TW202509152A - Contact lens formulation and contact lens - Google Patents

Abstract

Silicone hydrogel contact lens formulations are described. The formulations have a silicone component and a silicone-free component. The silicone component includes two or three compounds represented by Formula 1, Formula 2, or Formula 3. The silicone-free component includes a methacrylate component and an N-vinyl amide component. The methacrylate component includes hydroxybutyl methacrylate (HOB) and isobornyl methacrylate (IBM). The N-vinyl amide component includes N-vinyl N-methyl acetamide. When the compounds of Formula 1 and Formula 2 are present in the formulations in a specified ratio to each other, providing the HOB and IBM in specific amounts to achieve the specified ratios results in desirable silicone hydrogel contact lenses. The silicone hydrogel contact lenses are also described.

Description

Contact lens formulations and contact lenses

The present invention relates to novel silicone hydrogel contact lens formulations, and ophthalmic lenses, particularly contact lenses and more particularly silicone hydrogel contact lenses comprising the reaction product of a polymerizable composition.

Silicone hydrogel contact lenses have proven to be an acceptable alternative to hydrogel contact lenses. Contact lens manufacturers are often asked to introduce new contact lenses to meet market needs. Therefore, there is a continuing need to develop new silicone hydrogel contact lenses to address this need.

In developing silicone hydrogel contact lenses, it is difficult to predict whether a novel silicone hydrogel contact lens formulation will result in a clinically acceptable silicone hydrogel contact lens. Achieving a successful fit, acceptable comfort, acceptable handling experience, and acceptable visual improvement is affected by various changes in lens chemistry, lens design, and manufacturing processes. For example, changing the formulation of a silicone hydrogel contact lens can change oxygen permeability, water content, lens surface wettability, and mechanical properties (such as modulus, tensile strength, and elasticity). Therefore, it is unpredictable what combination of chemicals in a formulation will result in the desired lens properties.

The present invention addresses this continuing need. The inventors have discovered that when using specific combinations of certain silicone compounds in silicone hydrogel contact lens formulations, it is necessary to adjust other monomers in the formulation in a previously unknown manner to achieve certain desired contact lens properties. The disclosure herein describes the present invention in more detail.

Applicants have identified that suitable silicone hydrogel contact lens formulations can be formed using a reaction mixture comprising a silicone component and a silicone-free component. The silicone component comprises, and preferably consists essentially of, two compounds, namely, Formula 1: wherein _R1 is selected from hydrogen or methyl; _R2 is selected from hydrogen or _C1-4 alkyl; m represents an integer from 0 to 10; n represents an integer from 4 to 100; a and b represent 1 or more integers; a+b is 20 to 500; b/(a+b) is 0.01 to 0.22, and the configuration of the siloxane unit includes a random configuration; and

Formula 2: Where n is an integer between 10 and 25.

It is critical that the compound of formula 1 and the compound of formula 2 are in a ratio of 50:50 to 77:23 and in a combined amount of 45 to 55% by weight. Preferably, the ratio of the compound of formula 1 and the compound of formula 2 is 53:47 to 77:23.

In certain embodiments, in the compound of Formula 1, R ₁ is selected from hydrogen or methyl; R ₂ is selected from hydrogen or C _1-4 alkyl; m is 0; n represents an integer from 4 to 15; a represents an integer from 50 to 250, and b represents an integer from 5 to 50; and the configuration of the siloxane unit includes a random configuration, wherein the ratio of a:b is 5:1 to 30:1, preferably 10:1 to 20:1.

In another embodiment, the polysilicone component further comprises another polysilicone compound of Formula 3: wherein m represents an integer of 3 to 12, n represents an integer of 1 to 10, ^R1 is selected from an alkyl group having 1 to 4 carbon atoms, ^R2 is a hydrogen atom or a methyl group, and ^R3 is a hydrogen atom or a methyl group.

In some embodiments, in the compound of Formula 3, m is 4, and n is 1, ^R1 is butyl, ^R2 is H, and ^R3 is methyl.

Where the compound of formula 3 is present, it is used in an amount of less than 1% of the total contact lens formulation. In a preferred embodiment of the formulation of the present invention, the polysilicone component consists essentially of formula 1, formula 2 and formula 3.

The combination of the compound of formula 1 and the compound of formula 2 advantageously allows the use of lower amounts of the silicone component while still producing a contact lens with good oxygen permeability. This also allows for high water content, which is beneficial for wettability.

However, when the compounds of Formula 1 and 2 are used to prepare contact lens formulations, even at these lower amounts, the tensile strength and Young's modulus can be high, as seen in Examples 15 to 17 of US8129442.

Applicants have identified that lenses having tensile strengths substantially lower than those seen in formulations containing compounds of Formula 1 and Formula 2 can be prepared by focusing on selecting ratios and/or amounts of specific additional monomers.

The silicone-free component comprises an N-vinyl amide component and a methacrylate component.

The methacrylate component comprises, and in some embodiments consists essentially of or consists of, hydroxybutyl methacrylate (HOB) and isobornyl methacrylate (IBM). It is critical that HOB and IBM are present in an amount of 8.5 to 16 weight percent and that the total amount of IBM is less than 5 weight percent. HOB and IBM are preferably present in the formulation in a ratio of 70:30 to 90:10. Preferably, the weight ratio of HOB to IBM is 85:15 to 90:10, more preferably the ratio is about 88:12.

The N-vinylamide component comprises N-vinyl N-methylacetamide (VMA). In some embodiments, the N-vinylamide component also comprises N-vinylpyrrolidone (NVP). Where the N-vinylamide component comprises NVP and VMA, the ratio of NVP to VMA is preferably 70:30 to 30:70. In preferred embodiments, the N-vinylamide component consists essentially of NVP and VMA and more preferably consists of them. Preferably, the N-vinylamide component is present in an amount of 33 to 37 wt %.

It has been unexpectedly discovered that specific ratios of HOB and IBM, along with the inclusion of VMA and optionally NVP, result in lenses having desirable properties, specifically low tensile strength and low Young's modulus, compared to previous lenses formed using a combination of polysiloxane compounds of Formula 1 and Formula 2.

The N-vinyl amide component consists essentially of, and in some embodiments, consists of, N-vinyl pyrrolidone (NVP) and N-vinyl N-methylacetamide (VMA).

