Stabilizing formulations for contact lenses

Abstract

The present invention provides a silicone hydrogel contact lens formulation comprising a polymerizable siloxane component, a hydrophilic N-vinylamide monomer, triphenylphosphine (TPP), and one or more of an anthraquinone blue tint, a benzophenone UV absorber, or a benzotriazole HEVL absorber; a silicone hydrogel contact lens formed from the polymerization of the silicone hydrogel contact lens formulation; and the use of an anthraquinone blue tint, a benzophenone UV absorber, and / or a benzotriazole HEVL absorber to stabilize a formulation comprising a polymerizable siloxane component, a hydrophilic N-vinylamide monomer, and TPP.

Description

[Technical Field]

[0001] The present invention relates to silicone hydrogel contact lens formulations comprising triphenylphosphine, and silicone hydrogel contact lenses manufactured from such formulations. In particular, the present invention relates to the use of colored tints and / or radiation blockers to improve the stability of such silicone hydrogel contact lens formulations. [Background technology]

[0002] Monomer mixtures formulated for contact lenses need to have sufficient stability against polymerization ("pot life") to allow for storage before use and to minimize gelation resulting from premature polymerization if used during lens manufacturing. As described in U.S. Patent Application Publication No. 2014 / 0330053, trace amounts of inhibitors, such as hydroquinone, are typically incorporated into commercially available monomers by monomer manufacturers to inhibit polymerization. Since these inhibitors function in the presence of oxygen, this is facilitated by having airhead space in the containers where the monomers and monomer-containing formulations are stored. Triphenylphosphine (TPP) may be added to formulated mixtures to act as an oxygen scavenger. This can not only improve lens finish properties, but may also negate the action of hydroquinone inhibitors, leading to premature polymerization of bulk liquid monomer mixtures, and thus a reduction in pot life. Therefore, there is a need for contact lens formulations that contain TPP and are more stable in their pre-polymerization form, particularly silicone hydrogel contact lens formulations. [Overview of the Initiative]

[0003] It has been observed that adding TPP to silicone hydrogel contact lens formulations containing high levels of polymerizable siloxane can improve the processability of the formulation and reduce the level of lens defects that occur during the cast molding process. Therefore, TPP may play a role as a processing aid for contact lens formulations containing high levels of siloxane. However, it has also been observed that contact lens formulations containing a considerable amount of hydrophilic N-vinylamide monomer and polymerizable siloxane are particularly susceptible to premature polymerization in the presence of TPP. The object of the present invention is to improve the stability of a contact lens formulation containing at least 40% (wt / wt) of polymerizable siloxane components, at least 30% (wt / wt) of hydrophilic N-vinylamide monomer and triphenylphosphine (TPP).

[0004] In a first aspect, the present invention relates to a silicone hydrogel contact lens formulation, a. At least 40% (wt / wt) of polymerizable siloxane components, b. At least 30% (wt / wt) of hydrophilic N-vinylamide monomer, c. Triphenylphosphine (TPP) and, d. 1,4-Bis[(2-methacryloxyethyl)amino]-9,10-anthraquinone (RB247) and Includes, e. Provide a formulation which may contain a benzophenone UV absorber and / or a benzotriazole HEVL absorber. It has been found that by including the tint agent RB247 in a contact lens formulation comprising (a) at least 40% (wt / wt) polymerizable siloxane components, (b) at least 30% (wt / wt) hydrophilic N-vinylamide monomer, and (c) TPP, it is possible to obtain a contact lens formulation that is more stable in its pre-polymerization form and less susceptible to gelation than similar compositions that do not contain RB247 and / or contain other colorants. Benzophenone UV absorbers, such as UV416, and benzotriazole HEVL absorbers, particularly UV13 or UV28, have also been found to enhance the stability of contact lens formulations comprising (a) at least 40% (wt / wt) polymerizable siloxane components, (b) at least 30% (wt / wt) hydrophilic N-vinylamide monomer, and (c) TPP. Benzophenone UV absorbers, such as UV416, and benzotriazole HEVL absorbers, such as UV13 or UV28, are effective, both on their own and when used in combination with the tinting agent RB247, in stabilizing contact lens formulations containing (a) at least 40% (wt / wt) polymerizable siloxane components, (b) at least 30% (wt / wt) hydrophilic N-vinylamide monomers, and (c) TPP. When two or more of RB247, benzophenone UV absorbers, and benzotriazole HEVL absorbers are used in combination, a synergistic effect has been observed that enhances the stability of contact lens formulations containing (a) at least 40% (wt / wt) polymerizable siloxane components, (b) at least 30% (wt / wt) hydrophilic N-vinylamide monomers, and (c) TPP. Therefore, the formulation of the first embodiment of the present invention is advantageous in that, in addition to RB247, further comprises a benzophenone UV absorber and / or a benzotriazole HEVL absorber, particularly both a benzophenone UV absorber and a benzotriazole HEVL absorber.

[0005] Since benzophenone UV absorbers and benzotriazole HEVL absorbers have been shown to have a positive effect on the stability of formulations that do not contain RB247, comprising (a) at least 40% (wt / wt) polymerizable siloxane components, (b) at least 30% (wt / wt) hydrophilic N-vinylamide monomer, and (c) TPP, the present invention also provides a formulation that does not contain RB247, comprising a benzophenone UV absorber and / or a benzotriazole HEVL absorber. Accordingly, in a second aspect, the present invention relates to a contact lens formulation, a. At least 40% (wt / wt) of polymerizable siloxane components, b. At least 30% (wt / wt) of hydrophilic N-vinylamide monomer, c. Triphenylphosphine (TPP) and Includes, d. 1,4-Bis[(2-methacryloxyethyl)amino]-9,10-anthraquinone (RB247), e. Benzophenone UV absorber and / or benzotriazole HEVL absorber The present invention provides a formulation which may contain [a certain substance]. A formulation according to a second aspect of the present invention advantageously comprises both a benzophenone UV absorber, for example UV416, and a benzotriazole HEVL absorber, for example UV13 or UV28. In addition to the components listed above, the silicone hydrogel contact lens formulation of the present invention typically further comprises polymerizable monomers, oligomers, and / or prepolymers, one or more crosslinking agents, and one or more polymerization initiators.

[0006] In a third aspect, the present invention provides a silicone hydrogel contact lens formed from the polymerization of the formulation of the first aspect of the present invention. Therefore, the polymer lens material of the silicone hydrogel contact lens of the third aspect of the present invention is a polymer product obtained by polymerizing the composition, a. At least 40% (wt / wt) of polymerizable siloxane components, b. At least 30% (wt / wt) of hydrophilic N-vinylamide monomer, c. Triphenylphosphine (TPP) and, d. 1,4-Bis[(2-methacryloxyethyl)amino]-9,10-anthraquinone (RB247) and Includes, e. Benzophenone UV absorber and / or benzotriazole HEVL absorber Products that may contain [the specified substance].

[0007] In a fourth aspect, the present invention provides a silicone hydrogel contact lens formed from the polymerization of the formulation of the second aspect of the present invention. Therefore, the polymer lens material of the silicone hydrogel contact lens of the fourth aspect of the present invention is a polymer product obtained by polymerizing the composition, a. At least 40% (wt / wt) of polymerizable siloxane components, b. At least 30% (wt / wt) of hydrophilic N-vinylamide monomer, c. Triphenylphosphine (TPP) and Includes, d. 1,4-Bis[(2-methacryloxyethyl)amino]-9,10-anthraquinone (RB247), e. Benzophenone UV absorber and / or benzotriazole HEVL absorber Products that may contain [the specified substance].

[0008] In a fifth aspect, the present invention is a. At least 40% (wt / wt) of polymerizable siloxane components, b. At least 30% (wt / wt) of hydrophilic N-vinylamide monomer, c. Triphenylphosphine (TPP) and The present invention provides the use of anthraquinone blue tints, benzophenone UV absorbers, and / or benzotriazole HEVL absorbers to stabilize formulations containing these substances.

