(19)
(11)EP 3 419 961 B1

(12)EUROPEAN PATENT SPECIFICATION

(45)Mention of the grant of the patent:
02.09.2020 Bulletin 2020/36

(21)Application number: 17709806.8

(22)Date of filing:  16.02.2017
(51)International Patent Classification (IPC): 
C07C 225/22(2006.01)
C07C 237/32(2006.01)
C07C 233/33(2006.01)
C07C 237/34(2006.01)
(86)International application number:
PCT/IB2017/050873
(87)International publication number:
WO 2017/145022 (31.08.2017 Gazette  2017/35)

(54)

UV/VISIBLE-ABSORBING VINYLIC MONOMERS AND USES THEREOF

UV-/SICHTBAR-ABSORBIERENDE VINYLISCHE MONOMERE UND DEREN VERWENDUNGEN

MONOMÈRES VINYLIQUES ABSORBANT LES UV ET LA LUMIÈRE VISIBLE, ET LEURS UTILISATIONS


(84)Designated Contracting States:
AL AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HR HU IE IS IT LI LT LU LV MC MK MT NL NO PL PT RO RS SE SI SK SM TR

(30)Priority: 22.02.2016 US 201662298124 P

(43)Date of publication of application:
02.01.2019 Bulletin 2019/01

(73)Proprietor: Alcon Inc.
1701 Fribourg (CH)

(72)Inventors:
  • HOLLAND, Troy Vernon
    Johns Creek, Georgia 30097 (US)
  • CHANG, Frank
    Johns Creek, Georgia 30097 (US)
  • LAREDO, Walter R.
    Fort Worth, Texas 76134 (US)
  • JIANG, Xuwei
    Fort Worth, Texas 76134 (US)
  • DESOUSA, Ryan
    Johns Creek, Georgia 30097 (US)

(74)Representative: Bohest AG 
Holbeinstrasse 36-38
4051 Basel
4051 Basel (CH)


(56)References cited: : 
WO-A1-2014/018208
US-A- 5 741 924
  
  • DATABASE WPI Week 198746 Thomson Scientific, London, GB; AN 1987-324524 XP002769134, -& JP S62 230759 A (NIPPON SHOKUBAI KAGAKU KOGYO CO LTD) 9 October 1987 (1987-10-09)
  • DATABASE CA [Online] CHEMICAL ABSTRACTS SERVICE, COLUMBUS, OHIO, US; NAKAGAWA, HIROO ET AL: "Polyurethane coating compositions with excellent weatherability", XP002769135, retrieved from STN Database accession no. 1995:169562 -& JP H06 207142 A (NIPPON CATALYTIC CHEM IND) 26 July 1994 (1994-07-26)
  • TAKEHIKO NISHIO ET AL: "A Novel Intramolecular Photocyclization ofN-(2-Bromoalkanoyl) Derivatives of 2-Acylanilinesvia 1,8-Hydrogen Abstraction", HELVETICA CHIMICA ACTA, vol. 88, no. 5, 1 May 2005 (2005-05-01), pages 996-1003, XP55363162, CH ISSN: 0018-019X, DOI: 10.1002/hlca.200590095
  
Note: Within nine months from the publication of the mention of the grant of the European patent, any person may give notice to the European Patent Office of opposition to the European patent granted. Notice of opposition shall be filed in a written reasoned statement. It shall not be deemed to have been filed until the opposition fee has been paid. (Art. 99(1) European Patent Convention).


Description


[0001] This invention is related to amino benzophenone vinylic monomers capable of absorbing ultra-violet (UV) radiation and high-energy-violet (HEVL) radiation and their uses for producing hydrogel contact lenses capable of blocking ultra-violet ("UV") radiation and violet radiation with wavelengths from 380 nm to 440 nm from a water-based hydrogel lens formulation.

BACKGROUND



[0002] The health risks of UVA and UVB light to the human eye and skin have been well documented. Recently short wavelength visible light, both violet and blue, were shown to be damaging to cells both in in vitro and in vivo studies reported in Experimental Eye Research 2006, 83, 1493; J. Cataract Refrac Surg 2009, 35, 354; Graefe's Arch Clin Exp Ophthalmol 2008, 246, 671; Acta Ophthalmologica Scandinavica 2006, 84, 4; Br J Ophthalmol 2006, 90, 784; Optometry and Vision Science 2011, 88(6), 1. It would be advantageous to have violet and blue light blocking contact lenses which can block some light in the region of 380 nm to 460 nm.

[0003] UV absorbers are known as ingredients for polymeric materials used to make ophthalmic lenses. Such absorbers are preferably polymerizable so as to be covalently bound to the polymeric network of the lens material instead of simply physically entrapped in the material, thereby preventing them from migrating, phase separating or leaching out of the lens material. Such stability is particularly important for ophthalmic lenses because the leaching of the absorber may present both toxicological issues and lead to the loss of UV/visible blocking activity of the ophthalmic lenses.

[0004] Polymerizable benzatriazole, benzophenone and triazine absorbers are known. Most of these compounds are known as UV absorbers, though some may be known to also absorb some portion of visible light. Many absorbers contain ethylenically unsaturated groups, such as methacrylate, acrylate, methacrylamide, acrylamide or styrene groups. Copolymerization with other ingredients in the lens materials incorporates the absorbers into the resulting polymer chain.

[0005] U.S. Pat. Nos. 8,153,703, 8,232,326, 8,262,947, and 8,585,938 disclose benzotriazole vinylic monomers which can block HEVL. Although the benzotriazoles vinylic monomers are typically photo-stable and can absorb a large amount of both visible and UV light, they may be difficult and expensive to make. Also, they may not be soluble in a lens formulation. If the absorber does not have sufficient solubility in a lens formulation, the absorber may coalesce into domains that could interact with light and result in decreased optical clarity of the lens.

[0006] WO2014/018208 recently discloses new UV/visible light absorbing vinylic monomers with anthraquinone structures. Anthroquinone vinylic monomers may not have a desired photo-stability for use in ophthalmic lenses.

[0007] Helv. Chim. Acta 88, pp. 996-1003 (2005), describing intramolecular photocyclization of N-(2-bromoalkanoyl) derivatives of 2-acylanilines, discloses a photoproduct of the formula

wherein X = Cl, R1 = Ph and R2 = H.

[0008] US-A-5,741,924 discloses acrolyl derivatives and their use in the production of lenses.

[0009] There is a need for a visible light absorbing vinylic monomer that absorbs lights between 380 and 460 nm, shows good solubility in formulations, is photo-stable, and is inexpensive to make.

SUMMARY



[0010] In one aspect, the invention provides an UV-absorbing vinylic monomer comprising a moiety of amino benzophenone and a (meth)acryloyl group.

[0011] In another aspect, the invention provides a method for producing UV-absorbing contact lenses from a lens formulation comprising a UV-absorbing vinylic monomer of the invention.

[0012] The invention provides in a further aspect hydrogel contact lenses comprising monomeric units of an UV-absorbing vinylic monomer of the invention.

BRIEF DESCRIPTION OF THE DRAWINGS



[0013] Figure 1 shows the UV/Vis spectra of contact lenses. A: a contact lens containing an UV-absorbing vinylic monomer of the invention according to preferred embodiment; B: a contact lens free of UV-absorbing vinylic monomer as control.

DETAILED DESCRIPTION



[0014] Unless defined otherwise, 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 belongs. Generally, the nomenclature used herein and the laboratory procedures are well known and commonly employed in the art. Conventional methods are used for these procedures, such as those provided in the art and various general references. Where a term is provided in the singular, the inventors also contemplate the plural of that term. The nomenclature used herein and the laboratory procedures described below are those well-known and commonly employed in the art.

[0015] "About" as used herein means that a number referred to as "about" comprises the recited number plus or minus 1-10% of that recited number.

[0016] "Optional" or "optionally" means that the subsequently described event or circumstance can or cannot occur, and that the description includes instances where the event or circumstance occurs and instances where it does not.

[0017] A "contact Lens" refers to a structure that can be placed on or within a wearer's eye. A contact lens can correct, improve, or alter a user's eyesight, but that need not be the case.

[0018] As used in this application, the term "hydrogel" or "hydrogel material" refers to a crosslinked polymeric material which is insoluble in water, but can hold at least 10 percent by weight of water in its three-dimensional polymer networks (i.e., polymer matrix) when it is fully hydrated.

[0019] A "vinylic monomer" refers to a compound that has one sole ethylenically-unsaturated group.

[0020] The term "soluble", in reference to a compound or material in a solvent, means that the compound or material can be dissolved in the solvent to give a solution with a concentration of at least about 0.1% by weight at room temperature (i.e., from about 20°C to about 30°C).

[0021] The term "insoluble", in reference to a compound or material in a solvent, means that the compound or material can be dissolved in the solvent to give a solution with a concentration of less than 0.005% by weight at room temperature (as defined above).

