Stable formulations for contact lenses

Abstract

The present invention provides a silicone hydrogel contact lens formulation comprising a polymerizable siloxane component, a hydrophilic N-vinyl amide monomer, a triphenylphosphine (TPP), and one or more of an anthraquinone blue colorant, a benzophenone UV absorber, or a benzotriazole HEVL absorber; a silicone hydrogel contact lens formed by polymerizing the silicone hydrogel contact lens formulation; and the use of an anthraquinone blue colorant, a benzophenone UV absorber and / or a benzotriazole HEVL absorber to stabilize a formulation comprising a polymerizable siloxane component, a hydrophilic N-vinyl amide 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 a tint and / or a radiation blocking agent to improve the stability of such silicone hydrogel contact lens formulations. BACKGROUND

[0002] Formulated contact lens monomer mixtures need to have sufficient stability to polymerize ("pot-life") to allow them to be stored prior to use and to minimize gelling due to premature polymerization when used during lens manufacturing.

[0003] Trace amounts of inhibitors, such as hydroquinone, are often incorporated into commercially available monomers by the monomer manufacturer to inhibit polymerization, as described in U.S. Publication No. 2014 / 0330053 Al. These inhibitors work in the presence of oxygen, thus facilitated by having an air headspace in the containers in which the monomers and monomer-containing formulations are stored.

[0004] Triphenylphosphine (TPP) can be added to formulated mixtures to act as an oxygen scavenger. This can provide improved finished lens properties, but also stops the hydroquinone inhibitor from working and can result in premature polymerization of the overall liquid monomer mixture, i.e. poor pot-life.

[0005] Therefore, there is a need for contact lens formulations, especially silicone hydrogel contact lens formulations, containing TPP that are more stable in their pre-polymerized form. SUMMARY

[0006] It has been found that the addition of TPP to silicone hydrogel contact lens formulations comprising high levels of polymerizable siloxane can improve the processability of the formulation and reduce the degree of lens defects introduced during the cast-molding process. Therefore, TPP has the potential to be used as a processing aid for contact lens formulations comprising high levels of siloxane. However, it has also been found that contact lens formulations comprising a substantial content of a combination of hydrophilic N-vinyl amide monomers and polymerizable siloxane are particularly prone to premature polymerization when TPP is present. It is an object of the present invention to increase the stability of contact lens formulations comprising at least 40% (wt / wt) of a polymerizable siloxane component, at least 30% (wt / wt) of a hydrophilic N-vinyl amide monomer and triphenylphosphine (TPP).

[0007] In a first aspect, the present invention provides a silicone hydrogel contact lens formulation comprising:

[0008] a. at least 40% (wt / wt) of a polymerizable siloxane component;

[0009] b. at least 30% (wt / wt) of a hydrophilic N-vinyl amide monomer;

[0010] c. triphenylphosphine (TPP);

[0011] d. 1,4-bis[(2-methacryloyloxyethyl)amino]-9,10-anthraquinone (RB247); and

[0012] e. optionally, a benzophenone UV absorber and / or a benzotriazole HEVL absorber.

[0013] It has been found that by including tinting agent RB247 in a contact lens formulation comprising (a.) at least 40% (wt / wt) of a polymerizable siloxane component, (b.) at least 30% (wt / wt) of a hydrophilic N-vinyl amide monomer, and (c.) TPP, a more stable and less gellable contact lens formulation than its pre-polymerized form of a similar composition lacking RB247 and / or comprising other tinting agents can be obtained. It has also been found that a benzophenone UV absorber (such as UV416), and a benzotriazole HEVL absorber (especially UV13 or UV28), can enhance the stability of a contact lens formulation comprising (a.) at least 40% (wt / wt) of a polymerizable siloxane component, (b.) at least 30% (wt / wt) of a hydrophilic N-vinyl amide monomer, and (c.) TPP. Each of the benzophenone UV absorber (such as UV416) and benzotriazole HEVL absorber (such as UV13 or UV28) is effective in stabilizing a contact lens formulation comprising (a.) at least 40% (wt / wt) of a polymerizable siloxane component, (b.) at least 30% (wt / wt) of a hydrophilic N-vinyl amide monomer, and (c.) TPP, both by itself and when used in combination with tinting agent RB247. When two or more of RB247, a benzophenone UV absorber, and a benzotriazole HEVL absorber are used in combination, a synergistic effect has been found in enhancing the stability of a contact lens formulation comprising (a.) at least 40% (wt / wt) of a polymerizable siloxane component, (b.) at least 30% (wt / wt) of a hydrophilic N-vinyl amide monomer, and (c.) TPP. Accordingly, the formulations of the first aspect of the present application advantageously additionally comprise a benzophenone UV absorber and / or a benzotriazole HEVL absorber, especially both a benzophenone UV absorber and a benzotriazole HEVL absorber, in addition to RB247.

[0014] As benzophenone UV absorbers and benzotriazole HEVL absorbers have been found to have a positive effect on the stability of formulations comprising (a.) at least 40% (wt / wt) of a polymerizable siloxane component, (b.) at least 30% (wt / wt) of a hydrophilic N-vinyl amide monomer, and (c.) TPP in the absence of RB247, the present invention also provides formulations comprising a benzophenone UV absorber and / or a benzotriazole HEVL absorber in the absence of RB247. Thus, in a second aspect, the present invention provides a contact lens formulation comprising:

[0015] a. at least 40% (wt / wt) of a polymerizable siloxane component;

[0016] b. at least 30% (wt / wt) of a hydrophilic N-vinyl amide monomer;

[0017] c. triphenylphosphine (TPP);

[0018] d. optionally, 1,4-bis[(2-methacryloyloxyethyl)amino]-9,10-anthracene (RB247); and

[0019] e. a benzophenone UV absorber and / or a benzotriazole HEVL absorber.

[0020] The formulation of the second aspect of the present invention advantageously comprises both a benzophenone UV absorber (such as UV416) and a benzotriazole HEVL absorber (such as UV13 or UV28).

[0021] In addition to the components listed above, the silicone hydrogel contact lens formulations of the present invention typically contain other polymerizable monomers, oligomers, and / or prepolymers, one or more crosslinking agents, and one or more polymerization initiators.

[0022] In a third aspect, the present invention provides a silicone hydrogel contact lens formed by polymerization of the formulation of the first aspect of the present invention. Thus, the polymeric lens material of the silicone hydrogel contact lens of the third aspect of the present invention comprises the polymerization product of polymerizing a composition comprising:

[0023] a. at least 40% (wt / wt) of a polymerizable siloxane component;

[0024] b. at least 30% (wt / wt) of a hydrophilic N-vinyl amide monomer;

[0025] c. triphenylphosphine (TPP);

[0026] d. 1,4-bis[(2-methacryloyloxyethyl)amino]-9,10-anthracene (RB247); and

[0027] e. optionally, a benzophenone UV absorber and / or a benzotriazole HEVL absorber.

[0028] In a fourth aspect, the present application provides a silicone hydrogel contact lens formed by polymerization of the formulation of the second aspect of the present application. Thus, the polymeric lens material of the silicone hydrogel contact lens of the fourth aspect of the present application comprises the polymerization product of polymerizing a composition comprising:

[0029] a. at least 40% (wt / wt) of a polymerizable siloxane component;

[0030] b. at least 30% (wt / wt) of a hydrophilic N-vinyl amide monomer;

[0031] c. triphenylphosphine (TPP);

[0032] d. optionally, 1,4-bis[(2-methacryloyloxyethyl)amino]-9,10-anthraquinone (RB247); and

[0033] e. a benzophenone UV absorber and / or a benzotriazole HEVL absorber.

[0034] In a fifth aspect, the present application provides the use of an anthraquinone blue colorant, a benzophenone UV absorber and / or a benzotriazole HEVL absorber to stabilize a formulation comprising:

[0035] a. at least 40% (wt / wt) of a polymerizable siloxane component;

[0036] b. at least 30% (wt / wt) of a hydrophilic N-vinyl amide monomer; and

[0037] c. triphenylphosphine (TPP).

