Stabilized formulations for contact lenses

Abstract

Batches of a thermally-curable, silicone hydrogel, contact lens formulation having a mass of at least 1 kg and a dynamic viscosity of greater than 15 CP at 25 o c comprising a thermally-activated radi

Description

[001] The present disclosure relates to silicone hydrogel contact lens formulations and silicone hydrogel contact lenses manufactured from such formulations. In particular, the present disclosure relates to the use of a combination in formulations that include both an oxygen scavenger and an oxygen-independent polymerisation inhibitor to improve the stability of such silicone hydrogel contact lens formulations. BACKGROUND

[002] The surfaces of contact lenses are typically smooth and it is desirable to produce lenses that are free from surface imperfections such as rippling which can affect the optical properties of the lenses. Furthermore, for manufacturing ease it is preferable for formulations for the production of contact lenses comprising curable monomer mixtures to be prepared in bulk, stored in batches and piped into the molding stations of contact lens production facilities when needed. As such the monomer mixtures are required to have sufficient stability to polymerisation (“pot-life”) to allow them to be stored before use and to minimise gelation arising from premature polymerization both during storage and during lens manufacture.

[003] Formulations for the preparation of silicone hydrogel contact lenses by UV-initiated radial curing which are highly viscous (e.g. 15 cP or more at 25 °C) and include high levels of siloxane monomer (e.g. 40% (wt / wt) or more, can be cured to prepare lenses with acceptably smooth surfaces. However, it has been found that when such formulations are thermally cured they are prone to producing silicone hydrogel contact lenses with undesirable levels of surface imperfections. Thus, there is a need for thermal curing formulations that do not suffer from surface imperfections. SUMMARY OF THE DISCLOSURE

[004] It has been found that the addition of triphenyl phosphine (TPP) into thermally-curable silicone hydrogel contact lens formulations that include high levels of polymerizable siloxanes together with significant quantities of 7V-vinyl amide monomers can improve the processability of the formulations and reduce the level of lens defects that are introduced during cast molding processes. In particular, the percentage of lenses with undesirable surface rippling has been found to be reduced. Thus, TPP has the potential to serve as a processing aid for thermally-curable contact lens formulations that include high levels of siloxanes.

[005] It has been found that while the addition of TPP may be beneficial when small batches of formulations are prepared on-demand and used immediately, for example on a laboratory scale, difficulties have been encountered when using large batches of TPP-containing formulations in full scale manufacturing facilities. In facilities designed to manufacture large quantities of contact lenses for commercial sale, batches of formulations are typically prepared in bulk, i.e. in quantities of at least 1 kg, are stored in containers and are piped to molding stations via supply lines.

[006] The present inventors have observed that some, but not all, formulations undergoing development that include TPP suffer from premature gelation during storage. For example, it has been found that some formulations that include TPP in combination with certain tinting agents together with certain UV and / or high energy visible light blockers, in particular, do not appear to suffer from either surface rippling or premature gelation.

[007] The present inventors have sought to understand what factors affect whether a silicone hydrogel contact lens formulation produces lenses with undesirable surface ripples and what factors lead to premature gelation of such formulations with the aim of being able to predict whether a formulation will suffer from those problems.

[008] An aim of the present disclosure is to both increase the stability of a batch of silicone hydrogel contact lens formulation for thermal curing that has a dynamic viscosity of greater than 15 cP at 25 °C and the quality and consistency of the lenses produced from such a batch of formulation. The contact lens formulation may, for example, comprise at least 40% (wt / wt) of a polymerizable siloxane component and at least 30% (wt / wt) hydrophilic N-vinyl amide monomer(s).

[009] The present inventors have compared formulations that include TPP with other similar formulations in order to understand what properties of TPP provide the beneficial effect on reducing surface rippling. Those studies have let the inventors to conclude that the oxygen scavenging properties of TPP are an important factor in its ability to prevent surface rippling of thermally-cured lenses. As such the present inventors have concluded that in order to alleviate surface rippling of lenses produced from thermally-curing a viscous silicone hydrogel polymerizable formulation, such as a formulation that comprises greater than 40% (wt / wt) of a polymerizable siloxane component and at least 30% (wt / wt) of hydrophilic N-vinyl amide monomer(s), the formulation should additionally comprise an oxygen scavenger. In particular, each 1 kg of the formulation should include an amount of oxygen scavenger(s) sufficient to provide the formulation with a capacity to react with at least 3 mmol O2 (at 50% RH, 101,000 Pa and 20 °C).

[010] The present inventors have also investigated why some formulations that include TPP gel prematurely whereas others do not. It has been determined that the oxygen scavenger ability of TPP may be reducing the effectiveness of polymerisation inhibitors that are present in batches of commercially available monomers by the monomer manufacturer to inhibit radical-mediated polymerization. Trace amounts of inhibitors, such as hydroquinones, for example, toluhydroquinone (THQ), mono-te / 7-butyl hydroquinone (MTBHQ) and 2,5-di-te / 7-butyl hydroquinone (DTBHQ), and 4-methoxyphenol (MEHQ), are typically incorporated in batches of ethylenically unsaturated monomers, as is described in U.S. Publ. no. 2014 / 0330053 Al. These inhibitors function when oxygen is present, so are facilitated by having an air headspace in containers in which monomers and formulations containing monomer mixtures are stored. Further information on the requirement for oxygen to be present for polymerisation inhibitors to function can be found in: “Inhibition of Free Radical Polymerisation: A Review", I. M. Maafa, Polymers 2023, 15, 488. That document classifies inhibitors into those that are “not effective in the absence of oxygen”, those that are “oxygen-independent” whose activity appears to be independent of the amount of oxygen present, and those which are “effective even in the absence of oxygen” that can function if oxygen is entirely excluded from a formulation. As such the present inventors have concluded that in order to alleviate premature gelation, a polymerizable formulation that has a dynamic viscosity of greater than 15 cP at 25 °C and / or comprises greater than 40% (wt / wt) of a polymerizable siloxane component and at least 30% (wt / wt) of hydrophilic N-vinyl amide monomer(s), each 1 kg of the formulation should include an amount of oxygen scavengers sufficient to provide the formulation with a capacity to react with at least 3 mmol O2 (at 50% RH, 101,000 Pa and 20 °C) and include a polymerization inhibitor that is effective in the absence of oxygen. [OH] In a first aspect, the present disclosure provides a batch of a thermally-curable, silicone hydrogel, contact lens formulation having a mass of at least 1 kg and a dynamic viscosity of greater than 15 cP at 25 °C, comprising: a. a thermally-activated radical polymerization initiator; b. one or more oxygen scavengers; and c. one or more polymerization inhibitors that are effective in the absence of oxygen. The one or more polymerization inhibitors are optionally present in an amount that allows the dynamic viscosity of the formulation to increase by at least 2%, while preventing the formulation from solidifying, when 10 mL of the formulation is stored at 17 °C for 48 hours in a 14 mL sealed container. The oxygen scavenger is optionally present in an amount that provides 1 kg of the formulation with a capacity to react with at least 3 mmol O2 (at 50% RH, 101,000 Pa and 20 °C). The contact lens formulation of the first aspect of the disclosure optionally comprises at least 40% (wt / wt) of a polymerizable siloxane component and at least 30% (wt / wt) of hydrophilic 7V-vinyl amide monomer(s), based on the total weight of the formulation.

[012] It has been found that by including both (b.) an oxygen scavenger and (c.) one or more polymerization inhibitor(s) that are effective in the absence of oxygen in batches of thermally curable silicone hydrogel contact lens formulations having a mass of at least 1 kg and a dynamic viscosity of greater than 15 cP at 25 °C, especially formulations comprising at least 40% (wt / wt) of a polymerizable siloxane component and at least 30% (wt / wt) of hydrophilic N-vinyl amide monomer(s), it is possible to obtain a contact lens formulation which provides lenses with minimal levels of undesirable surface rippling and which formulation is more stable in its pre-polymerised form and less susceptible to gelation than similar compositions that lack a polymerization inhibitor that is effective in the absence of oxygen.

