Contact lenses and contact lens formulations with reduced corrugation

Abstract

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

Description

Technical Field

[0001] The present invention relates to a polymerizable formulation comprising triphenylphosphine for use in the manufacture of contact lenses, and contact lenses incorporating a polymer matrix formed from the polymerizable formulation. In particular, the present invention relates to polymerizable formulations that have been found to impart advantageous properties (such as reduced surface waviness) to hydrogel contact lenses. Background Art

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

[0003] There remains a need to reduce surface waviness of silicone hydrogel contact lenses while maintaining favorable lens properties. Summary of the invention

[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, especially 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) triphenylphosphine (TPP).

[0008] In addition, 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.

[0009] It has been discovered 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, particularly at least 8,000 Daltons, and (b.) at least 30% (wt / wt) of a hydrophilic N-vinylamide monomer, the resulting formulation is resistant to surface waviness, yet the formulation maintains favorable lens properties, such as high water content, low contact angle, and high oxygen permeability (Dk), compared to a similar formulation not comprising TPP.

[0010] In a second aspect, the present invention provides a silicone hydrogel contact lens formed by polymerizing the formulation of the first aspect of the present invention. Thus, the polymer lens material of the silicone hydrogel contact lens of the second aspect of the present invention comprises the polymer product of polymerizing the formulation, 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) triphenylphosphine (TPP).

[0014] In a third aspect, the present invention provides a use of TPP in improving 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-vinylamide monomer.

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

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

[0019] It has been found that the formulations of the present invention reduce the amount of surface waviness present on cast-molded contact lenses compared to lenses cast from otherwise identical polymerizable formulations lacking TPP. The reduction in surface waviness 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 to the polymerizable formulation from which the lenses are formed does not deleteriously affect the properties of the resulting cast-molded lenses, such as water content, contact angle, and oxygen permeability (Dk), compared to those lenses cast from polymerizable formulations lacking TPP. DETAILED DESCRIPTION

[0020] The invention will be more fully understood and other advantages will become apparent when reference is made to the following detailed description of embodiments of the invention. The invention will be described in detail with further particular reference to the formulation of the first aspect of the invention (hereinafter referred to as the "formulation of the invention"). However, it should be understood that since the contact lens of the second aspect of the invention (hereinafter referred to as the "contact lens of the invention") can be obtained by polymerizing the formulation of the first aspect of the invention and therefore, the ingredients of the formulation of the first aspect of the invention will be present in polymerized form in the polymer lens material of the contact lens of the second aspect of the invention. Similarly, contact lenses that have been found to benefit particularly from the use of TPP according to the third aspect of the invention in improving surface properties are those having the features described herein for the lens of the second aspect of the invention and / or those obtained by polymerizing the formulation having the features described herein for the formulation of the first aspect of the invention. Therefore, the ingredients of the formulation of the first aspect of the invention will be present in polymerized form in the polymer lens material of the contact lens in which TPP is used according to the third aspect of the invention. The features of the formulation or lens or its components mentioned herein, or the features of using TPP (depending on the context) can be combined with any combination of the features described previously or subsequently, unless a particular combination of features is mutually exclusive, or if the context indicates otherwise. In addition, 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 dictates 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.