[0038] It has been found that the formulations of the present application are stable against pre-polymerization gelling for more than 1 day and avoid complete gelling (formation of a solid gel) for more than 3 days. In comparison, similar formulations containing TPP can show gelling within 1 day and form a solid gel within 3 days, sometimes within 2 days, or as little as 1 day. DETAILED DESCRIPTION

[0039] The present invention will be more fully understood and further advantages will become apparent when reference is made to the following detailed description of embodiments of the present invention. The present invention will be further described in detail with particular reference to the formulations of the first and second aspects of the present invention (hereinafter referred to as "the present invention formulations"). However, it should be understood that since the contact lenses of the third or fourth aspects of the present invention (hereinafter referred to as "the present invention contact lenses") can be obtained by polymerizing the formulations of the first and second aspects of the present invention, and therefore, the components of the formulations of the first and second aspects of the present invention will be present in polymerized form in the polymer lens material of the present invention contact lenses. Similarly, contact lenses that have been found to particularly benefit from the use of TPP according to the fifth aspect of the present invention to improve surface properties are those having the characteristics described herein for the lenses of the third and fourth aspects of the present invention and / or those obtained by polymerizing formulations having the characteristics described herein for the formulations of the first and second aspects of the present invention. Therefore, the components of the formulations of the first and second aspects of the present invention will be present in polymerized form in the polymer lens material of the contact lenses in which TPP is used according to the fifth aspect of the present invention. Features of the formulations or lenses or components thereof, or features using anthraquinone colorants, benzophenone UV absorbers, and / or benzotriazole HEVL absorbers (depending on the context) mentioned herein may be combined with any combination of features previously described or subsequently described, unless a particular combination of features is mutually exclusive, or if the context indicates otherwise. Furthermore, as used in this specification, the singular forms "a," "an," and "the" include plural referents (e.g., at least one or more) unless the context clearly indicates otherwise. Thus, for example, reference to "a contact lens" includes a single lens as well as two or more of the same or different lenses.

[0040] The present invention is based on the discovery that by including one or more of an anthraquinone colorant, a benzophenone UV absorber, and a benzotriazole HEVL diluent in a polymerizable formulation for preparing contact lenses, contact lenses with improved finished lens properties can be provided from formulations containing TPP, including good pot life due to reduced premature polymerization of the formulation. It has been found that other combinations of formulations containing TPP with different colorants and / or UV absorbers have poor pot life and have been found to be prone to premature polymerization. Contact lens formulations containing at least 40% (wt / wt) of a polymerizable siloxane component, at least 30% (wt / wt) of a hydrophilic N-vinylamide monomer, and TPP have been found to be particularly prone to premature polymerization. Including an anthraquinone colorant and / or a benzophenone UV absorber and / or a benzotriazole HEVL absorber in such formulations has been found to be effective in preventing or reducing premature polymerization. The polymerizable components of the present formulations are typically incorporated into contact lenses of the present invention.

[0041] References herein to the amount of an ingredient or component present in a formulation expressed as a weight percentage (i.e., % (wt / wt)) are based on the amount of all formulation ingredients, excluding diluents and / or solvents that are not incorporated into the polymeric lens material of the finished contact lens. Thus, for example, the amount of TPP in a formulation prepared by mixing together 0.5 parts of TPP, 40 parts of a silicone component, 30 parts of a hydrophilic N-vinyl amide monomer, 4.5 parts of other active ingredients (e.g., polymerization initiators, colorants, oxygen scavengers, etc.), and 25 parts of an organic solvent and / or water (totaling 100 parts) is 0.67% (wt / wt). As used herein, a "component" of a formulation refers collectively to all ingredients of a particular type. For example, if a formulation contains 20% (wt / wt) of a first silicone monomer and 25% of a second silicone monomer and no other silicones, the formulation can be described as containing 45% (wt / wt) of a silicone component.

[0042] The polymerizable formulations of the present application include triphenylphosphine (TPP; CAS No: 603-35-0).

[0043]

[0044] The TPP can be present in the polymerizable formulations of the present application, e.g., in the formulations of the first aspect of the present application, in an amount of at least 0.10% (wt / wt), typically in an amount of at least 0.15% (wt / wt), such as at least 0.20%, especially at least 0.25%. For example, the TPP can be present in the polymerizable formulations in an amount of from about 0.15% (wt / wt) to about 2.0% (wt / wt), such as from 0.20% (wt / wt) to 1.0% (wt / wt), typically in an amount of from about 0.25% (wt / wt) to about 1% (wt / wt).

[0045] The polymerizable formulations of the first aspect of the present application further include 1,4-bis[(2-methacryloyloxyethyl)amino]-9,10-anthracenedione (Reactive Blue 247, RB247; CAS No: 109561-07-1; commercially available from Arran Chemical Company, Co. Roscommon, Ireland and also from Pharnorcia Inc., Edison, New Jersey, USA), referred to herein as "RB247".

[0046]

[0047] The RB247 can be present in the formulations of the present application in an amount of at least 0.003% (wt / wt), typically in an amount of from about 0.005% (wt / wt) to 0.1% (wt / wt), such as from 0.006% (wt / wt) to 0.05% (wt / wt), or from 0.007% (wt / wt) to 0.03% (wt / wt).

[0048] It is known to include an anthraquinone colorant as a colorant in a contact lens formulation to color the resulting contact lens, for example to facilitate handling of the lens by making it more visible to impart an attractive blue tint to the lens and / or to counteract an unattractive yellow tint. However, the present inventors have surprisingly found that anthraquinone colorants, especially anthraquinone blue colorants, can also be used to inhibit pre-polymerization gelling of a lens formulation comprising TPP, especially a lens formulation comprising TPP together with at least 40% (wt / wt) of a polymerizable siloxane component and at least 30% (wt / wt) of a hydrophilic N-vinyl amide monomer.

[0049] The formulations of the present application can further comprise 1,4-bis[4-(2- methacryloyloxyethyl)phenylamino]-9,10-anthraquinone (CAS No. 121888-69-5, Reactive Blue 246, RB246, available from Alfa Chemistry, Roscommon, Ireland and from Warner Jenkinson, Edison, New Jersey, USA), referred to herein as "RB246". Although RB246 has been found to be less effective than RB247 in stabilizing a polymerizable formulation comprising at least 40% (wt / wt) of a polymerizable siloxane component, at least 30% (wt / wt) of a hydrophilic N-vinyl amide monomer and TPP; RB246 has been found to have a beneficial effect on the stability of such formulations.

[0050]

[0051] Advantageously, RB246 is present in the formulations of the second aspect of the present application which lack RB247. The RB246 can be present in the contact lens formulations of the present application, especially in the formulations of the second aspect of the present application, in an amount of at least 0.003% (wt / wt), typically in an amount of from about 0.005% (wt / wt) to 0.1% (wt / wt), such as from 0.006% (wt / wt) to 0.05% (wt / wt), or from 0.007% (wt / wt) to 0.03% (wt / wt).

[0052] The formulation of the second aspect of the application comprises a benzophenone UV absorber and / or a benzotriazole HEVL absorber, preferably both a benzophenone UV absorber and a benzotriazole HEVL absorber. In addition to RB247, the formulation of the first aspect of the application advantageously comprises a benzophenone UV absorber and / or a benzotriazole HEVL absorber, preferably both a benzophenone UV absorber and a benzotriazole HEVL absorber.

[0053] The term "UV absorber" refers to a compound comprising a chromophore that absorbs light in the UV spectrum, i.e. at wavelengths in the range of 100 to 400 nm. In particular, a 0.003 wt% solution in ethyl acetate of the UV absorber has an absorbance maximum (λmax) in the range of 220 to 350 nm, especially in the range of 250 to 350 nm. As a 0.003 wt% solution in ethyl acetate, the UV absorbers present in the formulations and lenses of the application advantageously have an absorbance maximum (λmax) in the range of 250 to 350 nm, between 260 nm and 320 nm, especially between 270 nm and 310 nm.