[013] Preferably, the batch of a thermally-curable, silicone hydrogel, contact lens formulation of the first aspect of the disclosure having a mass of at least 1 kg and a dynamic viscosity of greater than 15 cP at 25 °C, comprises: a. a thermally-activated radical polymerization initiator; b. one or more oxygen scavengers, wherein the oxygen scavengers are present in an amount that provides 1 kg of the formulation with a capacity to react with of at least 3 mmol O2 (at 50% RH, 101,000 Pa and 20 °C); and c. one or more polymerization inhibitors that are effective in the absence of oxygen, wherein the one or more polymerization inhibitors are present in an amount that allows the dynamic viscosity of the formulation to increase by at least 2% while preventing the formulation from solidifying, when 10 mL of the formulation is stored at 17 °C for 48 hours in a 14 mL sealed container. The preferred batch of thermally-curable, silicone hydrogel, contact lens formulation of the first aspect of the disclosure optionally comprises at least 40% (wt / wt) of a polymerizable siloxane component and at least 30% (wt / wt) of hydrophilic 7V-vinyl amide monomer(s), based on the total weight of the formulation.

[014] In addition to the components listed above, the silicone hydrogel contact lens formulations of the disclosure typically contain further polymerizable monomers, oligomers and / or pre-polymers, and one or more crosslinkers.

[015] In a second aspect, the disclosure provides a silicone hydrogel contact lens, formed from the polymerisation of the formulation of the first aspect of the disclosure. Thus, the polymeric lens material of the silicone hydrogel contact lens of the second aspect of the disclosure comprises the polymeric product of thermally curing a formulation comprising: a. a thermally-activated radical polymerization initiator; b. one or more oxygen scavengers, wherein the amount of oxygen scavengers advantageously provides 1 kg of the formulation with a capacity to react with at least 3 mmol O2 (at 50% RH, 101,000 Pa and 20 °C); and c. one or more polymerization inhibitors that are effective in the absence of oxygen, wherein the polymerisation inhibitors are advantageously present in an amount that allows the dynamic viscosity of the formulation to increase by at least 2% while preventing the formulation from solidifying, when stored at 17 °C for 48 hours in a sealed container.

[016] The thermally cured composition can be the product of curing a composition having either (i) a dynamic viscosity of greater than 15 cP at 25 °C, or (ii) comprising at least 40% (wt / wt) of a polymerizable siloxane component and at least 30% (wt / wt) of hydrophilic N-vinyl amide monomer(s), or both (i) and (ii).

[017] The silicone hydrogel contact lens of the second aspect of the disclosure is typically a daily disposable lens for use in correcting vision. The silicone hydrogel contact lens of the second aspect of the disclosure typically: (i) has a chord diameter from 13.8 to 14.9 mm, (ii) a base curve from 8.1 to 8.9 mm, and / or (iii) an optical power of from -14.0 diopter to +10.0 diopter.

[018] In a third aspect, the disclosure provides the use of one or more polymerization inhibitors that are effective in the absence of oxygen to stabilise a batch of a thermally-curable contact lens formulation having a mass of at least 1 kg and a dynamic viscosity of greater than 15 cP at 25 °C, comprising an oxygen scavenger, especially an amount of oxygen scavenger sufficient to provide 1 kg of the formulation with a capacity to react with at least 3 mmol O2 (at 50% RH, 101,000 Pa and 20 °C), wherein the one or more polymerisation inhibitors are present in an amount that allows the dynamic viscosity of the formulation to increase by at least 2% while preventing the formulation from solidifying, when 10 mL of the formulation is stored at 17 °C for 48 hours in a 14 mL sealed container.

[019] In a fourth aspect, the disclosure provides the use of a combination of an oxygen scavenger and one or more polymerization inhibitors that are effective in the absence of oxygen, to prepare a thermally-cured silicone hydrogel contact lens with lower levels of undesirable surface rippling compared to lenses prepared from identical formulations that lack the oxygen scavenger. Optionally, an amount of oxygen scavenger sufficient to provide 1 kg of the formulation from which the lens is prepared with a capacity to react with at least 3 mmol O2 (at 50% RH, 101,000 Pa and 20 °C) may be used. The one or more polymerisation inhibitors are optionally used in an amount that allows the dynamic viscosity of the formulation from which the lens is prepared to increase by at least 2% while preventing the formulation from solidifying when 10 mL of the formulation is stored at 17 °C for 48 hours in a 14 mL sealed container.

[020] Formulations of the disclosure have been found to be stable to prepolymerisation gelation for upwards of 1 day, and avoid complete gelation (forming a solid gel) for at least 2 days, preferably for at least 3 days. In comparison, similar formulations containing oxygen scavengers such as TPP without the addition of a polymerization inhibitor that is effective in in the absence of oxygen can show gelation within 1 day, and form a solid gel within 3 days, sometimes within 2 days, or as little as 1 day. DETAILED DESCRIPTION

[021] The present disclosure will be more fully understood and further advantages will become apparent when reference is made to the following detailed description of embodiments of the present disclosure. The disclosure will be described in further detail with particular reference to the formulations of the first aspect of the disclosure, hereinafter referred to as “formulations of the disclosure”. However, it is to be understood that as the contact lenses of the second aspect of the disclosure are obtainable from polymerising the formulations of the first aspect of the disclosure, hereinafter referred to as “contact lenses of the disclosure” and constituents of the formulations of the first aspect of the disclosure will, therefore, be present in polymerised form in the polymeric lens material of the contact lenses of the disclosure. Further, 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.

[022] The present disclosure is based on the discovery that it is possible to provide contact lenses having improved finished lens properties and that have good pot-life due to a reduction in the premature polymerisation of the formulation, by including both an oxygen scavenger and a polymerization inhibitor that is effective in the absence of oxygen in batches of formulations for silicone hydrogel contact lenses, especially in contact lens formulations having a dynamic viscosity of greater than 15 cP at 25 °C and / or comprising at least 40% (wt / wt) of a polymerizable siloxane component, at least 30% (wt / wt) of hydrophilic 7V-vinyl amide monomer(s).

[023] The term “viscosity” refers to dynamic viscosity as measured in a rotational viscometer in units of centipoise (cP), where 1 cP = 0.001 Pascal-second (Pa.s), at a shear rate of 1.32 Newtons and at standard atmospheric pressure. The dynamic viscosity of the formulation may be measured immediately after the formulation is prepared. Viscosity measurements were determined at 25 °C using a Brookfield Viscometer Model DV-I+ with the Small Sample Adaptor (SSA), spindle SC4-18 at a shear rate of 1.32 Newtons at standard atmospheric pressure.

[024] References herein to an amount of an ingredient or component present in a formulation expressed in terms of weight percent (i.e. % (wt / wt)) are based on the amount of all formulation ingredients excluding diluents and / or solvents that are not incorporated into the polymeric lens material of the finished contact lens. 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 can be described as comprising 45% (wt / wt) of a siloxane component. Oxygen Scavengers

[025] The polymerizable formulations of the present disclosure include one or more oxygen scavengers. The oxygen scavengers are advantageously present in an amount that provides 1 kg of the formulation with a capacity of reacting with at least 3 mmol O2 (at 50% RH, 101,000 Pa and 20 °C). The polymerizable formulations of the present disclosure may include an amount of oxygen scavengers sufficient to provide 1 kg of the formulation with a capacity to react with of at least 5 mmol O2, especially at least 10 mmol O2 (at 50% RH, 101,000 Pa and 20 °C). The polymerizable formulations of the present disclosure may include an amount of oxygen scavengers sufficient to provide 1 kg of the formulation with the capacity to react with no more than 100 mmol O2, such as no more than 50 mmol O2 especially no more than 30 mmol O2 (at 50% RH, 101,000 Pa and 20 °C). The polymerizable formulations of the present disclosure may, for example, include an amount of oxygen scavengers sufficient to provide 1 kg of the formulation with a capacity to react with from 3 to 100 mmol O2, such as from 5 to 50 mmol O2 especially from 10 to 30 mmol O2 (at 50% RH, 101,000 Pa and 20 °C). Capacity to react with oxygen is determined by ascertaining the theoretical capacity of the oxygen scavenger to react with a mole of O2. For example, if each mol of scavenger reacts with 0.5 mol O2, then at least 6 mmol of the scavenger needs to be present in 1 kg of the formulation in order to impart the capacity to react with at least 3 mmol O2. If each mol of the oxygen scavenger reacts with 1 mol O2, then 3 mmol of the scavenger needs to be present in 1 kg of the formulation. As most oxygen scavengers react with 0.5 mol O2 per mol of scavenger, the formulation typically comprises at least 6 mmol of oxygen scavenger per kg of formulation.

