) was dissolved in 100 mL of dichloromethane and then added to the flask. The resulting reaction mixture was heated to reflux under nitrogen. The reaction was monitored by thin-layer chromatography until completion (2 hours). The reactive mixture was cooled to room temperature. The solvent was removed on a rotary evaporator, and the desired product, 1-cyano-2-oxo-1-(9H-thioxanth-9-ene)-6,9,12-trioxa-3-azatetradecane-14-yl methacrylate, was isolated after passing through a short silica gel column (dichloromethane to remove unreacted 9H-thioxanth-9-ene, followed by a dichloromethane solution of 30% ethyl acetate), as a thick, yellow, oily substance. 1H-NMR (CDCl3, 500MHz): ẟ 8.10 (1H, dd, J = 5.0Hz, J = 10.0Hz), 7.72 (1H, dd, J = 5.0Hz, J = 10.0Hz), 7.56 - 7.59 (2H, m), 7.42 - 7.47 (2H,m), 7.36 - 7.40 (1H, m), 7.29 - 7.32 (1H, m), 6.11 (1H, s), 5.57 (1H, s), 4.26 - 4.28 (2H, m), 3.69 - 3.71 (2H, m), 3.58 - 3.64 (4H, m), 3.50 - 3.52(2H, m), 3.38 - 3.42 (6H, m), 1.94 (3H, s). Figure 5 The UV-VIS absorption spectrum of 1-cyano-2-oxo-1-(9H-thioxanthyl-9-ylidene)-6,9,12-trioxa-3-azatetradecane-14-yl methacrylate in 0.2 mM methanol solution is shown.

[0750] Example 8—1-(10-butyl-2-methoxyacrylic acid-9(10H)-ylidene)- as shown in Scheme 9 1-Cyano-2-oxo-6,9,12,15,18-pentaoxa-3-aza-20-yl ester (hypothetical example) .

[0751]

[0752] Option 9

[0753] Synthesis of 2-((4-methoxyphenyl)amino)benzoic acid

[0754] 2-Iodobenzoic acid (1.0 equivalent), 4-methoxyaniline (2 equivalent), potassium carbonate (1.0 equivalent), and 300 mg of copper powder were placed in a 100 mL three-necked round-bottom flask equipped with a magnetic stir bar and a reflux condenser. Deionized water (30 mL) was added to the solid mixture, and the reaction mixture was heated under reflux for 6 hours with constant stirring. The mixture solidified upon cooling to room temperature. The reaction mixture was diluted with deionized water and gradually poured into a 1 equivalent of hydrochloric acid aqueous solution with stirring. The reaction mixture was stirred at room temperature for 30 minutes, then filtered through a sintered glass funnel and dried in a vacuum oven at 60 °C. The resulting 2-((4-methoxyphenyl)amino)benzoic acid was washed with deionized water (3 × 100 mL) and used “as is” for intramolecular cyclization.

[0755] Synthesis of 2-methoxyacridin-9(10H)-one

[0756] 12.5 g of 2-((4-methoxyphenyl)amino)benzoic acid and 100 mL of Eaton acid (10 wt% methanesulfonic acid solution of P₂O₅) were added to a 250 mL round-bottom flask equipped with a magnetic stir bar and a reflux condenser. The mixture was heated at 90 °C (covered temperature) for 5 hours with constant stirring, while monitoring the reaction progress by thin-layer chromatography. After cooling to room temperature, the reaction mixture was poured onto crushed ice, stirred for 30 minutes, and filtered through a sintered glass funnel. The resulting 2-methoxyacridin-9(10H)-one was washed with deionized water (3 × 100 mL), then with acetonitrile, and dried in a vacuum oven at 60 °C.

[0757] Synthesis of 2-methoxy-10-butylacridin-9(10H)-one

[0758] 5.4 g of 2-methoxyacridin-9(10H)-one (0.0244 mol) and 12.9 g of cesium carbonate (1.5 equivalents) were charged into a 250 mL round-bottom flask equipped with a magnetic stir bar and a reflux condenser. The solids were dried under vacuum at 80 °C, and then the system was placed under a nitrogen atmosphere and 80 mL of anhydrous N,N-dimethylformamide was added to the flask. 6.0 g of 1-bromobutane (2 equivalents) was added to the flask, and the mixture was heated at 50 °C (hood temperature) for 36 hours. Thin-layer chromatography showed the presence of two compounds (O-alkylated and N-alkylated). The organic matter was poured into 200 mL of deionized water and extracted into about 150 mL of ethyl acetate. The organic matter was then washed with deionized water (3 × 100 mL), followed by washing with dilute HCl aqueous solution (3 × 100 mL) to remove the O-alkylated acridine byproduct, and finally washed with deionized water. Thin-layer chromatography of the organic fraction confirmed the presence of a single compound, 2-methoxy-10-propylacridin-9(10H)-one, which was dried under reduced pressure and used for subsequent conversion.

[0759] 1-(10-Butyl-2-methoxyacrylamide-9(10H)-ylidene)-1-cyano-2-oxo-6,9,12, Synthesis of 15,18-pentaoxa-3-aza-20-yl ester

[0760] A 250 mL three-necked round-bottom flask equipped with a magnetic stir bar and a reflux condenser was loaded with 2-methoxy-10-butylacridin-9(10H)-one (1.0 equivalent), 1-cyano-2-oxo-6,9,12,15,18-pentaoxa-3-aza-20-yl methacrylate (compound H, 2.0 equivalent), and 20 mL of dichloromethane. The system was placed under nitrogen and the reaction mixture was stirred until homogeneous. After cooling the system in an ice bath, titanium tetrachloride (2.5 equivalent) was added dropwise to the reaction mixture, and stirring was continued for 15 minutes. 5 mL of pyridine (0.33 equivalent) was added to the reaction mixture, which was then heated to ambient temperature and refluxed for 8 hours. After cooling the reaction mixture to room temperature, it was poured into a dilute aqueous hydrochloric acid solution, and the aqueous phase was extracted with dichloromethane. The organic fractions were combined, and volatile components were removed by rotary evaporation under reduced pressure. The desired product, 1-(10-butyl-2-methoxyacryl-9(10H)-ylidene)-1-cyano-2-oxo-6,9,12,15,18-pentaoxa-3-aza-20-yl ester, was purified by rapid chromatography to give a deep yellow solid.

[0761] Example 9—17-((9-(dicyanomethylene)-9H-xanthon-3-yl)oxymethacrylic acid as shown in Scheme 9 Synthesis of (-3,6,9,12,15-pentaoxepadecayl ester (hypothetical example) .

