Contact lenses and contact lens formulations with reduced ripples

Abstract

The invention provides a silicone hydrogel contact lens formulation comprising a difunctional siloxane, a hydrophilic N-vinyl amide monomer, and at least 0.10% (wt / wt) triphenylphosphine (TPP); a silicone hydrogel contact lens formed by polymerizing the silicone hydrogel contact lens formulation, and the use of TPP to improve the surface properties of a contact lens prepared from a formulation comprising a difunctional siloxane and a hydrophilic N-vinyl amide monomer.

Description

TECHNICAL FIELD

[0001] The present invention relates to a polymerizable formulation comprising triphenylphosphine for use in the manufacture of contact lenses, and to contact lenses incorporating a polymer matrix formed from the polymerizable formulation. In particular, the present invention relates to a polymerizable formulation which has been found to impart advantageous properties to hydrogel contact lenses, such as reduced surface ripples. BACKGROUND

[0002] Silicone hydrogel contact lenses have been developed which have advantageous lens properties, such as high water content, low contact angle and high oxygen permeability (Dk). However, surface ripples have been observed when casting certain polymerizable compositions into silicone hydrogel contact lenses, particularly when casting silicone hydrogel contact lenses in polypropylene (PP) molds. It has been found that surface ripples are particularly severe when casting contact lenses from polymerizable compositions having a relatively high proportion of high molecular weight siloxane components.

[0003] There remains a need to reduce surface ripples of silicone hydrogel contact lenses while maintaining advantageous lens properties. SUMMARY

[0004] In a first aspect, the present invention provides a silicone hydrogel contact lens formulation comprising:

[0005] a. at least 40% (wt / wt) of a polymerizable siloxane component, wherein at least 50% (wt / wt) of the polymerizable siloxane content is a difunctional siloxane having a molecular weight of at least 5,000 Daltons, particularly at least 8,000 Daltons;

[0006] b. at least 30% (wt / wt) of a hydrophilic N-vinyl amide monomer; and

[0007] c. at least 0.10% (wt / wt) of triphenylphosphine (TPP).

[0008] Furthermore, the silicone hydrogel contact lens formulation of the present invention typically contains other polymerizable monomers, oligomers and / or prepolymers, one or more crosslinking agents and one or more polymerization initiators.

[0009] It has been found that by including at least 0.10% (wt / wt) TPP in a contact lens formulation comprising: (a.) at least 40% (wt / wt) of a polymerizable siloxane component, wherein at least 50% (wt / wt) of the polymerizable siloxane content is a difunctional siloxane having a relatively high molecular weight, i.e., at least 5,000 Daltons, especially at least 8,000 Daltons, and (b.) at least 30% (wt / wt) of a hydrophilic N-vinyl amide monomer, the resulting formulation is resistant to surface ruffling compared to a similar formulation that does not include TPP, but the formulation maintains advantageous lens properties such as high water content, low contact angle, and high oxygen permeability (Dk).

[0010] In a second aspect, the present application provides a silicone hydrogel contact lens formed by polymerizing the formulation of the first aspect of the present application. Thus, the polymer lens material of the silicone hydrogel contact lens of the second aspect of the present application comprises the polymerization product of polymerizing the formulation comprising:

[0011] a. at least 40% (wt / wt) of a polymerizable siloxane component, wherein at least 50% (wt / wt) of the polymerizable siloxane content is a difunctional siloxane having a molecular weight of at least 5,000 Daltons, especially at least 8,000 Daltons;

[0012] b. at least 30% (wt / wt) of a hydrophilic N-vinyl amide monomer; and

[0013] c. at least 0.10% (wt / wt) of triphenylphosphine (TPP).

[0014] In a third aspect, the present application provides the use of TPP to improve the surface properties of a contact lens prepared from a formulation comprising:

[0015] a. at least 40% (wt / wt) of a polymerizable siloxane component, wherein at least 50% (wt / wt) of the polymerizable siloxane content is a difunctional siloxane having a molecular weight of at least 5,000 Daltons, especially at least 8,000 Daltons; and

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

[0017] Advantageously, the TPP is used in an amount of at least 0.10% (wt / wt) based on the total weight of the formulation in the third aspect of the present application.