[0022] The term "ethylenically unsaturated group" is employed herein in a broad sense and is intended to encompass any groups containing at least one >C=C< group. Exemplary ethylenically unsaturated groups include (meth)acryloyl

and/or

), allyl, vinyl (-CH=CH2), 1-methylethenyl

), styrenyl, or the likes.

[0023] The term "(meth)acryloylamido group" refers to a radical of

and/or

in which R° is hydrogen or a C1-C6 alkyl.

[0024] The term "(meth)acryloyloxy group" refers to a radical of

and/or



[0025] The term "(meth)acrylamide" refers to methacrylamide and/or acrylamide.

[0026] The term "(meth)acrylate" refers to methacrylate and/or acrylate.

[0027] A "hydrophilic vinylic monomer", as used herein, refers to a vinylic monomer which can be polymerized to form a homopolymer that is water-soluble or can absorb at least 10 percent by weight of water.

[0028] A "hydrophobic vinylic monomer" refers to a vinylic monomer which can be polymerized to form a homopolymer that is insoluble in water and can absorb less than 10 percent by weight of water.

[0029] "UVA" refers to radiation occurring at wavelengths between 315 and 380 nanometers; "UVB" refers to radiation occurring between 280 and 315 nanometers; "Violet" refers to radiation occurring at wavelengths between 380 and 440 nanometers.

[0030] "UVA transmittance" (or "UVA %T"), "UVB transmittance" or "UVB %T", and "violet-transmittance" or "Violet %T" are calculated by the following formula





in which Luminescence %T is the luminescence percent transmittance is the ratio of luminous flux transmitted by the lens to the incident luminous flux (ISO 13666:1998).

[0031] As used in this application, the term "macromer" or "prepolymer" refers to a medium and high molecular weight compound or polymer that contains two or more ethylenically unsaturated groups. Medium and high molecular weight typically means average molecular weights greater than 700 Daltons.

[0032] As used in this application, the term "vinylic crosslinker" refers to a compound having at least two ethylenically unsaturated groups. A "vinylic crosslinking agent" refers to a vinylic crosslinker having a molecular weight of about 700 Daltons or less.

[0033] As used in this application, the term "polymer" means a material formed by polymerizing/crosslinking one or more monomers or macromers or prepolymers.

[0034] As used in this application, the term "molecular weight" of a polymeric material (including monomeric or macromeric materials) refers to the weight-average molecular weight unless otherwise specifically noted or unless testing conditions indicate otherwise.

[0035] The term "alkyl" refers to a monovalent radical obtained by removing a hydrogen atom from a linear or branched alkane compound. An alkyl group (radical) forms one bond with one other group in an organic compound.

[0036] The term "alkylene divalent group" or "alkylene diradical" or "alkyl diradical" interchangeably refers to a divalent radical obtained by removing one hydrogen atom from an alkyl. An alkylene divalent group forms two bonds with other groups in an organic compound.

[0037] The term "alkyl triradical" refers to a trivalent radical obtained by removing two hydrogen atoms from an alkyl. A alkyl triradical forms three bonds with other groups in an organic compound.

[0038] The term "alkoxy" or "alkoxyl" refers to a monovalent radical obtained by removing the hydrogen atom from the hydroxyl group of a linear or branched alkyl alcohol. An alkoxy group (radical) forms one bond with one other group in an organic compound.

[0039] In this application, the term "substituted" in reference to an alkyl diradical or an alkyl radical means that the alkyl diradical or the alkyl radical comprises at least one substituent which replaces one hydrogen atom of the alkyl diradical or the alkyl radical and is selected from the group consisting of hydroxy (-OH), carboxy (-COOH), -NH2, sulfhydryl (-SH), C1-C4 alkyl, C1-C4 alkoxy, C1-C4 alkylthio (alkyl sulfide), C1-C4 acylamino, C1-C4 alkylamino, di-C1-C4 alkylamino, halogen atom (Br or CI), and combinations thereof.

[0040] A "photoinitiator" refers to a chemical that initiates free radical crosslinking/polymerizing reaction by the use of light.

[0041] A "spatial limitation of actinic radiation" refers to an act or process in which energy radiation in the form of rays is directed by, for example, a mask or screen or combinations thereof, to impinge, in a spatially restricted manner, onto an area having a well-defined peripheral boundary. A spatial limitation of UV radiation is obtained by using a mask or screen having a radiation (e.g., UV and/or visible light) permeable region, a radiation (e.g., UV and/or visible light) impermeable region surrounding the radiation-permeable region, and a projection contour which is the boundary between the radiation-impermeable and radiation-permeable regions, as schematically illustrated in the drawings of U.S. Patent Nos. 6,800,225 (Figs. 1-11), and 6,627,124 (Figs. 1-9), 7,384,590 (Figs. 1-6), and 7,387,759 (Figs. 1-6). The mask or screen allows to spatially projects a beam of radiation (e.g., UV radiation and/or visible radiation) having a cross-sectional profile defined by the projection contour of the mask or screen. The projected beam of radiation (e.g., UV radiation and/or visible radiation) limits radiation impinging on a lens formulation located in the path of the projected beam from the first molding surface to the second molding surface of a mold. The resultant contact lens comprises an anterior surface defined by the first molding surface, an opposite posterior surface defined by the second molding surface, and a lens edge defined by the sectional profile of the projected UV and/or visible beam (i.e., a spatial limitation of radiation). The radiation used for the crosslinking is radiation energy, especially UV radiation (and/or visible radiation), gamma radiation, electron radiation or thermal radiation, the radiation energy preferably being in the form of a substantially parallel beam in order on the one hand to achieve good restriction and on the other hand efficient use of the energy.

[0042] The term "modulus" or "elastic modulus" in reference to a contact lens or a material means the tensile modulus or Young's modulus which is a measure of the stiffness of a contact lens or a material. The modulus can be measured using a method in accordance with ANSI Z80.20 standard. A person skilled in the art knows well how to determine the elastic modulus of a silicone hydrogel material or a contact lens. For example, all commercial contact lenses have reported values of elastic modulus.

[0043] In general, the invention is directed to a class of amino benzophenone vinylic monomer which absorbs between 380 and 460 nm, shows good solubility in formulations, is photo-stable, and is inexpensive to make. An amino benzophenone vinylic monomer of the invention is suitable for making UV-absorbing hydrogel contact lenses capable of absorbing a light between 380 and 460 nm.

[0044] In one aspect, the present invention provides the following UV-absorbing vinylic monomers:



















and



[0045] An above UV-absorbing vinylic monomer can be prepared from commercially available 2-aminobenzophenones with various substituents. Examples of such 2-aminobenzophenones with various substituents include with limitation 2-amino-5-chlorobenzophenone, 2-amino-5-chloro-2'-fluorobenzophenone, 2-amino-2',5-dichlorobenzophenone, 2-amino-5-nitrobenzophenone, 2-amino-4'-bromobenzophenone, 2-amino-4-methylbenzophenone, 2-amino-5-chloro-2',6'-diflorobenzophenone, 2-amino-2',4'-dimethylbenzophnenone, 2-amino-4,4'-dimethylbenzophenone, 2-amino-4'-methoxybenzophenone, 2-amino-4-methoxybenzophenone, 2-amino-3'-methoxybenzophenone, 2-amino-5-chloro-4-methylbenzophenone, 2-amino-5-chloro-4'methoxybenzophenone, 2-amino-5-chloro-4'-methylbenzophenone, 2-amino-5-chloro-4'-methoxybenzophenone, and 2-amino-benzopheonone-2'carboxylic acid. Examples of synthetic procedures for their preparations are illustrated in Schemes 1 to 3.







[0046] These UV-absorbing vinylic monomers or a UV-absorbing vinylic monomer of the following formula:

can find particular use for making hydrogel contact lenses.

[0047] In another aspect, the invention provides a method for producing UV-absorbing contact lenses as defined in claim 10.

[0048] It is understood that the amount of UV-absorbing units present in the prepolymer in the aqueous lens formulation is sufficient to render a resultant contact lens, which is obtained from the curing of the lens formulation, ability of blocking or absorbing (i.e., the inverse of transmittance) at least 90% (preferably at least about 95%, more preferably at least about 97.5%, even more preferably at least about 99%) of UVB (between 280 and 315 nanometers), at least 70% (preferably at least about 80%, more preferably at least about 90%, even more preferably at least about 95%) of UVA transmittance (between 315 and 380 nanometers), and optionally (but preferably) at least 30% (preferably at least about 40%, more preferably at least about 50%, even more preferably at least about 60%) of violet light between 380 nm and 440 nm, which impinge on the lens.

[0049] In accordance with the invention, any thermal free-radical initiators can be used in the invention. Examples of suitable thermal initiators include 2,2'-azobis (2,4-dimethylpentanenitrile), 2,2'-azobis (2-methylpropanenitrile), 2,2'-azobis (2-methylbutanenitrile), peroxides such as benzoyl peroxide, and the like. Preferably, the thermal initiator is 2,2'-azobis(isobutyronitrile) (AIBN).