[026] The polymerizable formulations of the present disclosure may include triphenylphosphine (TPP; CAS #: 603-35-0).

[027] The formulation may optionally comprise TPP in an amount of from 0.1 to 2.0% (wt / wt). Preferably, TPP is present in the polymerizable formulations in an amount of at least 0.15% (wt / wt), especially an amount of at least 0.2% (wt / wt), for example in an amount of from 0.16% (wt / wt) to 2.0% (wt / wt) or an amount of from 0.2% (wt / wt) to 1.5% (wt / wt). When TPP is present in the polymerizable formulations as the sole oxygen scavenger, TPP is advantageously present in an amount of at least 0.16% (wt / wt).

[028] TPP can react with molecular oxygen to form triphenylphosphine oxide (TPPO). Each mole of TPP reacts with 0.5 mol of O2 in the formation of TPPO. It has been found that when TPP is present in the polymerizable formulation as the sole oxygen scavenger, an amount of at least 0.15% (wt / wt) is effective in preventing rippling. The Mw of TPP is 262.292 g / mol and thus a formulation comprising 0.15% (wt / wt) TPP, i.e. 1.5 g / kg, includes 5.72 mmol / kg TPP and is capable of scavenging 2.86 mol of O2. In order for TPP to provide 1 kg of the formulation with a capacity to react with at least 3 mmol O2 (at 50% RH, 101,000 Pa and 20 °C) when TPP is present as the sole oxygen scavenger, at least 6 mmol of TPP needs to be present, i.e. 1.574 g, which is 0.1574% (wt / wt).

[029] Butylated hydroxytoluene (BHT) is an example of an oxygen scavenger that is typically included in contact lens packaging which may also be suitable for inclusion in the polymerizable formulations of the present disclosure. Sodium thiosulphate may also be used as an oxygen scavengers. Polymerisation Inhibitors

[030] The polymerizable formulations of the first aspect of the present disclosure include a polymerization inhibitor that is effective in the absence of oxygen. The polymerization inhibitor that is effective in the absence of oxygen is advantageously present in a batch of formulation in an amount that prevents the formulation from solidifying prior to use, e.g. when being stored in a sealed container or in the lines of a contact lens production facility, while also still enabling complete and rapid curing of the formulation when exposed to thermal curing conditions. It has been found that if an amount of polymerisation inhibitor that is sufficient to entirely prevent increases in viscosity when a contact lens formulation is stored in a sealed container, the formulation can be difficult to fully cure leading to lens defects and / or slow curing to such an extent it is not viable to manufacture contact lenses from the formulation at a commercial scale. Thus, the inclusion of large quantities of polymerization inhibitors is undesirable as they can prevent complete and / or rapid curing of the formulation when required.

[031] The polymerization inhibitor that is effective in the absence of oxygen can be present in the formulations of the disclosure in an amount that prevents 10 mL of the formulation from solidifying when stored at 17 °C for 48 hours in a 14 mL sealed container, preferably in an amount that prevents 10 mL of the formulation from solidifying when stored at 17 °C for 60 hours in a 14 mL sealed container, e.g. a glass vial with a screw cap lid, 58 mm tall and 22.5 mm in internal diameter. A formulation is considered to have solidified when it is immobilised such that when the container is unsealed and inverted, no material leaks out after 10 seconds.

[032] Increases in viscosity over time may be determined by comparing the viscosity of the freshly prepared formulation with the formulation after storage for the specified time period (e.g. 48 hours) under the specified conditions (e.g. storage of a 10 mL sample in a 14 mL sealed vial at 17 °C). The polymerization inhibitor that is effective in the absence of oxygen can be present in the formulations of the disclosure in an amount that results in the dynamic viscosity of 10 mL of the formulation increasing by at least 2% when stored at 17 °C for 48 hours in a 14 mL sealed container, for example, in an amount that results in the dynamic viscosity of 10 mL of the formulation increasing by at least 3% when stored at 17 °C for 48 hours in a 14 mL sealed container.

[033] The % increase can be determined as follows: % increase = [(Vst - Vso) / Vso] * 100 wherein: Vso= Initial viscosity of formulation with polymerisation inhibitor Vst = Viscosity of formulation with polymerisation inhibitor at time t For example, when the viscosity of a formulation increases from 20 to 22 cP over a time period, the % increase is 10%.

[034] The polymerization inhibitor that is effective in the absence of oxygen can be present in the formulations of the disclosure in an amount that results in the dynamic viscosity of 10 mL of the formulation increasing by from 2% to 200% when stored at 17 °C for 48 hours in a 14 mL sealed container, for example, in an amount that results in the dynamic viscosity of 10 mL of the formulation increasing by from 3% to 100% when stored at 17 °C for 48 hours in a 14 mL sealed container.

[035] The effect of a polymerisation inhibitor on the rate of increase in viscosity can be determined by comparing the viscosity of identical samples, one control formulation including no polymerisation inhibitor and another formulation that includes an amount of polymerization inhibitor, at various time points. The control formulation comprising no polymerisation inhibitor includes all other constituents in the same parts by weight (but not therefore the same weight % based on the total weight of the formulation) as in the formulation that includes the polymerisation inhibitor. Advantageously, the formulation includes an amount of polymerisation inhibitor that decreases the rate at which the viscosity of the formulation increases to less than 50%, especially to less than 20% of that of an identical formulation that lacks the polymerisation inhibitor. The % rate of increase can be determined as follows: % rate of increase = [(Vst - Vso) / Vso] / [(Vet - Vco) / Vco] * 100 wherein: Vco = Initial viscosity of control formulation without polymerisation inhibitor Vet = Viscosity of control formulation without polymerisation inhibitor at time t Vso= Initial viscosity of formulation with polymerisation inhibitor Vst = Viscosity of formulation with polymerisation inhibitor at time t For example, if the control formulation without polymerisation inhibitor increases in viscosity from 20 to 30 cP between time 0 and time t, (Vet - Vco) / Vco = 0.5, and the formulation of the disclosure with polymerisation inhibitor increases in viscosity from 20 to 22 cP between time 0 and time t, (Vst - Vso) / Vso = 0.1, then the rate of increase is slowed to 20%.

[036] In the event that the viscosity of the control formulation has increased to a level that cannot be measured at time t, e.g. because the formulation has solidified, then [(Vet - Vco) / Vco] is set to a maximum value of 4 for the purposes of determining the % rate of increase. In the event that the viscosity of the control formulation has increased to a level that cannot be measured at time t, e.g. because the formulation has solidified, then the % rate of increase is considered to be 100%.

[037] Advantageously, the formulation includes an amount of polymerisation inhibitor that decreases the % rate at which the viscosity of the formulation increases to from 1 to 50%, especially from 1.5 to 30%, especially from 2 to 20% of that of an identical formulation that lacks the polymerisation inhibitor, over a 48-hour period when 10 mL of contact lens formulation is stored in a sealed 14 mL container at 17 °C.

[038] The 14 mL container contains 10 mL of contact lens formulation and 4 mL of air. The 14 mL container is a glass vial, 58 mm tall and 22.5 mm in internal diameter with an airtight screw cap lid. The formulations are dispensed into the vials immediately on production with no gas purging of the formulation or the vials.

[039] The polymerisation inhibitor is advantageously a free radical scavenger that does not require the presence of oxygen to function.

[040] Examples of polymerization inhibitors that are known to be effective in in the absence of oxygen include phenothiazine (PTZ), 2,4-dinitrophenol (DNP) and 2,4-dinitro-6-sec-butyl phenol (DNBP). Such known polymerisation inhibitors can be very effective in slowing the rate of polymerisation, and as such very low amounts may be included in the formulations of the present disclosure. It has been found that amounts of no more than 50 ppm, such as no more than 20 ppm or no more than 10 ppm of such inhibitors can be effective, for example amount of from 1 to 20 ppm such as from 2 to 10 ppm.

