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EP-4735923-A1 - BLUE FILTER COMBINATIONS FOR OPHTHALMIC DEVICES

EP4735923A1EP 4735923 A1EP4735923 A1EP 4735923A1EP-4735923-A1

Abstract

The invention provides ophthalmic devices provided with improved blue filtering, mimicking the transmittance of the human ageing eye closer than hitherto possible. The invention furthermore provides methods to obtain such ophthalmic devices, as well as application thereof for prevention or treatment of a degenerative eye disease.

Inventors

  • CAROLI, Giuseppe

Assignees

  • Teleon Holding B.V.

Dates

Publication Date
20260506
Application Date
20250904

Claims (13)

  1. 1. An ophthalmic device comprising a copolymer of one or more (meth)acrylate monomers, said copolymer further comprising at least two (meth)acrylic monomers selected from monomer 1, monomer 2 and monomer 3: wherein One of R 2 , R 3 , R 9 , R 10 or R 11 is a (meth)acrylic portion o X is NR 12 or O; o R 1 is H or methyl; • R 2 - R 11 can be independently selected from the group consisting of H; a linear or branched alkyl group having 1 - 5 carbon atoms, optionally substituted with one or more R 13 ; CF3; CH2F; CHF2; CCI3; CH2CI; CHCI2; CBr 3 ; CH 2 Br; CHBr 2 ; CI 3 ; CH 2 I; CHI 2 ; F; Cl; Br; I; CN; NO2; OR 12 ; CO2R 12 and NR 12 2, provided that R 6 is not NO2, CF3, CCI3, CBrs or CI3, and/or any two adjacent positions of R 4 - R 8 can be a cyclic aromatic or a cyclic non-aromatic substituent selected from Cl - C5 cycloalkyl; Cl - C4 alkylene dioxy; phenyl; and an aromatic five or six membered heterocycle comprising one or more N, S and/or O heteroatoms, which cyclic aromatic or cyclic non-aromatic substituent is optionally substituted with one or more R 12 and/or one or more R 13 o R 12 can be, independently, on each occurrence, H or a linear or branched alkyl group having 1 - 5 carbon atoms o R 13 can be selected, independently, on each occurrence, from the group of CF 3 ; CH 2 F; CHF 2 ; CC1 3 ; CH 2 C1; CHC1 2 ; CBr 3 ; CH 2 Br; CHBr 2 ; CI 3 ; CH 2 I; CHI 2 ; F; Cl; Br; I; CN; NO 2 ; OR 12 ; CO 2 R 12 and NR 12 2 ; o X is NR 14 or O; o R 1 is H or methyl; • R 2 - R 13 can be independently selected from the group consisting of H; a linear or branched alkyl group having 1 - 5 carbon atoms, optionally substituted with one or more R 15 ; CF 3 ; CH 2 F; CHF 2 ; CC1 3 ; CH 2 C1; CHC1 2 ; CBr 3 ; CH 2 Br; CHBr 2 ; CI 3 ; CH 2 I; CHI 2 ; F; Cl; Br; I; CN; NO 2 ; OR 14 ; CO 2 R 14 and NR 14 2 , provided that R 8 is not NO 2 , CF 3 , CC1 3 , CBr 3 or CI 3 , and/or wherein any two adjacent positions of R 2 - R 13 can be a cyclic aromatic or a cyclic non-aromatic substituent selected from the group of Cl - C5 cycloalkyl; Cl - C4 alkylene dioxy; phenyl; and an aromatic five or six membered heterocycle comprising one or more N, S and/or O heteroatoms, which cyclic aromatic or cyclic nonaromatic substituent is optionally substituted with one or more R 14 and/or one or more R 15 ; o R 14 can be selected, independently, on each occurrence, from the group consisting of H or a linear or branched alkyl group having 1 - 5 carbon atoms; o R 15 can be selected, independently, on each occurrence, from the group of CF 3 ; CH 2 F; CHF 2 ; CC1 3 ; CH 2 C1; CHC1 2 ; CBr 3 ; CH 2 Br; CHBr 2 ; CI 3 ; CH 2 I; CHI 2 ; F; Cl; Br; I; CN; NO 2 ; OR 14 ; CO 2 R 14 and NRi 4 2 ; wherein R 1 One of R 2 , R 3 , R 9 , R 10 or R 11 is a (meth)acrylic portion o X is NR 12 or O; o R 1 is H or methyl; • R6 is NO 2 , CF 3 , CC1 3 , CBr 3 or CI 3 ; • R 2 - R 5 and R 7 - R 11 can be independently selected