[0050] Suitable photoinitiators are benzoin methyl ether, diethoxyacetophenone, a benzoylphosphine oxide, 1-hydroxycyclohexyl phenyl ketone and Darocur and Irgacur types, preferably Darocur 1173® and Darocur 2959®, Germanium-based Norrish Type I photoinitiators. Examples of benzoylphosphine initiators include 2,4,6-trimethylbenzoyldiphenylophosphine oxide; bis-(2,6-dichlorobenzoyl)-4-N-propylphenylphosphine oxide; and bis-(2,6-dichlorobenzoyl)-4-N-butylphenylphosphine oxide. Reactive photoinitiators which can be incorporated, for example, into a macromer or can be used as a special monomer are also suitable. Examples of reactive photoinitiators are those disclosed in EP 632 329. Examples of Germanium-based Norrish Type I photoinitiators are acylgermanium compounds described in US 7,605,190 and water-soluble Germanium-based Norrish Type I photoinitiators disclosed in U.S. Pat. Appl. No. 62/169/722. The polymerization can then be triggered off by actinic radiation, for example light, in particular UV/visible light of a suitable wavelength. The spectral requirements can be controlled accordingly, if appropriate, by addition of suitable photosensitizers.

[0051] Polymerizable components for making contact lenses are well known to a person skilled in the art, including, for example, such as, vinylic monomers, vinylic macromers, prepolymers, vinylic crosslinking agents, or combinations thereof, as known to a person skilled in the art. A lens formulation can further include other components, such as a visibility tinting agent, antimicrobial agents (e.g., Ag-nanoparticles), lubricant/wetting agents, and the like.

[0052] Nearly any hydrophilic vinylic monomer can be used in the invention. Suitable hydrophilic vinylic monomers are, without this being an exhaustive list, N,N-dimethylacrylamide (DMA), N,N-dimethyl methacrylamide (DMMA), 2-acrylamidoglycolic acid, N-hydroxypropyl acrylamide, N-hydroxyethyl acrylamide, N-hydroxypropyl methacrylamide, N-hydroxyethyl methacrylamide, N-[tris(hydroxymethyl)methyl]-acrylamide, N-vinylpyrrolidone (NVP), N-vinyl formamide, N-vinyl acetamide, N-vinyl isopropylamide, N-vinyl-N-methyl acetamide (VMA), N-methyl-3-methylene-2-pyrrolidone, 1-methyl-5-methylene-2-pyrrolidone, 5-methyl-3-methylene-2-pyrrolidone, 2-hydroxyethylmethacrylate (HEMA), 2-hydroxyethyl acrylate (HEA), hydroxypropyl acrylate, hydroxypropyl methacrylate, methoxyethylmethacrylate (i.e., ethylene glycol methyl ether methacrylate, EGMA), trimethylammonium 2-hydroxy propylmethacrylate hydrochloride, aminopropyl methacrylate hydrochloride, dimethylaminoethyl methacrylate (DMAEMA), glycerol methacrylate (GMA), a C1-C4-alkoxy polyethylene glycol (meth)acrylate having a weight average molecular weight of up to 1500, polyethylene glycol (meth)acrylate having a weight average molecular weight of up to 1500, methacrylic acid, acrylic acid, and mixtures thereof.

[0053] Nearly any non-silicone hydrophobic vinylic monomer can be used. Examples of preferred non-silicone hydrophobic vinylic monomers include methylacrylate, ethylacrylate, propylacrylate, isopropylacrylate, cyclohexylacrylate, 2-ethylhexylacrylate, methylmethacrylate, ethylmethacrylate, propylmethacrylate, vinyl acetate, vinyl propionate, vinyl butyrate, vinyl valerate, styrene, chloroprene, vinyl chloride, vinylidene chloride, acrylonitrile, 1-butene, butadiene, methacrylonitrile, vinyl toluene, vinyl ethyl ether, perfluorohexylethyl-thio-carbonyl-aminoethyl-methacrylate, isobornyl methacrylate, trifluoroethyl methacrylate, hexafluoro-isopropyl methacrylate, hexafluorobutyl methacrylate. By incorporating a certain amount of non-silicone hydrophobic vinylic monomer in a lens formulation, the mechanical properties (e.g., modulus of elasticity) of the resultant polymer may be improved.

[0054] Examples of preferred vinylic crosslinking agents include tetraethyleneglycol di(meth)acrylate, triethyleneglycol di(meth)acrylate, diethyleneglycol di(meth)acrylate, ethyleneglycol di(meth)acrylate, tetraethyleneglycol divinyl ether, triethyleneglycol divinyl ether, diethyleneglycol divinyl ether, ethyleneglycol divinyl ether, trimethylopropane trimethacrylate, pentaerythritol tetramethacrylate, bisphenol A dimethacrylate, vinyl methacrylate, ethylenediamine di(meth)acrylamide, glycerol di(meth)acrylate, triallyl isocyanurate, triallyl cyanurate, allyl(meth)acrylate, N-allyl-(meth)acrylamide, 1,3-bis(methacrylamidopropyl)-1,1,3,3-tetrakis(trimethylsiloxy)disiloxane, N,N'-methylenebisacrylamide, N,N'-methylenebismethacrylamide, N,N'-ethylenebisacrylamide, N,N'-ethylenebismethacrylamide,1,3-bis(N-methacrylamidopropyl)-1,1,3,3-tetrakis-(trimethylsiloxy)disiloxane, 1,3-bis(methacrylamidobutyl)-1,1,3,3-tetrakis(trimethylsiloxy)-disiloxane, 1,3-bis(acrylamidopropyl)-1,1,3,3-tetrakis(trimethylsiloxy)disiloxane, 1,3-bis(methacryloxyethylureidopropyl)-1,1,3,3-tetrakis(trimethylsiloxy)disiloxane, and combinations thereof. The amount of a cross-linking agent used is expressed in the weight content with respect to the total polymer and is preferably in the range from about 0.05% to about 3%, and more preferably in the range from about 0.1% to about 2%.

[0055] Any suitable siloxane-containing vinylic monomers can be used in the invention. Examples of preferred siloxane-containing vinylic monomers include N-[tris(trimethylsiloxy)silylpropyl]-(meth)acrylamide, N-[tris(dimethylpropylsiloxy)-silylpropyl]-(meth)acrylamide, N-[tris(dimethylphenylsiloxy)silylpropyl] (meth)acrylamide, N-[tris(dimethylethylsiloxy)silylpropyl] (meth)acrylamide, N-(2-hydroxy-3-(3-(bis(trimethylsilyloxy)-methylsilyl)propyloxy)propyl)-2- methyl acrylamide; N-(2-hydroxy-3-(3-(bis(trimethylsilyloxy)-methylsilyl)propyloxy)propyl) acrylamide; N,N-bis[2-hydroxy-3-(3-(bis(trimethylsilyloxy)-methylsilyl)propyloxy)propyl]-2-methyl acrylamide; N,N-bis[2-hydroxy-3-(3-(bis(trimethylsilyloxy)-methylsilyl)propyloxy)propyl] acrylamide; N-(2-hydroxy-3-(3-(tris(trimethylsilyloxy)silyl)-propyloxy)propyl)-2-methyl acrylamide; N-(2-hydroxy-3-(3-(tris(trimethylsilyloxy)silyl)propyloxy)-propyl)acrylamide; N,N-bis[2-hydroxy-3-(3-(tris(trimethylsilyloxy)silyl)propyloxy)propyl]-2-methyl acrylamide; N,N-bis[2-hydroxy-3-(3-(tris(trimethylsilyloxy)silyl)propyloxy)propyl]acrylamide; N-[2-hydroxy-3-(3-(t-butyldimethylsilyl)propyloxy)propyl]-2-methyl acrylamide; N-[2-hydroxy-3-(3-(t-butyldimethylsilyl)propyloxy)propyl]acrylamide; N,N-bis[2-hydroxy-3-(3-(t-butyldimethylsilyl)-propyloxy)propyl]-2-methyl acrylamide; N,N-bis[2-hydroxy-3-(3-(t-butyldimethylsilyl)propyloxy)-propyl]acrylamide; 3-methacryloxy propylpentamethyldisiloxane, tris(trimethylsilyloxy)silylpropyl methacrylate (TRIS), (3-methacryloxy-2-hydroxypropyloxy)propylbis(trimethylsiloxy)-methylsilane), (3-methacryloxy-2-hydroxypropyloxy)propyltris(trimethylsiloxy)silane, 3-methacryloxy-2-(2-hydroxyethoxy)-propyloxy)propylbis(trimethylsiloxy)methylsilane, N-2-methacryloxyethyl-O-(methyl-bis-trimethylsiloxy-3-propyl)silyl carbamate, 3-(trimethylsilyl)-propylvinyl carbonate, 3-(vinyloxycarbonylthio)propyl-tris(trimethyl-siloxy)silane, 3-[tris(trimethyl-siloxy)silyl]propylvinyl carbamate, 3-[tris(trimethylsiloxy)silyl] propyl allyl carbamate, 3-[tris(trimethylsiloxy)silyl]propyl vinyl carbonate, t-butyldimethyl-siloxyethyl vinyl carbonate; trimethylsilylethyl vinyl carbonate, and trimethylsilylmethyl vinyl carbonate); monomethacrylated or monoacrylated polydimethylsiloxanes of various molecular weight (e.g., mono-3-methacryloxypropyl terminated, mono-butyl terminated polydimethylsiloxane or mono-(3-methacryloxy-2-hydroxypropyloxy)propyl terminated, mono-butyl terminated polydimethylsiloxane); mono-vinyl carbonate-terminated polydimethylsiloxanes; mono-vinyl carbamate-terminated polydimethylsiloxane; mono-methacrylamide-terminated polydimethylsiloxanes; mono-acrylamide-terminated polydimethylsiloxanes; carbosiloxane vinylic monomers disclosed in US Patent Nos. 7915323 and 8420711, in US Patent Applicaton Publication Nos. 2012/244088 and 2012/245249; combinations thereof.