[0009] The formulation of the present invention is stable for more than one day against prepolymerization gelation and has been shown to avoid complete gelation (formation of a solid gel) for more than three days. In comparison, similar formulations containing TPP may exhibit gelation within one day and form a solid gel within three days, sometimes within two days, or as short as one day. [Modes for carrying out the invention]

[0010] The Disclosure will be more fully understood and further advantages will become apparent upon reference to the following detailed description of embodiments of the Disclosure. The Invention will be described in more detail with particular reference to the formulations of the First and Second Embodiments of the Invention, hereafter referred to as “Formulations of the Invention.” However, since the contact lenses of the Third or Fourth Embodiment of the Invention, hereafter referred to as “Contact Lenses of the Invention,” are available from polymerizing the formulations of the First and Second Embodiments of the Invention, it should be understood that the components of the formulations of the First and Second Embodiments of the Invention will therefore exist in a polymerized form as the polymer lens material of the Contact Lenses of the Invention. Similarly, contact lenses for which particular advantages are found from the use of TPP to improve surface properties according to the Fifth Embodiment of the Invention are obtained from the polymerization of formulations having the properties described herein with respect to lenses of the Third and Fourth Embodiments of the Invention and / or formulations having the properties described herein with respect to formulations of the First and Second Embodiments of the Invention. Therefore, the components of the formulations of the First and Second Embodiments of the Invention will exist in a polymerized form in the polymer lens material of contact lenses in which TPP is used according to the Fifth Embodiment of the Invention. The features of formulations or lenses or their components as referred to herein, or the features of the use of anthraquinone tints, benzophenone UV absorbers, and / or benzotriazole HEVL absorbers (as contextually indicated), may be combined with any combination of the features described herein or thereafter, unless any particular combination of features is mutually exclusive or unless otherwise indicated in the context. Furthermore, as used in this specification, the singular forms "a," "an," and "the" include plural references (e.g., at least one or more) unless otherwise clearly indicated in the context. Thus, for example, a reference to "a contact lens" includes a single lens as well as two or more lenses, one or more of the same or different lenses.

[0011] This disclosure is based on the discovery that by including one or more of anthraquinone tints, benzophenone UV absorbers, and benzotriazole HEVL absorbers in a polymerizable formulation for manufacturing contact lenses, it is possible to provide contact lenses with improved lens finish characteristics, resulting from reduced premature polymerization of the formulation, from formulations containing TPP. Other combinations of formulations containing TPP and various tints and / or UV absorbers have been shown to have reduced pot life and to be highly susceptible to premature polymerization. Contact lens formulations containing at least 40% (wt / wt) of polymerizable siloxane components, at least 30% (wt / wt) of hydrophilic N-vinylamide monomers, and TPP have been shown to be particularly susceptible to premature polymerization. The inclusion of anthraquinone tints and / or benzophenone UV absorbers and / or benzotriazole HEVL absorbers in such formulations has been shown to be effective in preventing or reducing premature polymerization. The polymerizable components of the formulation of the present invention are typically incorporated into the contact lenses of the present invention.

[0012] References herein to the amount of components or constituents present in a formulation expressed in mass percentage (i.e., %(wt / wt)) are based on the amount of all formulation components except diluents and / or solvents not incorporated into the polymer lens material of the finished contact lens. Therefore, for example, the amount of TPP in a formulation (total 100 parts) prepared by mixing 0.5 parts TPP, 40 parts siloxane components, 30 parts hydrophilic N-vinylamide monomer, 4.5 parts other active ingredients (e.g., polymerization initiators, colorants, oxygen scavengers, etc.) and 25 parts organic solvent and / or water is 0.67%(wt / wt). As used herein, “components” of a formulation refer collectively to all components of a particular type. For example, if a formulation contains 20%(wt / wt) of a first siloxane monomer and 25% of a second siloxane monomer, and no other siloxanes, it may be stated that the formulation contains 45%(wt / wt) of siloxane components.

[0013] The polymerizable formulation of the present invention contains triphenylphosphine (TPP; CAS No.: 603-35-0).

Chemical formula

[0014] TPP may be present in the polymerizable formulation of the present invention, for example, in the formulation of the first aspect of the present invention, in an amount of at least 0.10% (wt / wt), typically in an amount of at least 0.15% (wt / wt), for example in an amount of at least 0.20%, and particularly in an amount of at least 0.25%. For example, TPP may be present in the polymerizable formulation in an amount of about 0.15% (wt / wt) to about 2.0% (wt / wt), for example in an amount of 0.20% (wt / wt) to 1.0% (wt / wt), and typically in an amount of about 0.25% (wt / wt) to about 1% (wt / wt).

[0015] The polymerizable formulation of the first aspect of the present invention also contains 1,4-bis[(2-methacryloxyethyl)amino]-9,10-anthraquinone (Reactive Blue 247, RB247; CAS No. 109561-07-1; available from Arran Chemical Company, Co. Roscommon, Ireland and also from Pharnorcia Inc., Edison, New Jersey, USA), which is referred to herein as "RB247".

Chemical formula

[0016] RB247 may be present in the formulation of the present invention in an amount of at least 0.003% (wt / wt), typically in an amount of about 0.005% (wt / wt) to 0.1% (wt / wt), for example in an amount of 0.006% (wt / wt) to 0.05% (wt / wt) or 0.007% (wt / wt) to 0.03% (wt / wt).

[0017] For example, it is known that anthraquinone tints are included in contact lens formulations as tints to color the resulting contact lenses, for instance, to facilitate lens handling by making them more visible, to give the lenses an attractive blue tint, and / or to counteract an unattractive yellow tint. However, the inventors have surprisingly found that anthraquinone tints, in particular anthraquinone blue tints, may also function to inhibit prepolymerization gelation of lens formulations containing TPP, especially lens formulations containing TPP together with at least 40% (wt / wt) polymerizable siloxane components and at least 30% (wt / wt) hydrophilic N-vinylamide monomers.

[0018] The formulations of the present invention may further comprise 1,4-bis[4-(2-methacryloxyethyl)phenylamino]-9,10-anthraquinone (CAS No. 121888-69-5, Reactive Blue 246, RB246, available from Arran Chemical Company, Co. Roscommon, Ireland and Pharnorcia Inc., Edison, New Jersey, USA), referred herein as "RB246". RB246 has been shown to be less effective than RB247 in stabilizing polymerizable formulations containing at least 40% (wt / wt) polymerizable siloxane components, at least 30% (wt / wt) hydrophilic N-vinylamide monomers, and TPP; however, RB246 has been shown to have a beneficial effect on the stability of such formulations. [ka]

[0019] Advantageously, RB246 is present in formulations of the second embodiment of the present invention that do not contain RB247. RB246 may be present in the contact lens formulations of the present invention, particularly in formulations of the second embodiment of the present invention, in an amount of at least 0.003% (wt / wt), typically about 0.005% (wt / wt) to 0.1% (wt / wt), for example, 0.006% (wt / wt) to 0.05% (wt / wt) or 0.007% (wt / wt) to 0.03% (wt / wt). A formulation according to a second aspect of the present invention comprises a benzophenone UV absorber and / or a benzotriazole HEVL absorber, preferably comprising both the benzophenone UV absorber and the benzotriazole HEVL absorber. A formulation according to a first aspect of the present invention advantageously comprises, in addition to RB247, a benzophenone UV absorber and / or a benzotriazole HEVL absorber, preferably comprising both the benzophenone UV absorber and the benzotriazole HEVL absorber.

[0020] The term "UV absorber" refers to a compound containing a chromophore that absorbs light in the UV spectrum, i.e., wavelengths in the range of 100 to 400 nm. In particular, the maximum absorbance (λmax) of a 0.003 mass% UV absorber solution in ethyl acetate is in the range of 220 to 350 nm, especially in the range of 250 to 350 nm. The maximum absorbance (λmax) of the UV absorber present in the formulation and lens of the present invention is, advantageously, in the range of 250 to 350 nm, between 260 to 320 nm, especially between 270 to 310 nm, as a 0.003 mass% solution in ethyl acetate.

[0021] The silicone hydrogel contact lens formulation of the present invention may contain a polymerizable UV absorber containing a benzophenone moiety. Similarly, the polymer lens material of the silicone hydrogel contact lens of the present invention may contain UV light absorbing units containing a benzophenone moiety. The UV light absorbing units containing a benzophenone moiety present in the polymer lens material of the contact lens of the present invention may be derived from a polymerizable UV absorber as described herein with reference to the formulation of the present invention.