[0018] Advantageously, in each of the first, second, and third aspects of the present application, at least 20% (wt / wt) of the polymerizable siloxane content is a monofunctional siloxane having a molecular weight of less than 3000 Daltons.

[0019] It has been found that the present formulations reduce the amount of surface ripples present on cast molded contact lenses compared to lenses cast from other identical polymerizable formulations lacking TPP. The reduction in surface ripples is particularly evident in silicone hydrogel contact lenses that have been cast molded in polypropylene (PP) molds. It has been found that the addition of TPP in the polymerizable formulation from which the lenses are formed does not adversely affect the properties of the resulting cast molded lenses, such as water content, contact angle, and oxygen permeability (Dk), compared to those cast from polymerizable formulations lacking TPP. DETAILED DESCRIPTION

[0020] The present application will be more fully understood and further advantages will become apparent when reference is made to the following detailed description of the embodiments of the application and the drawings in which: The application will be described in further detail with reference to the drawings in which: The application will be described in further detail with reference to the drawings in which:

[0021] It has been found that inclusion of at least 40% (wt / wt) of siloxane (at least 50% of which is at least 5,000 Dalton, especially 8,000 Dalton high molecular weight difunctional siloxane) and 30% (wt / wt) of N-vinylamide hydrophilic monomer in the present formulations can provide contact lenses with advantageously high water content, high surface wettability and high oxygen permeability (Dk). It has been found that optional inclusion of additional non-siloxane hydrophobic monomers, especially hydroxybutyl methacrylate and / or isobornyl methacrylate can enhance the mechanical strength of the resulting lens.

[0022] The present application is based on the further finding that when at least 0.10% (wt / wt) of TPP is included in a polymerizable formulation for the production of a contact lens, a contact lens can be provided which is both resistant to surface ruffling and has advantageous lens properties and its corresponding formulation. It has been found that other comparable formulations without TPP can exhibit surface ruffling. Surface ruffling is an undesirable property of a contact lens because surface ruffling can cause discomfort to the wearer. In addition, surface ruffling can reduce the optical properties of a contact lens. Thus, a formulation with little or no surface ruffling is advantageous. It has been found that a contact lens formed from a formulation having a high viscosity, such as a viscosity higher than 250 mm 2 / s at 25°C, for example a viscosity higher than 300 mm 2 / s at 25°C, is particularly prone to surface ruffling. Likewise, it has been found that a contact lens formed from a formulation comprising a high proportion of high molecular weight siloxane component, such as a formulation in which at least 40% (wt / wt) of the polymerizable siloxane component (at least 50% (wt / wt) of the polymerizable siloxane content is difunctional siloxane having a molecular weight of at least 5,000 Dalton, especially at least 8,000 Dalton) is particularly prone to surface ruffling. It has been found that inclusion of a large amount of high molecular weight siloxane (for example more than 20% by weight of siloxane having a viscosity of 300 mm 2 / s or more at 25°C according to the weight of the polymerizable formulation) can result in an overall formulation having a relatively high viscosity, for example a viscosity of 250 mm 2 / s or more at 25°C. It has been found that inclusion of TPP in such formulations can be effective in preventing or reducing surface ruffling. The polymerizable components of the present formulations are generally incorporated into the present contact lenses.

[0023] References herein to the amount of an ingredient or component present in a formulation expressed as a weight percent (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 silicone component, 30 parts of hydrophilic N-vinyl amide monomer, 4.5 parts of other active ingredients (e.g., polymerization initiators, colorants, oxygen scavengers, etc.), and 25 parts of 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 silicone component.

[0024] The present polymerizable formulation includes triphenylphosphine (TPP; CAS Number: 603-35-0). TPP is a common organophosphorus compound used in the synthesis of organic and organometallic compounds and an intermediate in the preparation of pharmaceuticals, phosphonium salts, and other phosphorus compounds.

[0025]

[0026] The present silicone hydrogel contact lens formulation includes at least 0.10% (wt / wt) TPP. The TPP can be present in the polymerizable formulation 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 formulation in an amount of from about 0.15% (wt / wt) to about 2.0% (wt / wt), such as 0.20% (wt / wt) to 1.0% (wt / wt), typically in an amount of from about 0.25% (wt / wt) to about 1.0% (wt / wt).