[041] The polymerisation inhibitor that is effective in the absence of oxygen may be an anthraquinone, a benzophenone or a benzotriazole compound. Preferably the formulation comprises at least one anthraquinone, benzophenone or benzotriazole compound, especially an anthraquinone compound in combination with at least one of a benzophenone or benzotriazole compound.

[042] The present inventors have surprisingly found anthraquinone compounds can be effective polymerisation inhibitors in the absence of oxygen, especially anthraquinone tinting agents. For example it is been found that the tinting agent 1,4-bis[(2-methacryloxyethyl)amino]-9,10-anthraquinone (Reactive Blue 247, RB247; CAS # 109561-07-1; available from Arran Chemical Company of Co. Roscommon, Ireland and also from Pharnorcia Inc. of Edison, New Jersey, USA), referred to herein as “RB247” can function as a polymerization inhibitor that is effective in in the absence of oxygen.

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

[044] It is known to include anthraquinone tinting agents in contact lens formulations as a tinting agent to colour the resulting contact lens, for example to facilitate handling of the lens by making it more visible, to impart an attractive blue tint to a lens and / or to counter an unattractive yellow colouration. However, the present inventors have surprisingly found that anthraquinone tinting agents, especially anthraquinone blue tinting agents may also function to inhibit pre-polymerisation gelation of lens formulations that include oxygen scavengers such as TPP.

[045] The formulations of the disclosure may further comprise 1,4-bis[4-(2- methacryloxyethyl) phenylamino]-9,10-anthraquinone (CAS# 121888-69-5, Reactive Blue 246, RB246 available from Arran Chemical Company of Co. Roscommon, Ireland and from Pharnorcia Inc. of Edison, New Jersey, USA), referred to herein as “RB246”. Although RB246 has been found to be less effective than RB247 in stabilising a polymerizable formulation comprising an oxygen scavenger; RB246 has been found to have a beneficial effect on the stability of such formulations.

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

[047] The present inventors have surprisingly found that benzophenone compounds and benzotriazole can be effective polymerisation inhibitors in the absence of oxygen, especially, benzophenone compounds and benzotriazole compounds that also function as high energy visible light (HEVL) and / or UV blockers. The formulations of the first aspect of the present disclosure can include a benzophenone UV absorbing agent and / or a benzotriazole HEVL absorber, preferably both a benzophenone UV absorbing agent and a benzotriazole HEVL absorber. The formulations of the first aspect of the present disclosure advantageously include a benzophenone UV absorbing agent and / or a benzotriazole HEVL absorber, preferably both a benzophenone UV absorbing agent and a benzotriazole HEVL absorber, in addition to an anthraquinone tinting agent, such as RB247.

[048] The term “UV absorbing agent”, refers to a compound that includes a chromophore that absorbs light in the UV spectrum, i.e. wavelengths in the range of 100-400 nm. In particular, a 0.003 wt% solution of a UV absorbing agent in ethyl acetate has a maximum absorbance (kmax) in the range of 220-350 nm, especially in the range of 250-350 nm. The UV absorbing agent present in the formulation and lenses of the present disclosure advantageously has a maximum absorbance (kmax) in the 250 to 350 nm range between 260 and 320 nm, especially between 270 and 310 nm, as a 0.003 wt% solution in ethyl acetate.

[049] The silicone hydrogel contact lens formulations of the disclosure can comprise a polymerizable UV absorbing agent comprising a benzophenone moiety. Likewise, the polymeric lens material of the silicone hydrogel contact lens of the disclosure can comprise a UV light absorbing unit comprising a benzophenone moiety. The UV light absorbing unit comprising a benzophenone moiety present in the polymeric lens materials of the contact lenses of the disclosure may be derived from the polymerizable UV absorbing agents described herein with reference to the formulations of the disclosure.

[050] Polymerizable UV absorbing agents are advantageously covalently bound to the polymeric matrix of the lens material instead of simply being physically entrapped in the material to prevent the absorbing agents from migrating, phase separating or leaching out of the lens material. Such stability is advantageous because leaching of the UV absorbing agent may present toxicological issues and / or lead to the loss of UV blocking activity of the contact lens. The UV absorbing agents used in the present disclosure are typically soluble in the contact lens formulation and are polymerizable so that they form part of the polymeric matrix of the lens and are retained in the lens during autoclaving and storage. The UV absorbing agent is advantageously a polymerizable UV absorbing agent that includes a reactive group or groups capable of participating in a curing reaction by which the polymer matrix of the polymeric lens material is formed such that the polymerizable UV absorbing agent becomes covalently bound into the polymeric lens material. A polymerizable UV absorbing agent typically includes an ethylenically unsaturated group that can participate in a radical polymerisation reaction, such as a vinyl or a (meth)acrylate, a(meth)acrylamide or a styrene group. Numerous co-polymerizable benzophenone UV absorbing agents are known. Many of these UV absorbing agents contain ethylenically unsaturated polymerizable groups. Copolymerization with other ingredients in the lens materials, typically with a radical initiator, incorporates the UV absorbing agents into the resulting polymer chain. Incorporation of additional functional groups on a UV absorbing agent may influence one or more of the UV absorbing agent’s UV absorbing properties, solubility or reactivity. If the UV absorbing agent does not have sufficient solubility in the remainder of the ophthalmic lens material ingredients or polymeric lens material, the UV absorbing agents may coalesce into domains that could interact with light and result in decreased optical clarity of the lens.

[051] The benzophenone UV absorbing agent can be present in the formulations of the disclosure in an amount of from about 0.05 up to about 5.0% (wt / wt), typically in an amount of from about 0.1% (wt / wt) to about 3.0% (wt / wt), or from about 0.2% (wt / wt) to about 3.0% (wt / wt), such as from 0.3% (wt / wt) to 3.0% (wt / wt).

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

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

[054] The benzophenone UV absorbing agent included in the formulations of the disclosure is favourably not a dual function HEVL absorber and UV absorbing agent. The benzophenone UV absorbing agent may have an absorbance cut off below the visible range, i.e. the benzophenone UV absorbing agent does not absorb significant amounts of light above 380 nm. For example, a 0.003 wt% solution of the benzophenone UV absorbing agent in ethyl acetate does not have an absorbance of at least 0.5 within the range of 375 to 450 nm.

[055] The polymerizable UV absorbing agent is optionally: 2-(4-benzoyl-3- hydroxyphenoxy)ethyl acrylate (UV416; CAS #: 16432-81-8).

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

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

[058] The silicone hydrogel contact lens formulation of the first aspect of the disclosure may comprise a HEVL absorber, such as a benzotriazole HEVL absorber, in addition to an anthraquinone tinting agent, such as RB247.

[059] Advantageously, HEVL absorbers used in contact lens formulations, including the contact lens formulations of the present disclosure, possess a polymerizable moiety, such as vinyl, acrylate or methacrylate functionality in their chemical structure, for covalent incorporation into the contact lens material during polymerization. Once incorporated into a polymeric contact lens material, the HEVL absorber imparts HEVL absorption properties to the polymeric contact lens material. The HEVL absorber used in the present disclosure is typically soluble in the contact lens formulation and is polymerizable so that it forms part of the polymeric matrix of the lens and is retained in the lens during autoclave and storage. The HEVL absorber may include a benzotriazole ring system.

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

[061] Examples of benzotriazole HEVL absorbers include: 2-(1, l-dimethylethyl)-4-[3-[(4-ethenyl phenyl) methoxy]propoxy]-6-(5-methoxy-2H-benzotriazol-2-yl)-phenol (UV1, CAS # 159732-06-6), 2-(5-chloro-2H-benzotriazol-2-yl)-6-(l,l-dimethylethyl)-4-ethenyl-phenol (UV5 / UVAM, CAS # 124883-10-9), 2-[2'-hydroxy-3'- / c / 7-butyl-5’-(3”-methacryloyloxypropoxy)phenyl]-5-methoxy-27 / -benzotriazole (UV13, CAS # 114166-71-1), 2-3'-t-butyl-2'-hydroxy-5'-(3"-dimethylvinylsilylpropoxy)-2'-hydroxy-phenyl)-5-methoxybenzotriazole (UV15, CAS # 122430-79-9), 2-[2'-hydroxy-3'- / c77-butyl-5’-(3”-methacryloyloxypropoxy)phenyl]-5-chloro-2J / -benzotriazole (UV28, CAS # 275371-71-6). All the above HEVL absorbers are available from LYNN Laboratories, Inc. of 2797 Irving Blvd STE 110, Dallas, TX 75207.