[0022] Polymerizable UV absorbers are advantageous because they covalently bond to the polymer matrix of the lens material rather than being merely physically trapped in the material, thus preventing the absorber from migrating, phase-separating, or leaching away from the lens material. Such stability is advantageous because leaching of UV absorbers presents toxicological problems, and / or such leaching may lead to a loss of UV-blocking activity in the contact lens. The UV absorbers used in the present invention are typically soluble in the contact lens formulation, polymerizable, and consequently form part of the polymer matrix of the lens, retained in the lens during autoclaving and storage. The UV absorbers are advantageous because they are polymerizable UV absorbers containing reactive groups that can participate in a curing reaction in which the polymer matrix of the polymer lens material is formed, resulting in the polymerizable UV absorber covalently bonding to the polymer lens material. Polymerizable UV absorbers typically contain ethylenically unsaturated groups, such as vinyl or (meth)acrylate, (meth)acrylamide, or styrene groups, that can participate in radical polymerization reactions. Numerous copolymerizable benzophenone UV absorbers are known. Many of these UV absorbers contain ethylenically unsaturated polymerizable groups. UV absorbers are incorporated into the resulting polymer chain by copolymerization with other components in the lens material, typically with radical initiators. The incorporation of additional functional groups into the UV absorber may affect one or more of its UV absorption properties, solubility, or reactivity. If the UV absorber does not have sufficient solubility in the ophthalmic lens material components or the rest of the polymer lens material, it may fuse in domains that interact with light, resulting in a decrease in the optical clarity of the lens.

[0023] The benzophenone UV absorber may be present in the formulation of the present invention in an amount of about 0.05 to about 5.0% (wt / wt), typically in an amount of about 0.1% (wt / wt) to about 3.0% (wt / wt) or about 0.2% (wt / wt) to about 3.0% (wt / wt), for example, in an amount of 0.3% (wt / wt) to 3.0% (wt / wt).

[0024] The silicone hydrogel contact lens formulation of the present invention may contain a polymerizable benzophenone UV absorber having a maximum absorbance (λmax) in the range of 250 to 380 nm, between 260 to 320 nm, and particularly between 270 to 310 nm, as a 0.003 mass% solution in ethyl acetate. Therefore, the polymer lens material of the silicone hydrogel contact lens of the present invention may contain UV light absorption units derived from a polymerizable benzophenone UV absorber having a maximum absorbance (λmax) in the range of 250 to 380 nm, between 260 to 320 nm, and particularly between 270 to 310 nm, as a 0.003 mass% solution in ethyl acetate. The silicone hydrogel contact lens formulation of the present invention may contain a polymerizable UV absorber containing a benzophenone moiety, having a maximum absorbance (λmax) in the range of 250 to 380 nm, between 260 to 320 nm, and particularly between 270 to 310 nm, as a 0.003% by mass solution in ethyl acetate.

[0025] The benzophenone UV absorber contained in the formulation of the present invention is preferably not a dual-function HEVL absorber and UV absorber. The benzophenone UV absorber may have an absorbance cutoff below the visible range; that is, the benzophenone UV absorber does not absorb large amounts of light above 380 nm. For example, a 0.003% by mass solution of benzophenone UV absorber in ethyl acetate does not have an absorbance of at least 0.5 in the range of 375-450 nm.

[0026] The polymerizable UV absorber may be 2-(4-benzoyl-3-hydroxyphenoxy)ethyl acrylate (UV416; CAS number: 16432-81-8). [ka]

[0027] UV416 may be present in the polymerizable formulation of the present invention, i.e., in the formulation of the first or second embodiment of the present invention, in an amount of about 0.05% (wt / wt) to about 5.0% (wt / wt), typically in an amount of about 0.1% (wt / wt) to about 3.0% (wt / wt) or about 0.2% (wt / wt) to about 3.0% (wt / wt), for example, in an amount of 0.3% (wt / wt) to 3.0% (wt / wt).

[0028] The silicone hydrogel contact lens formulation of the present invention may contain a high-energy visible light (HEVL) absorber. The HEVL absorber is a compound containing a chromophore that absorbs visible light in the violet to blue range from 350 to 455 nm. Typically, the maximum absorbance (λmax) of the HEVL absorber is in the range of 350 to 455 nm, particularly in the range of 350 to 400 nm. The term "high-energy visible light (HEVL) absorber," as used herein, may be defined as a compound or mixture of compounds having an absorbance of at least 0.5 in the range of 375 to 450 nm as a 0.003 mass% solution in ethyl acetate (≧99.8%, HPLC grade) (the solution was measured in a quartz cell with a path length of 10 mm, and the absorbance of the solution at 250 to 800 mm was measured using a Perkin Elmer Lambda 365). HEVL absorbers may also absorb short-wavelength light, such as light in the 250-350 nm range, and therefore function as both HEVL absorbers and UV absorbers, as described below. The silicone hydrogel contact lens formulation according to the first aspect of the present invention may contain a HEVL absorber, such as a benzotriazole HEVL absorber, in addition to the tinting agent RB247. The silicone hydrogel contact lens formulation according to the second aspect of the present invention may contain a benzotriazole HEVL absorber, or it may contain both a benzotriazole HEVL absorber and a benzophenone UV absorber.

[0029] Advantageously, the HEVL absorber used in contact lens formulations, including the contact lens formulation of the present invention, has polymerizable moieties in its chemical structure, such as vinyl functional groups, acrylate functional groups, or methacrylate functional groups, so that it can be covalently incorporated into the contact lens material during polymerization. When incorporated into the polymer contact lens material, the HEVL absorber imparts HEVL absorption properties to the polymer contact lens material. The HEVL absorber used in the present invention is typically soluble in the contact lens formulation, polymerizable, and as a result forms part of the polymer matrix of the lens, and is retained in the lens during autoclaving and storage. The HEVL absorber may be a benzotriazole ring system.

[0030] The HEVL absorber may be present in an amount of 0.3% to 3% (wt / wt), preferably 0.4% to 3% (wt / wt), based on the total amount of the formulation. If the HEVL absorber contains more than one compound, the total amount of the compounds having maximum absorbance (λmax) in the range of 350 to 455 nm is present in an amount of 0.3% to 3% (wt / wt), preferably 0.4% to 3% (wt / wt), based on the total amount of the formulation.

[0031] Examples of benzotriazole HEVL absorbers include: 2-(1,1-dimethylethyl)-4-[3-[(4-ethenylphenyl)methoxy]propoxy]-6-(5-methoxy-2H-benzotriazol-2-yl)-phenol (UV1, CAS number 159732-06-6): [ka] 2-(5-chloro-2H-benzotriazol-2-yl)-6-(1,1-dimethylethyl)-4-ethenylphenol (UV5 / UVAM, CAS number 124883-10-9): [ka] 2-[2'-Hydroxy-3'-tert-butyl-5'-(3"-methacryloyloxypropoxy)phenyl]-5-methoxy-2H-benzotriazole (UV13, CAS No. 114166-71-1): [ka] 2-3'-t-butyl-2'-hydroxy-5'-(3"-dimethylvinylsilylpropoxy)-2'-hydroxyphenyl)-5-methoxybenzotriazole (UV15, CAS No. 122430-79-9): [ka] 2-[2'-Hydroxy-3'-tert-butyl-5'-(3"-methacryloyloxypropoxy)phenyl]-5-chloro-2H-benzotriazole (UV28, CAS No. 275371-71-6): [ka] All of the above HEVL absorbers are available from LYNN Laboratories, Inc., 2797 Irving Blvd STE 110, Dallas, TX75207. Advantageously, the absorbance peak of a 0.003 mass% HEVL absorber solution in ethyl acetate is in the range of 360–410 nm, for example, 360–400 nm, and especially 360–390 nm.

[0032] The total amount of HEVL absorber and UV absorber present in the formulation of the present invention does not need to exceed 5% (wt / wt). The formulation of the present invention may contain HEVL absorber and UV absorber in a total amount of 0.2% to 5% (wt / wt), preferably 0.4% to 4% (wt / wt).