[0762]

[0763] Option 10

[0764] Synthesis of 17-chloro-3,6,9,12,15-pentaheptadecyl methacrylate

[0765] 17-Chloro-3,6,9,12,15-pentaheptadecane-1-ol (1.0 equivalent) and some 4-(dimethylamino)pyridine crystals (catalytic amount) were dissolved in 500 mL of dichloromethane in a round-bottom flask equipped with a pressure-equalizing feed funnel and nitrogen sealing. The reaction mixture was cooled to 0 °C using an ice bath, and then triethylamine (4.0 equivalent) was added. Then, acryloyl chloride (1.1 equivalent) containing about 400 parts per million parts (ppm) of butylated hydroxytoluene (BHT) or 2,6-di-tert-butyl-4-methylphenol was added dropwise, and the reaction mixture was stirred at 0 °C for two hours, then heated to ambient temperature and stirred for about 6 hours. The reaction mixture was quenched with 150 mL of deionized water, then poured into 200 mL of 1 mol hydrochloric acid and stirred. After adding some saturated sodium chloride solution, the phases were separated. The aqueous phase was extracted twice with ethyl acetate. The combined organic phases were washed with saturated sodium bicarbonate solution and saturated sodium chloride solution. After adding approximately 100 ppm BHT per gram of the desired product, the organic phase was concentrated by rotary evaporation under reduced pressure to obtain the crude product. The crude product was dissolved in a hexane solution of 30% (v / v) ethyl acetate and eluted with a hexane solution of 30% (v / v) ethyl acetate through a short silica gel column to give 17-chloro-3,6,9,12,15-pentaoxepadecanyl methacrylate.

[0766] 17-((9-oxo-9H-xanthon-3-yl)oxy)-3,6,9,12,15-pentaoxepadecamethyl methacrylate synthesis

[0767] A suspension of 3-hydroxy-9H-xanthon-9-one (1.0 equivalent), Cs₂CO₃ (1.0 equivalent), and sodium iodide (catalytic amount, approximately 200 mg) was dried under vacuum in a 500 mL round-bottom flask equipped with a magnetic stir bar. Anhydrous dimethyl sulfoxide (DMSO) (250 mL) was added, followed by 17-chloro-3,6,9,12,15-pentaoxyheptadecyl methacrylate (1.0 equivalent). The reaction mixture was heated overnight at 70 °C and monitored by thin-layer chromatography. The reaction mixture was cooled to room temperature and slowly poured into a dilute aqueous hydrochloric acid solution with continuous stirring. After stirring for 30 minutes, the grayish-white solid was separated by vacuum filtration through a sintered glass funnel. The filter cake was then washed with deionized water, followed by two washes with 200 mL of hexane. The obtained 17-((9-oxo-9H-xanthon-3-yl)oxy)-3,6,9,12,15-pentaoxoctadecanyl ester was dried under vacuum at 60 °C to constant weight.

[0768] 17-((9-(dicyanomethylene)-9H-xanthon-3-yl)oxy)-3,6,9,12,15-pentadecyloxymethacrylate Synthesis of heptaalkyl esters

[0769] 17-((9-oxo-9H-xanthon-3-yl)oxy)-3,6,9,12,15-pentaoxepadecanyl ester (1.0 equivalent) and thionyl chloride (7.0 equivalent) were dissolved in dichloromethane (50 mL), and the resulting reaction mixture was refluxed under nitrogen for 2 hours. The reaction mixture was cooled to room temperature, and excess thionyl chloride and dichloromethane were removed by rotary evaporation under reduced pressure while maintaining the bath temperature below 20 °C. Excess malononitrile (10.0 equivalent) was added to the flask, followed by 25 mL of anhydrous dichloromethane. The reaction mixture was stirred and refluxed for 2 hours. The mixture was cooled to room temperature, then rinsed through a short silica gel stopper and eluted with 5% methanol (v / v) in dichloromethane. The volatile components were evaporated under reduced pressure while maintaining the temperature below 20 °C, and the solids were then suspended in cold methanol (100 mL) and stirred for 20 minutes. The crude product was separated by vacuum filtration, and the filter cake was washed with additional cold methanol. 17-((9-(dicyanomethylene)-9H-xanthon-3-yl)oxy)-3,6,9,12,15-pentaoxepadecanyl ester of methacrylate was further purified by silica gel column chromatography and eluted with 5% methanol (v / v) in dichloromethane to give a pale yellow solid.

[0770] Example 10—Methacrylic acid 2-(2-(2-((9,10-dioxo-9,10-dihydroanthracene-) as shown in Scheme 11 Synthesis of 1-yl)amino)ethoxy)ethoxy)ethyl ester

[0771]

[0772] Option 11

[0773] Synthesis of 1-((2-(2-(2-hydroxyethoxy)ethoxy)ethyl)amino)anthracene-9,10-dione

[0774] Under nitrogen atmosphere and at room temperature, 2-(2-aminoethoxy)ethoxyethanol (153.62 g, 1.03 mmol) was added to a stirred solution of 1-chloroanthracene-9,10-dione (100.0 g, 0.412 mmol) in ethoxyethanol (400 mL), followed by the addition of copper powder (2.61 g, 0.0412 mmol). The mixture was then heated at 135 °C for 16 hours. The reaction progress was monitored by thin-layer chromatography (70% ethyl acetate in n-hexane solution). Upon completion, the mixture was cooled to room temperature and the solvent was removed under reduced pressure, yielding a red solid, which was dissolved in dichloromethane (DCM) and extracted with water. The organic layer was separated, and the aqueous layer was extracted with DCM. The combined organic extracts were washed with water and brine, dried over sodium sulfate, filtered, and concentrated under reduced pressure to give a red solid (180 g), which was then purified by silica gel column chromatography (5%-80% ethyl acetate in n-hexane solution) to give a red solid (85 g, 58% yield). 1H-NMR (CDCl3, 400MHz): ẟ 9.76 (t, 1H, J = 5.2Hz), 8.17 (d, 1H,J = 7.6Hz), 8.10 (d, 1H, J = 6.8Hz), 7.81-7.90 (m, 2H), 7.62 (m, 1H), 7.41(d, 1H, J = 6.8Hz), 7.25(d, 1H, J = 8.8Hz), 4.57 (t, 1H, J = 5.2Hz), 3.34-3.72 (m, 12H).