[062] Optionally, the total amount of HEVL absorber and UV absorbing agent present in the formulation of the disclosure does not exceed 5% (wt / wt). Optionally the formulation of the disclosure comprises HEVL absorber and UV absorbing agent in a total amount of from 0.2% to 5% (wt / wt), and preferably from 0.4% to 4% (wt / wt).

[063] A compound may function as both a HEVL absorber and a UV absorbing agent. The term “HEVL absorber” as used herein encompasses compounds that function solely as a HEVL absorber and compounds that function as both a HEVL absorber and a UV absorbing agent. The benzophenone UV absorbing agent included in the formulations of the disclosure is favourably not a dual function HEVL absorber and UV absorbing agent. The benzotriazole HEVL absorber included in the formulations of the disclosure may be a dual function HEVL absorber and UV absorbing agent in some embodiments. The UV absorbing agent may have an absorbance cut off below the visible range i.e. does not absorb significant amounts of light above 380 nm. For example, a 0.003 wt% solution of the UV absorbing agent in ethyl acetate does not have an absorbance of at least 0.5 within in the range of 375 to 450 nm. The HEVL absorber present in the formulations of the disclosure has an absorption above 0.5 in the range of 375 to 450 nm as a 0.003 wt% solution in ethyl acetate and may optionally also have a maximum absorbance (kmax) in the range of 220 to 350 nm, especially in the range of 250 to 350 nm.

[064] Formulations of the first aspect of the disclosure that comprise RB247, advantageously further comprise UV416 and a benzotriazole HEVL absorbing agent, especially UV13 or UV28 or both UV13 and UV28. A combination of RB247, UV416 and one or both of UV13 and UV28 has been found to be particularly effective in reducing the gelation of a polymerizable formulation comprising TPP. Polymerizable Formulations

[065] The polymerizable formulations of the present disclosure are formulations suitable for forming a silicone hydrogel contact lens that includes a mixture of polymerizable components. The mixture typically includes both a polymerizable siloxane component and hydrophilic A-vinyl amide monomer(s).

[066] A "silicone hydrogel" refers to a crosslinked polymeric material having a three-dimensional polymer network (i.e., polymer matrix) comprising siloxane units, that is insoluble in water, but contains at least 10 percent by weight of water in its polymer matrix when fully hydrated. A "silicone hydrogel" is obtained by polymerization of a polymerizable composition comprising at least one silicone-containing component, typically at least one silicone-containing monomer or at least one silicone-containing pre-polymer or at least one cross-linkable silicone-containing pre-polymer.

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

[068] A “monomer” is a molecule having one or more polymerizable groups that can react together with other monomers that are the same or different to form a larger polymer or copolymer chain or three-dimensional matrix in a polymerization process. A monomer having two or more polymerizable groups can be referred to as a “cross-linking agent”, as described further below. The term “monomer” encompasses macromonomers and polymerizable oligomers, i.e. a polymerizable molecule that contains one or more chains of repeating units, such as for example polymerizable polysiloxanes; thus there is no sizeconstraint (i.e. maximum molecular weight) of the monomer unless indicated otherwise. The term "polymer" refers a material formed by polymerizing and / or crosslinking one or more monomers.

[069] As used in this application, the term "molecular weight" of a polymeric material, including components comprising multiple siloxane units, refers to the absolute number average molecular weight (in units of daltons), for example determined by GPC using polystyrene standards or by 1H NMR end-group analysis, unless otherwise noted specifically. An “oligomer” is a compound that consists of 2 to 10 repeating units which could be derived, actually or conceptually, from monomers. A pre-polymer is a partially polymerized polymer comprising multiple monomeric units, typically more than 10, reacted to an intermediate-molecular mass state that retains the ability to continue reacting to fully cure into a higher molecular mass polymeric material.

[070] The silicone hydrogel contact lens formulations of the disclosure may include other hydrophilic monomers in addition to N-vinyl amide-containing monomers and may also include hydrophobic monomers.

[071] As used herein, a “hydrophilic monomer” refers to a silicone-free monomer in which at least 50 grams of the monomer are fully soluble in 1 litre of water at 20 °C (i.e., ~ 5% soluble in water) as determined visibly using a standard shake flask method.

[072] The silicone hydrogel contact lens formulation may comprise one or more hydrophilic N-vinyl amide-containing monomer in an amount of at least 30% (wt / wt), such as in an amount of at least 35% (wt / wt), especially in an amount of at least 35% (wt / wt). The formulation may additionally include other hydrophilic monomers such as hydrophilic vinyl ether-containing monomers.

[073] In some examples, the hydrophilic N-vinyl amide-containing monomers can be selected from N-vinyl-N-methyl acetamide (VMA), or N-vinyl pyrrolidone (NVP), or N-vinyl formamide, or N-vinyl acetamide, or N-vinyl-N-ethyl acetamide, or N-vinyl isopropyl ami de, or N-vinyl caprolactam, or N-vinyl-N-ethyl formamide, or any combination thereof. In some examples, the hydrophilic N-vinyl amide-containing monomer consists of VMA or NVP, or a combination of VMA and NVP. The optional vinyl ether-containing monomers can be selected from 1,4-butanediol vinyl ether (BVE), or ethylene glycol vinyl ether (EGVE), or di ethylene glycol vinyl ether (DEGVE), or 1,4-cyclohexanedimethanol vinyl ether (CHDMVE), or a poly(ethylene glycol) vinyl ether having from 4 to 10 ethylene glycol units, or a poly(ethylene glycol) vinyl ether having more than 10 ethylene glycol units, or any combination thereof. In some examples, the vinyl ether-containing monomer can be a poly(ethylene glycol) vinyl ether having at least 1, 2, or 3 ethylene glycol units and up to 4, 6, 8, or 10 ethylene glycol units. One or more vinyl-containing monomers, in addition to the hydrophilic N-vinyl amide-containing monomers and optional hydrophilic vinyl ether-containing monomers, may be included in the formulations of the disclosure described herein. For example, vinyl monomers having a vinyl ester or allyl ester polymerizable group may be included in the formulations of the disclosure in addition to the vinyl amide-containing monomers and vinyl ether-containing monomers. The hydrophilic monomer may be a (meth)acrylate or (meth)acrylamide group-containing hydrophilic monomer, examples of which include 2-hydroxyethyl methacrylate (HEMA), 4-hydroxybutyl acrylate glycerol methacrylate, 2-hydroxyethyl methacrylamide, ethoxyethyl methacrylamide (EOEMA), polyethyleneglycol monomethacrylate, methacrylic acid (MA) and acrylic acid.

[074] The formulations of the first aspect of the disclosure may include at least one N-vinyl amide hydrophilic monomer, in an amount of at least 30% (wt / wt), especially in an amount of at least 35% (wt / wt). The formulations of the first aspect of the disclosure may include N-vinyl amide hydrophilic monomers in an amount of from 35 to 55%, especially from 37 to 50%. The formulations of the first aspect of the disclosure may include N-methyl N-vinyl acetamide in an amount of from 30 to 55%, such as from 35 to 50%, especially from 37 to 50%.

[075] Where more than one hydrophilic monomer is included in the formulations of the disclosure, advantageously at least 70% or 80% by weight of the hydrophilic monomers have a solubility in water of >20%. In a specific example, 100% of the hydrophilic vinylcontaining monomer in the polymerizable composition has a solubility in water of >10%. The hydrophilic vinyl-containing monomer typically has a molecular weight of about 75 to about 500, and more typically about 75 to 250.

[076] The formulations of the disclosure may optionally include hydrophobic monomers that lack siloxane groups. The term "hydrophobic monomer", as used herein, refers to a monomer that lacks siloxane groups and which is less than 5% soluble in water at 20 °C as determined using a standard shake flask method.