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

[0022] The present invention is based on the further discovery that when at least 0.10% (wt / wt) TPP is included in a polymerizable formulation for producing contact lenses, contact lenses and corresponding formulations that are both resistant to surface waviness and have advantageous lens properties can be provided. It has been found that otherwise comparable formulations that do not contain TPP can exhibit surface waviness. Surface waviness is an undesirable property of contact lenses because surface waviness can cause discomfort to the wearer. In addition, surface waviness can reduce the optical properties of the contact lenses. Therefore, formulations with little or no surface waviness are advantageous. It has been found that by having a high viscosity, such as greater than 250 mm at 25°C, the surface waviness can be reduced. 2 / s viscosity, for example, higher than 300 mm at 25°C 2 Contact lenses formed from formulations having a viscosity of 100 to 200 daltons or less are particularly susceptible to surface waviness. Similarly, it has been found that contact lenses formed from formulations containing a high proportion of high molecular weight siloxane components, such as formulations in which at least 40% (wt / wt) is a polymerizable siloxane component (where 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) are particularly susceptible to surface waviness. It has been found that contact lenses formed from formulations containing a large proportion of high molecular weight siloxane components (e.g., greater than 20% by weight, based on the weight of the polymerizable formulation, of a difunctional siloxane having a molecular weight of 300 mm at 25°C) are particularly susceptible to surface waviness. 2 / s or more) can result in a relatively high viscosity at 25°C, for example, 250 mm 2 The invention relates to an overall formulation having a viscosity of 100 Å / s or greater. It has been found that the inclusion of TPP in such a formulation is effective in preventing or reducing surface waviness. The polymerizable components of the formulation of the invention are typically incorporated into the contact lenses of the invention.

[0023] References herein to ingredients or amounts of components present in a formulation expressed as a weight percentage, i.e., % (wt / wt), are based on the amounts of all formulation ingredients, excluding diluents and / or solvents that are not incorporated into the polymer 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 siloxane component, 30 parts of a hydrophilic N-vinylamide monomer, 4.5 parts of other active ingredients (e.g., polymerization initiator, colorant, oxygen scavenger, etc.), and 25 parts of an organic solvent and / or water (100 parts total) 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 comprises 20% (wt / wt) of a first siloxane monomer and 25% of a second siloxane monomer and no other siloxanes, the formulation may be described as comprising 45% (wt / wt) of a siloxane component.

[0024] The polymerizable formulation of the present invention includes triphenylphosphine (TPP; CAS No. 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 silicone hydrogel contact lens formulation of the present invention comprises at least 0.10% (wt / wt) TPP. The TPP may be present in the polymerizable formulation in an amount of at least 0.15% (wt / wt), such as at least 0.20%, and especially at least 0.25%. For example, TPP may be present in the polymerizable formulation in an amount of about 0.15% (wt / wt) to about 2.0% (wt / wt), such as 0.20% (wt / wt) to 1.0% (wt / wt), typically in an amount of about 0.25% (wt / wt) to about 1.0% (wt / wt).

[0027] The contact lens formulation of the present invention is a silicone hydrogel contact lens formulation comprising:

[0028] 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

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

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

[0031] "Silicone hydrogel" refers to a crosslinked polymer material having a three-dimensional polymer network (i.e., a polymer matrix) that is insoluble in water but contains at least 10% by weight of water in its polymer matrix when fully hydrated. "Silicone hydrogel" is obtained by polymerization of a polymerizable composition comprising at least one silicone-containing component (usually at least one silicone-containing monomer or at least one silicone-containing prepolymer or at least one crosslinkable silicone-containing prepolymer).

[0032] The polymerizable contact lens formulation of the first aspect of the present invention is suitable for forming a silicone hydrogel contact lens. Polymerizable formulations suitable for preparing silicone hydrogel contact lens bodies are well known in the art. In addition to TPP, polymerizable siloxane components and hydrophilic N-vinylamide monomers, the silicone hydrogel contact lens formulation of the first aspect of the present invention may include other components suitable for forming a contact lens body. The polymerizable formulation typically includes a crosslinking agent and a polymerization initiator. The polymerizable formulation may include additional polymerizable monomers, oligomers and / or prepolymers.

[0033] Typically, silicone hydrogel contact lenses are formed via a free radical propagation reaction involving the polymerization of terminal ethylenically unsaturated groups (also referred to herein as "polymerizable groups"). Exemplary polymerizable groups include (meth)acrylates, (meth)acrylamides, allyls, and vinyls and styrenes. As used herein, a "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. The reactivity of the 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 methacrylamide and / or acrylamide. The term "(meth)acrylate" refers to methacrylate and / or acrylate. The term "terminal (meth)acrylate" refers to a (meth)acrylate group at one of the two ends of the main chain (main chain / backbone) of an organic compound. "N-vinylamide monomer" refers to 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, whether the same or different, to form larger polymer or copolymer chains or three-dimensional matrices in a polymerization process. Monomers having two or more polymerizable groups may be referred to as "crosslinkers," 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 silanes; therefore, unless otherwise indicated, there are no size constraints (i.e., maximum molecular weight) for monomers. The term "polymer" refers to a material formed by polymerizing and / or crosslinking one or more monomers.