[0775] 2-(2-(2-((9,10-dioxo-9,10-dihydroanthracene-1-yl)amino)ethoxy)ethoxy) methacrylic acid Synthesis of ethyl ester (compound I)

[0776] Methacryloxychlorohydrin (30.0 g, 0.287 mmol) was slowly added at 0 °C to a stirred solution of 1-((2-(2-(2-hydroxyethoxy)ethoxy)ethyl)amino)anthracene-9,10-dione (68.0 g, 0.191 mmol) in dichloromethane (340.0 mL) and triethylamine (48.4 g, 0.478 mmol). The mixture was stirred for 30 min, and the progress was monitored by thin-layer chromatography (50% ethyl acetate in n-hexane). Upon completion, the mixture was quenched with water, the organic layer was separated, and the aqueous layer was extracted with dichloromethane (2 × 100 mL). The combined organic extracts were washed with water and brine, dried over sodium sulfate, filtered, and concentrated under reduced pressure to give a red oil (94 g), which was purified by silica gel column chromatography and eluted with 15%–21% ethyl acetate and n-hexane to give a red solid (45 g, 55%). 1 H-NMR (CDCl3, 400MHz): ẟ 9.78 (t, 1H, J =5.4Hz), 8.18 (d, 1H, J = 7.7Hz), 8.11 (d, 1H, J = 6.9Hz), 7.81-7.91 (m, 2H),7.66 (m, 1H), 7.43 (d, 1H, J = 6.9Hz), 7.27 (d, 1H, J = 8.7Hz), 5.98 (s, 1H), 5.62 (s, 1H), 4.21 (t, 1H, J = 5.3Hz), 3.50-3.74 (m, 12H), 1.83 (s, 3H). Figure 6 The UV-VIS absorption spectra of 2-(2-(2-((9,10-dioxo-9,10-dihydroanthracene-1-yl)amino)ethoxy)ethoxy)ethyl methacrylate or compound I in 0.2 mM methanol solution are shown.

[0777] Example 11—5-((9,10-dioxo-9,10-dihydroanthracene-1-yl)amino methacrylate as shown in Scheme 12 Synthesis of methyl pentyl ester

[0778]

[0779] Option 12

[0780] Synthesis of 1-((5-hydroxypentyl)amino)anthracene-9,10-dione (compound J)

[0781] Under nitrogen atmosphere and at room temperature, 5-aminopentanol (127.5 g, 1.23 mmol) was added to a stirred solution of 1-chloroanthracene-9,10-dione (75.0 g, 0.306 mmol) in ethoxyethanol (375 mL), followed by the addition of copper powder (1.95 g, 0.0306 mmol). The mixture was then heated at 135 °C for approximately 16 hours. The reaction was monitored by thin-layer chromatography (30% ethyl acetate in n-hexane). Upon completion, the mixture was cooled to room temperature and the solvent was removed under reduced pressure to give a red solid, which was dissolved in dichloromethane and water. The organic layer was separated and the aqueous layer was extracted with dichloromethane (2 × 100 mL). The combined organic extracts were washed with water and brine, dried over sodium sulfate, filtered, and concentrated under reduced pressure to give a crude red solid (approximately 240 g), which was purified by silica gel column chromatography and eluted with 20% ethyl acetate / n-hexane to give a red solid (75 g, 59% yield). 1 H-NMR (CDCl3, 400MHz): ẟ 9.62 (t, 1H, J = 4.8Hz), 8.16 (d, 1H, J = 6.8Hz), 8.13 (d, 1H, J = 7.2Hz), 7.79-7.90 (m, 2H), 7.58 (m, 1H), 7.41 (d, 1H, J =7.2Hz), 7.18 (d, 1H, J = 8.4Hz), 4.57 (t, 1H, J = 4.8Hz), 3.27-3.46 (m, 4H), 1.45-1.69 (m, 6H).

[0782] Synthesis of 5-((9,10-dioxo-9,10-dihydroanthracene-1-yl)amino)pentyl methacrylate

[0783] At 0 °C, methacryloyl chloride (30.0 mL, 0.306 mmol) was slowly added to a stirred solution of 1-((5-hydroxypentyl)amino)anthracene-9,10-dione (62.0 g, 0.204 mmol) in dichloromethane (310.0 mL) and triethylamine (70.4 mL, 0.501 mmol). The mixture was stirred for 30 min. At completion (progress monitored by thin-layer chromatography, 20% ethyl acetate / n-hexane), the mixture was quenched with water. The organic layers were separated and the aqueous layer was extracted with dichloromethane (2 × 100 mL). The combined organic extracts were washed with water and brine, dried over sodium sulfate, filtered, and reduced under reduced pressure to give a red solid (approximately 89.0 g), which was purified by silica gel column chromatography (eluting with 5% ethyl acetate in n-hexane) to give a red solid (35.1 g, 46% yield). 1 H-NMR (CDCl3, 400MHz): ẟ 9.71 (t, 1H, J = 5.2Hz), 8.20 (d, 1H, J= 7.6Hz), 8.14 (d, 1H, J = 7.2Hz), 7.82-7.92 (m, 2H), 7.64 (m, 1H), 7.43 (d,1H, J = 7.44Hz), 7.27 (d, 1H, J = 8.7Hz), 6.01 (s, 1H), 5.63 (s, 1H), 4.13(t, 1H, J = 6.4Hz), 3.36-3.40 (m, 2H), 1.86 (s, 3H), 1.71 (m, 4H), 1.52 (m, 2H). Figure 7 The UV-VIS absorption spectra of 5-((9,10-dioxo-9,10-dihydroanthracene-1-yl)amino)pentyl methacrylate or compound J in 0.2 mM methanol solution are shown.

[0784] Example 12—4-((4-acrylamidophenyl)amino)-1-amino-9,10-dioxane as shown in Scheme 13 Synthesis of sodium 9,10-dihydroanthracene-2-sulfonate

[0785]