In some embodiments, the total amount of the compound of Formula 2, VMA and HOB is greater than 28 wt %.

In a first particularly preferred embodiment, the contact lens formulation comprises a polysilicone component consisting essentially of Formula 1 and Formula 2, wherein the ratio of Formula 1 to Formula 2 is 53:47 to 57:43. The N-vinylamide component consists essentially of NVP and VMA, wherein the ratio of NVP:VMA is 68:32 to 72:28. The methacrylate component consists essentially of HOB and IBM, wherein the ratio of HOB to IBM is 85:15 to 90:10. Preferably, the polysilicone component is 45 to 55% by weight of the formulation. More preferably, the methacrylate component is 10 to 20% by weight of the formulation. Still more preferably, the N-vinylamide component is 30 to 40% by weight of the formulation.

In a second particularly preferred embodiment, the contact lens formulation comprises a polysilicone component consisting essentially of Formula 1 and Formula 2, wherein the ratio of Formula 1 to Formula 2 is 73:27 to 77:23. The N-vinylamide component consists essentially of NVP and VMA, wherein the ratio of NVP:VMA is 32:68 to 28:72. The methacrylate component consists essentially of HOB and IBM, wherein the ratio of HOB to IBM is 85:15 to 90:10. Preferably, the polysilicone component is 45 to 55% by weight of the formulation. More preferably, the methacrylate component is 10 to 20% by weight of the formulation. Still more preferably, the N-vinylamide component is 30 to 40% by weight of the formulation.

In a third particularly preferred embodiment, the contact lens formulation comprises a polysilicone component consisting essentially of Formula 1, Formula 2 and Formula 3, wherein Formula 3 is present in an amount less than 0.6% by weight of the formulation, wherein the ratio of Formula 1 to Formula 2 is 60:40 to 65:35. The N-vinylamide component consists essentially of VMA. The methacrylate component consists essentially of HOB and IBM, wherein the ratio of HOB to IBM is 75:25 to 80:20. Preferably, the polysilicone component is 45 to 55% by weight of the formulation. More preferably, the methacrylate component is 5 to 15% by weight of the formulation. Still more preferably, the N-vinylamide component is 30 to 40% by weight of the formulation.

Preferably, the formulation further comprises at least one of the following: a photoinitiator, a thermal initiator, a crosslinking monomer, a UV blocker and a colorant.

In another embodiment of the present invention, a silicone hydrogel contact lens is disclosed, which comprises the polymerization product of the formulation of any of the above embodiments.

The silicone hydrogel contact lens may have a tensile strength of 0.4 MPa to 1.0 MPa. The silicone hydrogel contact lens typically has a tensile strength of less than or equal to 1.0 MPa, and preferably less than or equal to 0.9 MPa. The silicone hydrogel contact lens typically has a tensile strength of at least 0.4 MPa, and more preferably at least 0.5 MPa. In at least some preferred embodiments, the silicone hydrogel contact lens has a tensile strength of 0.5 MPa to 0.9 MPa.

The silicone hydrogel contact lens may have a pedestal contact angle of less than 30°, more preferably less than 25°.

The silicone hydrogel contact lens may have an equilibrium water content of 45 to 55% by weight.

The silicone hydrogel contact lens may have an oxygen permeability greater than 100 barrers, preferably greater than 110 barrers, more preferably greater than 120 barrers, and especially 110 to 140 barrers.

The silicone hydrogel contact lens may have a Young's modulus less than or equal to 1.1 MPa, preferably less than or equal to 1.0 MPa. The Young's modulus is preferably at least 0.3 MPa, more preferably at least 0.5 MPa. The preferred range is 0.5 MPa to 0.95 MPa.

The silicone hydrogel contact lens may have a chord diameter of 13.5 to 15.5 mm and a base curve of 7.5 to 9.5 mm. The skilled person will know other suitable chord diameters and base curves.

By using these components in the above amounts, lenses having a good balance of properties and, in particular, suitably low modulus and tensile strength can be produced.

When using a particular selected silicone component, applicants have identified that a balance of silicone-free methacrylate components is important to providing good properties of the resulting lens.

One way to determine if a lens has good properties is to see if it meets the relative methacrylate flexibility product. Applicants have identified that good lenses have values for this product greater than 1.25. Preferably, they have values greater than 2.5 and more preferably greater than 5. Lenses with a product that meets this value show a good balance of physical properties, and in particular have a good degree of flexibility.

The relative methacrylate flexibility product is measured as follows:

(wt% HOB/wt% IBM)*(tensile strength/modulus)

This unitless parameter allows the skilled person to quickly assess whether a lens prepared from the primary monomers identified above will have good properties.

Described herein are silicone hydrogel contact lenses that have good dimensional stability, are ocularly acceptable, and can be manufactured without the use of volatile organic solvents or diluents in the formulation. The silicone hydrogel contact lenses comprise a polymer lens body that is the reaction product of a polymerizable composition or silicone hydrogel contact lens formulation comprising a silicone component and a silicone-free component. The silicone component comprises or consists essentially of two compounds, Formula 1 and Formula 2. It is critical that the compound of Formula 1 and the compound of Formula 2 are present in a ratio of 50:50 to 77:23 and in a combined amount of 45 to 55% by weight.

Reference herein to "at least one" of an ingredient refers to both a) a single ingredient, and b) a combination of two or more ingredients of the same type.

Throughout this disclosure, reference to the "total amount" of a particular component (ie, a combination of two or more ingredients of the same type) in a polymerizable composition refers to the sum of the amounts of all ingredients of the same type.

Unless the context requires otherwise, the following definitions of the quoted terms provided below shall apply herein:

"Monomer" refers to any molecule that can react with other molecules, whether the same or different, to form a polymer or copolymer. Thus, the term includes polymerizable prepolymers and macromonomers, and unless otherwise specified, there is no size limitation on the monomer.

A "silicone monomer" contains at least one Si-O group and is usually "monofunctional" or "multifunctional", meaning that it has one polymerizable group or two or more polymerizable groups, respectively. A "non-silicone monomer" is a monomer that does not contain any Si-O group.

"Silicone component" means the component or portion of the silicone hydrogel contact lens formulation composed of all siloxane monomers.