[0027] The present contact lens formulation is a silicone hydrogel contact lens formulation including:

[0028] a. at least 40% (wt / wt) of a polymerizable silicone component, wherein at least 50% (wt / wt) of the polymerizable silicone content is a difunctional siloxane having a molecular weight of at least 5,000 Daltons, especially at least 8,000 Daltons; and

[0029] b. at least 30% (wt / wt) of a hydrophilic N-vinyl amide monomer; and

[0030] c. at least 0.10% (wt / wt) of TPP, such as from about 0.20% (wt / wt) to about 2% (wt / wt) of TPP.

[0031] "Silicone hydrogel" means a crosslinked polymeric material having a three-dimensional polymeric network (i.e., a polymeric matrix) that is insoluble in water, but which contains at least 10% water by weight in its polymeric matrix when fully hydrated. "Silicone hydrogels" are 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 pre-polymer or at least one crosslinkable silicone-containing pre-polymer).

[0032] The polymerizable contact lens formulations of the first aspect of the present application are suitable for forming silicone hydrogel contact lenses. Polymerizable formulations suitable for use in making silicone hydrogel contact lens bodies are well known in the art. In addition to the TPP, the polymerizable siloxane component, and the hydrophilic N-vinyl amide monomer, the silicone hydrogel contact lens formulations of the first aspect of the present application can include other components suitable for forming a contact lens body. The polymerizable formulations typically include a crosslinker and a polymerization initiator. The polymerizable formulations can include additional polymerizable monomers, oligomers, and / or pre-polymers.

[0033] Typically, silicone hydrogel contact lenses are formed via a free radical propagation reaction involving polymerization of terminal ethylenically unsaturated groups (also referred to herein as "polymerizable groups"). Exemplary polymerizable groups include (meth)acrylic, (meth)acrylamide, allyl, and vinyl and styryl. As used herein, "vinyl-containing monomer" is any non-siloxane monomer having a single polymerizable carbon-carbon double bond (i.e., a 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. Vinyl groups are less reactive under free radical polymerization than the carbon-carbon double bonds present in acrylate or methacrylate polymerizable groups. The term "(meth)acrylamide" means methacrylamide and / or acrylamide. The term "(meth)acrylate" means methacrylate and / or acrylate. The term "terminal (meth)acrylic group" means one (meth)acrylic group at one of the two ends of the main chain / backbone of an organic compound. "N-vinyl amide monomer" means an amide compound having a vinyl group CH=CH2 directly attached to the nitrogen atom of the amide group.

[0034] A "monomer" is a molecule having one or more polymerizable groups that can react with other monomers, of 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 chains of repeating units, such as polymerizable siloxanes; thus, there is no size restriction (i.e., maximum molecular weight) on the monomers unless otherwise indicated. The term "polymer" refers to a material formed by polymerization and / or crosslinking of one or more monomers.

[0035] As used in this application, unless specifically indicated otherwise, the "molecular weight" of a polymeric material, including components comprising multiple siloxane units, refers to the absolute number average molecular weight (in units of Daltons), for example, by GPC using polystyrene standards or by 1 An "oligomer" is a compound consisting of 2 to 10 repeating units that can be actually or conceptually derived from a monomer. A pre-polymer is a partially polymerized polymer comprising multiple monomeric units, typically 10 or more, that is reacted to an intermediate molecular mass state that retains the ability to continue to react to fully cure into a higher molecular mass polymeric material.

[0036] In addition to the N-vinyl amide-containing monomers, the silicone hydrogel contact lens formulations of the present application can include other hydrophilic monomers, and can also include hydrophobic monomers.

[0037] As used herein, "hydrophilic monomer" refers to a non-silicone monomer in which at least 50 grams of the monomer is completely soluble in 1 liter of water at 20°C (i.e., about 5% soluble in water) as determined visually using the standard shake flask method.

[0038] The silicone hydrogel contact lens formulations include one or more N-vinyl amide-containing hydrophilic monomers in an amount of at least 30% (wt / wt), such as in an amount of at least 35% (wt / wt), especially in an amount of at least 37% (wt / wt). The formulations can additionally include other hydrophilic monomers, such as hydrophilic vinyl ether-containing monomers. The total amount of hydrophilic monomers in the formulations of the first aspect of the present application is typically no greater than 55% (wt / wt), such as no greater than 50% (wt / wt).