[0786] Option 13

[0787] A three-necked round-bottom flask was loaded with 1-amino-4-bromo-9,10-dioxo-9,10-dihydroanthracene-2-sulfonic acid (40.0 g, 104.66 mmol), N-(4-aminophenyl)acrylamide (32.6 g, 200.99 mmol), anhydrous copper sulfate (9.5 g, 289.64 mmol), sodium carbonate (14.42 g, 136.04 mmol), and deionized water (1.2 L), and heated at 90 °C for 2.0 h under a nitrogen atmosphere. The mixture (thick slurry) was cooled to room temperature and dissolved in a 40% methanol aqueous solution (2.5 L), and precipitated by adding saturated brine (2.5 L). The precipitate was filtered through a sintered funnel lined with a sand-diatomaceous earth-sand layer (approximately 4 inches). The filter cake was washed with a 10% methanol semi-saturated brine solution (36 L), at which point the filter cake sample... 1 ¹H-NMR analysis showed that N-(4-aminophenyl)acrylamide as an impurity was <3%. The crude product containing diatomaceous earth and sand was suspended in methanol (6.0 L) and filtered through a sintered funnel. The filter cake was washed with an additional 2.0 L of methanol. The filtrate was concentrated under reduced pressure to give crude sodium 4-((4-acrylamidophenyl)amino)-1-amino-9,10-dioxo-9,10-dihydroanthracene-2-sulfonate (83 g). The crude material was purified on an InterChim automated system (Biotage silica 350 g column) by gradient elution with a solution of 0% to 10% methanol in dichloromethane followed by a solution of 0% to 10% methanol in acetone to give sodium 4-((4-acrylamidophenyl)amino)-1-amino-9,10-dioxo-9,10-dihydroanthracene-2-sulfonate (19.7 g, 39% yield) as a dark blue solid. 1 H-NMR (DMSO-d6, 400MHz): ẟ 12.08 (s, 1H), 10.28 (s, 1H), 10.05-10.23 (m,1H), 8.19-8.31 (m, 2H), 7.96 (s, 1H), 7.68-7.89 (m, 4H), 7.37-7.57 (m, 1H), 7.26 (d, 2H, J = 8.8Hz), 6.47 (d, 1H, J = 8.8, 10.1Hz), 6.29 (d, 1H, J = 2.0, 17.0Hz), 5.74-580 (m, 1H). Figure 8 The UV-VIS absorption spectra of sodium 4-((4-acrylamidophenyl)amino)-1-amino-9,10-dioxo-9,10-dihydroanthracene-2-sulfonate or compound K and IMT blue in 0.2 mM methanol solution are shown.

[0788] Example 13—Contact Lens

[0789] A reactive monomer mixture was prepared, consisting of 77% by weight of the formulations listed in Table 2 and 23% by weight of diluent D3O. The reactive monomer mixture was then filtered under pressure through a 3 μm filter using a stainless steel syringe.

[0790] Table 2

[0791]

[0792] The reactive monomer mixture was degassed at ambient temperature under vacuum (40 Torr) for at least 20 minutes. Then, approximately 75 µL of the reactive mixture was dispensed into an FC made of a 90:10 (w / w) Z:TT blend at room temperature using an Eppendorf pipette in a glove box with a nitrogen atmosphere and less than about 0.1% to 0.2% oxygen. A BC made of a 90:10 (w / w) Z:TT blend was then placed on top of the FC. The molds were equilibrated in the glove box for at least twelve hours prior to dispensing. Pallets, each containing eight mold components, were transferred to adjacent glove boxes maintained at 62°C, and the lenses were cured from top to bottom for 10 minutes using a 405 nm LED lamp with an intensity of approximately 2.0 mW / cm².

[0793] The lenses are manually demolded and detached by suspending them in approximately one liter of 70% IPA for about one hour, then soaking them twice more in fresh 70% IPA for 30 minutes each time; then overnight in DIW; subsequently treated with fresh DIW for 30 minutes; and then soaked in a wetting solution for 30 minutes. Finally, the lenses are equilibrated and stored in a borate-buffered wetting solution. Those skilled in the art will recognize that the exact lens detachment process can vary depending on the lens formulation and molding material, in terms of the concentration of the isopropanol aqueous solution, the number of washes with each solvent, and the duration of each step. The aim of the lens detachment process is to detach all lenses without defects and to transform the network swollen by the diluent into a hydrogel swollen by the wetting solution. Figure 9 The UV-VIS transmission spectra of two different lenses (Example 13A and Example 13B) in borate buffer wetting solution are shown.

[0794] Example 14: Thermal stability and photochemical stability tests

[0795] A reactive monomer mixture was prepared, consisting of 77% by weight of the formulations listed in Table 3 and 23% by weight of diluent D3O. Lenses were manufactured from this reactive monomer mixture on a pilot production line, achieving a strength of 1.5 mW / cm. 2The double-sided 395nm LED was cured for 4 minutes, then an intensity of 5mW / cm was applied. 2 The double-sided 395nm LED-cured lens was cured for 4 minutes. The lens was packaged in a standard blister pack with a borate-buffered wetting solution containing approximately 50 ppm methyl ether cellulose; and the lens (Example 14A) was sterilized at 121°C for approximately 18 minutes.

[0796] Table 3

[0797]

[0798] The lenses of Example 14A (control lenses) were removed from their original blister packs and placed in individual glass vials containing 5 mL of borate buffer wetting solution. These vials containing the lenses were stored in a stability chamber at 89°C for one month. Subsequently, the lens parameters, mechanical properties, and UV-VIS spectral properties (average percentage of transmittance over the wavelength range) of these heat-treated lenses (Example 14B) were measured and compared with the control lenses. These data are shown in Tables 4 through 6. Standard deviations are shown in parentheses. Figure 10 The UV-VIS transmission spectra of Examples 14A and 14B are shown; Figure 11 The corresponding absorption spectra are shown between 400 nm and 550 nm.

[0799] The blister packs containing the lenses of Example 14A were placed in a controlled photostability chamber (foil side down, bowl side up, so that the lenses in the bowl could be exposed to light). The photostability chamber was maintained at 25°C ± 2°C and ambient relative humidity. These lenses were then sequentially exposed to 1,500,000 lux hours of visible light (168.8 hours of exposure) and 259.4 watt-hours / m² of light. 2 The lenses were exposed to ultraviolet light for 16.2 hours. Lens parameters, mechanical properties, and UV-VIS spectral properties (average percentage of transmittance over the wavelength range) of these photo-stressed lenses (Example 14C) were then measured and compared with control lenses. These data are shown in Tables 4 through 7. Standard deviations are shown in parentheses. Figure 10 The UV-VIS transmission spectrum of Example 14C is also shown, and Figure 11 The corresponding absorption spectrum is shown.

[0800] Table 4. Lens Parameters

[0801]

[0802] Table 5. Mechanical Properties

[0803]

[0804] Table 6. Spectral Properties

[0805]

[0806] Table 7. Thermal and optical stability at the maximum visible light absorption.

[0807]

[0808] As shown by minor changes in lens parameters, mechanical properties, and UV-VIS transmission spectra after heat treatment or light exposure, chromophores of Formula I (such as compound B) exhibit thermal and photostable stability in contact lenses while essentially mimicking the UV-VIS spectrum of macular pigment.

[0809] Example 15: Edge-to-edge apodization contact lens (hypothetical example)

[0810] A reactive monomer mixture was prepared, consisting of 77% by weight of the formulations listed in Table 8 and 23% by weight of diluent D3O. The reactive monomer mixture was individually filtered under pressure through a 3 μm filter using a stainless steel syringe.