[0056] Any suitable siloxane-containing vinylic macromers (or crosslinkers) can be used in the invention. Examples of preferred siloxane-containing vinylic macromers are dimethacrylated or diacrylated polydimethylsiloxanes of various molecular weight; di-vinyl carbonate-terminated polydimethylsiloxanes; di-vinyl carbamate-terminated polydimethylsiloxane; di-methacrylamide-terminated polydimethylsiloxanes; diacrylamide-terminated polydimethylsiloxanes; bis-3-methacryloxy-2-hydroxypropyloxypropyl polydimethylsiloxane; N,N,N',N'-tetrakis(3-methacryloxy-2-hydroxypropyl)-alpha,omega-bis-3-aminopropyl-polydimethylsiloxane; polysiloxanylalkyl (meth)acrylic monomers; siloxane-containing macromer selected from the group consisting of Macromer A, Macromer B, Macromer C, and Macromer D described in US 5,760,100; chain-extended polysiloxane vinylic crosslinkers disclosed in US201008843A1 and US20120088844A1; the reaction products of glycidyl methacrylate with amino-functional polydimethylsiloxanes; hydroxyl-functionalized siloxane-containing vinylic monomers or macromers; polysiloxane-containing macromers disclosed in U.S. Patent Nos. 4,136,250, 4,153,641, 4,182,822, 4,189,546, 4,343,927, 4,254,248, 4,355,147, 4,276,402, 4,327,203, 4,341,889, 4,486,577, 4,543,398, 4,605,712, 4,661,575, 4,684,538, 4,703,097, 4,833,218, 4,837,289, 4,954,586, 4,954,587, 5,010,141, 5,034,461, 5,070,170, 5,079,319, 5039,761, 5,346,946, 5,358,995, 5,387,632, 5,416,132, 5,451,617, 5,486,579, 5,962,548, 5,981,675, 6,039,913, and 6,762,264; polysiloxane-containing macromers disclosed in U.S. Patent Nos. 4,259,467, 4,260,725, and 4,261,875.

[0057] Examples of water-soluble prepolymers (free of silicone) include: a water-soluble crosslinkable poly(vinyl alcohol) prepolymer described in U.S. Pat. Nos. 5583163 and 6303687; a water-soluble vinyl group-terminated polyurethane prepolymer described in U.S. Pat. No. 6995192; derivatives of a polyvinyl alcohol, polyethyleneimine or polyvinylamine, which are disclosed in U.S. Pat. No. 5849841; a water-soluble crosslinkable polyurea prepolymer described in U.S. Patent No. 6479587 and 7977430; crosslinkable polyacrylamide; crosslinkable statistical copolymers of vinyl lactam, MMA and a comonomer, which are disclosed in U.S. Pat. No. 5712356; crosslinkable copolymers of vinyl lactam, vinyl acetate and vinyl alcohol, which are disclosed in U.S. Pat. No. 5665840; polyether-polyester copolymers with crosslinkable side chains which are disclosed in U.S. Pat. No. 6492478; branched polyalkylene glycol-urethane prepolymers disclosed in U.S. Pat. No. 6165408; polyalkylene glycol-tetra(meth)acrylate prepolymers disclosed in U.S. Pat. No. 6221303; crosslinkable polyallylamine gluconolactone prepolymers disclosed in U.S. Pat. No. 6472489.

[0058] Any suitable of silicone-containing prepolymers with hydrophilic segments and hydrophobic segments can be used in the invention. Examples of such silicone-containing prepolymers include those described in commonly-owned US Patent Nos. 6,039,913, 7,091,283, 7,268,189 and 7,238,750, 7,521,519; commonly-owned US patent application publication Nos. US 2008-0015315 A1, US 2008-0143958 A1, US 2008-0143003 A1, US 2008-0234457 A1, US 2008-0231798 A1, and commonly-owned US patent application Nos. 61/180,449 and 61/180,453.

[0059] A lens formulation of the invention can further comprise visibility tinting agents (e.g., D&C Blue No. 6, D&C Green No. 6, D&C Violet No. 2, carbazole violet, certain copper complexes, certain chromium oxides, various iron oxides, phthalocyanine green, phthalocyanine blue, titanium dioxides, or mixtures thereof), antimicrobial agents (e.g., silver nanoparticles), a bioactive agent (e.g., a drug, an amino acid, a polypeptide, a protein, a nucleic acid, 2-pyrrolidone-5-carboxylic acid (PCA), an alpha hydroxyl acid, linoleic and gamma linoleic acids, vitamins, or any combination thereof), leachable lubricants (e.g., a non-crosslinkable hydrophilic polymer having an average molecular weight from 5,000 to 500,000, preferably from 10,000 to 300,000, more preferably from 20,000 to 100,000 Daltons), leachable tear-stabilizing agents (e.g., a phospholipid, a monoglyceride, a diglyceride, a triglyceride, a glycolipid, a glyceroglycolipid, a sphingolipid, a sphingo-glycolipid, a fatty acid having 8 to 36 carbon atoms, a fatty alcohol having 8 to 36 carbon atoms, or a mixture thereof), and the like, as known to a person skilled in the art.

[0060] In accordance with the invention, a lens formulation is preferably a solution of all desirable components dissolved in a suitable solvent (i.e., one chemical that cannot participate in free-radical polymerization reaction) or a mixture of suitable solvents or a liquid mixture free of any organic solvent.

[0061] A lens formulation can be prepared by blending all components thoroughly or by dissolving all of the desirable components in any suitable solvent, such as, a mixture of water and one or more organic solvents miscible with water, an organic solvent, or a mixture of one or more organic solvents, as known to a person skilled in the art.

[0062] Example of preferred organic solvents includes tetrahydrofuran, tripropylene glycol methyl ether, dipropylene glycol methyl ether, ethylene glycol n-butyl ether, ketones (e.g., acetone, methyl ethyl ketone, etc.), diethylene glycol n-butyl ether, diethylene glycol methyl ether, ethylene glycol phenyl ether, propylene glycol methyl ether, propylene glycol methyl ether acetate, dipropylene glycol methyl ether acetate, propylene glycol n-propyl ether, dipropylene glycol n-propyl ether, tripropylene glycol n-butyl ether, propylene glycol n-butyl ether, dipropylene glycol n-butyl ether, tripropylene glycol n-butyl ether, propylene glycol phenyl ether dipropylene glycol dimetyl ether, polyethylene glycols, polypropylene glycols, ethyl acetate, butyl acetate, amyl acetate, methyl lactate, ethyl lactate, i-propyl lactate, methylene chloride, 2-butanol, 1-propanol, 2-propanol, menthol, cyclohexanol, cyclopentanol and exonorborneol, 2-pentanol, 3-pentanol, 2-hexanol, 3-hexanol, 3-methyl-2-butanol, 2-heptanol, 2-octanol, 2-nonanol, 2-decanol, 3-octanol, norborneol, tert-butanol, tert-amyl alcohol, 2-methyl-2-pentanol, 2,3-dimethyl-2-butanol, 3-methyl-3-pentanol, 1-methylcyclohexanol, 2-methyl-2-hexanol, 3,7-dimethyl-3-octanol, 1-chloro-2-methyl-2-propanol, 2-methyl-2-heptanol, 2-methyl-2-octanol, 2-2-methyl-2-nonanol, 2-methyl-2-decanol, 3-methyl-3-hexanol, 3-methyl-3-heptanol, 4-methyl-4-heptanol, 3-methyl-3-octanol, 4-methyl-4-octanol, 3-methyl-3-nonanol, 4-methyl-4-nonanol, 3-methyl-3-octanol, 3-ethyl-3-hexanol, 3-methyl-3-heptanol, 4-ethyl-4-heptanol, 4-propyl-4-heptanol, 4-isopropyl-4-heptanol, 2,4-dimethyl-2-pentanol, 1-methylcyclopentanol, 1-ethylcyclopentanol, 1-ethylcyclopentanol, 3-hydroxy-3-methyl-1-butene, 4-hydroxy-4-methyl-1-cyclopentanol, 2-phenyl-2-propanol, 2-methoxy-2-methyl-2-propanol 2,3,4-trimethyl-3-pentanol, 3,7-dimethyl-3-octanol, 2-phenyl-2-butanol, 2-methyl-1-phenyl-2-propanol and 3-ethyl-3-pentanol, 1-ethoxy-2-propanol, 1-methyl-2-propanol, t-amyl alcohol, isopropanol, 1-methyl-2-pyrrolidone, N,N-dimethylpropionamide, dimethyl formamide, dimethyl acetamide, dimethyl propionamide, N-methyl pyrrolidinone, and mixtures thereof.