[0035] 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 measured, for example, by GPC using polystyrene standards or by 1 H NMR end group analysis. An "oligomer" is a compound composed of 2 to 10 repeating units that may be derived actually or conceptually from a monomer. A prepolymer is a partially polymerized polymer comprising a plurality of monomer units, usually 10 or more, which react to an intermediate molecular mass state that retains the ability to continue to react to fully cure to a higher molecular mass polymer material.

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

[0037] 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 visually using the standard shake flask method.

[0038] 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), especially at least 37% (wt / wt). The formulation may additionally comprise other hydrophilic monomers, such as hydrophilic vinyl ether-containing monomers. The total amount of hydrophilic monomers in the formulation of the first aspect of the invention is typically not greater than 55% (wt / wt), such as not greater than 50% (wt / wt).

[0039] In some examples, the hydrophilic N-vinylamide-containing monomer can be selected from N-vinyl-N-methylacetamide (VMA), or N-vinylpyrrolidone (NVP), or N-vinylformamide, or N-vinylacetamide, or N-vinyl-N-ethylacetamide, or N-vinylisopropylamide, or N-vinylcaprolactam, or N-vinyl-N-ethylformamide, or any combination thereof. In some examples, the hydrophilic 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 may 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-vinyl amide-containing monomer and the hydrophilic vinyl ether-containing monomer, one or more vinyl-containing monomers may be included in the inventive polymerizable formulations described herein. For example, in addition to the N-vinyl amide-containing monomer and the vinyl ether-containing monomer, a vinyl monomer having a vinyl ester or allyl ester polymerizable group may be included in the inventive formulation. The hydrophilic monomer may 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 formulation of the first aspect of the present invention comprises at least 30% (wt / wt), especially at least 35% (wt / wt) of at least one N-vinylamide hydrophilic monomer. The formulation of the first aspect of the present invention generally comprises no more than 55% (wt / wt) of N-vinylamide hydrophilic monomer, such as less than 50% (wt / wt) of N-vinylamide hydrophilic monomer. The formulation of the first aspect of the present invention may comprise 35 to 55%, especially 37 to 50% of N-vinylamide hydrophilic monomer. The formulation of the first aspect of the present invention may comprise 30 to 55%, such as 35 to 50%, especially 37 to 50% of N-methyl N-vinylacetamide.

[0041] In the case where more than one hydrophilic monomer is included in the formulation of the present invention, it is advantageous that at least 70% or 80% by weight of the hydrophilic monomer has a solubility in water of ≥20%. In a specific 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 formulations of the present invention may optionally comprise a hydrophobic monomer lacking a siloxane group.The term "hydrophobic monomer" as used herein refers to a monomer lacking a siloxane group and being less than 5% soluble in water at 20°C as determined using a standard shake flask method.

[0043] Hydrophobic monomers can be hydrophobic monomers containing (meth) acrylate groups. As used herein, "hydrophobic acrylate-containing monomers" are any non-siloxane monomers (e.g., methyl methacrylate, acrylamide, etc.) with a single polymerizable acrylate group. In a specific 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, tert-butyl methacrylate (tBMA), methacrylate perfluorohexylethylthiocarbonylaminoethyl ester, methacrylate isobornyl (IBM), methacrylate trifluoroethyl, methacrylate hexafluoroisopropyl, methacrylate hexafluorobutyl, methacrylate 2-hydroxybutyl (HOB), methacrylate 2-hydroxypropyl (HPMA) and ethylene glycol methyl ether methacrylate (EGMA). Advantageous non-silicone hydrophobic monomers include hydroxybutyl methacrylate, isobornyl methacrylate, or a combination of hydroxybutyl methacrylate and isobornyl methacrylate.Silicone hydrogel contact lens formulations may 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 monomer lacking a siloxane group is not limited to a (meth)acrylate-containing monomer and may include a vinyl or other ethylenically unsaturated reactive group. Other examples of hydrophobic monomers include vinyl acetate, vinyl propionate, vinyl butyrate, styrene, chloroprene, vinyl chloride, vinylidene chloride, acrylonitrile, and methacrylonitrile.