from the group consisting of H; a linear or branched alkyl group having 1 - 5 carbon atoms optionally substituted with one or more R 12 ; CF 3 ; CH 2 F; CHF 2 ; CC1 3 ; CH2CI; CHCI2; CBr 3 ; CH 2 Br; CHBr 2 ; CI 3 ; CH 2 I; CHI 2 ; F; Cl; Br; I; CN; NO2; OR 12 ; CO2R 12 and NR 12 2, and/or wherein any two adjacent positions of R 2 - R 5 and/or R 7 - R 11 can be a cyclic aromatic or a cyclic non-aromatic substituent selected from the group consisting of Cl - C5 cycloalkyl; Cl - C4 alkylene dioxy; phenyl; and an aromatic five or six membered heterocycle comprising one or more N, S and/or O heteroatoms, which cyclic aromatic or cyclic non-aromatic substituent is optionally substituted with one or more R 12 and/or one or more R 13 ; o R 12 can be selected, independently, on each occurrence, from the group consisting of H or a linear or branched alkyl group having 1 - 5 carbon atoms; o R 13 can be selected, independently, on each occurrence, from the group of CF 3 ; CH 2 F; CHF 2 ; CC1 3 ; CH 2 C1; CHC1 2 ; CBr 3 ; CH 2 Br; CHBr 2 ; CI 3 ; CH 2 I; CHI 2 ; F; Cl; Br; I; CN; NO 2 ; OR 12 ; CO2R 12 and NR 12 2.
  2. 2. An ophthalmic device according to claim 1, wherein the copolymer comprises • at least one monomer 1 and at least one monomer 2; or • at least one monomer 1 and at least one monomer 3; or • at least one monomer 2 and at least one monomer 3; or • at least one monomer 1 and at least one monomer 2 and at least one monomer 3.
  3. 3. An ophthalmic device according to claim 1 or 2, wherein • monomer 1 is a compound of formula 1 wherein R 1 is H or methyl, and wherein R 2 - R 11 can be independently selected from the group consisting of H; a linear or branched alkyl group having 1 - 5 carbon atoms, preferably methyl; NR 12 2, OR 12 or CO2R 12 , preferably NR 12 2; wherein R 12 can be H or a linear or branched alkyl group having 1 - 5 carbon atoms, wherein preferably, the (meth)acrylic portion is present as R 11 , and/or wherein further preferably X = NR 12 , with R 12 preferably being H, and/or wherein further preferably, all of R 2 - R 11 except the (meth)acrylic portion is H and/or NR 12 2 and/or methyl, most preferably R 11 is the (meth)acrylic portion, R 6 is NR 12 2 and the remainder of R 2 - R 11 is H, or R 11 is the (meth)acrylic portion, R 2 and/or R 4 and/or R 8 and/or R 10 are a linear or branched alkyl group having 1 - 5 carbon atoms, preferably methyl, and the remainder of R 2 - R 11 is H, or R 11 is the (meth)acrylic portion and the remainder of R 2 - R 11 is H; and/or • monomer 2 is a compound of formula 2 wherein R 1 is H or methyl, and wherein R 2 - R 13 can be independently selected from the group consisting of H, a linear, branched or cyclic group having 1 - 5 carbon atoms, OR 14 or CO2R 14 , wherein R 14 can be H or a linear or branched alkyl group having 1 - 5 carbon atoms which linear, branched or cyclic group may be saturated, unsaturated or aromatic, wherein preferably the (meth)acrylic portion is present as R 11 or as R 13 , wherein if the (meth)acrylic portion is present R 13 , preferably X = NR 14 , with R 14 preferably being H, and wherein if the (meth)acrylic portion is present as R 11 , preferably X = O; and/or wherein further preferably, all of R 2 - R 13 except the (meth)acrylic portion is H and/or a linear branched or cyclic group which may be saturated, unsaturated or aromatic, consisting of only 1 - 5 carbon atoms and hydrogen atoms; and/or • monomer 3 is a compound of formula 3 wherein R 1 is H or methyl, wherein R 6 is NO2, CF3 or CCI3, preferably NO2, and wherein R 2 - R 5 and R 7 - R 11 can be independently selected from the group consisting of H, a linear or branched alkyl group having 1 - 5 carbon atoms, OR 12 or CO2R 12 , wherein R 12 can be H or a linear or branched alkyl group having 1 - 5 carbon atoms, wherein preferably, the (meth)acrylic portion is present as R 11 , and/or wherein further preferably X = NR 12 , with R 12 preferably being H, and/or wherein further preferably, all of R 2 - R 5 and R 7 - R 11 except the (meth)acrylic portion is H.