[077] Hydrophobic monomers may be (meth)acrylate group-containing hydrophobic monomers. As used herein, a “hydrophobic acrylate-containing monomer” is any nonsiloxane monomer that has a single polymerizable acrylate group (e.g. methyl methacrylate, acrylamide, etc.). In a specific example, the hydrophobic acrylate-containing monomer has a polymerizable methacrylate group. Numerous suitable acrylate-containing monomers are known in the field. Exemplary hydrophobic acrylate-containing monomers include methyl acrylate, isopropyl acrylate, cyclohexyl acrylate, methyl methacrylate (MMA), butyl acrylate, tert-butyl methacrylate (tBMA), perfluorohexylethylthiocarbonylaminoethyl methacrylate, isobornyl methacrylate (IBM), trifluoroethyl methacrylate, hexafluoroisopropyl methacrylate, hexafluorobutyl methacrylate, 2-hydroxybutyl methacrylate (HOB), 2-hydroxypropyl methacrylate (HPMA), and ethylene glycol methyl ether methacrylate (EGMA). Favoured non-siloxane hydrophobic monomers include hydroxybutyl methacrylate, isobornyl methacrylate or a combination of hydroxybutyl methacrylate and isobornyl methacrylate. A silicone hydrogel contact lens formulation may comprise an acrylate-containing hydrophobic monomer to further enhance mechanical strength and / or stiffness of the lens, or confer other desired properties.

[078] Hydrophobic monomers that lack siloxane groups are not restricted to (meth)acrylate group-containing monomers and may comprise vinyl or other ethylenically unsaturated reactive groups. Further examples of hydrophobic monomers include vinyl acetate, vinyl propionate, vinyl butyrate, styrene, chloroprene, vinyl chloride, vinylidene chloride, acrylonitrile, and methacrylonitrile.

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

[080] A “siloxane component”, as used herein, refers to a polymerizable compound having at least one siloxane group. The siloxane may comprise a terminal acrylate or methacrylate group. (Meth)acrylate-containing siloxanes that can be used in the formulations of the disclosure described herein are well-known in the field. The siloxane compound may be mono-functional (meth)acrylate-containing siloxanes, di-functional (meth)acrylate-containing siloxanes or comprise a combination of mono- and di-functional (meth)acrylate-containing siloxanes. In examples where the (meth)acrylate-containing siloxanes consists of one or more mono-functional (meth)acrylate-containing siloxanes (i.e. it does not contain any multi-functional (meth)acrylate-containing siloxanes), the polymerizable composition will typically further comprise a (meth)acrylate-containing cross-linking agent, described further below. In a specific example, the (meth)acrylate-containing siloxane has one or more polymerizable methacrylate groups. Various non-limiting examples of suitable acrylate-containing siloxanes include 3-[tris(trimethylsiloxy)silyl]propyl methacrylate (“TRIS”), 3-methacryloxy-2-hydroxypropyloxy) propylbis(trimethylsiloxy)methylsilane (“SiGMA”), methyldi(trimethylsiloxy)sylylpropylglycerolethyl methacrylate (“SiGEMA”), and monomethacryloxypropyl functional polydimethylsiloxanes such as MCR-M07 and MCS-Mll, all available from Gelest (Morrisville, PA, USA).

[081] The silicone hydrogel contact lens formulations of the disclosure typically comprise a polymerizable siloxane component in an amount of at least 40% (wt / wt), such as in an amount of at least 42% (wt / wt), especially in an amount of at least 45% (wt / wt). The polymerizable siloxane component typically constitutes no more than 60% (wt / wt) of the formulation, for example no more than 55% (wt / wt) of the formulation. It has been found that thermally-curable formulations comprising high amounts of a polymerizable siloxane components are particularly prone to the formation of lenses that have high levels of surface rippling when oxygen scavengers are absent.

[082] The silicone hydrogel contact lens formulation may include at least one di functional siloxane having a molecular weight of at least 5,000 daltons. At least 30% (wt / wt) of the siloxane content may be di-functional siloxanes having a molecular weight of at least 5,000 daltons. Advantageously, at least 40% (wt / wt) of the siloxane content is di-functional having a molecular weight of at least 5,000 daltons. The formulation may comprise between 15 and 45% (wt / wt) di-functional siloxane, for example, between 20 and 40% (wt / wt) di-functional siloxane having a molecular weight of at least 5,000 daltons. The di-functional siloxanes typically have molecular weight of less than 25,000 daltons, such as a molecular weight of less than 20,000 daltons, especially a molecular weight of less than 15,000 daltons. It has been found that including siloxanes having higher molecular weights can result in formulations that have an unacceptably high viscosity. The silicone hydrogel contact lens formulation may include at least one di-functional siloxane having a molecular weight of from 5,000 to 25,000 daltons, for example at least one di-functional siloxane having a molecular weight of from 6,500 to 20,000 daltons, especially at least one di-functional siloxane having a molecular weight of at least 8,000 to 15,000 daltons. It has been found that thermally-curable formulations comprising high amounts of a di-functional siloxanes having a molecular weight of at least 5,000 daltons are particularly prone to gelling on storage.

[083] The silicone hydrogel contact lens formulation may include at least one mono functional siloxane, for example, having a molecular weight of less than 3000 daltons. At least 20% (wt / wt) of the siloxane content may be mono-functional siloxanes having a molecular weight of less than 3000 daltons. Advantageously, at least 30% (wt / wt) of the siloxane content is mono-functional having a molecular weight of less than 3000 daltons. The formulation may comprise between 10 and 30% (wt / wt) mono-functional siloxane monomer(s), for example, between 10 and 30% (wt / wt) mono-functional siloxane monomer(s) having a molecular weight of less than 3000 daltons. The mono-functional siloxanes typically have a molecular weight of at least 200 daltons.

[084] In one example, the mono-functional siloxane may comprise a (meth)acrylate- containing siloxane monomer represented by formula (I), r2 p3 ch3 ch3 | T R1-Si-(OSi)m-CH2CHCH2O(CH2CH2O)nCOC=CH2 ch3 ch3 (I) where m is an integer from 3 to 10, n is an integer from 0 to 10, R1 is an alkyl group having 1 to 4 carbon atoms, R2 is hydrogen or a methyl group, and R3 is hydrogen or a methyl group. In a further specific example, the acrylate-containing siloxane is represented by formula I, wherein R1 is a butyl group, R2 is hydrogen, R3 is a methyl group, m is 4, and n is 1. Methods of making siloxane monomers represented by formula (I) are described in U.S. Publ. no. 2009 / 0299022, incorporated herein by reference.

[085] In another example, the mono-functional siloxane may comprise a (meth)acrylate-containing siloxane monomer represented by formula (II), where 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 U.S. Pat. No. 6,867,245 and U.S. Pat. No. 6,310,169, both incorporated herein by reference.

[086] Examples of suitable commercially available mono-functional siloxanes include 2-propenoic acid, 2-methyl-, 2-[3-(9-butyl-l, 1,3,3,5,5,7,7,9,9- decamethylpentasiloxane-l-yl)propoxy]ethyl ester, X-22-1622 available from Shin-Etsu Chemical Co., Ltd., Tokyo, Japan (CAS # 1052075-57-6): \ 22 1^2 'V the methacryloxypropyl terminated poly(dimethyl) siloxane FMM Shin-Etsu Silicones of America, Akron, Ohio, USA (CAS # 697234-76-7): and 3-methacryloxy-2-hydroxypropyloxy)propylbis (trimethylsiloxy)methylsilane SiGMA:

[087] The silicone hydrogel contact lens formulation typically includes at least one di-functional siloxane having a molecular weight of at least 5,000 daltons, for example at least 6,500 daltons, especially at least 8,000 daltons. The formulation may comprise between 10 and 45 wt% di-functional siloxane monomer(s), especially between 20 and 40 wt% difunctional siloxane(s). The formulation may comprise between 10 and 45 wt% or between 20 and 40 wt% di-functional siloxane(s) having a molecular weight of at least 8,000 daltons.

[088] In one example, the di-functional siloxane(s) may comprise a siloxane monomer represented by formula (III), (III) wherein Ri is selected from either hydrogen or a methyl group; R2 is selected from either hydrogen or a C1-4 hydrocarbon group; m represents an integer of from 0 to 10; n represents an integer of from 4 up to about 15, 25, or 100; a and b represent integers of 1 or more; a+b is equal to 20-500; b / (a+b) is equal to 0.01-0.22; and the configuration of siloxane units includes a random configuration.