[0033] The compounds may function as both HEVL absorbers and UV absorbers. The term "HEVL absorber," as used herein, encompasses compounds that function solely as HEVL absorbers and compounds that function as both HEVL absorbers and UV absorbers. The benzophenone UV absorbers contained in the formulations of the present invention are preferably not dual-function HEVL absorbers and UV absorbers. The benzotriazole HEVL absorbers contained in the formulations of the present invention may, in some embodiments, function as both HEVL absorbers and UV absorbers. The UV absorbers may have an absorbance cutoff below the visible spectrum, i.e., they do not absorb large amounts of light above 380 nm. For example, a 0.003% by mass UV absorber solution in ethyl acetate does not have an absorbance of at least 0.5 in the range of 375-450 nm. The HEVL absorber present in the formulation of the present invention may, as a 0.003% by mass solution in ethyl acetate, have an absorption of more than 0.5 in the range of 375 to 450 nm, and may also have a maximum absorbance (λmax) in the range of 220 to 350 nm, particularly in the range of 250 to 350 nm.

[0034] A formulation according to a first aspect of the present invention, comprising RB247, advantageously further comprises UV416 and a benzotriazole HEVL absorbent, particularly UV13 or UV28. The combination of RB247, UV416, and UV13 or UV28 has been shown to be particularly effective in reducing the gelation of polymerizable formulations comprising at least 40% (wt / wt) of polymerizable siloxane components, at least 30% (wt / wt) of hydrophilic N-vinylamide monomer, and TPP.

[0035] A formulation according to a second aspect of the present invention is advantageous in comprising both UV416 and a benzotriazole HEVL absorber, particularly UV13 or UV28. The combination of UV416 and UV13 or UV28 has been shown to be effective in reducing the gelation of polymerizable formulations comprising at least 40% (wt / wt) of polymerizable siloxane components, at least 30% (wt / wt) of hydrophilic N-vinylamide monomer and TPP. A formulation according to a second aspect of the present invention may also comprise a benzotriazole UV absorber and / or a benzotriazole HEVL absorber in addition to RB246. A formulation according to a second aspect of the present invention may comprise UV416, UV13 or UV28, and RB246. The contact lens formulation of the present invention is a silicone hydrogel contact lens formulation, a. At least 40% (wt / wt) of polymerizable siloxane components, b. At least 30% (wt / wt) of hydrophilic N-vinylamide monomer and It is a pharmaceutical product containing [the specified ingredient].

[0036] A "silicone hydrogel" refers to a crosslinked polymer material having a three-dimensional polymer network (i.e., polymer matrix) containing siloxane units, which is insoluble in water but contains at least 10 mass percent of water in its polymer matrix when fully hydrated. A "silicone hydrogel" is obtained by polymerizing a polymerizable composition containing at least one silicone-containing component, typically at least one silicone-containing monomer or at least one silicone-containing prepolymer or at least one crosslinkable silicone-containing prepolymer.

[0037] Typically, silicone hydrogel contact lenses are formed by free radical propagation reactions involving the polymerization of terminal ethylenically unsaturated groups, also referred to herein as “polymerizable groups.” Exemplary polymerizable groups include (meth)acrylic, (meth)acrylamide, allyl, vinyl, and styrene groups. As used herein, “vinyl-containing monomer” refers to any nonsiloxane monomer having a single polymerizable carbon-carbon double bond (i.e., a vinyl group) in its molecular structure, where the carbon-carbon double bond of the vinyl group is bonded to a carbon atom in an sp3 hybrid orbital. The vinyl group is less reactive under free radical polymerization than the carbon-carbon double bond present in acrylate polymerizable groups or methacrylate polymerizable groups. The term “(meth)acrylamide” refers to methacrylamide and / or acrylamide. The term “(meth)acrylate” refers to methacrylate and / or acrylate. The term “terminal (meth)acrylic group” refers to a single (meth)acrylic group at one of two ends of the main chain (or backbone) of an organic compound. "N-vinylamide monomer" refers to an amide compound that has a vinyl group CH=CH2 directly bonded to the nitrogen atom of the amide group.

[0038] A “monomer” is a molecule having one or more polymerizable groups that can react with the same or different other monomers in a polymerization process to form a large polymer chain, copolymer chain, or three-dimensional matrix. Monomers having two or more polymerizable groups may be further referred to as “crosslinkers,” as described below. The term “monomer” encompasses macromonomers and polymerizable oligomers, i.e., polymerizable molecules containing one or more chains of repeating units, such as polymerizable polysiloxanes; therefore, unless otherwise specified, there are no restrictions on the size (i.e., maximum molecular weight) of the monomer. The term “polymer” refers to a material formed by polymerizing and / or crosslinking one or more monomers.

[0039] As used in this application, the term "molecular weight" of a polymer material containing a component comprising multiple siloxane units refers to the average absolute molecular weight (in daltons) determined, for example, by GPC using a polystyrene standard or by 1H NMR end-group analysis, unless otherwise specifically noted. "Oligomer" is a compound consisting of 2 to 10 repeating units, which may be practically or conceptually derived from monomers. A prepolymer is a partially polymerized polymer containing multiple, typically more than 10, monomer units, which react to form an intermediate molecular weight state, retaining the ability to continue the reaction to fully cure and become a high molecular weight polymer material. The silicone hydrogel contact lens formulation of the present invention may contain other hydrophilic monomers in addition to the N-vinylamide-containing monomer, and may also contain hydrophobic monomers.

[0040] As used herein, "hydrophilic monomer" means a silicone-free monomer in which at least 50 grams of monomer is completely soluble in 1 liter of water at 20°C (i.e., approximately 5% soluble in water) as determined by visual inspection using the standard shake flask method. The silicone hydrogel contact lens formulation contains one or more hydrophilic N-vinylamide-containing monomers in an amount of at least 30% (wt / wt), for example, at least 35% (wt / wt), and particularly at least 35% (wt / wt). The formulation may further contain other hydrophilic monomers, such as hydrophilic vinyl ether-containing monomers.

[0041] In some examples, the hydrophilic N-vinylamide-containing monomer may be selected from N-vinyl-N-methylacetamide (VMA), or N-vinylpyrrolidone (NVP), or N-vinylformamide, or N-vinylacetamide, or N-vinyl-N-ethylacetamide, or N-vinylisopropylamide, or N-vinylcaprolactam, or N-vinyl-N-ethylformamide, or any combination thereof. In some examples, the hydrophilic N-vinylamide-containing monomer consists of VMA or NVP, or a combination of VMA and NVP. Any vinyl ether-containing monomer may be selected from 1,4-butanediol vinyl ether (BVE), or ethylene glycol vinyl ether (EGVE), or diethylene glycol vinyl ether (DEGVE), or 1,4-cyclohexanedimethanol vinyl ether (CHDMVE), or poly(ethylene glycol) vinyl ether having 4 to 10 ethylene glycol units, or poly(ethylene glycol) vinyl ether having more than 10 ethylene glycol units, or any combination thereof. In some examples, the vinyl ether-containing monomer may be a poly(ethylene glycol) vinyl ether having at least one, two, or three ethylene glycol units and up to four, six, eight, or ten ethylene glycol units. In addition to the hydrophilic N-vinylamide-containing monomer and any hydrophilic vinyl ether-containing monomer, one or more vinyl-containing monomers may be included in the formulations of the present invention as described herein. For example, in addition to the vinylamide-containing monomer and the vinyl ether-containing monomer, a vinyl monomer having a vinyl ester polymerizable group or an allyl ester polymerizable group may be included in the formulations of the present invention. The hydrophilic monomer may be a (meth)acrylate group or (meth)acrylamide group-containing hydrophilic monomer, examples of which include 2-hydroxyethyl methacrylate (HEMA), 4-hydroxybutyl acrylate glycerol methacrylate, 2-hydroxyethyl methacrylamide, ethoxyethyl methacrylamide (EOEMA), polyethylene glycol monomethacrylate, methacrylic acid (MA), and acrylic acid.

[0042] The formulations of the first and second embodiments of the present invention contain at least 30% (wt / wt), and particularly at least 35% (wt / wt), of at least one N-vinylamide hydrophilic monomer. The formulations of the first and second embodiments of the present invention may contain 35-55%, and particularly 37-50%, of the N-vinylamide hydrophilic monomer. The formulations of the first and second embodiments of the present invention may contain 30-55%, for example, 35-50%, and particularly 37-50%, of N-methyl N-vinylacetamide.