[0063] Lens molds for making contact lenses are well known to a person skilled in the art and, for example, are employed in cast molding or spin casting. For example, a mold (for cast molding) generally comprises at least two mold sections (or portions) or mold halves, i.e. first and second mold halves. The first mold half defines a first molding (or optical) surface and the second mold half defines a second molding (or optical) surface. The first and second mold halves are configured to receive each other such that a lens forming cavity is formed between the first molding surface and the second molding surface. The molding surface of a mold half is the cavity-forming surface of the mold and in direct contact with lens-forming material.

[0064] Methods of manufacturing mold sections for cast-molding a contact lens are generally well known to those of ordinary skill in the art. The process of the present invention is not limited to any particular method of forming a mold. In fact, any method of forming a mold can be used in the present invention. The first and second mold halves can be formed through various techniques, such as injection molding or lathing. Examples of suitable processes for forming the mold halves are disclosed in U.S. Patent Nos. 4,444,711 to Schad; 4,460,534 to Boehm et al.; 5,843,346 to Morrill; and 5,894,002 to Boneberger et al..

[0065] Virtually all materials known in the art for making molds can be used to make molds for making contact lenses. For example, polymeric materials, such as polyethylene, polypropylene, polystyrene, PMMA, Topas® COC grade 8007-S10 (clear amorphous copolymer of ethylene and norbornene, from Ticona GmbH of Frankfurt, Germany and Summit, New Jersey), or the like can be used. Other materials that allow UV light transmission could be used, such as quartz glass and sapphire.

[0066] In a preferred embodiment, reusable molds are used and the silicone-hydrogel lens-forming composition is cured actinically under a spatial limitation of actinic radiation to form a SiHy contact lens. Examples of preferred reusable molds are those disclosed in U.S. patent application Nos. 08/274,942 filed July 14, 1994, 10/732,566 filed December 10, 2003, 10/721,913 filed November 25, 2003, and U.S. Patent No. 6,627,124. Reusable molds can be made of quartz, glass, sapphire, CaF2, a cyclic olefin copolymer (such as for example, Topas® COC grade 8007-S10 (clear amorphous copolymer of ethylene and norbornene) from Ticona GmbH of Frankfurt, Germany and Summit, New Jersey, Zeonex® and Zeonor® from Zeon Chemicals LP, Louisville, KY), polymethylmethacrylate (PMMA), polyoxymethylene from DuPont (Delrin), Ultem® (polyetherimide) from G.E. Plastics, PrimoSpire®, etc..

[0067] In accordance with the invention, the lens formulation can be introduced (dispensed) into a cavity formed by a mold according to any known methods.

[0068] After the lens formulation is dispensed into the mold, it is cured (i.e., polymerized) to produce a contact lens. Curing may be initiated thermally or upon exposure to a light source including a light in a region between 390 nm to 500 nm to crosslink the polymerizable components in the lens formulation.

[0069] In accordance with the invention, light source can be any ones emitting light in the 390-500 nm range sufficient to activate photoinitiators. Blue-light sources are commercially available and include: the Palatray CU blue-light unit (available from Heraeus Kulzer, Inc., Irvine, Calif.), the Fusion F450 blue light system (available from TEAMCO, Richardson, Tex.), Dymax Blue Wave 200, LED light sources from Opsytec (385 nm, 395 nm, 405 nm, 435 nm, 445 nm, 460 nm), LED light sources from Hamamatsu (385 nm), and the GE 24" blue fluorescent lamp (available from General Electric Company, U.S.). A preferred blue-light source is the UV LED from Opsytec (those described above).

[0070] Opening of the mold so that the molded lens can be removed from the mold may take place in a manner known per se.

[0071] The molded contact lens can be subjected to one or more post-molding processes, such as, for example, lens extraction to remove unpolymerized vinylic monomers and macromers, surface modification to improve the surface hydrophilicity and wettability of a molded lens, hydration, packaging, sterilization (e.g., autoclave), as known to a person skilled in the art.

[0072] Lens packages (or containers) are well known to a person skilled in the art for autoclaving and storing a soft contact lens. Any lens packages can be used in the invention. Preferably, a lens package is a blister package which comprises a base and a cover, wherein the cover is detachably sealed to the base, wherein the base includes a cavity for receiving a sterile packaging solution and the contact lens.

[0073] Lenses are packaged in individual packages, sealed, and sterilized (e.g., by autoclave at about 120°C or higher for at least 30 minutes under pressure) prior to dispensing to users. A person skilled in the art will understand well how to seal and sterilize lens packages.

[0074] In accordance with the invention, a packaging solution contains at least one buffering agent and one or more other ingredients known to a person skilled in the art. Examples of other ingredients include tonicity agents, surfactants, antibacterial agents, preservatives, and lubricants (e.g., cellulose derivatives, polyvinyl alcohol, polyvinyl pyrrolidone).

[0075] The packaging solution contains a buffering agent in an amount sufficient to maintain a pH of the packaging solution in the desired range, for example, preferably in a physiologically acceptable range of about 6.5 to about 7.5. Any known, physiologically compatible buffering agents can be used. Suitable buffering agents as a constituent of the contact lens care composition according to the invention are known to the person skilled in the art. Examples are boric acid, borates, e.g. sodium borate, citric acid, citrates, e.g. potassium citrate, bicarbonates, e.g. sodium bicarbonate, TRIS (2-amino-2-hydroxymethyl-1,3-propanediol), Bis-Tris (Bis-(2-hydroxyethyl)-imino-tris-(hydroxymethyl)-methane), bis-aminopolyols, triethanolamine, ACES (N-(2-hydroxyethyl)-2-aminoethanesulfonic acid), BES (N,N-Bis(2-hydroxyethyl)-2-aminoethanesulfonic acid), HEPES (4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid), MES (2-(N-morpholino)ethanesulfonic acid), MOPS (3-[N-morpholino]-propanesulfonic acid), PIPES (piperazine-N,N'-bis(2-ethanesulfonic acid), TES (N-[Tris(hydroxymethyl)methyl]-2-aminoethanesulfonic acid), salts thereof, phosphate buffers, e.g. Na2HPO4, NaH2PO4, and KH2PO4 or mixtures thereof. A preferred bis-aminopolyol is 1,3-bis(tris[hydroxymethyl]-methylamino)propane (bis-TRIS-propane). The amount of each buffer agent in a packaging solution is preferably from 0.001 % to 2%, preferably from 0.01% to 1%; most preferably from about 0.05% to about 0.30% by weight.

[0076] The packaging solution has a tonicity of from about 200 to about 450 milliosmol (mOsm), preferably from about 250 to about 350 mOsm. The tonicity of a packaging solution can be adjusted by adding organic or inorganic substances which affect the tonicity. Suitable occularly acceptable tonicity agents include sodium chloride, potassium chloride, glycerol, propylene glycol, polyols, mannitols, sorbitol, xylitol and mixtures thereof.

[0077] A packaging solution of the invention has a viscosity of from about 1 centipoise to about 8 centipoises, more preferably from about 1.5 centipoises to about 5 centipoises, at 25°C.

[0078] In still a further aspect, the invention provides a contact lens comprising a crosslinked polymeric material.

[0079] A contact lens of the invention preferably is characterized by having an UVB transmittance of about 10% or less (preferably about 5% or less, more preferably about 2.5% or less, even more preferably about 1% or less) between 280 and 315 nanometers and a UVA transmittance of about 30% or less (preferably about 20% or less, more preferably about 10% or less, even more preferably about 5% or less) between 315 and 380 nanometers and optionally (but preferably) a Violet transmittance of about 60% or less, preferably about 50% or less, more preferably about 40% or less, even more preferably about 30% or less) between 380 nm and 440 nm.

[0080] In a preferred embodiment, a contact lens of the invention is a non-silicone hydrogel contact lens which has a water content of preferably from about 15% to about 80%, more preferably from about 30% to about 70% by weight (at room temperature, about 22°C to 28°C) when fully hydrated.