[089] Other suitable di-functional siloxane monomers are represented by formula (IV): wherein R3 is selected from either hydrogen or a methyl group, m represents an integer from 0 to 10, and n represents an integer from 1 to 500. In a specific example, a suitable difunctional siloxane monomer is a methacryloxypropyl-terminated polydimethylsiloxane represented by formula IV where R3 is a methyl group, m is 0, and n is an integer from 40 to 60 having a Mw of 4500 to 5500 is available from Gelest (Morrisville, PA, USA) and is referred to as “DMS-R18” from the manufacturer. Additional suitable methacryloxypropyl-terminated polydimethylsiloxanes include DMS-R22 and DMS-R31, also available from Gelest.

[090] Yet another suitable di-functional siloxane monomer is represented by formula (V), ch s I CH, CH, ; ■ s i ' r ' I i 1 ■ i i ' i "i wherein n is an integer of about 100 to 150, m and p are both integers of about 5 to 10, and h is an integer of about 2 to 8. Methods of making compounds of formula V are described in U.S. Pat. No. 6,867,245, incorporated herein by reference. Additional siloxanes that can be used in the formulations of the disclosure described herein are known in the field (see e.g. U.S. Pat. No. 7,572,841, U.S. Pat. No. 2006 / 0063852, and U.S, Pat. No. 5,998,498, each incorporated herein by reference).

[091] In one example, the siloxanes may comprise a combination of a mono functional (meth)acrylate-containing siloxane and a di-functional (meth)acrylate-containing siloxane. In one such example, the mono-functional (meth)acrylate-containing siloxane has a molecular weight of less than 2,000, 1,000, or 750 daltons and the di-functional acrylate-containing siloxane has a molecular weight of at least 3,000, 5,000 or 8,000 daltons. In a specific example, the mono-functional (meth)acrylate-containing siloxane has a molecular weight of from about 250 to about 1000 daltons. In a further specific example, the mono functional (meth)acrylate-containing siloxane has a molecular weight of from about 500 to about 1000 daltons.

[092] The silicone hydrogel contact lens formulations of the disclosure advantageously comprise one or more thermally-activated polymerization initiators in the monomer mixture, i.e., the formulations can comprise a thermal initiator, or can comprise a thermal initiator component comprising two or more thermal polymerization initiators or a combination of thermal polymerization initiators, synergists and activators. The term “initiator” refers to a chemical that initiates crosslinking / polymerizing reaction. The thermal initiator is typically a free radical initiator that forms radicals that initiate radical propagated polymerisation reactions. Polymerization initiators that may be included in the formulations of the disclosure include, for example, azo compounds, or organic peroxides, or both. The initiator is a thermal initiator that is activated on exposure to heat. Initiators that can be present in the polymerizable formulations include, for example, azobisisobutyronitrile (AIBN), benzoyl peroxide (BPO), tert-butyl peroxyacetate (TBPA), benzoin ethyl ether, benzyl dimethyl ketal, alpha-diethoxyacetophenone, 2,4,6-trimethylbenzoyl diphenyl phosphine oxide, benzoin peroxide, t-butyl peroxide, or azobisdimethylvaleronitorile, or any combination thereof. Advantageously the polymerization initiator is a thermal initiator. Examples of suitable thermal initiators include 2,2'-azobis-2-methyl propanenitrile (VAZO-64 from E.I. DuPont de Nemours &Co., Wilmington, Del., USA), 2,2'-azobis(2,4-dimethylpentanenitrile) (VAZO-52) and l,l'-azo bis(cyanocyclohexane) (VAZO-88 also from E.I. DuPont). The thermal polymerization initiator or thermal initiator component can be present in the silicone hydrogel contact lens formulations of the disclosure in an amount from about 0.1% (wt / wt) to about 1.5% (wt / wt), or from about 0.2% (wt / wt) to about 1.0% (wt / wt), especially from about 0.2 to about 0.8% (wt / wt). Thermal curing methods are well-known to a person skilled in the art.

[093] The silicone hydrogel contact lens formulation may further comprise a cross linking agent in the polymerizable mixture. A cross-linking agent can react with functional groups on two or more polymer chains to bridge one polymer to another. As used herein, a “cross-linking 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, “acrylate-containing cross-linking agent” has at least two polymerizable acrylate groups, and no other type of polymerizable group. A “vinyl-containing cross-linking agent” has at least two polymerizable vinyl groups, and no other type of polymerizable group. The vinyl-containing cross-linking agents, as well as the acrylate-containing cross-linking agents, typically can have a molecular weight of less than 1500, 1000, 500, or 250 daltons. Examples of vinyl-containing cross-linking agents that can be used in the formulations of the disclosure disclosed herein include, without limitation, divinyl ethers, or divinyl sulfones, or triallyl isocyanurates, and any combination thereof. Exemplary divinyl ethers include di ethyleneglycol divinyl ether, or tri ethyleneglycol divinyl, or 1,4-butanediol divinyl ether, or 1,4-cyclohexanedimethanol divinyl ether, or any combination thereof. Typically, the vinylcontaining 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 mol. % up to about 0.10, 0.15, or 0.20 mol. %. Examples of acrylate-containing cross-linking agents that can be used in the formulations of the disclosure, include, without limitation, lower alkylene glycol di(meth)acrylate, poly(lower alkylene) glycol di(meth)acrylate, lower alkylene di(meth)acrylate, trimethylolpropane tri(meth)acrylate, pentaerythritol tetra(meth)acrylate, bisphenol A di(meth)acrylate, methylenebis(meth)acrylamide, and 1,3-bis(3-methacryloxypropyl) tetramethyldisiloxane. In certain examples the acrylate-containing cross-linking agent is a non-siloxane cross-linking agent. When present, the total amount of acrylate-containing cross-linking agent in the silicone hydrogel contact lens formulation is typically from about 0.20, 0.25, 0.30, or 0.35 mol. % up to about 0.50, 0.60, 0.70, 0.80, or 1.0 mol. %. For the avoidance of doubt, multi-functional polymerizable compounds having a molecular weight of more than 2000 daltons are not considered to be cross-linking agents. Thus di-functional siloxanes as described herein having a molecular weight of more than 2000 daltons are not considered to be cross-linking agents.

[094] The polymerizable formulations may optionally further comprise a chain transfer agent in the monomer mixture. 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, halocarbon compounds or C3-C5 hydrocarbons, such as allyloxy ethanol.

[095] The formulations of the disclosure may comprise non-polymerizable ingredients, in addition to the polymerizable ingredients, that are conventionally used in contact lens formulations. Additional ingredients may also be included such as an organic diluent or an oxygen scavenger. Non-limiting examples of these and additional ingredients that may be included in the polymerizable composition are provided in US 2007 / 0296914.

[096] The formulations of the disclosure typically have a dynamic viscosity of greater than 15 cP at 25 °C when freshly prepared, for example a dynamic viscosity of greater than 16 cP at 25 °C when freshly prepared. It has been found that formulations having a dynamic viscosity of greater than 15 cP at 25 °C are particularly prone to the formation of surface ripples on curing and / or the premature gelation on storage. The formulations of the disclosure optionally have a dynamic viscosity of less than 55 cP at 25 °C when freshly prepared, and typically have a dynamic viscosity of between 15 and 35 cP at 25 °C when freshly prepared, such as from 16 to 30 cP at 25 °C when freshly prepared.

[097] Favoured formulations of the disclosure comprise a siloxane component present in an amount of at least 40% (wt / wt), wherein at least 40% of the siloxane content is di-functional siloxanes having a molecular weight of at least 5,000 daltons; and an N-vinyl amide monomer component present in an amount of at least 37% (wt / wt). The contact lenses of the disclosure favourably comprise a polymeric lens material derived from a favoured formulation of the disclosure comprising a monomers and siloxane components described above.