[0039] 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 vinylamide-containing monomer consists of VMA or NVP, or a combination of VMA and NVP. The 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 up to 4, 6, 8, or 10 ethylene glycol units. In addition to the hydrophilic N-vinylamide-containing monomer and the hydrophilic vinyl ether-containing monomer, one or more vinyl-containing monomers can be included in the present polymerizable formulations described herein. For example, in addition to the N-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 present 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.

[0040] The formulations of the first aspect of the present application 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 aspect of the present application generally comprise no more than 55% (wt / wt) of N-vinylamide hydrophilic monomer, such as less than 50% (wt / wt) of N-vinylamide hydrophilic monomer. The formulations of the first aspect of the present application can comprise N-vinylamide hydrophilic monomer in an amount of 35 to 55%, in particular 37 to 50%. The formulations of the first aspect of the present application can comprise N-methyl N-vinyl acetamide in an amount of 30 to 55%, such as 35 to 50%, in particular 37 to 50%.

[0041] 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 formulation 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.

[0042] The present formulations can optionally include hydrophobic monomers that lack siloxane groups. The term "hydrophobic monomer" as used herein refers to monomers that lack siloxane groups and are less than 5% soluble in water at 20°C, as determined using the standard shake flask method.

[0043] The hydrophobic monomers can be (meth)acrylate-containing hydrophobic monomers. As used herein, "hydrophobic acrylate-containing monomers" are any non-siloxane monomers having a single polymerizable acrylate group (e.g., methyl methacrylate, acrylamide, etc.). In one particular example, the hydrophobic acrylate-containing monomers have 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, tertiary butyl methacrylate (tBMA), perfluorohexylethylsulfylcarbonylaminylethyl 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 desired properties.

[0044] The hydrophobic monomers that lack siloxane groups are not limited to (meth)acrylate-containing monomers and can include vinyl or other olefinically unsaturated reactive groups. Other examples of hydrophobic monomers include vinyl acetate, vinyl propionate, vinyl butyrate, styrene, chlorobutadiene, chloroethylene, vinylidene chloride, acrylonitrile, and methacrylonitrile.

[0045] 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.

[0046] 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 include 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 formulation 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 methyl di(triethylsiloxy)silylpropyl glyceryl ester ("SiGEMA"), and monomethacryloxypropyl functional polydimethylsiloxanes such as MCR-M07 and MCS-M11, all commercially available from Gelest (Morrisville, PA, USA).

[0047] The inventive silicone hydrogel contact lens formulation comprises 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.

[0048] The silicone hydrogel contact lens formulations can include at least one monofunctional siloxane monomer, for example, having a molecular weight of less than 3000 Daltons. At least 10% (wt / wt) of the siloxane content can be monofunctional siloxane having a molecular weight of less than 3000 Daltons. At least 20% (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 monomers, for example, between 10 and 30 weight percent monofunctional siloxane monomers having a molecular weight of less than 3000 Daltons. The monofunctional siloxane typically has a molecular weight of at least 200 Daltons.

[0049] In one example, the monofunctional siloxane monomer can include a (meth)acrylate-containing siloxane monomer represented by formula (I),

[0050]

[0051] where 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, where R 1 is butyl, R 2 is hydrogen, R 3 is methyl, m is 4, and n is 1. Methods of making siloxane monomers represented by formula (I) are described in U.S. Publication No. 2009 / 0299022, which is incorporated herein by reference.

[0052] In another example, the monofunctional siloxane monomer can include a (meth)acrylate-containing siloxane monomer represented by formula (II),

[0053]

[0054] where 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.

[0055] 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-decamethyl- pentasiloxane-1 -yl)propoxy]ethyl 2-propenoate X-22-1622 / KF-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-hydroxypropyloxypropyl bis(trimethylsiloxy)methylsilane SiGMA.