“Silicone-free components” are components or portions of silicone hydrogel contact lens formulations that are composed of all non-silicone monomers.

The "N-vinylamide component" is a component or portion of the silicone-free component of the silicone hydrogel contact lens formulation that is composed of at least one non-silicone monomer having a vinyl group directly bonded to a nitrogen atom.

A "methacrylate component" is a component or portion of the silicone-free component of a silicone hydrogel contact lens formulation that is composed of at least one non-silicone monomer having a single polymerizable methacrylate group.

A "(meth)acrylate-containing monomer" is any non-silicone monomer having a single polymerizable (meth)acrylate group (e.g., methyl methacrylate, etc.). Siloxane monomers having at least one polymerizable (meth)acrylate group are referred to herein as "(meth)acrylate-containing siloxane monomers." "(Meth)acrylate" covers both methacrylate groups and acrylate groups. In the case of covering only methacrylate or acrylate, it will be explicitly mentioned.

"Consisting of" means that the formulation or composition contains only the listed ingredients, compounds or monomers.

"Consisting essentially of" means that the formulation or composition contains not only the listed compounds or monomers, but may contain other monomers or compounds that fall within the definition of the formulation or composition, such as dimers or polymer impurities. Such additional monomers or compounds may be present in amounts that have no effect on the final lens formulation. Additional monomers or reactive entities may be present in amounts less than 5%, 2%, 1%, 0.5%, or 0.1% based on the total amount of the particular formulation or composition.

A "polymerizable composition" is a composition comprising polymerizable ingredients, wherein the composition has not been subjected to conditions that cause the polymerizable ingredients to polymerize. Thus, the silicone hydrogel contact lens formulations of the present invention are considered to be polymerizable compositions.

In the case of polyorganosiloxane prepolymers and other polydisperse monomers, as used herein, the term "molecular weight" refers to the absolute number average molecular weight Mn (in Dalton/Da or g/mol) of the monomer. The number average molecular weight is typically determined using GPC using polystyrene standards. In addition, the number average molecular weight can be determined by identifying the number average molecular weight on the technical data sheet or specification sheet provided by the chemical supplier to the contact lens manufacturer.

In the present invention, where a value is given for repeated groups in a structural formula (such as Formula 1, Formula 2 or Formula 3), it is an average value. The skilled person will appreciate that complex molecules of this type contain a mixture of components.

As used herein, the term "total formulation" or "total contact lens formulation" refers to all formulation ingredients, excluding diluents and/or solvents that are not incorporated into the final polymer contact lens material. It should be understood that when the weight % of an ingredient of the total formulation is provided, it refers to the weight % of the ingredient based on the total weight of the formulation.

Throughout the present invention, reference to "an example" or "a specific example" or similar phrases is intended to introduce one or more features of a contact lens, a polymerizable composition, or a method of manufacture (depending on the context), unless a particular combination of features is mutually exclusive or if the context dictates otherwise, it can be combined with any combination (i.e., features) of previously described or subsequently described examples.

Throughout this disclosure, when a list of lower ranges and a list of upper ranges are provided, all combinations of the provided ranges are contemplated as if each combination were explicitly listed. Likewise, throughout this disclosure, when a list of values is presented with a modifier preceding the first value, the modifier is intended to implicitly precede each value in the list unless the context dictates otherwise. For example, with respect to the values listed above, it is intended that the modifier "about" implicitly precedes the ratio of 50:50, and the modifier "to about" implicitly precedes the ratio of 80:20.

As used herein, unless otherwise specified, ratios refer to weight ratios. As used herein, a weight ratio refers to the ratio between the weight of a first component and the weight of a second component in a formulation.

Disclosed herein are silicone hydrogel contact lens formulations comprising a silicone component; and a silicone-free component.

The polysilicone component comprises, consists essentially of, or, in some embodiments, consists of, a difunctional (meth)acrylate-containing siloxane monomer and a monofunctional methacrylate-containing siloxane monomer.

The siloxane monomer containing difunctional (meth)acrylate is represented by Formula 1: wherein _R1 is selected from hydrogen or methyl; _R2 is selected from hydrogen or _C1-4 alkyl; m represents an integer from 0 to 10; n represents an integer from 4 to 100; a and b represent 1 or more integers; a+b is 20 to 500; b/(a+b) is 0.01 to 0.22, and the configuration of the siloxane unit includes a random configuration.

The difunctional (meth)acrylate-containing siloxane monomer of Formula 1 may have an average molecular weight Mw of at least 8,000, 10,000, 12,000 or 15,000 Da. The difunctional (meth)acrylate-containing siloxane monomer of Formula 1 may have an average molecular weight Mw of less than 25,000, 20,000, 12,000, 11,000, 10,000 or 9,000 Da. Preferably, the difunctional (meth)acrylate-containing siloxane monomer has an average molecular weight Mw of 8,000 to 20,000 Da. In a preferred embodiment, the difunctional (meth)acrylate-containing siloxane monomer of Formula 1 has an average molecular weight Mw of 8,000 to 11,000 Da. In another preferred embodiment, the difunctional (meth)acrylate-containing siloxane monomer of Formula 1 has an average molecular weight Mw of 15,000 to 20,000 Da.

In certain embodiments, in the compound of Formula 1, R ₁ is selected from hydrogen or methyl; R ₂ is selected from hydrogen or C _1-4 alkyl; m is 0; n represents an integer from 4 to 15; a represents an integer from 50 to 250, and b represents an integer from 5 to 50; and the configuration of the siloxane unit includes a random configuration, wherein the ratio of a:b is 5:1 to 30:1, preferably 10:1 to 20:1.

Preferably, _R1 is methyl. Preferably, _R2 is H or methyl, and more preferably methyl. Also preferably, m is 0. Preferably, n is 6 to 9.

In a preferred embodiment, a is 60 to 100, more preferably 70 to 80, and b is 4 to 8, more preferably 5 to 8. More preferably, _R1 is methyl, _R2 is methyl, m is 0 and n is 7 to 8.

A particularly preferred difunctional (meth)acrylate-containing siloxane monomer has a CAS registration number of 1216820-69-7.