  4. 4. An ophthalmic device according to any of claims 1 - 3, wherein the one or more (meth)acrylate monomers comprise (meth)acrylate monomers selected from the group of methyl (meth)acrylate, ethyl (meth)acrylate, propyl (meth)acrylate, butyl (meth)acrylate, isobornyl (meth)acrylate, dodecyl (meth)acrylate, 2-ethylhexyl (meth)acrylate, phenyl (meth)acrylate, benzyl (meth)acrylate, 2-phenylethyl (meth)acrylate, 2 -phenoxy ethyl (meth)acrylate, ethylene glycol di(meth)acrylate, tetra (ethylene glycol) di(meth)acrylate, trimethylol propane tri(meth)acrylate, tri(ethylene glycol) di(meth)acrylate, and hydroxyethyl (meth)acrylate.
  5. 5. An ophthalmic device according to any of claims 1 - 4, wherein the concentration of monomer 1 is 0.01 - 0.5 wt.%, preferably 0.02 - 0.35 wt.%, more preferably 0.03 - 0.25 wt.%, and/or wherein the concentration of monomer 2 is 0.005 - 0.5 wt.%, preferably 0.01 - 0.35 wt.%, more preferably 0.02 - 0.25 wt.%, and/or wherein the concentration of monomer 3 is 0.005 - 0.5 wt.%, preferably 0.01 - 0.45 wt.%, more preferably 0.015 - 0.40 wt.%, more preferably 0.02 - 0.35 wt.%, all quantities being expressed relative to the quantity of all monomers for incorporation in the ophthalmic device which are not monomers of formulae 1, 2 or 3.
  6. 6. An ophthalmic device according to any of claims 1 - 5, wherein the ophthalmic device is an intraocular lens.
  7. 7. A polymerizable composition, comprising the monomers defined in any of claims 1 - 5.
  8. 8. A method for making an ophthalmic device, comprising a. preparing a mixture of the monomers defined in any of claims 1-5; b. initiating polymerization; c. allowing polymerization of the mixture of monomers to obtain an ophthalmic copolymer; d. Optionally, performing an extraction to remove side products and/or residual unreacted monomer from the ophthalmic copolymer.
  9. 9. A method for making an ophthalmic device according to claim 8, wherein initiating polymerization comprises addition of a radical polymerization initiator, preferably a diazo-initiator, such as 2,2-azobis(2,4- dimethylvaleronitrile) and/or azobisisobutyronitrile, an organic peroxide, such as di-t-butyl peroxide, benzoyl peroxide or methyl ethyl ketone peroxide, or a photo-initiator, such as phenylbis(2,4,6- trimethylbenzoyl)phosphine oxide.
  10. 10. A method for making an ophthalmic device according to claims 8 or 9, further comprising a step of lathing, molding and/or polishing of the ophthalmic device.
  11. 11. A method for preventing, delaying or halting a degenerative eye disease, comprising a step of contacting the ophthalmic device according to any of claims 1 - 6 with a human eye.
  12. 12. A method according to claim 11, wherein the method slows or halts the onset of age-related macular disease (AMD), said method comprising a step of surgically implanting the ophthalmic device of claim 6 into a human eye in need of said treatment.
  13. 13. An ophthalmic device according to any of claims 1 - 6 for use in preventing, delaying or halting a degenerative eye disease, preferably age- related macular disease (AMD).