[0811] Table 8

[0812]

[0813] These reactive monomer mixtures were degassed at ambient temperature under vacuum (40 Torr) for at least 20 minutes. Then, approximately 75 µL of the reactive mixture was dispensed into an FC made of a 90:10 (w / w) Zeonor / TT blend at room temperature using an Eppendorf pipette in a glove box with a nitrogen atmosphere and less than about 0.1% to 0.2% oxygen. A BC made of a 90:10 (w / w) Z:TT blend was then placed on top of the FC. The molds were equilibrated in the glove box for at least twelve hours prior to dispensing. Pallets, each containing eight mold components, were transferred to adjacent glove boxes maintained at 65°C, and the lenses were cured from top to bottom for 3 minutes using a 435 nm LED lamp with an intensity of approximately 1.5 mW / cm², followed by curing from top to bottom for 7 minutes using a 435 nm LED lamp with an intensity of approximately 2.5 mW / cm².

[0814] Lenses were manually demolded, with most adhering to the FC, and detached by suspending them in approximately one liter of 70% IPA for about one hour, then soaking twice in fresh 70% IPA for 30 minutes each time; then soaking twice in fresh DIW for 15 minutes each time; and then soaking twice in a wetting solution for 30 minutes each time. The lenses were then equilibrated and stored in a borate-buffered solution. The lenses were then placed in vials containing a borate-buffered solution and autoclaved at 121°C for about 30 minutes. Those skilled in the art will recognize that the exact lens detachment process can vary depending on the lens formulation and molding material, in terms of the concentration of the isopropanol aqueous solution, the number of washes with each solvent, and the duration of each step. The aim of the lens detachment process is to detach all lenses without defects and to transform the network swollen by the diluent into a hydrogel swollen by the wetting solution. The physical and mechanical properties of the sterile lenses in Examples 15A to 15G were measured.

[0815] Example 16: Contact lens with only pupil agnostic features

[0816] A reactive monomer mixture was prepared, consisting of 77% by weight of the formulations listed in Table 9 and 23% by weight of diluent D3O. The RMM was then filtered under pressure through a 3μm filter using a stainless steel syringe and degassed by applying a vacuum (approximately 40 mm Hg). Approximately 75 µL of the reactive monomer mixture was dispensed into a FC (focal condenser) made from Zeonor under a nitrogen atmosphere and approximately 3% oxygen. A BC (focal condenser) made from Zeonor was then placed onto the FC to form a negative-one diopter lens mold assembly. Trays, each containing eight lens mold assemblies, were conveyed through a two-stage curing tunnel, during which the trays were used at 65°C with approximately 4 mW / cm² at the tray surface. 2 Irradiate with a 435nm LED light of a certain intensity for approximately 3.8 minutes, then use approximately 12mW / cm². 2 Irradiate with an LED light of a certain intensity for approximately 2.2 minutes. The light source is positioned above the tray. BC is mechanically removed under yellow light irradiation. The tray containing the FC with the adhered lens is stored in a nitrogen atmosphere and in darkness until further use. The adhered lens is a cross-linked substrate network lens with covalently bonded monoacylphosphine oxide groups, and is referred to as the "MAPO substrate lens" in the experiments described below.

[0817] Table 9

[0818]

[0819] The operation was carried out in a glove box under a nitrogen atmosphere and under yellow light. The FC, which still had the MAPO substrate lens attached, was placed in... Figure 12The in-mold fixture is then attached to an optical lens forming apparatus equipped with a digital light projection unit. This unit uses micromirrors to modulate and guide the light onto the FC and into the attached MAPO substrate lens. The light source of this apparatus has an intensity of 120 mW / cm². 2 The 405 nm LED was then used. Approximately 150 μL of the degassed grafting solution (50:50 (v / v) 1-propanol:DIW) listed in Table 10 was then dispensed into the FC for nine minutes to allow the visible light filter compound to be absorbed into the MAPO substrate lens, after which excess grafting solution was removed. Then, the FC was used as follows: Figure 13 and Figure 14 The 9 mm diameter pupil-only DMD image (Examples 16A, 16C to 16E) abbreviated as “9mmPUPO” or the 10 mm diameter Gaussian apodization image abbreviated as “10mm DMD image A”, shown, was obtained by irradiating the impregnated MAPO substrate lens for sixty seconds, thereby grafting the visible light filtering compound into the MAPO substrate lens.

[0820] Table 10. Grafted solutions and DMD images in 50:50 (v / v) 1-propanol:DIW

[0821]

[0822] The in-mold fixture was removed from the equipment, and the grafted lens was separated by mechanically removing the FC. The lens was then immersed in a 70% (v / v) IPA aqueous solution for fifteen hours, followed by rinsing twice with DIW and twice with PS, and then stored in vials containing PS. The UV-VIS spectrum of the pupil lens alone was measured, and... Figure 15 and Figure 16 As shown in the figure, the UV-VIS spectrum clearly demonstrates that the UV-VIS spectrum of the final apodization lens can be altered by changing the concentration of the visible light filtering compound in the grafted composition. Examples 16A-E show that the transmittance remains relatively constant between 480 nm and 660 nm.

[0823] Example 17: Lens with only pupil agnostic contact

[0824] A reactive monomer mixture was prepared, consisting of 77% by weight of the formulations listed in Table 11 and 23% by weight of diluent D3O. The RMM was then filtered under pressure through a 3μm filter using a stainless steel syringe and degassed by applying a vacuum (approximately 40 mm Hg). Approximately 75 µL of the reactive monomer mixture was dispensed into a FC (focal condenser) made of Zeonor under a nitrogen atmosphere and approximately 3% oxygen. A BC (focal condenser) made of Zeonor was then placed onto the FC to form a negative-one diopter lens mold assembly. Trays, each containing eight lens mold assemblies, were conveyed through a two-stage curing tunnel, during which the trays were used at 65°C with approximately 4 mW / cm² at the tray surface. 2 Irradiate with a 435nm LED light of a certain intensity for approximately 3.8 minutes, then use approximately 12mW / cm². 2 Irradiate with an LED light of a certain intensity for approximately 2.2 minutes. The light source is positioned above the tray. BC is mechanically removed under yellow light irradiation. The tray containing the FC with the adhered lens is stored in a nitrogen atmosphere and in darkness until further use. The adhered lens is a cross-linked substrate network lens with covalently bonded monoacylphosphine oxide groups, and is referred to as the "MAPO substrate lens" in the experiments described below.