[0043] When more than one hydrophilic monomer is included in the formulation of the present invention, it is advantageous that at least 70% or 80% by mass of the hydrophilic monomers have a solubility of 20% or more in water. In certain examples, 100% of the hydrophilic vinyl-containing monomers in the polymerizable composition have a solubility of 10% or more in water. The hydrophilic vinyl-containing monomers typically have a molecular weight of about 75 to about 500, more typically about 75 to about 250. The formulations of the present invention may contain hydrophobic monomers that do not have a siloxane group. As used herein, the term "hydrophobic monomer" refers to a monomer that does not have a siloxane group and is less than 5% soluble in water at 20°C as determined by the standard shake flask method.

[0044] The hydrophobic monomer may be a (meth)acrylate group-containing hydrophobic monomer. As used herein, “hydrophobic acrylate-containing monomer” is any nonsiloxane monomer having a single polymerizable acrylate group (e.g., methyl methacrylate, acrylamide, etc.). In certain examples, the hydrophobic acrylate-containing monomer has a polymerizable methacrylate group. Numerous suitable acrylate-containing monomers are known in the art. Exemplary hydrophobic acrylate-containing monomers include methyl acrylate, isopropyl acrylate, cyclohexyl acrylate, methyl methacrylate (MMA), butyl acrylate, tert-butyl methacrylate (tBMA), perfluorohexylethylthiocarbonylaminoethyl methacrylate, isobornyl methacrylate (IBM), trifluoroethyl methacrylate, hexafluoroisopropyl methacrylate, hexafluorobutyl methacrylate, 2-hydroxybutyl methacrylate (HOB), 2-hydroxypropyl methacrylate (HPMA), and ethylene glycol methyl ether methacrylate (EGMA). Preferred nonsiloxane hydrophobic monomers include hydroxybutyl methacrylate, isobornyl methacrylate, or a combination of hydroxybutyl methacrylate and isobornyl methacrylate. Silicone hydrogel contact lens formulations may also contain acrylate-containing hydrophobic monomers to further enhance the mechanical strength and / or rigidity of the lens or to provide other desired properties.

[0045] Hydrophobic monomers that do not contain a siloxane group are not limited to monomers containing a (meth)acrylate group, but may also contain a vinyl group or other ethylenically unsaturated reactive group. Further examples of hydrophobic monomers include vinyl acetate, vinyl propionate, vinyl butyrate, styrene, chloroprene, vinyl chloride, vinylidene chloride, acrylonitrile, and methacrylonitrile. Polymerizable formulations may contain approximately 2% (wt / wt) to approximately 20% (wt / wt), for example, 4% (wt / wt) to 16% (wt / wt), and particularly 6% (wt / wt) to 12% (wt / wt), of nonsiloxane hydrophobic monomer components. Formulations containing 2% to 20% (wt / wt), and particularly 5% to 15% (wt / wt), may contain hydroxybutyl methacrylate, isobornyl methacrylate, or a combination of hydroxybutyl methacrylate and isobornyl methacrylate.

[0046] As used herein, "siloxane monomer" refers to a monomer having at least one siloxane group. Siloxane monomers may contain terminal acrylate groups or methacrylate groups. (Meth)acrylate-containing siloxane monomers that may be used in the formulations of the present invention as described herein are well known in the art. Siloxane monomers may be monofunctional (meth)acrylate-containing siloxanes, difunctional (meth)acrylate-containing siloxanes, or combinations of monofunctional and difunctional (meth)acrylate-containing siloxane monomers. In examples where the (meth)acrylate-containing siloxane monomer consists of one or more monofunctional (meth)acrylate-containing siloxane monomers (i.e., does not contain any polyfunctional (meth)acrylate-containing siloxane monomers), the polymerizable composition typically further comprises (meth)acrylate-containing crosslinking agents as described below. In certain cases, (meth)acrylate-containing siloxane monomers have one or more polymerizable methacrylate groups. Various non-limiting examples of suitable acrylate-containing siloxane monomers include 3-[tris(trimethylsiloxy)silyl]propyl methacrylate ("Tris"), 3-methacryloxy-2-hydroxypropyloxy)propylbis(trimethylsiloxy)methylsilane ("SiGMA"), methyldi(trimethylsiloxy)silylpropylglycerol ethyl methacrylate ("SiGEMA"), and monomethacryloxypropyl functionalized polydimethylsiloxanes, e.g., MCR-M07 and MCS-M11, all of which are available from Gelest (Morrisville, PA, USA). The silicone hydrogel contact lens formulation of the present invention contains a polymerizable siloxane component in an amount of at least 40% (wt / wt), for example, at least 42% (wt / wt), and particularly at least 45% (wt / wt). The polymerizable siloxane component typically constitutes 60% (wt / wt) or less of the formulation, for example, 55% (wt / wt) or less of the formulation.

[0047] Silicone hydrogel contact lens formulations may contain at least one difunctional siloxane having a molecular weight of at least 5,000 daltons. At least 30% (wt / wt) of the siloxane content may be difunctional siloxane having a molecular weight of at least 5,000 daltons. Advantageously, at least 40% (wt / wt) of the siloxane content may be difunctional having a molecular weight of at least 5,000 daltons. The formulation may contain difunctional siloxanes having a molecular weight of at least 5,000 daltons in a range of 15 (wt / wt) to 45 (wt / wt), for example, difunctional siloxanes between 20 (wt / wt) and 40 (wt / wt). Difunctional siloxanes typically have a molecular weight of less than 25,000 daltons, for example less than 20,000 daltons, and particularly less than 15,000 daltons. It has been observed that as the amount of siloxane with a high molecular weight increases, formulations with unacceptably high viscosity may result. Silicone hydrogel contact lens formulations may contain at least one difunctional siloxane having a molecular weight of 5,000 to 25,000 daltons, for example, at least one difunctional siloxane having a molecular weight of 6,500 to 20,000 daltons, and in particular at least one difunctional siloxane having a molecular weight of at least 8,000 to 15,000 daltons.

[0048] Silicone hydrogel contact lens formulations may contain, for example, at least one monofunctional siloxane monomer having a molecular weight of less than 3000 daltons. At least 20% (wt / wt) of the siloxane content may be monofunctional siloxanes having a molecular weight of less than 3000 daltons. Advantageously, at least 30% (wt / wt) of the siloxane content are monofunctional monomers having a molecular weight of less than 3000 daltons. The formulation may contain between 10 and 30 wt% of monofunctional siloxane monomers, for example, between 10 and 30 wt% of monofunctional siloxane monomers having a molecular weight of less than 3000 daltons. Monofunctional siloxanes typically have a molecular weight of at least 200 daltons.

[0049] In one example, a monofunctional siloxane monomer is given by formula (I) [ka] (In the formula, m is an integer between 3 and 10, n is an integer between 0 and 10, R 1 R is an alkyl group having 1 to 4 carbon atoms. 2 R is a hydrogen or methyl group, 3 (This is either a hydrogen or methyl group.) It may also contain (meth)acrylate-containing siloxane monomers represented by formula I (wherein R 1 is a butyl group, R 2 is hydrogen, R 3 (where is a methyl group, m is 4, and n is 1). A method for producing the siloxane monomer represented by formula (I) is described in U.S. Patent Application Publication No. 2009 / 0299022, which is incorporated herein by reference.

[0050] In another example, monofunctional siloxane monomers are given by formula (II) [ka] (In the formula, n is an integer between approximately 10 and 25, especially between 10 and 20.) It may also contain (meth)acrylate-containing siloxane monomers represented by . Siloxane monomers of formula II and other suitable monomers are described in U.S. Patent No. 6,867,245 and U.S. Patent No. 6,310,169, both of which are incorporated herein by reference.

[0051] Suitable examples of commercially available monofunctional siloxane monomers include 2-propenoic acid, 2-methyl-,2-[3-(9-butyl-1,1,3,3,5,5,7,7,9,9-decamethylpentasiloxane-1-yl)propoxy]ethyl ester, X-22-1622 (CAS No. 1052075-57-6), methacryloxypropyl-terminated poly(dimethyl)siloxane, FMM, Shin-Etsu Silicones of America, Akron, Ohio, USA (CAS No. 697234-76-7), and 3-methacryloxy-2-hydroxypropyloxy)propylbis(trimethylsiloxy)methylsilane, SiGMA, available from Shin-Etsu Chemical Co., Ltd., Tokyo, Japan. [ka]

[0052] The silicone hydrogel contact lens formulation contains at least one difunctional siloxane having a molecular weight of at least 5,000 daltons, for example, at least 6,500 daltons, and particularly at least 8,000 daltons. The formulation may also contain a difunctional siloxane monomer between 10% and 45% by mass, particularly between 20% and 40% by mass. The formulation may also contain a difunctional siloxane monomer having a molecular weight of at least 8,000 daltons, in an amount between 10% and 45% by mass or between 20% and 40% by mass.