[0054] The silicone hydrogel contact lens formulations of the application can contain a polymerizable UV absorber comprising a benzophenone moiety. Likewise, the polymeric lens material of the silicone hydrogel contact lenses of the application can contain a UV light absorbing unit comprising a benzophenone moiety. Said UV light absorbing unit comprising a benzophenone moiety present in the polymeric lens material of the contact lenses of the application can be derived from the polymerizable UV absorbers described herein with reference to the formulations of the application.

[0055] The polymerizable UV absorbers advantageously covalently bond to the polymer matrix of the lens material rather than simply physically entrapped in the material to prevent migration, phase separation, or leaching of the absorber from the lens material. Such stability is advantageous because leaching of the UV absorber can present toxicological problems and / or result in loss of UV blocking activity of the contact lens. The UV absorbers used in the present invention are generally soluble in the contact lens formulation and become part of the polymer matrix of the lens and remain in the lens during autoclave sterilization and storage. The UV absorbers are advantageously polymerizable UV absorbers that include one or more reactive groups capable of participating in a curing reaction by which the polymer matrix of the polymeric lens material is formed, such that the polymerizable UV absorber becomes covalently bound into the polymeric lens material. Polymerizable UV absorbers generally include ethylenically unsaturated groups such as vinyl or (meth)acrylate, (meth)acrylamide, or styryl groups that can participate in a free radical polymerization reaction. Many copolymerizable benzophenone UV absorbers are known. Many of these UV absorbers contain ethylenically unsaturated polymerizable groups. Copolymerization with other ingredients in the lens material, typically with a free radical initiator, incorporates the UV absorber into the resulting polymer chains. Incorporation of additional functional groups on the UV absorber can affect one or more of the UV absorption properties, solubility, or reactivity of the UV absorber. If the UV absorber does not have sufficient solubility in the ophthalmic lens material ingredients or the rest of the polymeric lens material, the UV absorber can coalesce into domains that can interact with light and cause a reduction in the optical clarity of the lens.

[0056] The benzophenone UV absorbers can be present in the formulations 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), such as 0.3% (wt / wt) to 3.0% (wt / wt).

[0057] The silicone hydrogel contact lens formulations of the present invention optionally comprise a polymerizable benzophenone UV absorber that has a maximum absorbance (Amax) in the range of 250 to 380 nm, between 260 nm and 320 nm, especially between 270 nm and 310 nm, as a 0.003 wt% solution contained in ethyl acetate. Thus, the polymeric lens material of the silicone hydrogel contact lenses of the present invention optionally comprises a UV light absorbing unit derived from a polymerizable benzophenone UV absorber that has a maximum absorbance (Amax) in the range of 250 to 380 nm, between 260 nm and 320 nm, especially between 270 nm and 310 nm, as a 0.003 wt% solution contained in ethyl acetate.

[0058] The silicone hydrogel contact lens formulations of the present application optionally comprise a polymerizable UV absorber comprising a benzophenone moiety which has an absorbance maximum (Amax) in the range from 250 to 380 nm, between 260 nm and 320 nm, especially between 270 nm and 310 nm, as a 0.003 wt% solution in ethyl acetate.

[0059] The benzophenone UV absorber comprised in the formulations of the present application is advantageously not a dual function HEVL absorber and UV absorber. The benzophenone UV absorber can have an absorbance cut-off below the visible range, i.e. the benzophenone UV absorber does not absorb a substantial amount of light above 380 nm. For example, a 0.003 wt% solution of the benzophenone UV absorber in ethyl acetate does not have an absorbance of at least 0.5 in the range from 375 to 450 nm.

[0060] The polymerizable UV absorber is optionally 2-(4-benzoyl-3-hydroxyphenoxy)ethyl acrylate (UV416; CAS No: 16432-81-8).

[0061]

[0062] UV416 can be present in the polymerizable formulations of the present application, i.e. in the formulations of the first or second aspect of the present application, in an amount of from about 0.05% (wt / wt) to about 5.0% (wt / wt), typically in an amount of from about 0.1% (wt / wt) to about 3.0% (wt / wt), or from about 0.2% (wt / wt) to about 3.0% (wt / wt), such as 0.3% (wt / wt) to 3.0% (wt / wt).

[0063] The silicone hydrogel contact lens formulations of the present application optionally comprise a high energy visible light (HEVL) absorber. A HEVL absorber is a compound comprising a chromophore that absorbs visible light in the violet-blue range from 350 to 455 nm. Typically, a HEVL absorber has an absorbance maximum (Amax) in the range from 350 to 455 nm, especially in the range from 350 to 400 nm. The term "high energy visible light (HEVL) absorber" as used herein can be defined as a compound or mixture of compounds which as a 0.003 wt% solution in ethyl acetate (> 99.8%, HPLC grade) has an absorbance in the range from 375 to 450 nm of at least 0.5 (the solution is measured in a quartz cell of 10 mm path length and the absorbance of the solution is measured from 250 to 800 nm using a Perkin Elmer Lambda 365). The HEVL absorber can additionally absorb shorter wavelength light, for example in the range from 250 to 350 nm, and thus function as both a HEVL absorber and a UV absorber, as discussed below.

[0064] In addition to colorant RB247, the silicone hydrogel contact lens formulations of the first aspect of the present application can comprise a HEVL absorber, such as a benzotriazole HEVL absorber. The silicone hydrogel contact lens formulations of the second aspect of the present application can comprise a benzotriazole HEVL absorber or can comprise both a benzotriazole HEVL absorber and a benzophenone UV absorber.

[0065] Advantageously, the HEVL absorber used in contact lens formulations, including the contact lens formulations of the present application, has a polymerizable moiety in its chemical structure, such as a vinyl, acrylate or methacrylate functionality, to be covalently incorporated into the contact lens material during polymerization. Once incorporated into the polymeric contact lens material, the HEVL absorber imparts HEVL absorbing properties to the polymeric contact lens material. The HEVL absorber used in the present application is typically soluble in the contact lens formulation and is polymerizable such that it forms part of the polymeric matrix of the lens and remains in the lens during autoclave sterilization and storage. The HEVL absorber can comprise a benzotriazole ring system.

[0066] The HEVL absorber can be present in an amount from 0.3% to 3% (wt / wt), preferably from 0.4% to 3% (wt / wt) based on the total amount of the formulation. If the HEVL absorber comprises more than one compound, the total amount of compounds having an absorbance maximum (Amax) in the range from 350 to 455 nm is present in an amount from 0.3% to 3% (wt / wt), preferably from 0.4% to 3% (wt / wt) based on the total amount of the formulation.

[0067] Examples of benzotriazole HEVL absorbers include:

[0068] 2-(1,1 -dimethylethyl)-4-[3-[(4-vinylphenyl)methoxy]propoxy]-6-(5-methoxy- 2H-benzotriazol-2-yl)-phenol (UV1, CAS No. 159732-06-6):

[0069]

[0070] 2-(5-chloro-2H-benzotriazol-2-yl)-6-(1,1 -dimethylethyl)-4-vinyl-phenol (UV5 / UVAM, CAS No. 124883-10-9):

[0071]

[0072] 2-[2'-hydroxy-3'-tert-butyl-5'-(3"-methacryloyloxypropoxy)phenyl]-5- methoxy-2H-benzotriazole (UV13, CAS No. 114166-71 -1 ):

[0073]

[0074] 2-[2'-hydroxy-3'-tert-butyl-5'-(3"-methacryloyloxypropoxy)phenyl]-5- methoxy-2H-benzotriazole (UV13, CAS No. 114166-71 -1 ):

[0075]

[0076] 2-[2'-hydroxy-3'-tert-butyl-5'-(3"-methacryloyloxypropoxy)phenyl]-5- methoxy-2H-benzotriazole (UV13, CAS No. 114166-71 -1 ):

[0077]

[0078] All of the above HEVL absorbers are commercially available from LYNN Laboratories, Inc., 2797 Irving Blvd STE 110, Dallas, TX 75207.