In another preferred embodiment, a is 140 to 220, more preferably 150 to 200, and b is 8 to 15, more preferably 9 to 13. Further preferably, _R1 is methyl, _R2 is methyl, m is 0 and n is 7 to 8.

Methods for preparing compounds of Formula 1 are described in U.S. Patent No. 8,129,442 (which is incorporated herein by reference).

The siloxane monomer containing monofunctional methacrylate is represented by Formula 2: Wherein n is an integer between 10 and 25, preferably between 13 and 18.

The monofunctional methacrylate-containing siloxane monomer of Formula 2 has an average molecular weight of less than 2,000, preferably less than 1,800 Da, and greater than 800, preferably greater than 1,000 Da. In another specific example, the monofunctional methacrylate-containing siloxane monomer may have an average molecular weight of 1,000 to 1,800 Da.

Preferably, the monofunctional methacrylate-containing siloxane monomer has a CAS registration number of 697234-76-7.

Siloxane monomers of Formula 2 are described in U.S. Patent No. 6,310,169 (which is incorporated herein by reference).

The weight ratio of the compound of formula 1 and the compound of formula 2 is 50:50 to 77:23. In a preferred embodiment, the weight ratio of the compound of formula 1 to the compound of formula 2 is 53:47 to 77:23. In some specific embodiments, the weight ratio is 52:48 to 58:42. In some specific embodiments, the weight ratio is 60:40 to 65:35. In some specific embodiments, the weight ratio is 70:30 to 77:23. In some specific embodiments, the weight ratio is about 55:45, about 63:37 or about 75:25.

The compound of formula 1 and the compound of formula 2 are used in a combined amount of 45 to 55 weight %.

In another embodiment, the polysilicone component comprises an additional polysilicone compound, which is a siloxane monomer containing a monofunctional (meth)acrylate of Formula 3: wherein m of Formula 3 represents an integer of 3 to 12, n represents an integer of 1 to 10, ^R1 is selected from an alkyl group having 1 to 4 carbon atoms, and ^R2 and ^R3 are each independently selected from a hydrogen atom or a methyl group.

In some embodiments, in the compound of formula 3, m is 4, and n is 1. More preferably, ^R1 is butyl, ^R2 is H, and ^R3 is methyl.

Where the compound of formula 3 is present, it is used in an amount of less than 1 wt %, preferably less than 0.8 wt %, and more preferably less than 0.6 wt % of the total contact lens formulation. In a preferred embodiment of the formulation of the present invention, the polysilicone component consists essentially of formula 1, formula 2, and formula 3, preferably consisting thereof.

In some embodiments, the weight % of the polysilicone component is greater than 48%, 48.5%, or 49%. In some embodiments, the weight % of the polysilicone component is less than 53%, 52.5%, 52%, 51.5%, 51%, or 50.5%. In some embodiments, any of the lower limits of the weight % of the polysilicone component is combined with any of the upper limits of the weight % of the polysilicone component. For example, the polysilicone component can be present in the formulation at 48% (wt/wt) to 53% (wt/wt), preferably 48% to 51%.

In another preferred embodiment, preferably, the amount of the compound of Formula 2 is greater than 12% by weight of the total composition. Further preferably, the amount of the compound of Formula 2 is less than 25% by weight. For example, the compound of Formula 2 may be present in the formulation at 12 to 25% (wt/wt).

In another preferred embodiment, preferably, the amount of the compound of Formula 1 is less than 38% by weight. Further preferably, the amount of the compound of Formula 1 is greater than 26% by weight. For example, the compound of Formula 1 may be present in the formulation at 26 to 38% (wt/wt).

Particularly preferably, the amount of the compound of formula 2 is greater than 12 wt % and the amount of the compound of formula 1 is less than 38 wt %.

Furthermore, it is to be understood that the polysilicone component of the formulation of the present invention does not contain hydroxyl-functional siloxane compounds, does not contain TRIS, or does not contain both.

The silicone-free component comprises an N-vinyl amide component (c); and a methacrylate component (d).

The N-vinylamide component comprises N-vinyl N-methylacetamide (VMA). The N-vinylamide component may further comprise N-vinylpyrrolidone (NVP) as appropriate. Further preferably, the N-vinylamide component consists essentially of NVP and VMA, and preferably consists thereof.

In a preferred embodiment, when the N-vinylamide component comprises both NVP and VMA, the ratio of NVP to VMA is 70:30 to 30:70. In some embodiments, the ratio is about 70:30. In some embodiments, the ratio is about 30:70. In another specific example, the polymerizable composition has a weight ratio of the total amount of the N-vinylamide component to the total amount of the (meth)acrylate-containing siloxane monomer (i.e., monofunctional and difunctional (meth)acrylate-containing siloxane monomer) of about 40:60 to 45:55. Further preferably, the ratio is 41:59 to 42:58.

In some embodiments, the weight % of the N-vinylamide component is greater than 34% or 34.5%. In some embodiments, the weight % of the N-vinylamide component is less than 40%, 39%, 37%, 36%, or 35.5%. In some embodiments, any of the lower limits of the weight % of the N-vinylamide component is combined with any of the upper limits of the weight % of the N-vinylamide component. In some embodiments, the weight % of the N-vinylamide component is between 34.5% and 35.5%.

In a preferred embodiment, the N-vinylamide component consists essentially of VMA, and preferably consists of VMA. In another specific example, the polymerizable composition has a weight ratio of the total amount of the N-vinylamide component to the total amount of the (meth)acrylate-containing siloxane monomer (i.e., monofunctional and difunctional (meth)acrylate-containing siloxane monomer) of about 40:60 to 45:55. More preferably, the ratio is 44:56 to 45:55.

Where the N-vinylamide component consists essentially of or consists of VMA, the wt % of the N-vinylamide component is greater than 35% or 38%. The wt % of the N-vinylamide component is less than 40% or 39%. In some embodiments, any of the lower limits for the wt % of the N-vinylamide component is combined with any of the upper limits for the wt % of the N-vinylamide component. In some embodiments, the wt % of the N-vinylamide component is between 38% and 39%.

In another specific embodiment, the total amount of the compound of formula 2 and the N-vinylamide component is at least 47% by weight, preferably at least 50% by weight. The total amount of the compound of formula 2 and the N-vinylamide component is less than 70% by weight, preferably less than 60% by weight.