[0053] In one example, a bifunctional siloxane monomer is given by formula (III) [ka] (In the formula, R1 is selected from either hydrogen or a methyl group; R2 is hydrogen or C 1-4 Selected from any hydrocarbon group; m represents an integer between 0 and 10; n represents an integer between 4 and approximately 15, 4 and approximately 25, or 4 and approximately 100; a and b represent integers greater than or equal to 1; a+b is equal to 20 and 500; b / (a+b) is equal to 0.01 and 0.22. It may contain a siloxane monomer represented by, and the configuration of the siloxane unit includes a random configuration.

[0054] Other suitable difunctional siloxane monomers are of formula (IV)

Chemical formula

[0055] Yet another suitable difunctional siloxane monomer is of formula (V)

Chemical formula

[0056] In one example, the siloxane monomer may include a combination of monofunctional (meth)acrylate-containing siloxane monomers and difunctional (meth)acrylate-containing siloxane monomers. In one such example, the monofunctional (meth)acrylate-containing siloxane monomer has a molecular weight of less than 2,000 daltons, less than 1,000 daltons, or less than 750 daltons, and the difunctional acrylate-containing siloxane monomer has a molecular weight of at least 3,000 daltons, at least 5,000 daltons, or at least 8,000 daltons. In a particular example, the monofunctional (meth)acrylate-containing siloxane monomer has a molecular weight of about 250 to about 1,000 daltons. In a further particular example, the monofunctional (meth)acrylate-containing siloxane monomer has a molecular weight of about 500 to about 1,000 daltons.

[0057] The silicone hydrogel contact lens formulations of the present invention typically contain one or more polymerization initiators; that is, the formulation may contain an initiator, or may contain two or more polymerization initiators, or initiator components including a combination of polymerization initiators, synergists, and activators. The term "initiator" refers to a chemical substance that initiates a crosslinking / polymerization reaction. Initiators are typically free radical initiators that form radicals that initiate a radical propagation polymerization reaction. Polymerization initiators that may be included in the formulations of the present invention include, for example, azo compounds, or organic peroxides, or both. Initiators may be photoinitiators that are activated when exposed to chemical radiation, for example, UV light, or thermal initiators that are activated when exposed to heat. Potential initiators in polymerizable formulations include, for example, benzoin ethyl ether, or benzyl dimethyl ketal, or alpha,alpha-diethoxyacetophenone, or 2,4,6-trimethylbenzoyldiphenylphosphine oxide, or benzoin peroxide, or t-butyl peroxide, or azobisisobutyronitrile, or azobisdimethylvaleronitrile, or any combination thereof. UV photoinitiators may include, for example, phosphine oxides, such as diphenyl(2,4,6-trimethylbenzoyl)phosphine oxide, or benzoin methyl ether, or 1-hydroxycyclohexylphenyl ketone, or Darocur (available from BASF, Florham Park, NJ, USA), or Irgacur (also available from BASF), or any combination thereof. Advantageously, the polymerization initiator is a thermal initiator. Suitable thermal initiators include 2,2'-azobis-2-methylpropanenitrile (VAZO-64, EIDuPont de Nemours & Co., Wilmington, Del., USA), 2,2'-azobis(2,4-dimethylpentanenitrile) (VAZO-52), and 1,1'-azobis(cyanocyclohexane) (VAZO-88, also manufactured by EIDuPont).Polymerization initiators or initiator components may be present in the silicone hydrogel contact lens formulation of the present invention in an amount of about 0.1% (wt / wt) to about 1.5% (wt / wt), or about 0.2% (wt / wt) to about 1.0% (wt / wt), particularly about 0.2% to about 0.8% (wt / wt). The formulations of the first and second embodiments of the present invention may be thermosetting formulations containing at least one thermal initiator. Thermosetting methods and chemical beam curing methods are well known to those skilled in the art.

[0058] Silicone hydrogel contact lens formulations may further contain crosslinking agents. Crosslinking agents can react with functional groups on two or more polymer chains to crosslink one polymer to another. As used herein, “crosslinking agent” is any compound having a molecular weight of less than about 2,000 daltons, typically less than 700 daltons, and having two or more polymerizable groups. As used herein, “acrylate-containing crosslinking agent” has at least two polymerizable acrylate groups and no other types of polymerizable groups. “Vinyl-containing crosslinking agent” has at least two polymerizable vinyl groups and no other types of polymerizable groups. Vinyl-containing crosslinking agents and acrylate-containing crosslinking agents may typically have molecular weights of less than 1,500 daltons, less than 1,000 daltons, less than 500 daltons, or less than 250 daltons. Examples of vinyl-containing crosslinking agents that may be used in the formulations of the present invention disclosed herein include, but are not limited to, divinyl ethers, or divinyl sulfones, or triallyl isocyanurates, and any combination thereof. Examples of divinyl ethers include diethylene glycol divinyl ether, or triethylene glycol divinyl, or 1,4-butanediol divinyl ether, or 1,4-cyclohexanedimethanol divinyl ether, or any combination thereof. Typically, the vinyl-containing crosslinker may have two or three polymerizable vinyl groups. If present, the total amount of vinyl-containing crosslinker in the silicone hydrogel contact lens formulation is typically about 0.02, about 0.04, or about 0.06 mol.% to about 0.10, about 0.15, or about 0.20 mol.%. Examples of acrylate-containing crosslinking agents that may be used in the formulations of the present invention include, but are not limited to, lower alkylene glycol di(meth)acrylate, poly(lower alkylene) glycol di(meth)acrylate, lower alkylene di(meth)acrylate, trimethylolpropane tri(meth)acrylate, pentaerythritol tetra(meth)acrylate, bisphenol A di(meth)acrylate, methylenebis(meth)acrylamide, and 1,3-bis(3-methacryloxypropyl)tetramethyldisiloxane.In certain cases, acrylate-containing crosslinkers are non-siloxane crosslinkers. If present, the total amount of acrylate-containing crosslinkers in silicone hydrogel contact lens formulations is typically from about 0.20 mol.%, 0.25 mol.%, 0.30 mol.%, or 0.35 mol.%, up to about 0.50 mol.%, up to 0.60 mol.%, up to 0.70 mol.%, up to 0.80 mol.%, or up to 1.0 mol.%. To avoid misunderstanding, polyfunctional polymerizable compounds with a molecular weight greater than 2,000 daltons are not considered crosslinkers. Therefore, the bifunctional siloxanes described herein with a molecular weight greater than 2,000 daltons are not considered crosslinkers.

[0059] Polymerizable formulations may further contain chain transfer agents. Chain transfer is a polymerization reaction that transfers the activity of a growing polymer chain to another molecule, thereby reducing the average molecular weight of the final polymer. Examples of chain transfer agents include, for example, thiol compounds, halogenated carbon compounds, or C3-C5 hydrocarbons, such as allyloxyethanol. The formulations of the present invention may contain, in addition to polymerizable components, non-polymerizable components that have been commonly used in contact lens formulations. Additional components, such as organic diluents or oxygen scavengers, may also be included. Non-limiting examples of these components and additional components that may be included in the polymerizable composition are provided in US2007 / 0296914.

[0060] A preferred formulation of the present invention comprises a siloxane component present in an amount of at least 40% (wt / wt), wherein at least 40% of the siloxane content is a bifunctional siloxane having a molecular weight of at least 5,000 daltons; and an N-vinylamide monomer component present in an amount of at least 37% (wt / wt). The contact lenses of the present invention preferably comprise a polymer lens material derived from the preferred formulation of the present invention, comprising the above-mentioned monomer and siloxane component. The above-mentioned preferred formulation has been found to be particularly suitable for use in combination with (1) RB-247, (2) TPP, and (3) polymerizable UV absorbers containing a benzophenone moiety, such as UV416, and / or benzotriaziole HEVL absorbers.