[0081] In another preferred embodiment, a contact lens of the invention is a silicone hydrogel contact lens. It preferably has one property selected from the group consisting of: an oxygen permeability of at least about 40 barrers, preferably at least about 50 barrers, more preferably at least about 60 barrers, even more preferably at least about 70 barrers; an elastic modulus of about 1.5 MPa or less, preferably about 1.2 MPa or less, more preferably about 1.0 or less, even more preferably from about 0.2 MPa to about 1.0 MPa; a water content of from about 15% to about 70%, preferably from about 20% to about 65%, more preferably from about 25% to about 60%, even more preferably from about 30% to about 55% by weight when fully hydrated; and combinations thereof.

[0082] The previous disclosure will enable one having ordinary skill in the art to practice the invention. In order to better enable the reader to understand specific embodiments and the advantages thereof, reference to the following examples is suggested.

Example 1



[0083] Transmittance. Contact lenses are manually placed into a specially fabricated sample holder or the like which can maintain the shape of the lens as it would be when placing onto eye. This holder is then submerged into a 1 cm path-length quartz cell containing phosphate buffered saline (PBS, pH ∼ 7.0 - 7.4) as the reference. A UV/visible spectrpohotmeter, such as, Varian Cary 3E UV-Visible Spectrophotometer with a LabSphere DRA-CA-302 beam splitter or the like, can be used in this measurement. Percent transmission spectra are collected at a wavelength range of 250-800 nm with %T values collected at 0.5 nm intervals. This data is transposed onto an Excel spreadsheet and used to determine if the lenses conform to Class 1 UV absorbance. Transmittance is calculated using the following equations:





in which Luminescence %T (the percent transmittance) is the ratio of luminous flux transmitted by the lens to the incident luminous flux (ISO 13666:1998). Photo-rheology: The photo-rheology experiment measures the elastic (G') and viscous modulus (G") as a function of time during curing. The experiment is conducted by using an appropriate light source, optionally cutoff filters to select wavelengths of interest, and a rheometer. The light source is a Mercury bulb in a Hamamatsu light source. The intensity of light source is set by adjusting the shutter opening to get an appropriate intensity measured by a radiometer. The sample is placed between a quartz plate that allows UV light to pass through and the rheometer. The cure time is determined when the elastic modulus (G') reaches a plateau.

Example 2


Preparation of CE-PDMS Macromer



[0084] In the first step, α,ω-bis(2-hydroxyethoxypropyl)-polydimethylsiloxane (Mn = 2000, Shin-Etsu, KF-6001a) is capped with isophorone diisocyanate (IPDI) by reacting 49.85 g of α,ω-bis(2-hydroxyethoxypropyl)-polydimethylsiloxane with 11.1 g IPDI in 150 g of dry methyl ethyl ketone (MEK) in the presence of 0.063g of dibutyltindilaurate (DBTDL). The reaction is kept for 4.5 h at 40° C, forming IPDI-PDMS-IPDI. In the second step, a mixture of 164.8 g of α,ω-bis(2-hydroxyethoxypropyl)-polydimethylsiloxane (Mn = 3000, Shin-Etsu, KF-6002) and 50 g of dry MEK are added dropwise to the IPDI-PDMS-IPDI solution to which has been added an additional 0.063 g of DBTDL. The reactor is held for 4.5 h at about 40° C, forming HO-PDMS-IPDI-PDMS-IPDI-PDMS-OH. MEK is then removed under reduced pressure. In the third step, the terminal hydroxyl-groups are capped with methacryloyloxyethyl groups in a third step by addition of 7.77 g of isocyanatoethylmethacrylate (IEM) and an additional 0.063 g of DBTDL, forming IEM-PDMS-IPDI-PDMS-IPDI-PDMS-IEM (i.e., CE-PDMS terminated with methacrylate groups).

Alternate Preparation of CE-PDMS Macromer with Terminal Methacrylate Groups



[0085] 240.43 g of KF-6001 is added into a 1-L reactor equipped with stirring, thermometer, cryostat, dropping funnel, and nitrogen/vacuum inlet adapter, and then dried by application of high vacuum (2×10-2 mBar). Then, under an atmosphere of dry nitrogen, 320 g of distilled MEK is then added into the reactor and the mixture is stirred thoroughly. 0.235 g of DBTDL is added to the reactor. After the reactor is warmed to 45°C, 45.86 g of IPDI are added through an addition funnel over 10 minutes to the reactor under moderate stirring. The reaction is kept for 2 hours at 60°C. 630 g of KF-6002 dissolved in 452 g of distilled MEK are then added and stirred until a homogeneous solution is formed. About 0.235 g of DBTDL is added, and the reactor is held at about 55°C overnight under a blanket of dry nitrogen. The next day, MEK is removed by flash distillation. The reactor is cooled and 22.7 g of IEM are then charged to the reactor followed by about 0.235 g of DBTDL. After about 3 hours, an additional 3.3 g of IEM are added and the reaction is allowed to proceed overnight. The following day, the reaction mixture is cooled to about 18°C to obtain CE-PDMS macromer with terminal methacrylate groups.

Example 3


Synthesis of N-(2-benzoyl-4-chlorophenyl)methacrylamide



[0086] In a 500 mL Erlenmyer flask equipped with a magnetic stirrer was added 300 mL chloroform, 25.1 g (108 mmol) (2-amino-5-chlorophenyl)(phenyl)methanone, 21.2 g (138 mmol) methacrylic anhydride, 20 g pyridine,1 drop stannous octoate (Aldrich), and 50 mg 4-methoxyphenol (Aldrich). The reaction mixture was stirred at ambient temperature for 3 days, then 50 °C for 1 day. TLC (70/30 hexanes/acetone) still showed unreacted starting material. An additional 20.58 g methacrylic anhydride was added. The solution was heated at 50 °C for an additional 5 hours. 400ml dichloromethane was added and the mixture was washed with ∼2M sodium bicarbonate (3x1 L) and then ∼2M NaCl (1x1 L). The organic layer was dried with sodium sulfate and the solvent removed under reduced pressure to afford orange oil which crystallized upon sitting at ambient temperature. Prior to crystallizing, aliquots were dissolved in vials containing IPA, methanol, ethanol, toluene, and diethyl ether. IPA was the best recrystallization solvent. Recrystallization also took place readily in diethyl ether and methanol, but not toluene. The crude crystallized product was cooled for several hours at -20 °C and then cold (-20 °C) ethanol was added and the product was filtered. The yellow solid was recrystallized in IPA to afford 15.22 g (47%) of yellow needles. 1H NMR spectrum in CDCl3 was consistent with structure (δ=11.3 ppm, 1H, N-H; δ=7.4-8.9 ppm, 8H, aromatic protons; δ=5.5 and 6.0 ppm, 2H, vinyl protons; δ=2.1 ppm, 3H, alpha-methyl protons.

Example 4



[0087] Two lens formulations (4A and 4B) are prepared from the following components: L-PEG 2000 (N-(carbonyl-methoxypolyethylene glycol-2000)-1,2-disteaoyl-sn-glycero-3-phosphoethanolamin, sodium salt; CE-PDMS (chain-extended polydimethylsiloxane crosslinker prepared in Example 2); DMA (N,N-dimethylacrylamide); TRIS-Am (N-[tris(trimethylsiloxy)-silylpropyl]acrylamide); Ge-PI (Bis(4-methoxybenzoyl) diethyl germanium); DMPC (1,2-Dimyristoyl-sn-glycero-3-phosphorcholine); Darocur 1173 (2-Hydroxy-2-methylpropiophenone); UV-absorbing vinylic monomer (prepared in Example 3), to have the compositions shown in the following Table.
IngredientComposition (% by weight)
Formulation 4AFormulation 4B
LPEG2000 0.61 0.61
DMPC 0.76 0.76
UV-absorbing vinylic monomer of Example 3 0.5 -
CE PDMS of Example 2 31.83 31.83
Tris acrylamide 20.21 20.71
DMA 23.24 23.24
Ge PI 0.6 -
Darocur 1173 - 1.01
1-propanol 22.25 21.84

Example 5


PAA-coating solution.



[0088] A polyacrylic acid (PAA) coating solution is prepared by dissolving an amount of PAA (M.W.: 450kDa, from Lubrizol) in a given volume of 1-propanol (1-PrOH) to have a concentration of about 0.44% by weight and the pH is adjusted with formic acid to about 2.0.

Preparation of In-Package-Coating solution (IPC saline).



[0089] Poly(AAm-co-AA)(90/10) partial sodium salt (∼90% solid content, poly(AAm-co-AA) 90/10, Mw 200,000) is purchased from Polysciences, Inc. and used as received. Polyamidonamine epichlorohydrin (PAE) (Kymene, an azetidinium content of 0.46 assayed with NMR) is purchased from Ashland as an aqueous solution and used as received. IPC saline is prepared by dissolving about 0.07% w/w of poly(AAm-co-AA)(90/10) and about 0.15% of PAE (an initial azetidinium millimolar equivalents of about 8.8 millimole) in phosphate-buffered saline (PBS) (about 0.044 w/w% NaH2PO4·H2O, about 0.388 w/w/% Na2HPO4·2H2O, about 0.79 w/w% NaCl) and adjusting the pH to 7.2-7.4. Then the IPC saline is heat pre-treated for about 4 hours at about 70°C (heat pretreatment). During this heat pretreatment, poly(AAm-co-AA) and PAE are partially crosslinked to each other (i.e., not consuming all azetidinium groups of PAE) to form a water-soluble and thermally-crosslinkable hydrophilic polymeric material containing azetidinium groups within the branched polymer network in the IPC saline. After the heat pre-treatment, the IPC is cooled to room temperature then filtered using a 0.22micron PES membrane filter.