[0056]

[0057] Silicone hydrogel contact lens formulations include at least one difunctional siloxane having a molecular weight of at least 5,000 Daltons, such as at least 6,500 Daltons, especially at least 8,000 Daltons. The difunctional siloxane can include or consist of a difunctional (meth)acrylate-containing siloxane monomer having a molecular weight of at least 5,000 Daltons, such as at least 6,500 Daltons, especially at least 8,000 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, such as 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. At least 50% (wt / wt) of the siloxane content is a difunctional siloxane having a molecular weight of at least 5,000 Daltons, especially a difunctional (meth)acrylate-containing siloxane. At least 50% (wt / wt) of the siloxane content can be a difunctional siloxane having a molecular weight of at least 6,500 Daltons, especially a difunctional (meth)acrylate-containing siloxane. Advantageously, at least 50% (wt / wt) of the siloxane content is a difunctional siloxane having a molecular weight of at least 8,000 Daltons, especially a difunctional (meth)acrylate-containing siloxane. The formulation can include between 20% (wt / wt) and 45% (wt / wt) of a difunctional siloxane, such as between 20% (wt / wt) and 40% (wt / wt) of a difunctional siloxane, especially a difunctional (meth)acrylate-containing siloxane. The formulation can include between 20% (wt / wt) and 45% (wt / wt) of a difunctional siloxane having a molecular weight of at least 5,000 Daltons, especially a difunctional (meth)acrylate-containing siloxane, such as between 20% (wt / wt) and 40% (wt / wt) of a difunctional siloxane having a molecular weight of at least 5,000 Daltons, especially a difunctional (meth)acrylate-containing siloxane.The formulation can comprise between 15% (wt / wt) and 45% (wt / wt) of difunctional siloxanes having a molecular weight of at least 8,000 Daltons, especially difunctional (meth)acrylate-containing siloxanes, for example between 20% (wt / wt) and 45% (wt / wt) or between 20% (wt / wt) and 40% (wt / wt) of difunctional siloxanes having a molecular weight of at least 8,000 Daltons, especially difunctional (meth)acrylate-containing siloxanes. It has been found that the inclusion of TPP is particularly advantageous in formulations comprising high amounts of high molecular weight siloxanes, such as formulations comprising at least 20% (wt / wt), especially at least 25% (wt / wt) of siloxanes having a molecular weight of at least 5,000 Daltons, especially at least 8,000 Daltons.

[0058] In one example, the difunctional siloxane monomer can comprise a (meth)acrylate-containing siloxane monomer represented by formula (III),

[0059]

[0060] 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 up to about 15, 25 or 100; a and b represent integers of 1 or more; a + b equals 20 to 500; b / (a + b) equals 0.01 to 0.22; and the configuration of siloxane units comprises a random configuration.

[0061] For example, difunctional siloxane monomer M5A is represented by formula (III) wherein R1is methyl, R2is methyl, m is 0, n is about 7, a is about 75, and b is about 10. M5A has a molecular weight of between 8,000 Daltons and 11,000 Daltons.

[0062] Other suitable difunctional siloxane monomers are represented by formula (IV):

[0063]

[0064] 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, the difunctional siloxane monomer is represented by formula (IV (wherein R 3Methyldimethicone terminated with methacryloxypropyl groups having a Mw of 4500 to 5500 represented by the formula (CH3)2SiO[(CH3)2SiO]mSi(CH3)2C(O)CH=CH2 (wherein m is 0 and n is an integer from 40 to 60) is commercially available from Gelest (Morrisville, PA, USA) and is designated by the manufacturer as "DMS-R18". Additional suitable methacryloxypropyl terminated polydimethylsiloxanes include DMS-R22 and DMS-R31, also commercially available from Gelest.

[0065] Yet another suitable difunctional siloxane monomer is represented by formula (V),

[0066]

[0067] 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 compounds of formula (V) are described in U.S. Patent No. 6,867,245, which is incorporated herein by reference. One example of a suitable siloxane monomer represented by formula (V) is (a-oo)-bis(methacryloxyethy limido carboxyethoxy-propyl)-poly(dimethylsiloxane)-poly(trifluoropropylmethylsiloxane)-poly(co-methoxy-poly(ethylene glycol)propylmethylsiloxane) (M3U), wherein n is 121, m is 7.6, h is 4.4, and the molecular weight is 12,000 to 20,000 Daltons, typically about 12,800 Daltons. Additional (meth)acrylate-containing siloxane monomers useful in the inventive formulations described herein are known in the art (see, e.g., U.S. Patent Nos. 7,572,841, 2006 / 0063852, and 5,998,498, each of which is incorporated herein by reference).