[0061] A particularly preferred silicone hydrogel contact lens formulation of the present invention comprises 40% to 55% by mass of a siloxane component, for example, a siloxane monomer or a combination of siloxane monomers, and 30% to 55% by mass of an N-vinylamide monomer selected from NVP, VMA, or a combination thereof, and may also contain about 1% to about 20% by mass of a hydrophilic monomer selected from N,N-dimethylacrylamide (DMA), 2-hydroxyethyl methacrylate (HEMA), ethoxyethyl methacrylamide (EOEMA), or any combination thereof, and may also contain about 1% to about 20% by mass of a hydrophobic monomer selected from methyl methacrylate (MMA), isobornyl methacrylate (IBM), or 2-hydroxybutyl methacrylate (HOB), or any combination thereof.

[0062] In a fifth aspect, the present invention is a. At least 40% (wt / wt) of polymerizable siloxane components, b. At least 30% (wt / wt) of hydrophilic N-vinylamide monomer, c. Triphenylphosphine (TPP) and The present invention provides the use of one or more of anthraquinone blue tints, benzophenone UV absorbers, and benzotriazole HEVL absorbers to stabilize formulations containing these substances.

[0063] Anthraquinone blue tint, benzophenone UV absorber, and benzotriazole HEVL absorber may be used individually or in any combination. For example, a fifth aspect of the present invention is: a. At least 40% (wt / wt) of polymerizable siloxane components, b. At least 30% (wt / wt) of hydrophilic N-vinylamide monomer, c. Triphenylphosphine (TPP) and The present invention provides the use of (i) an anthraquinone blue tint and a benzophenone UV absorber, (ii) an anthraquinone blue tint and a benzotriazole HEVL absorber, (iii) a benzophenone UV absorber and a benzotriazole HEVL absorber, or (iv) an anthraquinone blue tint and a benzophenone UV absorber and a benzotriazole HEVL absorber to stabilize a formulation containing the above.

[0064] The anthraquinone blue tint used in the fifth aspect of the present invention is preferably 1,4-bis[(2-methacryloxyethyl)amino]-9,10-anthraquinone (RB247) or 1,4-bis[4-(2-methacryloxyethyl)phenylamino]-9,10-anthraquinone (RB246), particularly RB247. The benzophenone UV absorber used in the fifth aspect of the present invention is preferably UV416. The benzotriazole HEVL absorber used in the fifth aspect of the present invention may be any benzotriazole HEVL described herein, preferably UV13 or UV28. Advantageously, the amounts of the anthraquinone blue tint, benzophenone UV absorber, and benzotriazole HEVL absorber described above with respect to the formulation of the present invention are the amounts used to stabilize the formulation in the fifth embodiment of the present invention.

[0065] A stabilized formulation according to a fifth embodiment of the present invention is, advantageously, one of those described above with respect to formulations of other embodiments of the present invention. For example, a stabilized formulation according to a fifth embodiment of the present invention may contain any or all of the above-mentioned siloxane components, hydrophilic N-vinylamide monomers, any further hydrophilic monomers, any further hydrophobic monomers, any crosslinking agents, any chain transfer agents, and any radical initiators. Alternatively, for example, a stabilized formulation according to a fifth embodiment of the present invention may contain the siloxane components, hydrophilic N-vinylamide monomers, any further hydrophilic monomers, and any further hydrophobic monomers in the amounts described above with respect to formulations of the present invention. [Examples]

[0066] It should be understood that the following examples illustrate, but are not limiting, certain aspects and advantages of the present invention. Basic formulation 1a / 1b A basic polymerizable silicone hydrogel contact lens formulation 1a containing the following was prepared: • 9 parts by mass of hydrophobic monomer (consisting of 2 parts by mass of isobornyl methacrylate (IBM) and 7 parts by mass of hydroxybutyl methacrylate (HOB)), • 39 parts by mass of hydrophilic N-vinylamide monomer (8.6 parts by mass of N-vinyl N-methylacetamide (VMA) and 0.4 parts by mass of N-vinylpyrrolidone (NVP)), • 49 parts by mass of polymerizable siloxane (18.13 parts by mass of FMM, 30.38 parts by mass of M5A, and 0.49 parts by mass of X-22-1622), • 1 part by mass of another agent containing a thermal initiator (VAZO-64) and a crosslinking agent (triallyl isocyanate).

[0067] A basic polymerizable silicone hydrogel contact lens formulation 1b was prepared, containing the following: • 9 parts by mass of hydrophobic monomer (2 parts by mass of isobornyl methacrylate (IBM) and 7 parts by mass of hydroxybutyl methacrylate (HOB)), • 39 parts by mass of hydrophilic N-vinylamide monomer (N-vinyl N-methylacetamide (VMA)), • 49 parts by mass of polymerizable siloxane (18.04 parts by mass of FMM, 30.23 parts by mass of M5A, 0.49 parts by mass of X-22-1622), • 1 part by mass of another agent containing a thermal initiator (VAZO-64) and a crosslinking agent (triallyl isocyanate).

[0068] The monomers were obtained from a commercially available source and were assumed to contain trace amounts of polymerization inhibitors. Basic Formulation 2 Basic formulation 2 was prepared, containing the following: • 13 parts by mass of hydrophobic monomer (methyl methacrylate (MMA)), • 42 parts by mass of hydrophilic N-vinylamide monomer (N-vinyl N-methylacetamide (VMA)), • 6 parts by mass of hydrophilic acrylate monomer (ethylene glycol methacrylate (EGMA)), • 35 parts by mass of polymerizable siloxane (8.83 parts by mass of M5A and 26.48 parts by mass of X-22-1622), • 2 parts by mass of another agent containing a thermal initiator (VAZO-64) and a crosslinking agent (0.09 parts by mass of triethylene glycol divinyl ether (TEGDVE) and 0.44 parts by mass of ethylene glycol dimethacrylate (EGDMA)).

[0069] The monomers were obtained from a commercially available source and were thought to contain trace amounts of polymerization inhibitors. The effect of TPP on gelation The following examples illustrate the effect of TPP on the gelation of formulations, and how this changes depending on the color, UV absorber, and / or HEVL absorber during handling.

[0070] A new polymerizable mixture was prepared by combining basic formulations 1a and 2 with the tinting agent RB246, the UV absorber Norbloc (i.e., 2-(3-(2H-benzotriazol-2-yl)-4-hydroxyphenyl)ethyl methacrylate, CAS number 96478-09-0, NORBLOC 7966, Noramco, Athens, GA, USA), and either no TPP or the amount of TPP shown in Table 1. Either 25 g or 12.5 g of the mixture was placed in a sealed 37 ml vial to simulate small or large airhead spaces on the surface of the monomer mixture, respectively. These were then placed in a 17°C water bath, and the mixture was visually evaluated daily at regular intervals for gelation. [Table 1] Gelation was not observed in comparative mixes 1 and 2, which contained either basic formulation 1a or basic formulation 2 without TPP, after being stored in a water bath for 8 days, either in the large headspace sample or the small headspace sample.

[0071] Comparative mixes 3 and 4, containing either basic formulation 1a or basic formulation 2 along with approximately 0.4 parts by mass of TPP, were observed to rapidly gel in small headspace samples. Comparative mix 4 rapidly gelled in small headspace samples, but no gelation was observed in large headspace samples after 8 days.

[0072] These results demonstrate that a mixture based on formulation 2, which contains a larger amount of hydrophilic monomer and a smaller amount of siloxane than formulation 1a, can withstand TPP inclusion in the presence of oxygen, i.e., in a large headspace container. However, when oxygen is almost completely excluded, i.e., in a small headspace container, the presence of TPP leads to rapid gelation of the mixture within 1 day. A mixture based on formulation 1a, which contains a smaller amount of hydrophilic monomer and a larger amount of siloxane than formulation 2, cannot withstand TPP inclusion even in the presence of oxygen, i.e., even in a large headspace container.

[0073] The effects of tint and UV / HEVL blocker It was observed that the properties of the tint and UV / HEVL blocker present in the mixture affected the stability of the mixture containing basic formulations 1a / 1b. [Table 2]

[0074] Referring to Table 2, when comparing the stability of basic formulation 1a with comparative mix 3, which contains 0.41 parts TPP, 0.0082 parts RB246, and 1.36 parts Norbloc, and comparative mix 5, which contains basic formulation 1b with 0.40 parts TPP, 0.0135 parts RB247, and a combination of 0.27 parts benzophenone UV absorber and 1.58 parts benzotriazole HEVL absorber, a significant difference in gelation initiation time was observed. The fundamental difference between comparative mix 3 and comparative mix 5 of the present invention lies in the tint and UV / HEVL blocker properties, indicating that the mixture containing RB246 and Norbloc is less stable than the mixture containing RB247 and UV416. In all cases, light was removed from the containers containing the mixtures. Therefore, the differences in stability are not due to the light transmission properties imparted to the mixtures by the tint and UV / HEVL blockers.