The methacrylate component comprises hydroxybutyl methacrylate (HOB) and isobornyl methacrylate (IBM). It is critical that HOB and IBM are present in the formulation in an amount of 8.5 to 16 wt % and that the total amount of IBM is less than 5 wt %. Preferably, HOB and IBM are present in the formulation in a ratio of 70:30 to 90:10.

The methacrylate component (d) comprises, and in some embodiments, consists essentially of, and in some embodiments, consists of hydroxybutyl methacrylate (HOB) and isobornyl methacrylate (IBM). In some embodiments, the ratio of HOB to IBM is greater than 60:40, 65:35, 70:30, 75:25, 80:20, 85:15, or 87:13. In some embodiments, the ratio of HOB to IBM is less than 90:10, 89.5:10.5, 89:11, or 88.5:11.5. In some embodiments, any of the lower limits of the ratio of HOB to IBM is combined with any of the upper limits of the ratio of HOB to IBM. In some embodiments, the ratio of HOB to IBM is between 85:15 and 90:10 or is about 88:12. In some embodiments, the hydroxybutyl methacrylate and isobornyl methacrylate are present in the formulation at a weight % greater than 11, 12, or 13 weight %. In some embodiments, hydroxybutyl methacrylate and isobornyl methacrylate are present in the formulation at a weight % less than 16. In some embodiments, any of the lower limits for HOB and IBM are combined with any of the upper limits for HOB and IBM. Preferably, the total amount of HOB and IBM is 13.6 to 16 weight %.

In an alternative embodiment, the weight ratio of HOB to IBM is preferably 75:25 to 80:20, more preferably about 77:23. In this embodiment, the total amount of HOB and IBM is preferably less than 10 wt%.

Other silicone-free methacrylate-containing monomers are known in the art and may be present in contact lens formulations. Exemplary silicone-free methacrylate-containing monomers include methyl methacrylate (MMA), t-butyl methacrylate (tBMA), 2-hydroxyethyl methacrylate (HEMA), ethylene glycol methyl ether methacrylate (EGMA), and combinations thereof. A preferred additional silicone-free methacrylate-containing monomer is methyl methacrylate (MMA).

Preferably, such additional methacrylate-containing monomers are present in a total amount of less than 5% by weight of the contact lens formulation, more preferably less than 3% by weight, still more preferably less than 1% by weight and even more preferably, in the case where the methacrylate component consists essentially of HOB and IBM, in the minimum amount as defined above. Particularly preferably, no other methacrylate-containing monomers are present.

In a specific example, the polymerizable composition may have a weight ratio of the compound of Formula 2 to the total amount of non-silicone methacrylate-containing monomers greater than 0.9:1, preferably greater than 1:1.

In another specific example, the total amount of non-polysilicone and siloxane monomers containing monofunctional methacrylate is greater than 26 wt %, and preferably greater than 30 wt %.

Typically, the formulation further comprises one or more additional components commonly found in contact lens formulations. Suitable additional components include photoinitiators, thermal initiators, crosslinkers, UV blockers and colorants.

The polymerizable composition may further comprise at least one non-siloxane crosslinking agent. As used herein, a "crosslinking agent" is any compound having a molecular weight of less than about 2,000 Da and two or more olefinic unsaturated groups. Thus, a crosslinking agent can react with functional groups on two or more polymer chains in order to bridge one polymer to another. TAIC is particularly preferred as a crosslinking agent in the formulation of the present invention.

The crosslinking agent is preferably used in an amount of 0.03 to 0.2% by weight of the contact lens formulation.

The composition may additionally comprise one or more colorants. Preferred colorants are reactive colorants and in particular colorants identified as "reactive blue" dyes.

The composition may additionally comprise one or more UV blockers.

Contact lenses can be prepared from the polymerizable compositions described herein using curing and other processing methods known in the art (e.g., casting, rotational molding, injection molding, forming polymeric rods that are subsequently turned, etc.). In a specific example, the polymerizable composition is cast between molds formed from a thermoplastic polymer. Thermoplastic polymers are typically non-polar materials such as polypropylene, but polar mold materials such as ethylene vinyl alcohol are also used in the art. Briefly, a first mold member defining the front face of the contact lens (referred to as the "negative mold member") is filled with an amount of the polymerizable composition sufficient to form a single polymer lens body. A second mold member (referred to as a "positive mold member") defining the back side (i.e., the eye contacting side) of the contact lens is coupled to the negative mold member to form a mold assembly having a lens-shaped cavity with the amount of polymerizable composition therebetween.

The polymerizable composition in the contact lens mold assembly is polymerized using any suitable curing method. Typically, the polymerizable composition is exposed to a polymerizing amount of heat or ultraviolet light (UV). In the case of UV curing (also known as photopolymerization), the polymerizable composition typically includes a photoinitiator, such as benzoin methyl ether, 1-hydroxycyclohexyl phenyl ketone, Darocur or Irgacur (available from Ciba Specialty Chemicals). The photopolymerization method for contact lenses is described in U.S. Patent No. 5,760,100 (which is incorporated herein by reference). In the case of heat-curing (also known as thermal curing), the polymerizable composition typically includes a thermal initiator. Exemplary thermal initiators include 2,2′-azobis(2,4-dimethylvaleronitrile) (VAZO-52), 2,2′-azobis(2-methylpropionitrile) (VAZO-64), and 1,1′-azobis(cyanocyclohexane) (VAZO-88). The contact lens mold assembly containing the contact lens formulation is cured by exposing the contact lens mold assembly to heat or UV light for a time ranging from about 1 hour to about 5 hours. Additional thermal polymerization methods for contact lenses are described in U.S. Publication No. 2007/0296914 and U.S. Patent No. 7,854,866, which are incorporated herein by reference.