[0079] Advantageously, a 0.003 wt% solution of the HEVL absorber in ethyl acetate has a peak absorbance in the range of 360 to 410 nm, such as 360 to 400 nm, especially 360 to 390 nm.

[0080] Optionally, the total amount of HEVL absorbers and UV absorbers present in the present formulation is no more than 5% (wt / wt). Optionally, the present formulation comprises a total amount of 0.2% to 5% (wt / wt), and preferably 0.4% to 4% (wt / wt) of HEVL absorbers and UV absorbers.

[0081] The compounds can function as both HEVL absorbers and UV absorbers. The term "HEVL absorber" as used herein encompasses compounds that function only as HEVL absorbers and compounds that function as both HEVL absorbers and UV absorbers. The benzophenone UV absorbers included in the present formulation are advantageously not dual-function HEVL absorbers and UV absorbers. In some embodiments, the benzotriazole HEVL absorbers included in the present formulation can be dual-function HEVL absorbers and UV absorbers. The UV absorbers can have an absorbance cutoff below the visible range, i.e. do not absorb significant amounts of light above 380 nm. For example, a 0.003 wt% solution of the UV absorber in ethyl acetate has an absorbance of at least 0.5 in the range of 375 to 450 nm. The HEVL absorbers present in the present formulation have an absorbance of more than 0.5 in the range of 375 to 450 nm as a 0.003 wt% solution in ethyl acetate and can optionally also have a maximum absorbance (Amax) in the range of 220 to 350 nm, especially in the range of 250 to 350 nm.

[0082] The present formulation of the first aspect comprising RB247 advantageously further comprises UV416 and a benzotriazole HEVL absorber, especially UV13 or UV28. It has been found that the combination of RB247, UV416 and UV13 or UV28 is particularly effective in reducing gelation of polymerizable formulations comprising at least 40% (wt / wt) of a polymerizable siloxane component, at least 30% (wt / wt) of a hydrophilic N-vinyl amide monomer and TPP.

[0083] The present formulation of the second aspect advantageously comprises both UV416 and a benzotriazole HEVL absorber, especially UV13 or UV28. It has been found that the combination of UV416 and UV13 or UV28 is effective in reducing gelation of polymerizable formulations comprising at least 40% (wt / wt) of a polymerizable siloxane component, at least 30% (wt / wt) of a hydrophilic N-vinyl amide monomer and TPP. In addition to the benzotriazole UV absorber and / or the benzotriazole HEVL absorber, the present formulation of the second aspect can comprise RB246. The present formulation of the second aspect can comprise UV416, UV13 or UV28, and RB246.

[0084] The present contact lens formulation is a silicone hydrogel contact lens formulation comprising:

[0085] a. at least 40% (wt / wt) of a polymerizable siloxane component; and

[0086] b. at least 30% (wt / wt) of a hydrophilic N-vinyl amide monomer.

[0087] “Silicone hydrogel” refers to a crosslinked polymeric material having a three- dimensional polymeric network (i.e., polymeric matrix) comprising siloxane units, which is insoluble in water, but contains at least 10% water by weight in its polymeric matrix when fully hydrated. A “silicone hydrogel” is obtained by polymerization of a polymerizable composition comprising 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).

[0088] Typically, silicone hydrogel contact lenses are formed via a free radical propagation reaction involving polymerization of terminal ethylenic unsaturation groups (also referred to herein as “polymerizable groups”). Exemplary polymerizable groups include (meth)acrylic, (meth)acrylamide, allyl, and vinyl and styryl groups. As used herein, “vinyl-containing monomer” is any non-siloxane monomer having a single polymerizable carbon-carbon double bond (i.e., vinyl group) present in its molecular structure, wherein the carbon-carbon double bond of the vinyl group is attached to an sp3 hybridized carbon atom. The reactivity of a vinyl group under free radical polymerization is less than the carbon-carbon double bond present in an acrylate or methacrylate polymerizable group. The term “(meth)acrylamide” refers to a methacrylamide and / or an acrylamide. The term “(meth)acrylate” refers to a methacrylate and / or an acrylate. The term “terminal (meth)acrylic group” refers to one (meth)acrylic group at one of the two ends of the main chain / backbone of an organic compound. “N-vinyl amide monomer” refers to an amide compound having a vinyl group CH=CH2 directly attached to the nitrogen atom of the amide group.

[0089] “Monomer” is a molecule having one or more polymerizable groups that can react with other monomers, which can be the same or different, to form larger polymer or copolymer chains or three-dimensional matrices in a polymerization process. A monomer having two or more polymerizable groups can be referred to as a “crosslinker”, as further described below. The term “monomer” encompasses macromonomers and polymerizable oligomers, i.e., polymerizable molecules containing one or more repeating unit chains, such as, for example, polymerizable polysiloxanes; thus, there is no size restriction (i.e., maximum molecular weight) on monomers unless otherwise indicated. The term “polymer” refers to a material formed by polymerization and / or crosslinking of one or more monomers.

[0090] As used in this application, unless otherwise specifically noted, the term "molecular weight" of a polymeric material (including components comprising a plurality of siloxane units) refers to the absolute number average molecular weight (in Daltons), as determined, for example, by GPC using polystyrene standards or by 1 Determined by H NMR end group analysis. An "oligomer" is a compound composed of 2 to 10 repeating units that can be derived actually or conceptually from a monomer. A prepolymer is a partially polymerized polymer comprising multiple monomer units, usually 10 or more, that has been reacted to an intermediate molecular weight state that retains the ability to continue reacting to fully cure into a higher molecular weight polymeric material.

[0091] In addition to N-vinylamide-containing monomers, the present silicone hydrogel contact lens formulations can include other hydrophilic monomers, and can also include hydrophobic monomers.

[0092] As used herein, "hydrophilic monomer" refers to a silicone-free monomer wherein at least 50 grams of the monomer is completely soluble in 1 liter of water at 20°C (ie, about 5% soluble in water), as determined visibly using a standard shake flask method.

[0093] The silicone hydrogel contact lens formulation comprises one or more hydrophilic N-vinyl amide-containing monomers in an amount of at least 30% (wt / wt), such as at least 35% (wt / wt), and particularly at least 35% (wt / wt). The formulation may further comprise other hydrophilic monomers, such as hydrophilic vinyl ether-containing monomers.

[0094] In some examples, the hydrophilic N-vinylamide-containing monomer can be selected from N-vinyl-N-methyl acetamide (VMA), or N-vinyl pyrrolidone (NVP), or N-vinyl formamide, or N-vinyl acetamide, or N-vinyl-N-ethyl acetamide, or N-vinyl isopropylamide, or N-vinyl caprolactam, or N-vinyl-N-ethyl formamide, 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. The optional vinyl ether-containing monomer can 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 can be a poly(ethylene glycol) vinyl ether having at least 1, 2, or 3 ethylene glycol units and at most 4, 6, 8, or 10 ethylene glycol units. In addition to the hydrophilic N-vinylamide-containing monomer and the optional hydrophilic vinyl ether-containing monomer, one or more vinyl-containing monomers can be included in the inventive formulations described herein. For example, in addition to the vinylamide-containing monomer and the vinyl ether-containing monomer, a vinyl monomer having a vinyl ester or allyl ester polymerizable group can be included in the inventive formulations. The hydrophilic monomer can be a hydrophilic monomer containing a (meth)acrylate or (meth)acrylamide group, examples of which include 2-hydroxyethyl methacrylate (HEMA), 4-hydroxybutyl acrylate, glyceryl methacrylate, 2-hydroxyethyl methacrylamide, ethoxyethyl methacrylamide (EOEMA), polyethylene glycol monomethacrylate, methacrylic acid (MA), and acrylic acid.