[0075] The effects of UV and HEVL blockers A comparative trial was conducted using a mixture containing basic formulation 1b and 0.40 parts of TPP, and a small headspace container (see Table 3), to investigate the effects of tint and UV / HEVL blockers on stability. [Table 3]

[0076] These results demonstrate that the UV absorber Norbloc did not delay the initiation of polymerization, but RB246, UV416, UV13, and UV28 each had a moderate stabilizing effect. These results also demonstrate that the inclusion of the tint RB247 significantly delayed the initiation of polymerization, and that RB247 was more effective than RB246 loaded at an equivalent mass%. RB247, when used alone, appears to have the most significant stabilizing effect among all tints and UV / HEVL blockers. The stabilization effect was observed to be synergistic, and the most improved monomer mixture stability was achieved with the combination of RB247 and UV416 and benzotriazole HEVL absorber (mixes 16 and 17).

[0077] The disclosures herein refer to certain exemplary examples, and it should be understood that these examples are presented as illustrations and not as limitations. The intent of the foregoing detailed description is to cover all variations, alternatives, and equivalents of the examples that may fall within the spirit and scope of the invention as defined by the additional disclosures, although the exemplary examples are discussed. The entire contents of all references cited in this disclosure are incorporated herein by reference to the extent that they do not conflict with this disclosure.

[0078] Other embodiments of the present invention will be apparent to those skilled in the art from consideration of this specification and the practices of the present invention disclosed herein. This specification and examples are intended to be considered only as illustrative within the true scope and spirit of the invention as set forth by the following claims and equivalents.

Claims

1. A silicone hydrogel contact lens formulation, a. At least 40% (wt / wt) of polymerizable siloxane components, b. At least 30% (wt / wt) of hydrophilic N-vinylamide monomer, c. Triphenylphosphine (TPP) and, d. 1,4-bis[(2-methacryloxyethyl)amino]-9,10-anthraquinone (RB247) and A formulation containing the above.

2. e. Benzophenone UV absorbers, particularly 2-(4-benzoyl-3-hydroxyphenoxy)ethyl acrylate (UV416) The formulation according to claim 1, further comprising:

3. (e.) The formulation according to claim 2, wherein the benzophenone UV absorber is present in an amount of 0.1% (wt / wt) to 3.0% (wt / wt).

4. f. Benzotriazole HEVL absorbent A formulation according to any one of claims 1 to 3, including the formulation described in any one of claims 1 to 3.

5. Benzotriazole HEVL absorbers include 2-[3'-tert-butyl-2'-hydroxy-5'-(3"-methacryloyloxypropoxy)phenyl]-5-chloro-2H-benzotriazole (UV28), 2-(1,1-dimethylethyl)-4-[3-[(4-ethenylphenyl)methoxy]propoxy]-6-(5-methoxy-2H-benzotriazole-2-yl)-phenol (UV1), 2-(5-chloro-2H-benzotriazole-2-yl)-6-(1,1-dimethylethyl)-4-ethenyl-phenol (UV5 / UVAM), and 2-[2'-hydroxy-3'-tert-butyl-5'-(3"-methacryloyloxypropoxy The formulation according to claim 4, comprising [xy)phenyl]-5-methoxy-2H-benzotriazole (UV13), 2-3'-tert-butyl-2'-hydroxy-5'-(3"-dimethylvinylsilylpropoxy)-2'-hydroxy-phenyl)-5-methoxybenzotriazole (UV15), particularly 2-[2'-hydroxy-3'-tert-butyl-5'-(3"-methacryloyloxypropoxy)phenyl]-5-methoxy-2H-benzotriazole (UV13) or 2-[2'-hydroxy-3'-tert-butyl-5'-(3"-methacryloyloxypropoxy)phenyl]-5-chloro-2H-benzotriazole (UV28).

6. The formulation according to claim 4 or 5, wherein the benzotriazole HEVL absorbent is present in an amount of 0.1% (wt / wt) to 3.0% (wt / wt).

7. A formulation according to any one of claims 1 to 6, comprising 35 to 50% (wt / wt) of N-methyl N-vinylacetamide.

8. The formulation according to any one of claims 1 to 7, wherein the N-vinylamide monomer component is present in an amount of at least 37% (wt / wt).

9. g. At least 5% (wt / wt) of nonsiloxane hydrophobic monomers, especially hydrophobic methacrylate monomers. A formulation according to any one of claims 1 to 8, further comprising:

10. The formulation according to claim 9, wherein the hydrophobic monomer comprises hydroxybutyl methacrylate, isobornyl methacrylate, or a combination of hydroxybutyl methacrylate and isobornyl methacrylate.

11. The formulation according to any one of claims 1 to 10, wherein polymerizable siloxane components are present in an amount of at least 45% (wt / wt).

12. The formulation according to any one of claims 1 to 11, comprising a bifunctional siloxane having a molecular weight of at least 8,000 daltons, wherein the polymerizable siloxane component may be in an amount of 20 to 40% (wt / wt).

13. The formulation according to any one of claims 1 to 12, comprising a monofunctional (meth)acrylate-containing siloxane having a molecular weight of less than 3000 daltons, wherein the polymerizable siloxane component may be in an amount of 10 to 30% (wt / wt).

14. The formulation according to any one of claims 1 to 13, wherein at least 40% (wt / wt) of the polymerizable siloxane content is a bifunctional siloxane having a molecular weight of at least 8,000 daltons, and at least 25% (wt / wt) of the polymerizable siloxane content is a monofunctional siloxane having a molecular weight of less than 3,000 daltons.

15. A formulation according to any one of claims 1 to 14, wherein triphenylphosphine (TPP) is present in an amount of 0.1 to 2% (wt / wt).

16. a1. A bifunctional siloxane having a molecular weight of at least 8,000 daltons in an amount of 20-40% (wt / wt), a2. A siloxane containing a monofunctional (meth)acrylate having a molecular weight of less than 3000 daltons in an amount of 10 to 30 (wt / wt), b. 37-50% (wt / wt) of N-methyl-N-vinylacetamide, c. At least 0.2% (wt / wt) of the TPP, d. At least 0.005% (wt / wt) of RB247, e. At least 0.1% (wt / wt) of a benzophenone UV absorber, f. At least 0.1% (wt / wt) of benzotriazole HEVL absorbent, g. At least 5% (wt / wt) of nonsiloxane hydrophobic methacrylate monomers, including hydroxybutyl methacrylate, isobornyl methacrylate, or a combination of hydroxybutyl methacrylate and isobornyl methacrylate. The formulation according to claim 1, comprising:

17. The polymerizable siloxane component is of formula (III) 【Chemistry 1】 (In the formula, R 1 R is selected from either a hydrogen or a methyl group; 2 is hydrogen or C 1-4 Selected from any hydrocarbon group; m represents an integer from 0 to 10; n represents an integer from 4 to about 15, from 4 to about 25, or from 4 to about 100; a and b represent integers of 1 or greater; a + b is equal to 20 to 500; b / (a + b) is equal to 0.01 to 0.22; the stereoconfiguration of the siloxane unit is random. A formulation according to any one of claims 1 to 16, comprising a bifunctional siloxane monomer represented by

18. The polymerizable siloxane component is of formula (II) 【Chemistry 2】 (In the formula, n is an integer between approximately 10 and 15.) A formulation according to any one of claims 1 to 17, comprising a monofunctional methacrylate-containing siloxane monomer represented by [the specified method].

19. h. At least one thermal radical initiator The preparation according to any one of claims 1 to 18, further comprising a thermosetting preparation.

20. A silicone hydrogel contact lens obtained by polymerization of a formulation according to any one of claims 1 to 19.

21. a. At least 40% (wt / wt) of polymerizable siloxane components, b. At least 30% (wt / wt) of hydrophilic N-vinylamide monomer, c. Triphenylphosphine (TPP) and Use of anthraquinone blue tint, benzophenone UV absorber, and / or benzotriazole HEVL absorber to stabilize formulations containing the above.

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