Description

P130724PC00 Title: Blue filter combinations for ophthalmic devices The invention is in the field of ophthalmic devices. INTRODUCTION Ophthalmic devices are known devices which improve vision of (in particular) humans. A variety of different ophthalmic devices exists; in the present context, lens materials are particularly included, such as intraocular lenses or contact lenses. One important application of ophthalmic devices is to restore vision of a human subject, in particular upon aging. With aging, the natural lenses of the human eye will accumulate pigments comprised of 3-hydroxyl kynurenine. These pigments offer protection to the retina against UV light. As aging proceeds, also the transmission of the blue light will decrease. This natural increasing filtering of the blue light will further protect the retina from the phototoxicity of lipofuscin, a phototoxic pigment that also accumulates in the aging eye, in particular in the retina, and the phototoxicity of which is induced by blue light (Sparrow JR, Nakanishi K, Parish CA, “The lipofuscin fluorophore A2E mediates blue light -induced damage to retinal pigmented epithelial cells”, Invest Ophthalmol Vis Sci, 2000; 1981-9). In fact, it has been suggested that including blue filtering features in artificial lenses can potentially prevent the development and progression of age-related macular degeneration (AMD) (Braunstein RE, Sparrow JR, “A blue-blocking intraocular lens should be used in cataract surgery”, Arch Ophthalmol, 2005). An advantage of providing an ophthalmic device with a transmittance spectrum closely mimicking the transmittance of the human eye is that the artificial lens will mimic in the best possible manner the natural defense of the ageing eyes against high-energy (short-wavelength) visible light. Therefore, ophthalmic devices which mimic closely the (individual or average) blue light transmittance of the natural lens can be expected to prevent eye damage in the most optimal way. Ophthalmic devices comprising blue filters have generally been known. However, known lenses generally suffered from a transmittance spectrum which did not represent the transmittance spectrum of the naturally ageing eye. As such, such lenses often altered color perception, or contributed to the development of eye diseases. The present invention overcomes these drawbacks. FIGURES Figure 1: transmittance spectra of monomer lb-1, monomer 2b and the combination of monomer lb-1 and monomer 2b on the basis of calculation and in a real lens, as compared to the transmittance of the human eye at ages 40 - 49 and at ages 50 - 59. Figure 2: transmittance spectra of monomer lb-1, monomer 3b-l and the combination of monomer lb-1 and monomer 3b- 1 on the basis of calculation and in a real lens, as compared to the transmittance of the human eye at ages 40 - 49 and at ages 50 - 59. Figure 3: transmittance spectra of the human eye at ages 40 - 49 and at ages 50 - 59. Figure 4a: the transmittance spectra of monomer 3b-l, monomer lb-2, and of the combination of monomers 3b- 1 and lb-2. Figure 4b: the transmittance spectra of monomer 3b-l, monomer lb-2, and the sum %T of monomers 3b- 1 and lb-2 in the presence of a UV blocker. Figure 5: the transmittance spectra of monomer 3b- 1, 1c and the sum in the presence of a UV blocker. Figure 6: the transmittance spectra of monomer lb-2, 2b and the sum in the presence of a UV blocker. Figure 7: the transmittance spectra of monomer 1c, 2b and lc+2b in the presence of a UV blocker. Figure 8: the transmittance spectra of monomer Id, 3b-l and ld+3b-l in the presence of a UV blocker. Figure 9: the transmittance spectra of monomer Id, 2b and ld+2b in the presence of a UV blocker. Figure 10: the transmittance spectra of monomer 2d, 3b-l and 2d+3b-l in the presence of a UV blocker. Figure 11: the transmittance spectra of monomer 2b, lb-2, 3c-l and the sum of 2b+lb-2+3c-l. Figure 12: the transmittance spectra of monomer 3c-2 and 2c in the presence of a UV blocker. Figure 13: the transmittance spectra of monomer lb-2 and 3c- 1 in the presence of a UV blocker. Figure 14: the transmittance spectra of monomer 3c-2 and lb-1 in the presence of a UV blocker. Figure 15: the transmittance spectra of monomer 3c-2 and 2e in the presence of a UV blocker. Figure 16: the transmittance spectra of monomer 3c-2, lb-2 and 3b-2 in the presence of a UV blocker. Figure 17: the transmittance spectra of monomer 2b, 3c-l and lb-2 in the presence of a UV blocker. Figure 18: comparison of the transmission spectrum of a prior art product (Example 8 of US 5,662,707) with the transmission spectrum of the human eye. DETAILED DESCRIPTION The invention is directed to an ophthalmic device comprising a copolymer of one or more (meth) acrylate monomers, said copolymer further comprising a combination of at least two (meth)acrylic azobenzene dyes onomer 2 and monomer 3: • One of R2, R3, R9, R10 or R11 is (meth)acrylic portion o X = NR12 or O; o R1 is H or methyl; • R2 - R11 can