[0095] The formulations of the first and second aspects of the invention comprise at least one N-vinylamide hydrophilic monomer in an amount of at least 30% (wt / wt), in particular at least 35% (wt / wt). The formulations of the first and second aspects of the invention can comprise the N-vinylamide hydrophilic monomer in an amount of 35 to 55%, in particular 37 to 50%. The formulations of the first and second aspects of the invention can comprise N-methyl N-vinyl acetamide in an amount of 30 to 55%, such as 35 to 50%, in particular 37 to 50%.

[0096] In cases where more than one hydrophilic monomer is included in the present formulations, it is advantageous for at least 70% or 80% by weight of the hydrophilic monomers to have a solubility in water of >20%. In one particular example, 100% of the hydrophilic vinyl-containing monomers in the polymerizable composition have a solubility in water of >10%. The hydrophilic vinyl-containing monomers typically have a molecular weight of about 75 to about 500, and more typically about 75 to 250.

[0097] The present formulations can optionally include a hydrophobic monomer lacking a siloxane group. The term "hydrophobic monomer" as used herein refers to a monomer that lacks a siloxane group and is less than 5% soluble in water at 20°C, as determined using the standard shake flask method.

[0098] The hydrophobic monomer can be a (meth)acrylate-containing hydrophobic monomer. As used herein, a "hydrophobic acrylate-containing monomer" is any non-siloxane monomer having a single polymerizable acrylate group (e.g., methyl methacrylate, acrylamide, etc.). In one particular example, the hydrophobic acrylate-containing monomer has a polymerizable methacrylate group. Many 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, t-butyl methacrylate (tBMA), perfluorohexylethylthio carbonyl aminoethyl 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). Advantageous non-siloxane hydrophobic monomers include hydroxybutyl methacrylate, isobornyl methacrylate, or a combination of hydroxybutyl methacrylate and isobornyl methacrylate. Silicone hydrogel contact lens formulations can include acrylate-containing hydrophobic monomers to further enhance the mechanical strength and / or hardness of the lens, or to impart other desirable properties.

[0099] The hydrophobic monomers lacking a siloxane group are not limited to (meth)acrylate-containing monomers and can include vinyl or other ethylenically unsaturated reactive groups. Other examples of hydrophobic monomers include vinyl acetate, vinyl propionate, vinyl butyrate, styrene, chlorobutadiene, chloroethylene, vinylidene chloride, acrylonitrile, and methacrylonitrile.

[0100] The polymerizable formulation can comprise from about 2% to about 20% (wt / wt), such as 4% to 16% (wt / wt), especially 6% to 12% (wt / wt) of a non-silicone hydrophobic monomer component. From 2 to 20% (wt / wt) (especially 5 to 15% (wt / wt)) of the formulation can be hydroxybutyl methacrylate, isobornyl methacrylate or a combination of hydroxybutyl methacrylate and isobornyl methacrylate.

[0101] A "silicone monomer" as used herein refers to a monomer having at least one siloxane group. The silicone monomer can comprise a terminal acrylate or methacrylate group. (Meth)acrylate-containing silicone monomers useful in the inventive formulations described herein are well known in the art. The silicone monomer can be a monofunctional (meth)acrylate-containing silicone, a difunctional (meth)acrylate-containing silicone, or a combination of silicone monomers comprising monofunctional and difunctional (meth)acrylate-containing silicone monomers. In examples where the (meth)acrylate-containing silicone monomer consists of one or more monofunctional (meth)acrylate-containing silicone monomers (i.e., it does not contain any multifunctional (meth)acrylate-containing silicone monomers), the polymerizable composition will typically also comprise a (meth)acrylate-containing crosslinker described further below. In one particular example, the (meth)acrylate-containing silicone monomer has one or more polymerizable methacrylate groups. Various non-limiting examples of suitable acrylate-containing silicone monomers include 3-[tris(trimethylsiloxy)silyl]propyl methacrylate ("TRIS"), (3-methacryloyloxy-2-hydroxypropyloxy)propyl bis(trimethylsiloxy)methylsilane ("SiGMA"), methacrylic acid methyldi(tri- methylsiloxy)silylpropyl glyceryl ester ("SiGEMA"), and monomethacryloxypropyl functional polydimethylsiloxanes such as MCR-M07 and MCS-M11, all commercially available from Gelest (Morrisville, PA, USA).

[0102] The inventive silicone hydrogel contact lens formulations comprise a polymerizable silicone component in an amount of at least 40% (wt / wt), such as in an amount of at least 42% (wt / wt), especially in an amount of at least 45% (wt / wt). The polymerizable silicone component typically comprises no more than 60% (wt / wt) of the formulation, for example no more than 55% (wt / wt) of the formulation.

[0103] The silicone hydrogel contact lens formulation can include at least one difunctional siloxane having a molecular weight of at least 5,000 Daltons. At least 30% (wt / wt) of the siloxane content can be difunctional siloxane having a molecular weight of at least 5,000 Daltons. Advantageously, at least 40% (wt / wt) of the siloxane content is difunctional having a molecular weight of at least 5,000 Daltons. The formulation can include between 15 and 45 (wt / wt) difunctional siloxane, for example, between 20 and 40 (wt / wt) difunctional siloxane having a molecular weight of at least 5,000 Daltons. The difunctional siloxane typically has a molecular weight of less than 25,000 Daltons, such as a molecular weight of less than 20,000 Daltons, especially a molecular weight of less than 15,000 Daltons. It has been found that inclusion of siloxanes having higher molecular weights can result in formulations having unacceptably high viscosities. The silicone hydrogel contact lens formulation can include 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, especially at least one difunctional siloxane having a molecular weight of at least 8,000 to 15,000 Daltons.

[0104] The silicone hydrogel contact lens formulation can include at least one monofunctional siloxane monomer, for example, having a molecular weight of less than 3000 Daltons. At least 20% (wt / wt) of the siloxane content can be monofunctional siloxane having a molecular weight of less than 3000 Daltons. At least 30% (wt / wt) of the siloxane content is monofunctional having a molecular weight of less than 3000 Daltons. The formulation can include between 10 and 30 weight percent monofunctional siloxane monomer, for example, between 10 and 30 weight percent monofunctional siloxane monomer having a molecular weight of less than 3000 Daltons. The monofunctional siloxane typically has a molecular weight of at least 200 Daltons.

[0105] In one example, the monofunctional siloxane monomer can include a (meth)acrylate-containing siloxane monomer represented by formula (I),

[0106]

[0107] wherein m is an integer from 3 to 10, n is an integer from 0 to 10, R 1 is an alkyl group having 1 to 4 carbon atoms, R 2 is hydrogen or methyl, and R 3 is hydrogen or methyl. In another particular example, the acrylate-containing siloxane monomer is represented by formula I, wherein R 1 is butyl, R 2 is hydrogen, R 3R is methyl, m is 4, and n is 1. Methods of preparing siloxane monomers represented by formula (I) are described in U.S. Publication No. 2009 / 0299022, which is incorporated herein by reference.

[0108] In another example, the monofunctional siloxane monomer can comprise a (meth)acrylate-containing siloxane monomer represented by formula (II),

[0109]

[0110] wherein n is an integer from about 10 to 25, especially 10 to 20. 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.

[0111] Examples of suitable commercially available monofunctional siloxane monomers include 2-methyl-2-[3-(9-butyl-1,1,3,3,5,5,7,7,9,9- decamethylpentasiloxane-1 -yl)propoxy]ethyl 2-propenoate X-22-1622 (available from Shin-Etsu Chemical Co., Ltd., Tokyo, Japan) (CAS No. 1052075-57-6), methyl methacryloyloxypropyl-terminated poly(dimethyl)siloxane FMM (Shin-Etsu Silicones, America, Akron, Ohio, USA) (CAS No. 697234-76-7), and (3-methacryloyloxy-2-hydroxypropyloxy)propyl bis(trimethylsiloxy)methylsilane SiGMA.