[0045] The polymerizable formulation may include 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. 2 to 20% (wt / wt), especially 5 to 15% (wt / wt) of the formulation may be hydroxybutyl methacrylate, isobornyl methacrylate, or a combination of hydroxybutyl methacrylate and isobornyl methacrylate.

[0046] "Siloxane monomer" as used herein refers to a monomer having at least one siloxane group. The siloxane monomer may contain a terminal acrylate group or a methacrylate group. The (meth)acrylate-containing siloxane monomers that can be used in the formulations of the present invention described herein are well known in the art. The siloxane monomers may include monofunctional (meth)acrylate-containing siloxanes, difunctional (meth)acrylate-containing siloxanes, or a combination of monofunctional and difunctional (meth)acrylate-containing siloxane monomers. In examples where the (meth)acrylate-containing siloxane monomer consists of one or more monofunctional (meth)acrylate-containing siloxane monomers (i.e., it does not contain any multifunctional (meth)acrylate-containing siloxane monomers), the polymerizable formulation will typically also include a (meth)acrylate-containing crosslinking agent described further below. In a specific example, the (meth)acrylate-containing siloxane monomer has one or more polymerizable methacrylate groups. Various non-limiting examples of suitable acrylate-containing siloxane monomers include 3-[tris(trimethylsiloxy)silyl]propyl methacrylate ("TRIS"), 3-methacryloyloxy-2-hydroxypropyloxy)propyl bis(trimethylsiloxy)methylsilane ("SiGMA"), methylbis(trimethylsiloxy)silylpropyl glyceryl methacrylate ("SiGEMA"), and monomethacryloyloxypropyl functional polydimethylsiloxanes such as MCR-M07 and MCS-M11, all available from Gelest (Morrisville, PA, USA).

[0047] The silicone hydrogel contact lens formulations of the present invention comprise a polymerizable siloxane component in an amount of at least 40% (wt / wt), such as at least 42% (wt / wt), and especially at least 45% (wt / wt). The polymerizable siloxane component typically accounts for no more than 60% (wt / wt) of the formulation, such as no more than 55% (wt / wt) of the formulation.

[0048] The silicone hydrogel contact lens formulation may 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 silicone content may be a monofunctional siloxane having a molecular weight of less than 3000 Daltons. At least 20% (wt / wt) of the silicone content is a monofunctional having a molecular weight of less than 3000 Daltons. The formulation may include between 10% and 30% by weight of a monofunctional siloxane monomer, for example between 10% and 30% by weight of a 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.

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

[0050]

[0051] 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 In another specific example, the acrylate-containing siloxane monomer is represented by Formula I, wherein R 1 is butyl, R 2 is hydrogen, R 3 is methyl, m is 4, and n is 1. Methods for preparing siloxane monomers represented by formula (I) are described in US Publication No. 2009 / 0299022, which is incorporated herein by reference.

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

[0053]

[0054] wherein n is an integer from about 10 to 25, especially from 10 to 20. Siloxane monomers of Formula II and other suitable monomers are described in US Pat. Nos. 6,867,245 and 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-decamethylpentasiloxane-1-yl)propoxy]ethyl 2-acrylate X-22-1622 / KF-1622 (available from Shin-Etsu Chemical Co., Ltd., Tokyo, Japan) (CAS No. 1052075-57-6), methacryloxypropyl-terminated poly(dimethyl)siloxane FMM (Shin-Etsu Silicones, America, Akron, Ohio, USA) (CAS No. 697234-76-7), and 3-methacryloxy-2-hydroxypropyloxypropylbis(trimethylsiloxy)methylsilane SiGMA.