[0068] In one example, the siloxane monomer can comprise a combination of monofunctional (meth)acrylate-containing siloxane monomers and difunctional (meth)acrylate-containing siloxane monomers. In such an example, the monofunctional (meth)acrylate-containing siloxane monomers have a molecular weight of less than 3,000, 2,000, or 1,000 Daltons, and the difunctional (meth)acrylate-containing siloxane monomers have a molecular weight of at least 5,000, 6,500, or 8,000 Daltons. In one particular example, the monofunctional (meth)acrylate-containing siloxane monomers have a molecular weight of about 250 to about 1000 Daltons, and the difunctional (meth)acrylate-containing siloxane monomers have a molecular weight of about 5,000 to about 16,000 Daltons. In another particular example, the monofunctional (meth)acrylate-containing siloxane monomers have a molecular weight of about 500 to about 1000 Daltons, and the difunctional (meth)acrylate-containing siloxane monomers have a molecular weight of about 5,000 to about 12,000 Daltons.

[0069] 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 crosslinking / 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 benzoyl 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, abbreviated as "AIBN" (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 aspect of the present application are optionally thermally cured formulations comprising at least one thermal initiator. Thermal curing or actinic curing methods are well known to those skilled in the art.

[0070] The silicone hydrogel contact lens formulations can further 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 typically 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 (TAIC), 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. Typically, 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 typically from about 0.02, 0.04, or 0.06 mole % up to about 0.10, 0.15, or 0.20 mole %. Examples of acrylate-containing crosslinking agents that can be used in the presently disclosed 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 a 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 inventive formulations is typically from about 0.20, 0.25, 0.30, or 0.35 mole % up to about 0.50, 0.60, 0.70, 0.80, or 1.0 mole %. For the avoidance of doubt, monofunctional 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.

[0071] The inventive 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, 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.

[0072] 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 solvent diluents can also be included. Non-limiting examples of these and additional components that can be included in the polymerizable formulations are provided in US 2007 / 0296914. The formulations of the present application can include no more than 2% (wt / wt) of non-polymerizable components other than TPP, particularly no more than 1% (wt / wt) of non-polymerizable components other than TPP. In particular, the formulations of the present application can include no more than 2% (wt / wt) of organic solvent diluents, particularly no more than 1% (wt / wt) of organic solvent diluents.

[0073] Advantageous formulations of the present application include a silicone component present in an amount of at least 40% (wt / wt), wherein at least 50% 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 30% (wt / wt). The contact lenses of the second aspect of the present application advantageously include a polymeric lens material derived from an advantageous polymerizable formulation of the first aspect of the present application including the above-described monomer and silicone components.

[0074] The improved formulations in the third 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 improved formulations in the third aspect of the present application can include the above-described silicone component, hydrophilic N-vinylamide monomer, optional additional hydrophilic monomer, optional additional hydrophobic monomer, optional crosslinker, optional chain transfer agent, and any or all of the optional free radical initiators. Further, for example, the improved formulations in the third aspect of the present application include the silicone component, hydrophilic N-vinylamide monomer, optional additional hydrophilic monomer, and optional additional hydrophobic monomer in the amounts described above with respect to the formulations of the present application.

[0075] Examples

[0076] The following examples illustrate certain aspects and advantages of the present application, which should be understood not to be limited thereby.

[0077] Base Formulation

[0078] A base polymerizable silicone hydrogel contact lens formulation 1 was prepared containing:

[0079] • 11 wt% hydrophobic monomer (consisting of 8.29 wt% hydroxybutyl methacrylate and 2.49 wt% isobornyl methacrylate),

[0080] • 42 wt% hydrophilic N-vinyl amide monomers (consisting of 10.48 wt% N-vinyl N-methyl acetamide and 31.44 wt% N-vinyl pyrrolidone),

[0081] • 45 wt% polymerizable siloxanes (with different ratios of monomers - as shown in Table 1),

[0082] • 2 wt% other agents, including thermal initiator (azobisisobutyronitrile (AIBN)) and crosslinking agent (triallyl isocyanurate).