[0112]

[0113] The silicone hydrogel contact lens formulation comprises at least one difunctional siloxane having a molecular weight of at least 5,000 Daltons, for example at least 6,500 Daltons, especially at least 8,000 Daltons. The formulation can comprise between 10 and 45 weight percent difunctional siloxane monomer, especially between 20 and 40 weight percent difunctional siloxane monomer. The formulation can comprise between 10 and 45 weight percent or between 20 and 40 weight percent difunctional siloxane monomer having a molecular weight of at least 8,000 Daltons.

[0114] In one example, the difunctional siloxane monomer can comprise a siloxane monomer represented by formula (III),

[0115]

[0116] wherein R1is selected from hydrogen or methyl; R2is selected from hydrogen or C 1-4 hydrocarbyl; m represents an integer from 0 to 10; n represents an integer from 4 to about 15, 25, or 100; a and b represent integers of 1 or greater; a + b equals 20 to 500; b / (a + b) equals 0.01 to 0.22; and the configuration of the siloxane units comprises a random configuration.

[0117] Other suitable difunctional siloxane monomers are represented by formula (IV):

[0118]

[0119] wherein R 3 is selected from hydrogen or methyl, m represents an integer from 0 to 10, and n represents an integer from 1 to 500. In one particular example, a suitable difunctional siloxane monomer is a methacryloxypropyl-terminated polydimethylsiloxane having a Mw of 4500 to 5500, represented by formula IV (wherein R 3 is methyl, m is 0, and n is an integer from 40 to 60), commercially available from Gels, Inc. (Morrisville, PA, USA) and referred to by the manufacturer as "DMS-R18". Additional suitable methacryloxypropyl-terminated polydimethylsiloxanes include DMS-R22 and DMS-R31, also commercially available from Gels, Inc.

[0120] Yet another suitable difunctional siloxane monomer is represented by formula (V),

[0121]

[0122] wherein n is an integer from about 100 to 150, m and p are each integers from about 5 to 10, and h is an integer from about 2 to 8. Methods of preparing the compound of formula V are described in U.S. Patent No. 6,867,245, which is incorporated herein by reference. Additional siloxane monomers that can be used in the inventive formulations described herein are known in the art (see, for example, U.S. Patent Nos. 7,572,841, 2006 / 0063852, and 5,998,498, each of which is incorporated herein by reference).

[0123] In one example, the siloxane monomer can comprise a combination of a monofunctional (meth)acrylate-containing siloxane monomer and a difunctional (meth)acrylate-containing siloxane monomer. In such an example, the monofunctional (meth)acrylate-containing siloxane monomer has a molecular weight of less than 2,000, 1,000, or 750 Daltons and the difunctional (meth)acrylate-containing siloxane monomer has a molecular weight of at least 3,000, 5,000, or 8,000 Daltons. In a particular example, the monofunctional (meth)acrylate-containing siloxane monomer has a molecular weight of from about 250 to about 1000 Daltons. In another particular example, the monofunctional (meth)acrylate-containing siloxane monomer has a molecular weight of from about 500 to about 1000 Daltons.

[0124] The silicone hydrogel contact lens formulations of the present application generally comprise one or more polymerization initiators, i.e., the formulations can comprise an initiator, or can contain an initiator component comprising two or more polymerization initiators or a combination of polymerization initiators, synergists and activators. The term "initiator" refers to a chemical that initiates a cross-linking / polymerization reaction. The initiator is typically a free radical initiator that forms free radicals that initiate the propagation of the polymerization reaction. Polymerization initiators that can be included in the formulations of the present application include, for example, azo compounds, or organic peroxides, or both. The initiator can be a photoinitiator that is activated upon exposure to actinic radiation, such as UV light, or a thermal initiator that is activated upon exposure to heat. Initiators that can be present in the polymerizable formulations include, for example, benzoin ethyl ether, or benzyl dimethyl ketal, or α,α-diethoxyacetophenone, or 2,4,6-trimethylbenzoyldiphenylphosphine oxide, or benzoin peroxide, or t-butyl peroxide, or azobisisobutyronitrile, or azobisdimethylvaleronitrile, or any combination thereof. UV photoinitiators can include, for example, phosphine oxides such as diphenyl(2,4,6-trimethylbenzoyl)phosphine oxide, or benzoin methyl ether, or 1-hydroxycyclohexyl phenyl ketone, or Darocur (available from BASF, Florham Park, N.J., USA), or Irgacur (also available from BASF), or any combination thereof. Advantageously, the polymerization initiator is a thermal initiator. Examples of suitable thermal initiators include 2,2'-azobis-2-methylpropionitrile (VAZO-64, available from E. I. DuPont de Nemours & Co., Wilmington, Del., USA), 2,2'-azobis(2,4-dimethylvaleronitrile) (VAZO-52), and 1,1'-azobis(cyanocyclohexane) (VAZO-88, also available from E. I. DuPont). The polymerization initiator or initiator component can be present in the silicone hydrogel contact lens formulations of the present application in an amount of from about 0.1% (wt / wt) to about 1.5% (wt / wt), or from about 0.2% (wt / wt) to about 1.0% (wt / wt), especially from about 0.2 to about 0.8% (wt / wt). The formulations of the first and second aspects of the present application are optionally thermally cured formulations comprising at least one thermal initiator. Methods of thermal curing or actinic curing are well known to those skilled in the relevant art.

[0125] The silicone hydrogel contact lens formulations can also include a crosslinking agent. A crosslinking agent can react with functional groups on two or more polymer chains to bridge one polymer to another. As used herein, a "crosslinking agent" is any compound having two or more polymerizable groups with a molecular weight of less than about 2000 Daltons, typically less than 700 Daltons. As used herein, an "acrylate-containing crosslinking agent" has at least two polymerizable acrylate groups, and no other type of polymerizable group. A "vinyl-containing crosslinking agent" has at least two polymerizable vinyl groups, and no other type of polymerizable group. The vinyl-containing crosslinking agents, as well as the acrylate-containing crosslinking agents, can generally have a molecular weight of less than 1500, 1000, 500, or 250 Daltons. Examples of vinyl-containing crosslinking agents that can be used in the presently disclosed inventive formulations include, but are not limited to, a divinyl ether, or a divinyl sulfone, or triallyl isocyanurate, and any combination thereof. Exemplary 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. Generally, the vinyl-containing crosslinking agent can have two or three polymerizable vinyl groups. When present, the total amount of vinyl-containing crosslinking agent in the silicone hydrogel contact lens formulation is generally from about 0.02, 0.04, or 0.06 mole % to about 0.10, 0.15, or 0.20 mole %. Examples of acrylate-containing crosslinking agents that can be used in the inventive formulations include, but are not limited to, a lower alkylene glycol di(meth)acrylate, a poly(lower alkylene) glycol di(meth)acrylate, a lower alkylene di(meth)acrylate, a trimethylolpropane tri(meth)acrylate, a pentaerythritol tetra(meth)acrylate, a bisphenol A di(meth)acrylate, a methylene bis(meth)acrylamide, and 1,3-bis(3-methacryloyloxypropyl)tetramethyldisiloxane. In certain examples, the acrylate-containing crosslinking agent is a non-silicone crosslinking agent. When present, the total amount of acrylate-containing crosslinking agent in the silicone hydrogel contact lens formulation is generally from about 0.20, 0.25, 0.30, or 0.35 mole % to about 0.50, 0.60, 0.70, 0.80, or 1.0 mole %. For the avoidance of doubt, multifunctional polymerizable compounds having a molecular weight greater than 2000 Daltons are not considered crosslinking agents. Thus, difunctional silicones having a molecular weight greater than 2000 Daltons as described herein are not considered crosslinking agents.

[0126] The polymerizable formulations can optionally further include a chain transfer agent. Chain transfer is a type of polymerization reaction in which the activity of a growing polymer chain is transferred to another molecule, thereby reducing the average molecular weight of the final polymer. Examples of chain transfer agents include, for example, a thiol compound, a halogen-based carbon compound, or a C3-C5 hydrocarbon such as an allyloxy ethanol.