[0056]

[0057] The silicone hydrogel contact lens formulation comprises at least one difunctional siloxane having a molecular weight of at least 5,000 Daltons, such as at least 6,500 Daltons, and especially at least 8,000 Daltons. The difunctional siloxane may comprise a difunctional (meth)acrylate-containing siloxane monomer, especially a difunctional (meth)acrylate-containing siloxane having a molecular weight of at least 5,000 Daltons, such as at least 6,500 Daltons, and especially at least 8,000 Daltons or consist thereof. 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, and especially a molecular weight of less than 15,000 Daltons. It has been found that the inclusion of siloxanes having a higher molecular weight can result in formulations having unacceptably high viscosities. The silicone hydrogel contact lens formulation may 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, and 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 silicone 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 silicone content may 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 silicone content is a difunctional silicone having a molecular weight of at least 8,000 Daltons, especially a difunctional (meth)acrylate-containing silicone. The formulation may comprise between 20% (wt / wt) and 45% (wt / wt) of difunctional silicone, for example between 20% (wt / wt) and 40% (wt / wt) of difunctional silicone, especially a difunctional (meth)acrylate-containing silicone. The formulation may comprise between 20% (wt / wt) and 45% (wt / wt) of difunctional silicone having a molecular weight of at least 5,000 Daltons, especially a difunctional (meth)acrylate-containing silicone, for example between 20% (wt / wt) and 40% (wt / wt) of difunctional silicone having a molecular weight of at least 5,000 Daltons, especially a difunctional (meth)acrylate-containing silicone.The formulation may comprise between 15% (wt / wt) and 45% (wt / wt) of a difunctional siloxane having a molecular weight of at least 8,000 Daltons, in particular a difunctional (meth)acrylate-containing siloxane, for example between 20% (wt / wt) and 45% (wt / wt) or between 20% (wt / wt) and 40% (wt / wt) of a difunctional siloxane having a molecular weight of at least 8,000 Daltons, in particular a difunctional (meth)acrylate-containing siloxane. 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), in particular at least 25% (wt / wt) of a siloxane having a molecular weight of at least 5,000 Daltons, in particular at least 8,000 Daltons.

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

[0059]

[0060] 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 more; 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.

[0061] For example, difunctional siloxane monomer M5A is represented by formula (III) wherein R1 is methyl, R2 is methyl, m is 0, n is about 7, a is about 75, and b is about 10. M5A has a molecular weight between 8,000 and 11,000 Daltons.

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

[0063]

[0064] Where 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 a specific example, the difunctional siloxane monomer is a compound of formula (IV (wherein R 3A methacryloxypropyl terminated polydimethylsiloxane having a Mw of 4500 to 5500 represented by methyl, m is 0, and n is an integer from 40 to 60) is commercially available from Glaister (Morrisville, Pennsylvania, USA) and is referred to by the manufacturer as "DMS-R18". Additional suitable methacryloxypropyl terminated polydimethylsiloxanes include DMS-R22 and DMS-R31, also available from Glaister.

[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 both integers from about 5 to 10, and h is an integer from about 2 to 8. Methods for preparing compounds of formula (V) are described in U.S. Pat. No. 6,867,245, which is incorporated herein by reference. An example of a suitable siloxane monomer represented by formula (V) is (α-ω)-bis(methacryloyloxyethyliminocarboxyethoxy-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, for example, US Pat. No. 7,572,841, US Pat. No. 2006 / 0063852, and US Pat. No. 5,998,498, each of which is incorporated herein by reference).