[0825] Table 11

[0826]

[0827] The operation was carried out in a glove box under a nitrogen atmosphere and under yellow light. The FC, which still had the MAPO substrate lens attached, was placed in... Figure 12 The in-mold fixture is then attached to an optical lens forming apparatus equipped with a digital light projection unit. This unit uses micromirrors to modulate and guide the light onto the FC and into the attached MAPO substrate lens. The light source of this apparatus has an intensity of 120 mW / cm². 2 The 405 nm LED was then used. Approximately 150 μL of a degassed grafting solution (consisting of 0.27 wt% compound B, 0.90 wt% compound I, and 1.0 wt% compound E, in a 50:50 (v / v) 1-propanol:DIW ratio for Examples 17A-B, and in a 55:45 (v / v) 1-propanol:DIW ratio for Examples 17C-17F) was dispensed into the FC for nine minutes to allow the visible light filtering compound to be absorbed into the MAPO substrate lens. Excess grafting solution was then removed. The solution was then used as described above. Figure 13 and Figure 14The 9 mm diameter pupil-only DMD image (Examples 17A to 17B) abbreviated as “9mm PUPO” or the 10 mm diameter Gaussian DMD image abbreviated as “DMD AC”, shown, irradiates the impregnated MAPO substrate lens for different times, thereby grafting the visible light filtering compound into the MAPO substrate lens.

[0828] Table 12. Irradiation Time and DMD Images

[0829]

[0830] The in-mold fixture was removed from the equipment, and the grafted lens was separated by mechanically removing the FC. The lens was then immersed in a 70% (v / v) IPA aqueous solution for fifteen hours, rinsed twice with DIW, and rinsed twice with PS, and then stored in a vial containing PS. The apodization lens of Example 17A was subsequently sterilized by autoclaving at 121°C for approximately 30 minutes. Figure 17 The UV-VIS spectrum of the lens of sterile Example 17A is shown, demonstrating a relatively constant transmittance of about 5% between 480 nm and 660 nm. Figure 18 The UV-VIS spectrum of the lens of Example 17C is shown, demonstrating a relatively constant transmittance of approximately 15% between 480 nm and 660 nm. Figure 19 Photomicrographs of the apodization embodiments 17C to 17E lenses are shown.

[0831] Example 18. Contact lens with only pupil agnostic features

[0832] A reactive monomer mixture was prepared, consisting of 77% by weight of the formulations listed in Table 13A and 23% by weight of diluent D3O. The RMM was then filtered under pressure through a 3μm filter using a stainless steel syringe and degassed by applying a vacuum (approximately 40 mm Hg). Approximately 75 µL of the reactive monomer mixture was dispensed into a FC (focal condenser) made of Zeonor under a nitrogen atmosphere and approximately 1% oxygen. A BC (focal condenser) made of Zeonor was then placed onto the FC to form a negative-one diopter lens mold assembly. Trays, each containing eight lens mold assemblies, were conveyed through a two-stage curing tunnel, during which the trays were used at 65°C with a curing temperature of approximately 1.5 mW / cm² at the tray surface. 2 Irradiate with a 435nm LED light of a certain intensity for about 4.5 minutes, then use about 5mW / cm². 2Irradiate with an LED light of high intensity for approximately 7.5 minutes. The light source is positioned above and below the tray (double-sided curing). Mechanically remove BC under yellow light irradiation. Store the tray containing the FC with the adhered lens in a nitrogen atmosphere and in darkness until further use. The adhered lens is a cross-linked substrate network lens with covalently bonded monoacylphosphine oxide groups, and is referred to as the "MAPO substrate lens" in the experiments described below.

[0833] Table 13A

[0834]

[0835] The operation was carried out in a glove box under a nitrogen atmosphere and under yellow light. The FC, which still had the MAPO substrate lens attached, was placed in... Figure 12 The in-mold fixture is then attached to an optical lens forming apparatus equipped with a digital light projection unit. This unit uses micromirrors to modulate and guide the light onto the FC and into the attached MAPO substrate lens. The light source of this apparatus has an intensity of 120 mW / cm². 2 The 405 nm LED was then used. Approximately 150 μL of a degassed grafting solution (consisting of 0.27 wt% of compound B, 0.90 wt% of compound I, and 1.0 wt% of compound E in a 50:50 (v / v) 1-propanol:DIW solution) was dispensed into the FC for nine minutes to allow the visible light filter compound to be absorbed into the MAPO substrate lens. Excess grafting solution was then removed. The impregnated MAPO substrate lens was then irradiated for sixty seconds with a 9 mm diameter pupil-only DMD image to graft the visible light filter compound into the MAPO substrate lens.

[0836] Remove the in-mold fixture from the equipment and separate the grafted lens by mechanically removing the FC. Then, immerse the lens in a 70% (v / v) IPA aqueous solution for fifteen hours, rinse twice with DIW, rinse twice with PS, and then store it in a vial containing PS. Figure 20 The UV-VIS spectrum of the lens of Example 18 is shown, demonstrating a moderately constant transmittance of approximately 45% between 480 nm and 660 nm.

[0837] Example 19. Apozoic contact lenses with different light levels (hypothetical example)

[0838] A reactive monomer mixture was prepared, consisting of 77% by weight of the formulations listed in Table 13B and 23% by weight of diluent D3O. The RMM was then filtered under pressure through a 3μm filter using a stainless steel syringe and degassed by applying a vacuum (approximately 40 mm Hg). Approximately 75 µL of the reactive monomer mixture was dispensed into a FC (focal condenser) made of Zeonor under a nitrogen atmosphere and approximately 3% oxygen. A BC (focal condenser) made of Zeonor was then placed onto the FC to form a negative-one diopter lens mold assembly. Trays, each containing eight lens mold assemblies, were conveyed through a two-stage curing tunnel, during which the trays were used at 65°C with approximately 4 mW / cm² at the tray surface. 2 Irradiate with a 435nm LED light of a certain intensity for approximately 3.8 minutes, then use approximately 12mW / cm². 2 Irradiate with an LED light of a certain intensity for approximately 2.2 minutes. The light source is positioned above the tray. BC is mechanically removed under yellow light irradiation. The tray containing the FC with the adhered lens is stored in a nitrogen atmosphere and in darkness until further use. The adhered lens is a cross-linked substrate network lens with covalently bonded monoacylphosphine oxide groups, and is referred to as the "MAPO substrate lens" in the experiments described below.