When curing is complete, the polymer material between the mold members of the mold assembly has the shape of the contact lens, and is referred to herein as the "polymer lens body". The male and female mold members are demolded, i.e., separated, and the polymer lens body is removed from the mold members to which they are attached, i.e., demolded. These processes are each referred to as demolding and demolding, and various such methods are known to those of ordinary skill in the art. In some methods, the demolding and demolding processes may include a single process step, such as when a liquid is used to separate the mold, the liquid also removes the polymer lens body from the mold. In other methods, such as when a dry demolding process is used, the polymer lens body is typically retained on one of the mold members and is demolded in a subsequent process step. Demoling can also be a wet or dry process. In one example, demolding is performed by a "floating" method, in which the mold member with the polymer lens body attached is immersed in water. The water can be heated (e.g., up to about 100° C.) as appropriate. Typically, the polymer lens body floats from the mold member within about 10 minutes. Dry stripping can be performed manually, for example, using tweezers to remove the polymer lens body from the mold member, or it can be removed using an automated robotic process, such as described in U.S. Patent No. 7,811,483, which is incorporated herein by reference. Additional demolding and stripping methods for silicone hydrogel contact lenses are described in U.S. Publication No. 2007/0035049, which is incorporated herein by reference.

After de-lensing, the polymer lens body is washed to remove unreacted or partially reacted components from the polymer lens body and to hydrate the polymer lens body. For example, the contact lens may be exposed to an organic solvent, such as ethanol, isopropyl alcohol, industrial methylated spirits, and the like, or water, or a mixture thereof. Exemplary washing methods are described in U.S. Patent Publication No. 2007/0296914 (which is incorporated herein by reference) and in Example 1 below.

After washing, the hydrated polymer lens body is typically placed in a blister pack, glass vial, or other suitable container (referred to herein as a "package"). A packing solution is also added to the container, which is typically a buffered saline solution, such as a phosphate or borate buffered saline solution. The packing solution may contain additional ingredients, such as comfort agents, hydrophilic polymers, surfactants, or other additives to prevent the lens from sticking to the container, as appropriate. The package is sealed, and the sealed polymer lens body is sterilized by autoclaving. The final product is a sterile, packaged, ocularly acceptable contact lens.

In any of the above examples, the contact lens can be characterized by one or more of the following properties: contact angle, oxygen permeability, tensile strength, Young's modulus, and equilibrium water content, as described in detail below.

In any of the following examples, the contact lens may have a contact angle of less than about 30° or 25°, wherein the contact angle is a static advancing contact angle as determined using a sessile drop method. To determine the contact angle of a contact lens surface, the contact lens to be tested is soaked in phosphate buffered solution (PBS) for at least 12 hours. Using rubber tip tweezers, the lens is removed from the PBS and shaken to remove excess water. A 4 mm diameter segment of each lens is cut using a lens cutter. Blot the surface of the contact lens portion to be tested by placing it face down on a microscope lens wipe and using rubber tip tweezers to gently drag the lens segment through the wipe until no liquid is observed to be absorbed into the wipe. Place the lens segment on a microscope slide, making sure it lies flat with the blotted surface facing up. Take measurements promptly to ensure that the lens segment does not dry out (as evidenced by deformation of the lens segment). In the Krüss DSA-100, open the Drop Shape Analysis program and select the "Sedimentary Drop (VCA eq)" method with the following settings: Camera Tilt = +2; 100 μl syringe with straight needle; Dispensing Solution = Purified Water; Dispensing Volume = 0.75 μl; Dispensing Speed = 7.5 μl/min; and Dispensing Mode = Volume. Place a microscope slide on the sample stage so that the longer side of the lens segment is perpendicular to the camera. Move the syringe to fit the viewing screen and adjust the image until the maximum value is reached in the middle window. Dispense water onto the lens. Capture an image of the droplet between 10 and 15 seconds after dispensing the water. The calculation method was selected based on the contact angle as follows: <30° = circular method, 30° to 130° = tangent method −1; >130° = tangent method −2. The average contact angle measurement of the 5 lens segments was taken as the contact angle for the specific surface (i.e., posterior or anterior) of the contact lens.

For oxygen permeability, the Dk values provided in the following examples were determined using a Rehder 201T oxygen permeability meter/spectral cell according to the polarographic method described in Section 4.4.3 of ISO18369-4:2017.

In any of the following examples, the contact lens may have a Young's modulus (i.e., tensile modulus) of at least 0.3 MPa or 0.5 MPa to 0.95 MPa, 1.0 MPa or 1.1 MPa. In a preferred embodiment, the contact lens has a Young's modulus of 0.3 MPa to 1.1 MPa, and preferably 0.5 to 0.95 MPa.

The contact lens has a tensile strength of less than or equal to 1.0 MPa, preferably less than or equal to 0.9 MPa. The contact lens generally has a tensile strength of at least 0.4 MPa, more preferably at least 0.5 MPa. Preferred embodiments of the contact lens of the present invention have a tensile strength of 0.5 MPa to 0.9 MPa.

The modulus, elongation, and tensile strength values reported herein were determined using an Instron model 3342, 3343, or 5944 mechanical testing system (Instron Corporation, Norwood, Mass., USA) and Bluehill Materials Testing Software using a custom rectangular contact lens cutting die with a 4 mm gap to prepare rectangular sample strips. The modulus was determined in a room with a relative humidity of at least 70%. The lenses were soaked in phosphate buffered solution (PBS) for at least 10 minutes prior to testing. The center strip of the lens was cut using the cutting die while the concave surface of the lens was held facing upward. The thickness of the strip was determined using a calibrated gauge (Rehder Electronic Thickness Gauge, Rehder Development Company, Castro Valley, Calif., USA). Using tweezers, load the strip into the grips of a calibrated Instron apparatus with the strip covering at least 75% of the grip surface of each grip. Run a test method designed to determine the mean and standard deviation of Maximum Load (N), Tensile Strength (MPa), Strain at Maximum Load (% Elongation), and Tensile Modulus (MPa), and record the results.

In any of the above examples, the contact lens may have an equilibrium water content (EWC) of at least about 30 wt%, 40 wt%, or 45 wt%, and up to about 50 wt%, 55 wt%, 60 wt%, or 70 wt%. For example, the contact lens may have an EWC of 40 to 60 wt%. To measure the EWC, excess surface water is wiped off the lens and the lens is weighed to obtain the hydrated weight. The lens is dried in an oven at 105°C and weighed. The weight difference is determined by subtracting the weight of the dry lens from the weight of the hydrated lens. Weight % EWC of the lens = (weight difference/hydrated weight) x 100. In a specific example, the contact angle is ≦30° and the equilibrium water content is optimally at least 45 wt% and up to 55 wt%.