[0068] In one example, the siloxane monomer may include a combination of a monofunctional (meth)acrylate-containing siloxane monomer and a difunctional (meth)acrylate-containing siloxane monomer. In this example, the monofunctional (meth)acrylate-containing siloxane monomer has a molecular weight of less than 3,000, 2,000, or 1,000 Daltons, and the difunctional acrylate-containing siloxane monomer has a molecular weight of at least 5,000, 6,500, or 8,000 Daltons. In a specific example, the monofunctional (meth)acrylate-containing siloxane monomer has a molecular weight of about 250 to about 1000 Daltons, and the difunctional acrylate-containing siloxane monomer has a molecular weight of about 5,000 to about 16,000 Daltons. In another specific example, the monofunctional (meth)acrylate-containing siloxane monomer has a molecular weight of about 500 to about 1000 Daltons, and the difunctional (meth)acrylate-containing siloxane monomer has a molecular weight of about 5,000 to about 12,000 Daltons.

[0069] The silicone hydrogel contact lens formulations of the present invention typically include one or more polymerization initiators, i.e., the formulations may include an initiator, or may 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 a polymerization reaction that propagates free radicals. Polymerization initiators that may be included in the formulations of the present invention include, for example, azo compounds, or organic peroxides, or both. The initiator may be a photoinitiator that is activated when exposed to actinic radiation (e.g., UV light), or a thermal initiator that is activated when exposed to heat. Initiators that may be present in the polymerizable formulation include, for example, benzoin ethyl ether, or benzyl dimethyl ketal, or α,α-diethoxyacetophenone, or 2,4,6-trimethylbenzoyldiphenylphosphine oxide, or benzoin peroxide, or tert-butyl peroxide, or azobisisobutyronitrile, or azobisdimethylvaleronitrile, or any combination thereof. UV photoinitiators may include, for example, phosphine oxides such as diphenyl (2,4,6-trimethylbenzoyl)phosphine oxide, or benzoin methyl ether, or 1-hydroxycyclohexyl phenyl ketone, or Darocur (available from BASF, Florham Park, NJ, USA), or Irgacur (also available from BASF), or any combination thereof. Advantageously, the polymerization initiator is a thermal initiator. Examples of suitable thermal initiators include 2,2′-azobis-2-methylpropionitrile, abbreviated as “AIBN” (VAZO-64, available from EI 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 EI DuPont). The polymerization initiator or initiator component may be present in the silicone hydrogel contact lens formulation of the present invention in an amount of about 0.1% (wt / wt) to about 1.5% (wt / wt), or about 0.2% (wt / wt) to about 1.0% (wt / wt), especially about 0.2 to about 0.8% (wt / wt). The formulation of the first aspect of the invention is optionally a thermally cured formulation comprising at least one thermal initiator. Thermal or actinic curing methods are well known to those skilled in the art.

[0070] The silicone hydrogel contact lens formulation may further include a crosslinking agent. A crosslinking agent may react with functional groups on two or more polymer chains to bridge one polymer to another polymer. As used herein, a "crosslinking agent" is any compound having a molecular weight of less than about 2000 Daltons, typically less than 700 Daltons, with two or more polymerizable groups. As used herein, an "acrylate-containing crosslinking agent" has at least two polymerizable acrylate groups and no other types of polymerizable groups. A "vinyl-containing crosslinking agent" has at least two polymerizable vinyl groups and no other types of polymerizable groups. The vinyl-containing crosslinking agent and the acrylate-containing crosslinking agent may 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 formulations of the present invention disclosed herein include, but are not limited to, divinyl ether, or 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 cross-linking agent can have two or three polymerizable vinyl groups. When present, the total amount of vinyl-containing cross-linking 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 inventive formulations disclosed herein include, but are not limited to, lower alkanediol di(meth)acrylates, poly(lower alkylene)diol di(meth)acrylates, lower alkylene di(meth)acrylates, trimethylolpropane tri(meth)acrylates, pentaerythritol tetra(meth)acrylates, bisphenol A di(meth)acrylates, methylenebis(meth)acrylamide, and 1,3-bis(3-methacryloxypropyl)tetramethyldisiloxane. In certain examples, the acrylate-containing crosslinking agent is a non-siloxane crosslinking agent. When present, the total amount of acrylate-containing crosslinking agents in the inventive formulations is typically 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, monofunctional polymerizable compounds having a molecular weight greater than 2000 Daltons are not considered crosslinking agents. Therefore, difunctional siloxanes having a molecular weight greater than 2000 Daltons as described herein are not considered crosslinkers.