[0127] In addition to the polymerizable components, the present formulations can include non- polymerizable components conventionally used in contact lens formulations. Additional components such as organic diluents or oxygen scavengers can also be included. Non-limiting examples of these and additional components that can be included in the polymerizable compositions are provided in US 2007 / 0296914.

[0128] Advantageous present formulations include a silicone component present in an amount of at least 40% (wt / wt), wherein at least 40% of the silicone content is a difunctional silicone 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). Advantageous present contact lenses advantageously include a polymeric lens material derived from an advantageous present formulation including the above-described monomers and silicone components. It has been found that the above-described advantageous formulations are particularly suitable for use in combination with (1) RB-247, (2) TPP, and (3) a polymerizable UV absorber including a benzophenone moiety (e.g., UV416) and / or a benzotriazole HEVL absorber.

[0129] One particularly advantageous present silicone hydrogel contact lens formulation includes 40 to 55 weight percent of a silicone component (e.g., including a silicone monomer or a combination of silicone monomers), 30 to 55 weight percent of an N-vinylamide monomer selected from NVP, VMA, or a combination thereof, and optionally about 1 to about 20 weight percent of a hydrophilic monomer selected from N,N-dimethylacrylamide (DMA), 2-hydroxyethyl methacrylate (HEMA), ethoxyethyl methacrylamide (EOEMA), or any combination thereof, and optionally about 1 to about 20 weight percent of a hydrophobic monomer selected from methyl methacrylate (MMA), isobornyl methacrylate (IBM), or 2-hydroxybutyl methacrylate (HOB), or any combination thereof.

[0130] In a fifth aspect, the present application provides for the use of one or more of an anthraquinone blue colorant, a benzophenone UV absorber, and a benzotriazole HEVL absorber in stabilizing a formulation, the formulation comprising:

[0131] a. at least 40% (wt / wt) of a polymerizable silicone component;

[0132] b. at least 30% (wt / wt) of a hydrophilic N-vinylamide monomer; and

[0133] c. triphenylphosphine (TPP).

[0134] Anthraquinone blue colorants, benzophenone UV absorbers, and benzotriazole HEVL absorbers can be alone or in any combination. For example, the fifth aspect of the present application provides the use of (i) an anthraquinone blue colorant and a benzophenone UV absorber, (ii) an anthraquinone blue colorant and a benzotriazole HEVL absorber, (iii) a benzophenone UV absorber and a benzotriazole HEVL absorber, or (iv) an anthraquinone blue colorant and a benzophenone UV absorber and a benzotriazole HEVL absorber to stabilize a formulation comprising:

[0135] a. at least 40% (wt / wt) of a polymerizable siloxane component;

[0136] b. at least 30% (wt / wt) of a hydrophilic N-vinyl amide monomer; and

[0137] c. triphenylphosphine (TPP).

[0138] The anthraquinone blue colorant used in the fifth aspect of the present application is advantageously 1,4-bis[(2-methacryloyloxyethyl)amino]-9,10-anthracene (RB247) or 1,4-bis[4-(2-methacryloyloxyethyl)phenylamino]-9,10-anthracene (RB246), especially RB247. The benzophenone UV absorber used in the fifth aspect of the present application is advantageously UV416. The benzotriazole HEVL absorber used in the fifth aspect of the present application can be any of the benzotriazole HEVLs described herein, advantageously UV13 or UV28.

[0139] Advantageously, the amounts of the anthraquinone blue colorants, benzophenone UV absorbers, and benzotriazole HEVL absorbers described above with respect to the formulations of the present application are used to stabilize the formulations in the fifth aspect of the present application.

[0140] The formulations stabilized in the fifth aspect of the present application are advantageously those described above with respect to the formulations of the other aspects of the present application. For example, the formulations stabilized in the fifth aspect of the present application can comprise any or all of the siloxane components, hydrophilic N-vinyl amide monomers, optional other hydrophilic monomers, optional other hydrophobic monomers, optional crosslinkers, optional chain transfer agents, and optional free radical initiators described above. Further, for example, the formulations stabilized in the fifth aspect of the present application comprise the siloxane components, hydrophilic N-vinyl amide monomers, optional other hydrophilic monomers, and optional other hydrophobic monomers in the amounts described above with respect to the formulations of the present application.

[0141] Examples

[0142] The following examples illustrate certain aspects and advantages of the present application, which should be understood not to be limited thereby.

[0143] Base formulation 1a / 1b

[0144] A base polymerizable silicone hydrogel contact lens formulation 1a was prepared containing:

[0145] 9 parts by weight of a hydrophobic monomer (composed of 2 parts of isobornyl methacrylate (IBM) and 7 parts of hydroxybutyl methacrylate (HOB)),

[0146] 39 parts by weight of hydrophilic N-vinylamide monomer (8.6 parts of N-vinyl N-methylacetamide (VMA) and 0.4 parts of N-vinylpyrrolidone (NVP)),

[0147] 49 parts by weight of polymerizable siloxane (18.13 parts FMM, 30.38 parts M5A, and 0.49 parts X-22-1622), and

[0148] 1 part by weight of other agents, including a thermal initiator (VAZO-64) and a crosslinking agent (triallyl isocyanate).

[0149] A base polymerizable silicone hydrogel contact lens formulation 1b was prepared containing:

[0150] 9 parts by weight of hydrophobic monomer (2 parts isobornyl methacrylate (IBM) and 7 parts hydroxybutyl methacrylate (HOB)),

[0151] 39 parts by weight of a hydrophilic N-vinylamide monomer (N-vinyl N-methylacetamide (VMA)),

[0152] 49 parts by weight of polymerizable siloxane (18.04 parts FMM, 30.23 parts M5A, and 0.49 parts X-22-1622), and

[0153] 1 part by weight of other agents, including a thermal initiator (VAZO-64) and a crosslinking agent (triallyl isocyanate).

[0154] The monomers were obtained from commercial sources and are believed to contain trace amounts of polymerization inhibitors.

[0155] Base formulation 2

[0156] Base Formulation 2 was prepared containing:

[0157] 13 parts by weight of a hydrophobic monomer (methyl methacrylate (MMA)),

[0158] 42 parts by weight of a hydrophilic N-vinylamide monomer (N-vinyl N-methylacetamide (VMA)),

[0159] 6 parts by weight of a hydrophilic acrylate monomer (ethylene glycol methacrylate (EGMA)),

[0160] • 35 parts by weight of polymerizable siloxane (8.83 parts of M5A and 26.48 parts of X-22-1622), and

[0161] • 2 parts by weight of other agents including thermal initiator (Vazo-64) and crosslinking agents (0.09 parts of triethylene glycol divinyl ether (TEGDVE) and 0.44 parts of ethylene glycol dimethacrylate (EGDMA)).

[0162] The monomers were obtained from commercial sources and can be considered to contain trace amounts of polymerization inhibitors.

[0163] Effect of TPP on gelling

[0164] The following examples illustrate the effect of TPP on the gelling of formulations, and how this effect changes depending on the treatment of colorants, UV absorbers, and / or HEVL absorbers.

[0165] A polymerizable mixture was freshly prepared combining Base Formulation la and Formulation 2 with colorant RB246, UV absorber Norbloc (i.e., 2-(3-(2H-benzotriazol-2-yl)-4-hydroxy-phenyl)ethyl methacrylate, CAS No. 96478-09-0, NORBLOC 7966, available from Noramco, Athens, GA., USA) and either no TPP or TPP in the amounts shown in Table 1, and 25 g or 12.5 g of the mixture was placed in a closed 37 ml vial to simulate a small or large air headspace, respectively, above the surface of the monomer mixture. These were then placed in a water bath at 17 °C and visually assessed for gelling of the mixture at daily intervals.

[0166] Table 1. Gelling onset times with and without TPP

[0167] After 8 days of storage in the water bath, no gelling was observed for Comparative Mixtures 1 and 2, which respectively included Base Formulation la or Base Formulation 2, lacking TPP, in either the large or small headspace samples.