As is apparent from the disclosure of this application as a whole (including the claim scope structure and specific examples), the exemplary components of the polymerizable composition disclosed herein are generally combined in the embodiments of the present invention. For example, those skilled in the art will know that the polymerizable composition of the present invention advantageously includes the exemplary monofunctional (meth)acrylate-containing siloxane monomer disclosed herein in combination with the exemplary difunctional (meth)acrylate-containing siloxane monomer disclosed herein in combination with the exemplary N-vinylamide component disclosed herein in combination with the exemplary (meth)acrylate component disclosed herein.

As demonstrated by the specific examples, it has been found that the combination of the preferred monofunctional methacrylate-containing siloxane monomer, difunctional (meth)acrylate-containing siloxane monomer, N-vinyl amide component and methacrylate-containing monomer of the present invention provides contact lenses of the present invention having advantageous properties, such as reduced tensile strength.

The following examples illustrate certain aspects and advantages of the present invention, which should be understood not to be limited thereto. Table 1 details the reactants used in the examples, Table 2 describes the specific amounts of each component used as a % by weight of the total formulation, Table 3 presents the ratios and totals of the components, and Table 4 presents the properties.

The silicone hydrogel lenses of Examples 1 to 3 and Comparative Example were produced according to the following method.

The compounds or monomers are all mixed and stirred to form a polymerizable composition or silicone hydrogel contact lens formulation.

Pour the formulation into contact lens molds.

The lens is cured using UV light for about 1 hour (Examples 1 and 2 and Comparative Example) or heat for about 5 hours (Example 3). Those skilled in the art are aware of suitable methods for curing contact lens formulations.

The cured polymer is removed from the contact lens mold and washed by contacting it with an organic solvent, water or a combination thereof to remove unreacted materials, and then the washed contact lens is placed in a package and sterilized in an autoclave to obtain a sterilized packaged contact lens. The contact lenses of all Examples and Comparative Examples are transparent and flexible, and also have good wettability. Table 1 Abbreviations Compound Si-1 In the above formula 1, _R1 is a methyl group, _R2 is a methyl group, m is 0, a is 60 to 100, b is 4 to 7, and n is 6 to 8. Si-1a In the above formula 1, _R1 is a methyl group, _R2 is a methyl group, m is 0, a is 120 to 230, b is 6 to 15, and n is 6 to 8. Si-2 In the above formula 2, n is 16. Si-3 In the above formula 3, ^R1 is butyl, ^R2 is hydrogen, and ^R3 is methyl, and n is 1, and m is 5. VMA N-vinyl-N-methylacetamide[CAS No. 3195-78-6] NVP N-Vinylpyrrolidone[CAS No. 88-12-0] HOB Hydroxybutyl methacrylate[CAS No. 29008-35-3] IBM Isobornyl methacrylate [CAS No. 7534-94-3] TAIC Triallyl isocyanurate[CAS No. 1025-15-6] TPP Triphenylphosphine[CAS No. 603-35-0] TPO Diphenyl (2,4,6-trimethylbenzyl) phosphine oxide [CAS No. 75980-60-8] AIBN Azobis(isobutyronitrile)[CAS No. 78-67-1] AOT Sodium bis(2-ethylhexyl)sulfosuccinate (sodium dioctylsulfosuccinate) [CAS No. 577-11-7] AE 2-Allyloxyethanol[CAS No. 111-45-5] Table 2 Example 1 Example 2 Comparison Example 1 Comparison Example 2 Comparison Example 3 Comparison Example 4 Comparison Example 5 Example 3 Element TAIC 0.09 0.09 0.10 0.10 0.10 0.12 0.12 0.05 IBM 1.87 1.65 5.40 5.40 5.40 3.40 1.40 2.08 HOB 13.73 12.07 9.00 9.00 9.00 11.00 9.00 6.92 VMA 10.42 24.70 9.00 7.00 7.00 9.00 9.00 38.72 NVP 24.30 10.58 27.10 27.10 27.10 27.10 27.10 Si-1 26.97 37.76 30.15 Si-1a 39.80 39.80 34.80 37.78 41.78 Si-2 22.07 12.59 9.00 11.00 16.00 11.00 11.00 17.99 Si-3 0.49 AE 0.63 Reactive dyes 0.01 0.01 0.01 TPO 0.09 0.09 0.10 0.10 0.10 0.10 0.10 AIBN 0.45 TPP 0.40 AOT 0.45 0.45 0.50 0.50 0.50 0.50 0.50 UV Blocker 2.12 Total 100.0 100.0 100.0 100.0 100.0 100.0 100.0 100.0 Table 3 US8129442 Example 15 Example 16 Example 17 Example 1 Example 2 Comparison Example 1 Comparison Example 2 Comparison Example 3 Comparison Example 4 Comparison Example 5 Example 3 Total polysilicone(%) 48.82 48.82 48.82 49.04 50.35 48.80 50.80 50.80 48.78 52.78 48.63 Total NVP + VMA (%) 36.17 36.17 36.17 34.72 35.28 36.10 34.10 34.10 36.10 36.10 38.72 Total HOB + IBM (%) 14.47 14.47 14.47 15.60 13.72 14.40 14.40 14.40 14.40 10.40 9.00 Add up Si-2 (Formula 2) + Si-3 + IBM + HOB (%) 23.51 23.51 23.51 37.67 26.31 23.40 25.40 30.40 25.40 21.40 27.48 Add Si-2 (Formula 2) + Si-3 + VMA + NVP (%) 45.21 45.21 45.21 56.79 47.87 45.10 45.10 50.10 47.10 47.10 57.20 Ratio Si-1 (Si-1a):Si-2 (Formula 2) 81:19 81:19 81:19 55:45 75:25 82:18 78:22 69:31 77:23 79:21 63:37 Ratio NVP:VMA 75:25 75:25 75:25 70:30 30:70 75:25 79:21 79:21 75:25 75:25 0:1 RatioHOB:IBM 63:37 63:37 63:37 88:12 88:12 63:37 63:37 63:37 76:24 87:13 77:23 Ratio (NVA+VMA): (Si-1 (Si-1a) + Si-2 + Si-3) 42.6:57.4 42.6:57.4 42.6:57.4 41.5:58.5 41.2:58.8 42.5:57.5 40.2:59.8 40.2:59.8 42.5:57.5 41.5:58.5 44.3:55.7 Ratio Si-2 (Formula 2): (HOB+IBM) 38:62 38:62 38:62 59:41 48:52 38:62 43:57 53:47 43:57 51:49 67:33 Table 4 US8129442 Example 15 Example 16 Example 17 Example 1 Example 2 Comparison Example 1 Comparison Example 2 Comparison Example 3 Comparison Example 4 Comparison Example 5 Example 3 Diameter(mm) 14.23 14.22 14.4 14.26 14.3 14.47 14.44 14.20 Base arc(mm) 8.63 8.67 8.72 8.61 8.76 8.79 8.75 8.60 EWC(%) 44 55 30 47 47 49 48 47 49 49 51 Young's modulus (MPa) 0.76 0.91 0.71 0.74 0.68 0.74 0.85 0.64 Dk(Barriere) 115 90 150 128 140 127 131 124 139 129 Tensile strength(MPa) 3 3 2.8 0.61 0.63 1.02 1.3 0.85 0.85 0.86 0.54 Sessile drop contact angle (°) 44 40 50 20 twenty four 21.1 25.4 27.5 20.0 (wt% HOB/wt% IBM)*(tensile strength/modulus) 9.1 10.6 1.2 0.95 1.3 2.8 6.4 2.8