[0839] Table 13B

[0840]

[0841] The operation was carried out in a glove box under a nitrogen atmosphere and under yellow light. The FC, which still had the MAPO substrate lens attached, was placed in... Figure 11 The in-mold fixture is then attached to an optical lens forming apparatus equipped with a digital light projection unit. This unit uses micromirrors to modulate and guide the light onto the FC and into the attached MAPO substrate lens. The light source of this apparatus has an intensity of 120 mW / cm². 2 The 405 nm LED was then used. Approximately 150 μL of a degassed grafting solution (consisting of 0.25 wt% of compound B and 0.8 wt% of compound I in a 50:50 (v / v) 1-propanol:DIW solution) was dispensed into the FC for nine minutes to allow the visible light filtering compounds to be absorbed into the MAPO substrate lens. Excess grafting solution was then removed. The impregnated MAPO substrate lens was then irradiated for sixty seconds with a 9 mm diameter pupil-only DMD image.

[0842] The procedure was performed under yellow light in a glove box under a nitrogen atmosphere to prevent the covalently bonded monoacylphosphine oxide groups within the grafted lens from being irradiated or decomposed. The in-mold fixture was removed from the equipment, and the grafted lens was separated by mechanically removing the FC. Similarly, the procedure was performed under yellow light in a glove box under a nitrogen atmosphere, followed by immersion in a 70% (v / v) IPA aqueous solution for fifteen hours, and then rinsed twice with 50:50 (v / v) 1-propanol:DIW. The lens was then suspended in a degassed solution of 0.2 wt% compound E in 50:50 (v / v) 1-propanol:DIW. The suspension was then subjected to a solution with a strength of 1 mW / cm². 2 -5mW / cm 2 The lens was irradiated with 405 nm LED light for a sufficient time to substantially graft compound D into the periphery around the central apodization point composed of the grafted compounds B and I. The lens was then immersed in 50:50 (v / v) 1-propanol:DIW for several hours, rinsed twice with DIW, rinsed twice with PS, and then stored in a vial containing PS. The lens exhibited an orange center and a blue periphery. The level of brightness or darkness of the color can be controlled by varying the exposure time and / or the digital light projection intensity. This experiment can be repeated using any combination of visible light filtering compounds having formulas (I) to (VI), such as compounds B, I, and K.

[0843] Example 20. Lens with only pupil acuity contact (hypothetical example)

[0844] Example 17 was repeated, except that the grafting solution contained only compound B and compound I.

[0845] Example 21. Contact lens with only pupil agnostic features

[0846] A reactive monomer mixture was prepared, consisting of 77% by weight of the formulations listed in Table 14 and 23% by weight of diluent D3O. The RMM was then filtered under pressure through a 3μm filter using a stainless steel syringe and degassed by applying a vacuum (approximately 40 mm Hg). Approximately 75 µL of the reactive monomer mixture was dispensed into a FC (focal condenser) made of Zeonor under a nitrogen atmosphere and approximately 3% oxygen. A BC (focal condenser) made of Zeonor was then placed onto the FC to form a negative-one diopter lens mold assembly. Trays, each containing eight lens mold assemblies, were conveyed through a two-stage curing tunnel, during which the trays were used at 65°C with approximately 4 mW / cm² at the tray surface. 2 Irradiate with a 435nm LED light of a certain intensity for approximately 3.8 minutes, then use approximately 12mW / cm². 2Irradiate with an LED light of a certain intensity for approximately 2.2 minutes. The light source is positioned above the tray. BC is mechanically removed under yellow light irradiation. The tray containing the FC with the adhered lens is stored in a nitrogen atmosphere and in darkness until further use. The adhered lens is a cross-linked substrate network lens with covalently bonded monoacylphosphine oxide groups, and is referred to as the "MAPO substrate lens" in the experiments described below.

[0847] Table 14

[0848]

[0849] The operation was carried out in a glove box under a nitrogen atmosphere and under yellow light. The FC, which still had the MAPO substrate lens attached, was placed in... Figure 12 The in-mold fixture is then attached to an optical lens forming apparatus equipped with a digital light projection unit that uses micromirrors to modulate and guide the light onto the FC and into the attached MAPO substrate lens. The light source for this apparatus is a 405 nm LED.

[0850] Then, approximately 110 μL of the degassed grafting solution listed in Table 15 was dispensed into the FC for nine minutes to allow the UV-Vis light filtering compound to be absorbed into the MAPO substrate lens, after which excess grafting solution was removed. Then, as follows... Figure 13 and Figure 14 The 9 mm diameter pupil-only DMD images (Examples 21A, 21C, and 21E) abbreviated as “9 mm PUPO” or the 10 mm diameter Gaussian apodization images (Examples 21B, 21D, and 21F) abbreviated as “10 mm DMD Image A” are irradiated with the impregnated MAPO substrate lens under the conditions listed in Table 15, thereby grafting the UV-Vis light filtering compound into the MAPO substrate lens.

[0851] Table 15. Grafting solution, irradiation conditions, and DMD images

[0852]

[0853] The in-mold fixture was removed from the equipment, and the grafted lens was separated by mechanically removing the FC. The lens was then immersed in a 70% (v / v) IPA aqueous solution for fifteen hours, rinsed twice with DIW, and rinsed twice with PS, and then stored in a vial containing PS. The grafted portions of the lenses in Examples 21A and 21B were light purple-brown-orange. Figure 21 The UV-VIS spectrum of the lens of Example 21A is shown, revealing zero transmittance between 200 nm and 360 nm and a strong absorption band centered at 470 nm. The grafted portions of the lenses of Examples 21C and 21D are light purple. Figure 22The UV-VIS spectrum of the lens of Example 21C is shown, revealing its near-zero transmittance between 200 nm and 370 nm and a moderate-intensity absorption band centered at 460 nm. The grafted portions of the lenses of Examples 21E and 21F are shown in blue. Figure 23 The UV-VIS spectrum of the lens of Example 21E is shown, revealing its zero transmittance up to about 375 nm and a strong absorption band centered at 480 nm. Figure 24 Photomicrographs of the apodization embodiments 21A to 21D are shown.

Claims

1. An ophthalmic device, said ophthalmic device being a free radical reaction product of a reactive monomer mixture, said reactive monomer mixture comprising: (a) One or more monomers, said one or more monomers being suitable for manufacturing the ophthalmic device; (b) A first visible light filtering compound having a maximum visible light absorption between 430 nm and 480 nm and a full width at half maximum (FWHM) of at least 35 nm and at most 150 nm at the maximum visible light absorption, wherein the first visible light filtering compound is photostable, and wherein the first visible light filtering compound has a content of at least 7740 L·mol⁻¹. -1 .cm -1 The molar extinction coefficient; and (c) A second visible light filtering compound having a maximum visible light absorption between 480 nm and 530 nm and a full width at half maximum (FWHM) of at least 50 nm and at most 150 nm.