[0168] Comparative Mixtures 3 and 4, which contained Base Formulation la or Base Formulation 2, respectively, along with about 0.4 parts by weight of TPP, were seen to rapidly gel in the small headspace samples. While Comparative Mixture 4 rapidly gelled in the small headspace sample, no gelling was observed after 8 days in the large headspace sample.

[0169] These results demonstrate that the mixture based on Formulation 2, which contains a higher amount of hydrophilic monomer and a lower amount of siloxane than Formulation la, can tolerate the inclusion of TPP in the presence of oxygen (i.e., in a large headspace container). However, when oxygen is largely excluded (i.e., in a small headspace container), the presence of TPP causes the mixture to gel rapidly within a day. The mixture based on Formulation la, which contains a lower amount of hydrophilic monomer and a higher amount of siloxane than Formulation 2, is not able to tolerate the inclusion of TPP even in the presence of oxygen (i.e., in a large headspace container).

[0170] Effect of colorants and UV / HEVL blockers

[0171] It was observed that the nature of the colorant and UV / HEVL blocker present in the mixture affects the stability of the mixture comprising Base Formulation la / lb.

[0172] Table 2. Gelation onset time with TPP and various colorants / UV / HEVL blockers

[0173]

[0174]

[0175] Referring to Table 2, the stability of Comparative Mixture 3 comprising Base Formulation la and 0.41 parts of TPP, 0.0082 parts of RB246, and 1.36 parts of Norbloc was compared to Mixture 5 comprising Base Formulation lb and 0.40 parts of TPP, 0.0135 parts of RB247, and 0.27 parts of a combination of benzophenone UV absorber and 1.58 parts of benzotriazole HEVL absorber, and a significant difference in gelation onset time was observed. The fundamental difference between Comparative Mixture 3 and Inventive Mixture 5 is the nature of the colorant and UV / HEVL blocker under the mixture containing RB246 and Norbloc, which exhibits lower stability than the mixture containing RB247 and UV416.

[0176] In all cases, light was excluded from the container in which the mixture was housed. Thus, the difference in stability is not attributable to the light transmission properties imparted to the mixture by the colorant and UV / HEVL blocker.

[0177] UV and HEVL blocker effects

[0178] A comparative test was conducted using a mixture comprising Base Formulation lb and 0.40 parts of TPP using a small headspace container (see Table 3) to investigate the effect of colorant and UV / HEVL blocker on stability.

[0179] Table 3. Gelation state with various colorants and UV / HEVL blockers.

[0180]

[0181] These results demonstrate that while the UV absorber Norbloc does not delay the onset of polymerization, each of RB246, UV416, UV13, and UV28 has a modest stabilizing effect. These results also demonstrate that the inclusion of the colorant RB247 significantly delays the onset of polymerization, with RB247 being more effective than RB246 at equivalent weight % loading. RB247 appears to have the most significant stabilizing effect of all the colorants and UV / HEVL blockers when used alone.

[0182] The stabilizing effect was found to be synergistic, and the most improved monomer mixture stability was achieved using a combination of RB247 with UV416 and a benzotriazole HEVL absorber (mixtures 16 and 17).

[0183] The disclosure herein refers to certain illustrative examples, which should be understood is by way of example, not by way of limitation. While exemplary examples are discussed, it is to be understood that the foregoing detailed description is intended to be illustrative and not limiting of the scope of the application as it is defined by the appended claims and equivalents.

[0184] All cited references are incorporated herein by reference in their entirety to the extent that they are not inconsistent with this disclosure.

[0185] Other embodiments of the application will be apparent to those skilled in the art from consideration of the specification and practice of the application disclosed herein. It is intended that the specification and examples be considered as exemplary only, with the true scope and spirit of the application being indicated by the following claims and their equivalents.

Claims

1. A silicone hydrogel contact lens formulation comprising: a. at least 40% (wt / wt) of a polymerizable silicone component; b. at least 30% (wt / wt) of a hydrophilic N-vinyl amide monomer; c. triphenylphosphine (TPP); and d. 1,4-bis[(2-methacryloyloxyethyl)amino]-9,10-anthraquinone (RB247).

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

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

4. The formulation according to any one of claims 1 to 3, comprising: f. Benzotriazole HEVL absorbent.

5. The formulation of claim 4, wherein the benzotriazole HEVL absorber comprises 2-[3'-tert-butyl-2'-hydroxy-5'-(3"-methacryloyloxypropoxy)phenyl]-5-chloro-2H-benzotriazole (UV28), 2-(1,1-dimethylethyl)-4-[3-[(4-vinylphenyl)methoxy]propoxy]-6-(5-methoxy-2H-benzotriazol-2-yl)-phenol (UV1), 2-(5-chloro-2H-benzotriazol-2-yl)-6-(1,1-dimethylethyl)-4-vinyl-phenol (UV5 / UVAM), 2-[2'-hydroxy-3'- tert-butyl-5'-(3"-methacryloyloxypropoxy)phenyl]-5-methoxy-2H-benzotriazole (UV13), 2-3'-tert-butyl-2'-hydroxy-5'-(3"-dimethylvinylsilylpropoxy)-2'-hydroxy-phenyl)-5-methoxybenzotriazole (UV15), in particular 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 of claim 4 or 5, wherein the benzotriazole HEVL absorber is present in an amount of 0.1% (wt / wt) to 3.0% (wt / wt).

7. A formulation according to any preceding claim comprising N-methyl N-vinylacetamide in an amount of 35 to 50% (wt / wt).

8. A formulation according to any preceding claim, wherein the N-vinylamide monomer component is present in an amount of at least 37% (wt / wt).

9. A formulation according to any preceding claim, further comprising: g. At least 5% (wt / wt) of a non-silicone hydrophobic monomer, especially a hydrophobic methacrylate monomer.

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

11. The formulation of any preceding claim, wherein the polymerizable silicone component is present in an amount of at least 45% (wt / wt).

12. A formulation according to any preceding claim, wherein the polymerisable silicone component comprises a difunctional siloxane having a molecular weight of at least 8,000 Daltons, optionally in an amount of 20 to 40% (wt / wt).

13. A formulation according to any preceding claim, wherein the polymerisable silicone component comprises a monofunctional (meth)acrylate-containing silicone having a molecular weight of less than 3000 Daltons, optionally in an amount of 10 to 30% (wt / wt).

14. The formulation of any preceding claim, wherein at least 40% (wt / wt) of the polymerizable silicone content is a difunctional silicone having a molecular weight of at least 8,000 Daltons, and wherein at least 25% (wt / wt) of the polymerizable silicone content is a monofunctional silicone having a molecular weight of less than 3000 Daltons.

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

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

17. A formulation according to any preceding claim, wherein the polymerizable silicone component comprises a difunctional silicone monomer represented by formula (III), wherein R1 is selected from hydrogen or methyl; R2 is selected from hydrogen or C 1-4 m represents an integer from 0 to 10; n represents an integer from 4 to about 15, 25 or 100; a and b represent an integer of 1 or greater; a+b is equal to 20 to 500; b / (a+b) is equal to 0.01 to 0.22; and the configuration of the siloxane unit includes a random configuration.

18. The formulation of any preceding claim, wherein the polymerizable silicone component comprises a monofunctional methacrylate-containing silicone monomer represented by formula (II), wherein n is an integer from about 10 to 15.

19. The formulation of any preceding claim, which is a heat-cured formulation, further comprising: h. at least one thermal free radical initiator.

20. A silicone hydrogel contact lens obtained by polymerizing the formulation of any preceding claim.

21. Use of an anthraquinone blue colorant, a benzophenone UV absorber and / or a benzotriazole HEVL absorber to stabilize a formulation comprising: a. at least 40% (wt / wt) of a polymerizable silicone component; b. at least 30% (wt / wt) of a hydrophilic N-vinylamide monomer; and c. Triphenylphosphine (TPP).

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