In Table 3, "(Formula 2)" refers to the general structure of the compound of Formula 2 in this description, and Si-2 is a specific embodiment within Formula 2.

Surprisingly, the specific choice of non-polysiloxane monomers and the ratio of HOB to IBM can lead to such a significant reduction in the tensile strength of the resulting lens. The lenses of the present invention retain other favorable features seen in prior art lenses formed using the same combination of siloxane monomers, such as high Dk and good sessile drop contact angle.

Although the disclosure herein mentions certain illustrative examples, it should be understood that these examples are presented by way of example and not by way of limitation. While exemplary examples are discussed, the above-described embodiments are intended to be interpreted as covering all modifications, alternatives, and equivalents of the examples that may fall within the spirit and scope of the invention as defined by the additional disclosure.

A number of publications and patents have been cited above. The entire text of each of these cited publications and patents is incorporated herein by reference.

Claims (17)

A silicone hydrogel contact lens formulation comprising: (i) a silicone component; and (ii) a silicone-free component, wherein the silicone component comprises: (a) a compound of formula 1 wherein R ₁ is selected from hydrogen or methyl; R ₂ is selected from hydrogen or C _1-4 alkyl; m represents an integer from 0 to 10; n represents an integer from 4 to 100; a and b represent 1 or more integers; a+b is 20 to 500; b/(a+b) is 0.01 to 0.22, and the configuration of the siloxane unit includes a random configuration; and (b) a compound of formula 2 wherein n is 10 to 25, and the compound of formula 1 and the compound of formula 2 are present in the formulation in a ratio of 50:50 to 77:23 and in a combined amount of 45 to 55 wt %; and the silicone-free component comprises an N-vinylamide component (c); and a methacrylate component (d), wherein the N-vinylamide component (c) comprises N-vinyl N-methylacetamide (VMA); and the methacrylate component (d) comprises hydroxybutyl methacrylate (HOB) and isobornyl methacrylate (IBM), wherein the hydroxybutyl methacrylate and isobornyl methacrylate are present in the formulation in an amount of 8.5 to 16 wt % and the total amount of IBM is less than 5 wt %. The formulation of claim 1, wherein the total amount of the compound of formula 2, VMA and HOB is greater than 28 wt %. The formulation of claim 1 or 2, further comprising at least one of the following: a photoinitiator, a thermal initiator, a crosslinking monomer, a UV blocker and a colorant. The formulation of claim 1 or 2, wherein the N-vinylamide component (c) comprises VMA and N-vinylpyrrolidone (NVP). The formulation of claim 1 or 2, wherein the N-vinyl amide component is present in an amount of 33 to 39 wt%. The formulation of claim 1 or 2, wherein the ratio of HOB to IBM is 85:15 to 90:10. The formulation of claim 1 or 2, wherein the ratio of the compound of formula 1 to the compound of formula 2 is 55:45 to 75:25. The formulation of claim 1 or 2, wherein the ratio of HOB to IBM is about 88:12. The formulation of claim 1, wherein: the ratio of Formula 1 to Formula 2 is 53:47 to 57:43; the N-vinyl amide component is essentially composed of NVP and VMA, wherein the ratio of NVP:VMA is 68:32 to 72:28; and the methacrylate component is essentially composed of HOB and IBM, wherein the ratio of HOB to IBM is 85:15 to 90:10. The formulation of claim 1, wherein: the polysilicone component is essentially composed of Formula 1, Formula 2 and Formula 3: wherein m of Formula 3 represents an integer from 3 to 12, n represents an integer from 1 to 10, ^R1 is selected from an alkyl group having 1 to 4 carbon atoms, and ^R2 and ^R3 are each independently selected from a hydrogen atom or a methyl group, wherein Formula 3 is present in an amount less than 0.6% by weight of the formulation; wherein the ratio of Formula 1 to Formula 2 is 60:40 to 65:35; the N-vinyl amide component is essentially composed of VMA; and the methacrylate component is essentially composed of HOB and IBM, wherein the ratio of HOB to IBM is 75:25 to 80:20. A silicone hydrogel contact lens comprising a polymerization reaction product of the formulation of any one of claims 1 to 10. The silicone hydrogel contact lens of claim 11, having a tensile strength of 0.4 MPa to 1 MPa. The silicone hydrogel contact lens of claim 11 or 12, having a pedicle drop contact angle of less than 30°. The silicone hydrogel contact lens of claim 11 or 12, having an equilibrium water content of 45 wt % to 55 wt %. The silicone hydrogel contact lens of claim 11 or 12, having an oxygen permeability of 110 to 140 barrers. The silicone hydrogel contact lens of claim 11 or 12, having a Young’s modulus of 0.3 MPa to 1.1 MPa. A silicone hydrogel contact lens as claimed in claim 11 or 12, having a chord diameter of 13.5 to 15.5 mm and a base curve of 7.5 to 9.5 mm.