2. The ophthalmic device of claim 1, wherein the maximum visible light absorption of the first visible light filter compound is between 440 nm and 470 nm.

3. The ophthalmic device of claim 1, wherein the maximum visible light absorption of the second visible light filter compound is between 490 nm and 520 nm.

4. The ophthalmic device according to any one of the preceding claims, wherein the full width at half maximum (FWHM) of the first visible light filtering compound at the maximum visible light absorption is at least 40 nm and at most 95 nm.

5. The ophthalmic device according to any one of the preceding claims, wherein the full width at half maximum (FWHM) of the second visible light filtering compound at the maximum visible light absorption is at least 70 nm and at most 130 nm.

6. The ophthalmic device according to any one of claims 1 to 5, wherein the first visible light filtering compound has formula I:

1. 2.(I) Where m and n are independently 0, 1, 2, 3, or 4; T is a bond, O, or NR. 6 , where R 6 It is H, C1-C6 alkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, or YP g R is H, C1-C8 alkyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; Y is a linking group; P g It is a polymerizable group; R 1 and R 2 When present, it is independently C1-C6 alkyl, C1-C6 alkoxy, C1-C6 thioalkyl, C3-C7 cycloalkyl, aryl (preferably unsubstituted phenyl or phenyl substituted with alkyl or halogroup), halogroup, hydroxyl, amino, NR 3 R 4 , benzyl, SO3H, or SO3M (M is a monovalent cation, such as sodium or potassium ion), where R 3 and R 4 Independently H or C1-C6 alkyl, or two adjacent R 1 Or R 2 The groups combine with the carbon atoms to which they are attached to form cycloalkyl or aryl rings; and EWG is an electron-withdrawing group.

7. The ophthalmic device according to any one of claims 1 to 6, wherein the second visible light filtering compound comprises a visible light filter of formula II: (II) Where Y is a linking group, and P g It is a polymerizable group.

8. The ophthalmic device according to any one of claims 1 to 7, wherein the ophthalmic device further comprises a third light-filtering compound, the third visible light-filtering compound exhibiting one or more visible light absorption maximum values ​​between 550 nm and 660 nm.

9. The ophthalmic device of claim 8, wherein the third visible light filtering compound comprises a visible light filter of formula III: (III) Where Y is an independent linking group each time it appears and P g It is an independent polymerizable group each time it appears.

10. The ophthalmic device of claim 8, wherein the third visible light filtering compound comprises a visible light filter of formula IV: (IV) Where R 1 It is H, methyl, or Br, and R 2 Each time it appears independently, it is C1-C6 alkyl, C1-C6 alkoxy, C1-C6 thioalkyl, C3-C7 cycloalkyl, aryl (preferably unsubstituted phenyl or phenyl substituted with alkyl or halogroup), benzyl, halogroup, hydroxyl, amino, NR 3 R 4 SO3H or SO3M (where M is a monovalent cation, such as sodium or potassium ion), where R 3 and R 4 Independently H or C1-C6 alkyl, or two adjacent R 2 The groups combine with the carbon atoms to which they are attached to form cycloalkyl or aryl rings.

11. The ophthalmic device of claim 8, wherein the third visible light filtering compound comprises a visible light filter of formula V: (V) in: m and n are independently 0, 1, 2, 3, or 4; T is a bond, O, or NR; Y is a linking group; P g It is a polymerizable group; R is independently H, C1-C6 alkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, or YP each time it appears. g And R 1 and R 2 When present, it is independently C1-C6 alkyl, C1-C6 alkoxy, C1-C6 thioalkyl, C3-C7 cycloalkyl, aryl (preferably unsubstituted phenyl or phenyl substituted with alkyl or halogroup), halogroup, hydroxyl, amino, NR 3 R 4 , or benzyl, wherein R 3 and R 4 Independently H or C1-C6 alkyl, or two adjacent R 1 Or R 2 The groups combine with the carbon atoms to which they are attached to form cycloalkyl or aryl rings.

12. The ophthalmic device of claim 8, wherein the third visible light filtering compound comprises a visible light filter of formula VI: (VI) Where m and n are independently 0, 1, 2, 3, or 4; R 1 and R 2 Each occurrence is independently of H, an optional substituent, or -YP. g Or two adjacent R 1 Or R 2 Groups and the atoms they are attached to combine to form optionally -YP g Substituted cycloalkyl or aryl rings; EWG is an electron-withdrawing group independently each time it appears; P g Each occurrence of Y is independently a polymerizable group; and each occurrence of Y is independently a linking group; wherein the compound of formula VI contains at least one P g Group.

13. The ophthalmic device according to any one of the preceding claims, wherein the ophthalmic device is a contact lens having a central region and a peripheral region.

14. The ophthalmic device of claim 13, wherein the molar concentrations of the first visible light filtering compound, the second visible light filtering compound, and the third visible light filtering compound are independently distributed in the central region and the peripheral region.

15. The ophthalmic device of claim 13, wherein the molar concentrations of the first visible light filtering compound, the second visible light filtering compound, and the third visible light filtering compound are independently greater in the central region than in the peripheral region.

16. The ophthalmic device of claim 13, wherein the molar concentrations of the first visible light filtering compound, the second visible light filtering compound, and the third visible light filtering compound are independently distributed only in the central region.

17. The ophthalmic device according to any one of claims 13 to 16, wherein the molar concentrations of the first visible light filtering compound, the second visible light filtering compound, and the third visible light filtering compound vary spatially independently to form an apodization distribution.

18. The ophthalmic device of claim 17, wherein the molar concentrations of the first visible light filtering compound, the second visible light filtering compound, and the third visible light filtering compound vary independently along the radial, circumferential, or combinations thereof to form the apodization distribution.

19. The ophthalmic device according to any one of claims 17 to 18, wherein the apodization distribution varies according to a mathematical function.

20. The ophthalmic device of claim 19, wherein the mathematical function is a linear function, a polynomial function, a Gaussian function, a Lorentz function, a logarithmic function, an exponential function, a numerical function, or a combination thereof.

21. The ophthalmic device according to any one of claims 17 to 20, wherein the apodization distribution further comprises a transparent region located at the center of the contact lens.

22. The ophthalmic device of claim 21, wherein the transparent region is circular in shape having a diameter between 0.1 mm and 5 mm.

23. The ophthalmic device according to any one of the preceding claims, wherein the reactive monomer mixture comprises a hydrophilic component, an organosilicon-containing component, or a mixture thereof.

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