Lens Fabrication using Formulation 4A from Example 4



[0090] Lenses are prepared by cast-molding from the lens formulation prepared above in a reusable mold (quartz female mold half and glass male mold half), similar to the mold shown in Figs. 1-6 in U.S. patent Nos.7,384,590 and 7,387,759 (Figs. 1-6). Lens formulation 4A prepared in Example 4 in the molds is irradiated for about 25 seconds using a 450nm LED lamp. The measured total intensity from 350 to 500 nm is 50 mW/cm2. Cast-molded contact lenses are then extracted by dipping in the following series of baths: deionized (DI) water bath (about 56 seconds); 3 methyl ethyl ketone (MEK) baths (about 22, 78, 224 seconds respectively, (DI) water bath (about 56 seconds). After lens extraction, the lenses are in contact for 44 seconds with the PAA-coating solution prepared above to form a PAA coating on each lens, then equilibrated into water, and then placed into polypropylene shells containing 0.65 mL of IPC saline prepared above, and autoclaved for 45 minutes at 121 °C. The UV/Vis spectrum is shown in Figure 1A.

Lens Fabrication using Formulation 4B from Example 4



[0091] Lenses are prepared by cast-molding from the lens formulation prepared above in a reusable mold (quartz female mold half and glass male mold half), similar to the mold shown in Figs. 1-6 in U.S. patent Nos.7,384,590 and 7,387,759 (Figs. 1-6). Lens formulation 4B prepared in Example 4 in the molds is irradiated for about 25 seconds using a Hamamatsu lamp with the light below 328 nm blocked by a long pass filter. The measured total intensity from 310 to 400 nm is 50 mW/cm2. Cast-molded contact lenses are then extracted by dipping in the following series of baths: deionized (DI) water bath (about 56 seconds); 3 methyl ethyl ketone (MEK) baths (about 22, 78, 224 seconds respectively, (DI) water bath (about 56 seconds). After lens extraction, the lenses are in contact for 44 seconds with the PAA-coating solution prepared above to form a PAA coating on each lens, then equilibrated into water, and then placed into polypropylene shells containing 0.65 mL of IPC saline prepared above, and autoclaved for 45 minutes at 121°C. The UV/Vis spectrum is shown in Figure 1B.


Claims

1. A UV-absorbing vinylic monomer, being selected from the group consisting of:



















and


 
2. A contact lens comprising a crosslinked material which comprises monomeric units of a UV-absorbing vinylic monomer of claim 1 or of the following formula:


 
3. The contact lens of claim 2, wherein the contact lens is a hydrogel contact lens.
 
4. The contact lens of claim 2, wherein the contact lens is a silicone hydrogel contact lens.
 
5. The contact lens of any one of claims 2 to 4, wherein the contact lens has: an UVB transmittance of about 10% or less between 280 and 315 nanometers; a UVA transmittance of about 30% or less between 315 and 380 nanometers; and a water content of from about 15% to about 80% (at room temperature, about 22°C to 28°C) when being fully hydrated.
 
6. The contact lens of claim 5, wherein the contact lens has an UVB transmittance of about 5% or less, more preferably about 2.5% or less, even more preferably about 1% or less between 280 and 315 nanometers.
 
7. The contact lens of claim 5, wherein the contact lens has a UVA transmittance of about 20% or less, more preferably about 10% or less, even more preferably about 5% or less between 315 and 380 nanometers.
 
8. The contact lens of claim 5, wherein the contact lens has a water content of from about 30% to about 75% by weight (at room temperature, about 22°C to 28°C) when being fully hydrated.
 
9. The contact lens of claim 5, wherein the contact lens has a Violet transmittance of about 60% or less, preferably about 50% or less, more preferably about 40% or less, even more preferably about 30% or less between 380 nm and 440 nm.
 
10. A method for producing UV-absorbing contact lenses, comprising the steps of:

(1) obtaining a lens formulation comprising (a) a UV-absorbing vinylic monomer of formula (I) of claim 1 or or the following formula:

(b) a free-radical initiator, and (c) at least one polymerizable component selected from the group consisting of a hydrophilic vinylic monomer, a hydrophobic vinylic monomer free of silicone, a vinylic crosslinking agent, a siloxane-containing vinylic monomer, a siloxane containing vinylic macromer, a water-soluble prepolymer free of silicone, and a siloxane-containing amphiphilic prepolymer;

(2) introducing the lens formulation into a mold for making a soft contact lens, wherein the mold has a first mold half with a first molding surface defining the anterior surface of a contact lens and a second mold half with a second molding surface defining the posterior surface of the contact lens, wherein said first and second mold halves are configured to receive each other such that a cavity is formed between said first and second molding surfaces; and

(3) curing thermally or actinically the lens formulation in the mold to crosslink the UV-absorbing vinylic monomer and the polymerizable component in the lens formulation to form the UV-absorbing contact lens, wherein the formed UV-absorbing contact lens comprises an anterior surface defined by the first molding surface and an opposite posterior surface defined by the second molding surface and is characterized by having the UVB transmittance of about 10% or less (preferably about 5% or less, more preferably about 2.5% or less, even more preferably about 1% or less) between 280 and 315 nanometers and a UVA transmittance of about 30% or less (preferably about 20% or less, more preferably about 10% or less, even more preferably about 5% or less) between 315 and 380 nanometers.


 
11. The method of claim 10, wherein the formed UV-absorbing contact lens has a Violet transmittance of about 60% or less, preferably about 50% or less, more preferably about 40% or less, even more preferably about 30% or less between 380 nm and 440 nm.
 
12. The method of claim 10 or 11, wherein the free-radical initiator is a thermal initiator, wherein the step of curing is carried out thermally.
 
13. The method of claim 10 or 11, wherein the free-radical initiator is a photoinitiator, wherein the step of curing is carried out by irradiation with a light having a wavelength within the range from 380 nm to 500 nm.
 
14. The method of claim 13, wherein the mold is a reusable mold, wherein the step of curing is carried out under a spatial limitation of radiation.
 


Ansprüche

1. UV-absorbierendes Vinylmonomer aus der Gruppe bestehend aus:



















und


 
2. Kontaktlinse, die ein vernetztes Material umfasst, das Monomereinheiten eines UV-absorbierenden Vinylmonomers gemäß Anspruch 1 oder gemäß der folgenden Formel umfasst:


 
3. Kontaktlinse gemäß Anspruch 2, wobei die Kontaktlinse eine Hydrogel-Kontaktlinse ist.
 
4. Kontaktlinse gemäß Anspruch 2, wobei die Kontaktlinse eine Silikonhydrogel-Kontaktlinse ist.
 
5. Kontaktlinse gemäß einem der Ansprüche 2 bis 4, wobei die Kontaktlinse Folgendes aufweist: eine UVB-Durchlässigkeit von etwa 10 % oder weniger zwischen 280 und 315 Nanometer; eine UVA-Durchlässigkeit von etwa 30 % oder weniger zwischen 315 und 380 Nanometer und einen Wassergehalt von etwa 15 % bis etwa 80 % (bei Raumtemperatur, etwa 22 °C bis 28 °C) in vollständig hydratisiertem Zustand.
 
6. Kontaktlinse gemäß Anspruch 5, wobei die Kontaktlinse zwischen 280 und 315 Nanometer eine UVB-Durchlässigkeit von etwa 5 % oder weniger, weiter bevorzugt etwa 2,5 % oder weniger, noch weiter bevorzugt etwa 1 % oder weniger, aufweist.
 
7. Kontaktlinse gemäß Anspruch 5, wobei die Kontaktlinse zwischen 315 und 380 Nanometer eine UVA-Durchlässigkeit von etwa 20 % oder weniger, weiter bevorzugt etwa 10 % oder weniger, noch weiter bevorzugt etwa 5 % oder weniger, aufweist.
 
8. Kontaktlinse gemäß Anspruch 5, wobei die Kontaktlinse in vollständig hydratisiertem Zustand einen Wassergehalt von etwa 30 Gew.-% bis etwa 75 Gew.-% (bei Raumtemperatur, etwa 22 °C bis 28 °C) aufweist.
 
9. Kontaktlinse gemäß Anspruch 5, wobei die Kontaktlinse zwischen 380 und 440 Nanometer eine Violett-Durchlässigkeit von etwa 60 % oder weniger, vorzugsweise etwa 50 % oder weniger, weiter bevorzugt etwa 40 % oder weniger, noch weiter bevorzugt etwa 30 % oder weniger, aufweist.
 