[0071] The formulation of the present invention may optionally further comprise a chain transfer agent. Chain transfer is a 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, thiol compounds, halogenated carbon compounds or C3-C5 hydrocarbons, such as allyloxyethanol.

[0072] In addition to polymerizable ingredients, the formulations of the present invention may include non-polymerizable ingredients conventionally used in contact lens formulations. Additional ingredients may also be included, such as organic solvent diluents. Non-limiting examples of these and additional ingredients that may be included in the polymerizable formulations are provided in US2007 / 0296914. The formulations of the present invention may include no more than 2% (wt / wt) of non-polymerizable ingredients other than TPP, especially no more than 1% (wt / wt) of non-polymerizable ingredients other than TPP. Specifically, the formulations of the present invention may include no more than 2% (wt / wt) of organic solvent diluents, especially no more than 1% (wt / wt) of organic solvent diluents.

[0073] Advantageously, the inventive formulation comprises a siloxane component present in an amount of at least 40% (wt / wt), wherein at least 50% of the siloxane content is a difunctional siloxane 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 lens of the second aspect of the invention advantageously comprises a polymer lens material derived from the advantageous polymerizable formulation of the first aspect of the invention comprising the above-mentioned monomer and siloxane components.

[0074] The improved formulations in the third aspect of the present invention are advantageously those described above for the formulations of other aspects of the present invention. For example, the improved formulations in the third aspect of the present invention may include any or all of the above-mentioned siloxane components, hydrophilic N-vinyl amide monomers, optional other hydrophilic monomers, optional other hydrophobic monomers, optional crosslinking agents, optional chain transfer agents, and optional free radical initiators. In addition, for example, the improved formulations in the third aspect of the present invention include the siloxane components, hydrophilic N-vinyl amide monomers, optional other hydrophilic monomers, and optional other hydrophobic monomers in the amounts described above for the formulations of the present invention.

[0075] Examples

[0076] The following examples illustrate certain aspects and advantages of the present invention, which should not be construed as being 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-vinylamide monomer (composed of 10.48 wt% N-vinyl N-methylacetamide and 31.44 wt% N-vinylpyrrolidone),

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

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

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

[0084] 9% by weight of hydrophobic monomer (consisting of 9.94% hydroxybutyl methacrylate and 2.09% isobornyl methacrylate),

[0085] 39% by weight of hydrophilic N-vinylamide monomer (N-vinyl N-methylacetamide),

[0086] 49 wt% polymerizable siloxanes, in a 62:38 ratio of 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),

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

[0088] Evaluation of surface waviness

[0089] The severity of the waviness was assessed visually and rated from 0 to 5 using a zonometer or SAG optimec image of the lens using the following scale:

[0090] ●0 – No visible ripples.

[0091] ●1 – Very small, faint ripples.

[0092] ●2–Small ripples.

[0093] ●3 – Medium ripple.

[0094] ●4 – Severe ripples.

[0095] ●5 – Very severe, long and deep waves.

[0096] Surface ripples without TPP

[0097] The following example illustrates the severity of surface waviness that occurs with a formulation in a PP mold, and how this can be mitigated by the inclusion of TPP.

[0098] The severity of surface ripples was studied using polymerizable mixtures combining substrate formulation 1 with silicone content fixed at 46 parts by weight and different silicone ratios between M5A:KF-1622 and M5A:FMM. No TPP was included in the polymerizable mixtures and no further changes were made to the monomer formulations. 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 with increasing loading of M5A, with mixture 6 (containing 75:25 M5A:FMM) exhibiting the most severe surface ripples.

[0099] Table 1.