[0083] A base polymerizable silicone hydrogel contact lens formulation 2 was prepared containing:

[0084] • 9 wt% hydrophobic monomers (consisting of 9.94% hydroxybutyl methacrylate and 2.09% isobornyl methacrylate),

[0085] • 39 wt% hydrophilic N-vinyl amide monomers (N-vinyl N-methyl acetamide),

[0086] • 49 wt% polymerizable siloxanes, high molecular weight difunctional siloxane (30.23 wt% M5A, Mn 8,000 to 11,000): low molecular weight monofunctional siloxane (18.04 wt% FMM and 0.49 wt% KF-1622 Mn < 2,000) in a 62:38 ratio,

[0087] • 3 wt% other agents, including thermal initiator (azobisisobutyronitrile (AIBN)) and crosslinking agent (triallyl isocyanurate).

[0088] Evaluation of surface waviness

[0089] Using the following scale, the waviness severity was visually assessed according to the zonometer or SAG optimec images of the lenses and rated from 0 to 5:

[0090] • 0 - no visible waviness.

[0091] • 1 - very slight, faint waviness.

[0092] • 2 - slight waviness.

[0093] • 3 - moderate waviness.

[0094] • 4 - severe waviness.

[0095] • 5 - very severe, long and deep waviness.

[0096] Surface waviness without TPP

[0097] The following examples illustrate the severity of surface ripples that occur in PP molds for formulations, and how this can be mitigated by including TPP.

[0098] A polymerizable mixture was used to investigate the severity of surface ripples, combining Base Formulation 1, with a silicone content fixed at 46 parts by weight and different silicone ratios between M5A:KF-1622 and M5A:FMM. The polymerizable mixture did not include TPP and no further changes were made to the monomer formulation. All formulations were cast in the same PP mold. The results are summarized in Table 1 below. The table shows that the severity of ripples increases as the loading of M5A increases, with mixture 6 (containing 75:25 M5A:FMM) exhibiting the most severe surface ripples.

[0099] Table 1.

[0100] mixture formulation silicone mixture corrugation severity 1 formulation 1 M5A:KF-1622 (25:75) 1 2 formulation 1 M5A:KF-1622 (50:50) 2 3 formulation 1 M5A:KF-1622 (75:25) 3 4 formulation 1 M5A:FMM (25:75) 2 5 formulation 1 M5A:FMM (50:50) 4 6 formulation 1 M5A:FMM (75:25) 5 7 formulation 1 M3U:FMM (81:19) 5

[0101] Lenses made from mixture 7 (containing 81:19 M3U:FMM) were also observed to have severe ripples. In comparison, Stenfilcon A lenses (which include about 35% (wt / wt) of a silicone content containing 75:25 KF-1622:M5A) and fanfilcon A lenses (which include about 39% (wt / wt) of a silicone content containing 68:32 KF-1622:M5A) made using the same process in a PP mold did not show ripples (0).

[0102] Effect of TPP on surface ripples

[0103] Adding TPP to the monomer formulation resulted in contact lens manufacturing without surface ripples. As the loading of the TPP increased, a decrease in the degree of ripples was observed.

[0104] Adding TPP to Base Formulation 2 (with a total silicone content of 54 parts by weight, consisting of a formulation of 62:38 di-functional: mono-functional siloxanes) is shown in Table 2 below.

[0105] Table 2.

[0106] mixture formulation TPP weight percent corrugation severity 9 formulation 2 0.000％ 3 10 formulation 2 0.091％ 3 11 formulation 2 0.181％ 2 12 formulation 2 0.271％ 1 13 formulation 2 0.404％ 0

[0107] The table shows that the severity of ripples decreases as the loading of TPP increases. When TPP is not included (mixture 9), the ripples are at their most pronounced state. When 0.404% TPP is included (mixture 13), the ripples are mitigated to such an extent that they can no longer be visually observed.

[0108] The disclosure herein refers to certain illustrative examples, which should be understood in not by way of restriction, but rather by way of description and explanation. Encompassed by the foregoing detailed description are all modifications, alternatives, and equivalents that can fall within the spirit and scope of the application as defined by the additional disclosure.

[0109] The entire contents of all of the references cited herein are hereby incorporated by reference to the extent that they provide exemplary procedural or other details that are consistent with or supportive of the preceding detailed description.

[0110] 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.