10. Verfahren zur Herstellung von UV-absorbierenden Kontaktlinsen, umfassend die folgenden Schritte:

(1) Erhalten einer Linsenformulierung, umfassend (a) ein UV-absorbierendes Vinylmonomer der Formel (I) gemäß Anspruch 1 oder gemäß der folgenden Formel:

(b) einen Radikalinitiator und (c) mindestens eine polymerisierbare Komponente aus der Gruppe bestehend aus einem hydrophilen Vinylmonomer, einem hydrophoben Vinylmonomer, das frei von Silikon ist, einem Vinyl-Vernetzungsmittel, einem siloxanhaltigen Vinylmonomer, einem siloxanhaltigen Vinylmakromer, einem wasserlöslichen Prepolymer, das frei von Silikon ist, und einem siloxanhaltigen amphiphilen Prepolymer;

(2) Eintragen der Linsenformulierung in eine Form zur Herstellung einer weichen Kontaktlinse, wobei die Form eine erste Formhälfte mit einer ersten Formoberfläche, die die Vorderfläche einer Kontaktlinse definiert, und eine zweite Formhälfte mit einer zweiten Formoberfläche, die die Hinterfläche der Kontaktlinse definiert, aufweist, wobei die erste Formhälfte und die zweite Formhälfte konfiguriert sind, um einander so aufzunehmen, dass sich zwischen der ersten Formoberfläche und der zweiten Formoberfläche ein Hohlraum ergibt; und

(3) thermisches oder aktinisches Härten der Linsenformulierung in der Form zur Vernetzung des UV-absorbierenden Vinylmonomers und der polymerisierbaren Komponente in der Linsenformulierung, um so die UV-absorbierende Kontaktlinse zu bilden, wobei die gebildete UV-absorbierende Kontaktlinse eine durch die erste Formoberfläche definierte Vorderfläche und eine durch die zweite Formoberfläche definierte gegenständige Hinterfläche umfasst und dadurch gekennzeichnet ist, dass sie die UVB-Durchlässigkeit von etwa 10 % oder weniger (vorzugsweise etwa 5 % oder weniger, weiter bevorzugt etwa 2,5 % oder weniger, noch weiter bevorzugt etwa 1 % oder weniger) zwischen 280 und 315 Nanometer und eine UVA-Durchlässigkeit von etwa 30 % oder weniger (vorzugsweise etwa 20 % oder weniger, weiter bevorzugt etwa 10 % oder weniger, noch weiter bevorzugt etwa 5 % oder weniger) zwischen 315 und 380 Nanometer aufweist.


 
11. Verfahren gemäß Anspruch 10, wobei die gebildete UV-absorbierende Kontaktlinse zwischen 380 und 440 Nanometer eine Violett-Durchlässigkeit von etwa 60 % oder weniger, vorzugsweise etwa 50 % oder weniger, weiter bevorzugt etwa 40 % oder weniger, noch weiter bevorzugt etwa 30 % oder weniger, aufweist.
 
12. Verfahren gemäß Anspruch 10 oder 11, wobei der Radikalinitiator ein thermischer Initiator ist, wobei der Härtungsschritt thermisch durchgeführt wird.
 
13. Verfahren gemäß Anspruch 10 oder 11, wobei der Radikalinitiator ein Photoinitiator ist, wobei der Härtungsschritt durch Bestrahlung mit Licht mit einer Wellenlänge im Bereich von 380 nm bis 500 nm durchgeführt wird.
 
14. Verfahren gemäß Anspruch 13, wobei die Form eine wiederverwendbare Form ist, wobei der Härtungsschritt mit einer räumlich begrenzten Bestrahlung durchgeführt wird.
 


Revendications

1. Monomère vinylique absorbant les UV, qui est choisi dans le groupe constitué par :



















et


 
2. Lentille de contact comprenant un matériau réticulé qui comprend des unités monomères d'un monomère vinylique absorbant les UV selon la revendication 1 ou répondant à la formule suivante :


 
3. Lentille de contact selon la revendication 2, la lentille de contact étant une lentille de contact en hydrogel.
 
4. Lentille de contact selon la revendication 2, la lentille de contact étant une lentille de contact en hydrogel de silicone.
 
5. Lentille de contact selon l'une quelconque des revendications 2 à 4, la lentille de contact ayant : une transmittance des UVB inférieure ou égale à environ 10 % entre 280 et 315 nanomètres ; une transmittance des UVA inférieure ou égale à environ 30 % entre 315 et 380 nanomètres ; et une teneur en eau d'environ 15 % à environ 80 % (à température ambiante, environ 22 °C à 28 °C) lorsqu'elle est totalement hydratée.
 
6. Lentille de contact selon la revendication 5, la lentille de contact ayant une transmittance des UVB inférieure ou égale à environ 5 %, de préférence encore inférieure ou égale à environ 2,5 %, de préférence même encore inférieure ou égale à environ 1 % entre 280 et 315 nanomètres.
 
7. Lentille de contact selon la revendication 5, la lentille de contact ayant une transmittance des UVA inférieure ou égale à environ 20 %, de préférence encore inférieure ou égale à environ 10 %, de préférence même encore inférieure ou égale à environ 5 % entre 315 et 380 nanomètres.
 
8. Lentille de contact selon la revendication 5, la lentille de contact ayant une teneur en eau d'environ 30 % à environ 75 % en poids (à température ambiante, environ 22 °C à 28 °C) lorsqu'elle est totalement hydratée.
 
9. Lentille de contact selon la revendication 5, la lentille de contact ayant une transmittance du violet inférieure ou égale à environ 60 %, de préférence inférieure ou égale à environ 50 %, de préférence encore inférieure ou égale à environ 40 %, de préférence même encore inférieure ou égale à environ 30 % entre 380 nm et 440 nm.
 
10. Procédé pour la production de lentilles de contact absorbant les UV, comprenant les étapes consistant à :

(1) obtenir une formulation de lentille comprenant

(a) un monomère vinylique absorbant les UV de formule (I) selon la revendication 1 ou répondant à la formule suivante :

(b) un initiateur de radicaux libres et

(c) au moins un composant polymérisable choisi dans le groupe constitué par un monomère vinylique hydrophile, un monomère vinylique hydrophobe exempt de silicone, un agent de réticulation vinylique, un monomère vinylique contenant un siloxane, un macromère vinylique contenant un siloxane, un prépolymère hydrosoluble exempt de silicone et un prépolymère amphiphile contenant un siloxane ;

(2) introduire la formulation de lentille dans un moule pour la fabrication d'une lentille de contact souple, le moule ayant une première moitié de moule présentant une première surface de moulage définissant la surface antérieure d'une lentille de contact et une seconde moitié de moule présentant une seconde surface de moulage définissant la surface postérieure de la lentille de contact, lesdites première et seconde moitiés de moule étant conçues pour s'accueillir mutuellement de façon telle qu'une cavité est formée entre lesdites première et seconde surfaces de moulage ; et

(3) faire durcir thermiquement ou de manière actinique la formulation de lentille dans le moule pour réticuler le monomère vinylique absorbant les UV et le composant polymérisable présents dans la formulation de lentille pour former la lentille de contact absorbant les UV, la lentille de contact absorbant les UV formée comprenant une surface antérieure définie par la première surface de moulage et une surface postérieure opposée définie par la seconde surface de moulage et étant caractérisée en ce qu'elle a la transmittance des UVB inférieure ou égale à environ 10 % (de préférence inférieure ou égale à environ 5 %, de préférence encore inférieure ou égale à environ 2,5 %, de préférence même encore inférieure ou égale à environ 1 %) entre 280 et 315 nanomètres et une transmittance des UVA inférieure ou égale à environ 30 % (de préférence inférieure ou égale à environ 20 %, de préférence encore inférieure ou égale à environ 10 %, de préférence même encore inférieure ou égale à environ 5 %) entre 315 et 380 nanomètres.


 
11. Procédé selon la revendication 10, dans lequel la lentille de contact absorbant les UV formée a une transmittance du violet inférieure ou égale à environ 60 %, de préférence inférieure ou égale à environ 50 %, de préférence encore inférieure ou égale à environ 40 %, de préférence même encore inférieure ou égale à environ 30 % entre 380 nm et 440 nm.
 
12. Procédé selon la revendication 10 ou 11, dans lequel l'initiateur de radicaux libres est un initiateur thermique, dans lequel l'étape de durcissement est effectuée thermiquement.
 
13. Procédé selon la revendication 10 ou 11, dans lequel l'initiateur de radicaux libres est un photoinitiateur, dans lequel l'étape de durcissement est effectuée par exposition à une lumière ayant une longueur d'onde dans la plage de 380 nm à 500 nm.
 
14. Procédé selon la revendication 13, dans lequel le moule est un moule réutilisable, dans lequel l'étape de durcissement est effectuée sous une limitation spatiale de rayonnement.
 




Drawing








Cited references

REFERENCES CITED IN THE DESCRIPTION



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Patent documents cited in the description




Non-patent literature cited in the description