[0100] mixture Preparation Silicone mixture Ripple 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] Severe moire was also observed in lenses made from Mix 7 (containing 81:19 M3U:FMM). In comparison, Stenfilcon A lenses (containing about 35% (wt / wt) of a silicone content containing 75:25 KF-1622:M5A) and fanfilcon A lenses (containing about 39% (wt / wt) of a silicone content containing 68:32 KF-1622:M5A) made using the same process in a PP mold showed no moire (0).

[0102] Effect of TPP on surface ripples

[0103] The addition of TPP to the monomer formulation enabled contact lens manufacturing without surface waviness. As the TPP loading increased, a decrease in the degree of waviness was observed.

[0104] The addition of TPP to substrate Formulation 2 (having an overall silicone content of 54 parts by weight, consisting of a formulation of 62:38 difunctional:monofunctional siloxane) is shown in Table 2 below.

[0105] Table 2.

[0106] mixture Preparation TPP weight percentage Ripple 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 the ripples decreases with increasing TPP loading. When no TPP was included (Mix 9), the ripples were at their most pronounced. When 0.404% TPP was included (Mix 13), the ripples were mitigated to such an extent that they were no longer visually observable.

[0108] This disclosure mentions certain illustrative examples, which should be understood to be presented by way of example and not by way of limitation. Although exemplary examples are discussed, the foregoing detailed description is intended to be interpreted as covering all modifications, substitutions and equivalents of the examples as may fall within the spirit and scope of the invention as defined by the additional disclosure.

[0109] All references cited herein are hereby incorporated by reference in their entirety to the extent they are not inconsistent with the present invention.

[0110] Other embodiments of the invention will be apparent to those skilled in the art from consideration of the specification and practice of the invention disclosed herein. It is intended that the specification and examples be considered exemplary only, with the true scope and spirit of the invention 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 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; b. at least 30% (wt / wt) of a hydrophilic N-vinyl amide monomer; and c. At least 0.10% (wt / wt) triphenylphosphine (TPP).

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

3. A formulation according to any preceding claim comprising at least 37% (wt / wt) N-vinylamide monomer.

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

5. A formulation according to any preceding claim 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. A formulation according to any preceding claim comprising 20 to 40% (wt / wt) of a difunctional (meth)acrylate-containing siloxane having a molecular weight of at least 8,000 Daltons.

7. A formulation according to any preceding claim wherein from 20 to 50% (wt / wt) of the polymerisable siloxane content is a monofunctional siloxane having a molecular weight of less than 3000 Daltons.

8. A formulation according to any preceding claim comprising 10 to 30% (wt / wt) of a monofunctional (meth)acrylate-containing siloxane having a molecular weight of less than 3000 Daltons.

9. A formulation according to any preceding claim, further comprising: d. Non-silicone hydrophobic monomers, especially hydrophobic methacrylate monomers.

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

11. A formulation according to claim 9 or 10 wherein at least 5% (wt / wt) is non-silicone hydrophobic monomer.

12. A formulation according to any preceding claim comprising TPP in an amount of 0.2% to 2.0% (wt / wt).

13. The formulation according to claim 1, comprising: a1. a difunctional (meth) acrylate-containing 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; and d. At least 5% (wt / wt) of hydroxybutyl methacrylate, isobornyl methacrylate, or a combination of hydroxybutyl methacrylate and isobornyl methacrylate.

14. A formulation according to any preceding claim, wherein the polymerizable silicone component comprises a difunctional (meth)acrylate-containing silicone monomer represented by formula (III), wherein 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 about 15, 25 or 100; a and b represent an integer of 1 or more; 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.

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

16. A hydrogel or silicone hydrogel contact lens obtainable by polymerizing a formulation according to any preceding claim.

17. Use of TPP to improve the surface properties of a contact lens prepared from a 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 molecular weight of at least 5,000 Daltons, and wherein at least 20% (wt / wt) of the polymerizable siloxane content is a monofunctional siloxane having a molecular weight of less than 3000 Daltons; and b. At least 30% (wt / wt) of a hydrophilic N-vinylamide monomer.

18. Use according to claim 17, wherein the formulation is further defined as in any one of claims 2 to 15.

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