Claims

1. A silicone hydrogel contact lens formulation comprising: a. At least 40% (wt / wt) of a polymerizable siloxane component having polymerizable siloxane contents, wherein at least 50% (wt / wt) of the polymerizable siloxane contents are difunctional siloxanes having a molecular weight of at least 5,000 Daltons; b. At least 30% (wt / wt) of hydrophilic N-vinylamide monomer; and c. At least 0.10% (wt / wt) of triphenylphosphine (TPP).

2. The formulation according to claim 1, comprising 35 to 50% (wt / wt) of N-methyl-N-vinylacetamide monomer.

3. The formulation according to any of the preceding claims, comprising at least 37% (wt / wt) of N-vinylamide monomer.

4. The formulation according to claim 1 or 2, wherein the polymerizable siloxane component is present in an amount of at least 45% (wt / wt).

5. The formulation according to claim 1 or 2, wherein at least 50% (wt / wt) of the polymerizable siloxane content is a difunctional siloxane having a molecular weight of at least 8,000 Daltons.

6. The formulation according to claim 1 or 2, comprising 20 to 40% (wt / wt) of a difunctional (meth)acrylate siloxane having a molecular weight of at least 8,000 Daltons.

7. The formulation according to claim 1 or 2, wherein 20 to 50% (wt / wt) of the polymerizable siloxane content is a monofunctional siloxane having a molecular weight of less than 3000 Daltons.

8. The formulation according to claim 1 or 2, comprising 10 to 30% (wt / wt) of a monofunctional (meth)acrylate-containing siloxane having a molecular weight of less than 3000 Daltons.

9. The formulation according to claim 1 or 2, further comprising: d. Non-siloxane hydrophobic monomers.

10. The formulation according to claim 9, wherein the nonsiloxane hydrophobic monomer is a hydrophobic methacrylate monomer.

11. The formulation according to claim 9, wherein the non-siloxane hydrophobic monomer comprises, or isobornyl methacrylate, or a combination of, hydroxybutyl methacrylate and isobornyl methacrylate, or is composed thereof.

12. The formulation according to claim 9, wherein at least 5% (wt / wt) is a non-siloxane hydrophobic monomer.

13. The formulation according to claim 1 or 2, comprising 0.2% to 2.0% (wt / wt) of TPP.

14. The formulation according to claim 1, comprising: a1. A difunctional (meth)acrylate siloxane having a molecular weight of at least 8,000 Daltons, in an amount of 20 to 40% (wt / wt); a2. A monofunctional siloxane containing (meth)acrylate with a molecular weight of less than 3000 Daltons, in an amount of 10 to 30% (wt / wt); b. N-methyl-N-vinylacetamide, in an amount of 37 to 50% (wt / wt); c. At least 0.2% (wt / wt) TPP; and d. At least 5% (wt / wt) of hydroxybutyl methacrylate, isoborneol methacrylate, or a combination of hydroxybutyl methacrylate and isoborneol methacrylate.

15. The formulation according to claim 1 or 2, wherein the polymerizable siloxane component comprises a difunctional (meth)acrylate-containing siloxane monomer represented by formula (III), (III) Where R1 is selected from hydrogen or methyl; R2 is selected from hydrogen or C 1-4 Hydrocarbon group; m represents an integer from 0 to 10; n represents an integer from 4 to 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 unit includes random configuration.

16. The formulation according to claim 1 or 2, wherein the polymerizable siloxane component comprises a monofunctional methacrylate-containing siloxane monomer represented by formula (II), (II) Where n is an integer from 10 to 15.

17. A hydrogel or silicone hydrogel contact lens obtained by polymerizing a formulation according to any of the preceding claims.

18. Use of a TPP in improving the surface properties of contact lenses prepared from a formulation, said formulation comprising: a. At least 40% (wt / wt) of a polymerizable siloxane component having polymerizable siloxane contents, wherein at least 50% (wt / wt) of the polymerizable siloxane contents are difunctional siloxanes having a molecular weight of at least 5,000 Daltons, and wherein at least 20% (wt / wt) of the polymerizable siloxane contents are monofunctional siloxanes having a molecular weight of less than 3,000 Daltons; and b. At least 30% (wt / wt) of hydrophilic N-vinylamide monomer.

19. The use according to claim 18, wherein the formulation is further defined as in any one of claims 2 to 16.

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