[098] A particularly favoured silicone hydrogel contact lens formulation of the disclosure comprises from 40 wt% to 55 wt% of a siloxane component, e.g. comprising a siloxane monomer or a combination of siloxane monomers, from 30 wt% to 55 wt% of a N-vinyl amide monomer(s) selected from NVP, VMA, or combinations thereof, and optionally from about 1 wt% to about 20 wt% of a hydrophilic monomer selected from N,N-dimethylacrylamide (DMA), 2-hydroxyethyl methacrylate (HEMA), ethoxyethyl methacrylamide (EOEMA), or any combination thereof, and optionally from about 1 wt% to about 20 wt% of a hydrophobic monomer selected from methyl methacrylate (MMA), isobornyl methacrylate (IBM), or 2-hydroxybutyl methacrylate (HOB) or any combination thereof.

[099] The term “batch” refers to an amount of a thermally-curable, silicone hydrogel, contact lens formulation that is suitable for producing the polymeric lens bodies of multiple (e.g. 100 or more) silicone hydrogel contact lenses. The formulation is a liquid at 25 °C (having a viscosity as discussed above) that can be cured to form a solid formulation on exposure to heat (e.g. a temperature of at least 39 °C, such as a temperature of 50 °C or higher). The batch of formulation comprises at least the thermally-activated radical polymerization initiator, the one or more oxygen scavengers, the one or more polymerization inhibitors that are effective in the absence of oxygen, a polymerizable siloxane and one or more non-siloxane polymerizable monomers. The bath of formulation typically comprises all the constituents necessary to form the polymeric body of a silicone hydrogel contact lens. Optional additives that are not essential for the formation of a viable polymeric lens body may be added to the formulation shortly before curing and thus not be present in the batch of formulation. For example, a tinting agent may be added to the formulation used to form each lens, or a small number of lenses, on-demand and not be included in the batch of formulation. The batch of contact lens formulation is contained in a single container, typically a sealed vessel. The batch of formulation has a weight of at least 1 kg, and may have a weight of at least 2 kg. Uses of polymerization inhibitors and oxygen scavengers

[0100] In a third aspect, the disclosure provides the use of one or more polymerization inhibitors that are effective in the absence of oxygen to stabilise a batch of a thermally-curable contact lens formulation. The polymerisation inhibitors are advantageously used in the amounts described above with regards to the formulations of the first aspect of the disclosure. The thermally-curable contact lens formulation may include at least 40% (wt / wt) of a polymerizable siloxane component and at least 30% (wt / wt) of hydrophilic 7V-vinyl amide monomer(s) based on the total weight of the formulation.

[0101] In a fourth aspect, the disclosure provides the use of a combination of an oxygen scavenger and one or more polymerization inhibitors that are effective in the absence of oxygen, to prepare a thermally-cured silicone hydrogel contact lens with lower levels of surface rippling compared to lenses prepared from identical formulations that lack the oxygen scavenger. The silicone hydrogel contact lens is typically a daily disposable lens for use in correcting vision. The silicone hydrogel contact lens typically: (i) has a chord diameter from 13.8 to 14.9 mm, (ii) a base curve from 8.1 to 8.9 mm, and / or (iii) an optical power of from -14.0 diopter to +10.0 diopter.

[0102] The silicone hydrogel contact lens may be prepared from a formulation having a mass of at least 1 kg. The silicone hydrogel contact lens may be prepared from a formulation having a dynamic viscosity of greater than 15 cP at 25 °C and / or which includes at least 40% (wt / wt) of a polymerizable siloxane component and at least 30% (wt / wt) of hydrophilic 7V-vinyl amide monomer(s) based on the total weight of the formulation. The one or more polymerisation inhibitors are optionally present in the formulation from which the lens is prepared in an amount described above with respect to the formulations of the first aspect of the disclosure.

[0103] The formulations that are stabilised in the third aspect of the disclosure and which are employed in preparing thermally-cured silicone hydrogel contact lens in the fourth aspect of the disclosure, are advantageously those described above with respect to formulations of the other aspects of the disclosure. The polymerisation inhibitors and oxygen scavengers used may be those described above with respect to the formulations of the first aspect of the disclosure. For example, the oxygen scavenger may be TPP, or another oxygen scavenger described herein, for example with respect to the formulations of the first aspect of then disclosure. Also, for example, the polymerisation inhibitors used may include an anthraquinone, benzophenone or benzotriazole compound as described above with respect to the formulations of the first aspect of the disclosure. The formulations stabilised in the third aspect of the disclosure, and which are employed in preparing thermally-cured silicone hydrogel contact lens in the fourth aspect of the disclosure, may comprise any or all of the siloxane components, hydrophilic N-vinyl amide monomer(s), optional further hydrophilic monomers, optional further hydrophobic monomers, optional crosslinkers, optional chain transfer agents and optional radical initiators that are described above. Also, for example, the formulations stabilised in the third aspect of the disclosure and which are employed in preparing thermally-cured silicone hydrogel contact lens in the fourth aspect of the disclosure, comprise siloxane components, hydrophilic N-vinyl amide monomer(s), optional further hydrophilic monomers and optional further hydrophobic monomers in the amounts described above with respect to formulations of the disclosure. The formulations stabilised in the third aspect of the disclosure, and which are employed in preparing thermally-cured silicone hydrogel contact lens in the fourth aspect of the disclosure, may have the characteristics of the formulations with respect to the formulations of the first aspect of the disclosure. For example, the formulations may have the viscosity characteristics described above. Contact lenses

[0104] Contact lenses of the second aspect of the disclosure and the lenses prepared in the fourth aspect of the disclosure are typically contact lenses for use in correcting defects in vision, especially daily disposable lenses for use in correcting vision. Contact lens shapes that provide vision correction are well known to the skilled person. The lenses typically have a chord diameter from 13.8 to 14.9 mm, especially 13.9 to 14.8 mm, and / or a base curve from 8.1 to 8.9 mm, especially from 8.2 to 8.8 mm. The lenses typically have an optical power of from -14.0 diopter to +10.0 diopter, especially an optical power of from -12.0 diopter to +8.0 diopter. The lenses may, for example have a chord diameter from 13.8 to 14.9 mm, a base curve from 8.1 to 8.9 mm, and an optical power of from -14.0 diopter to +10.0 diopter. The lenses preferably have a chord diameter from 13.9 to 14.8 mm, a base curve from 8.2 to 8.8 mm and an optical power of from -12.0 diopter to +8.0 diopter. EXAMPLES

[0105] The following Examples illustrate certain aspects and advantages of the present disclosure, which should be understood not to be limited thereby. Base formulation

[0106] Base polymerizable silicone hydrogel contact lens formulation 1 was prepared containing: • 11 wt.% hydrophobic monomers (consisting of 8.29 wt% hydroxybutyl methacrylate and 2.49 wt% isobomyl methacrylate), • 42 wt.% hydrophilic A-vinyl amide monomers (consisting of 10.48 wt% A-vinyl N-methyl acetamide and 31.44 wt% 7V-vinyl pyrrolidone), • 45 wt.% polymerizable siloxanes (with a varying ratio of monomers - as shown in Table 1), • 2 wt.% of other agents including a thermal initiator (azobisisobutyronitrile (AIBN)) and a cross linker (triallyl isocyanate).

[0107] Base polymerizable silicone hydrogel contact lens formulation 2 was prepared containing: • 9 wt.% hydrophobic monomers (consisting of 6.94% hydroxybutyl methacrylate and 2.09% isobornyl methacrylate), • 39 wt.% hydrophilic A-vinyl amide monomers (A-vinyl A-methyl acetamide), • 49 wt.% polymerizable siloxanes, in a 62:38 ratio of high molecular weight, difunctional siloxane (30.23 wt% M5A, Mn 8,000 - 11,000) : low molecular weight, monofunctional siloxane (18.04 wt% FMM and 0.49wt% KF-1622 Mn <2,000), • 3 wt.% of other agents including a thermal initiator (azobisisobutyronitrile (AIBN)) and a cross linker (triallyl isocyanate).

[0108] Base polymerizable silicone hydrogel contact lens formulation 3 was prepared containing: • 9 parts by weight hydrophobic monomers (consisting of 2 parts isobomyl methacrylate (IBM) and 7 parts hydroxybutyl methacrylate (HOB)), • 39 parts by weight hydrophilic A-vinyl amide monomers (38.6 parts TV-vinyl N-methyl acetamide (VMA) and 0.4 parts A-vinyl pyrrolidone (NVP)), • 49 parts by weight of polymerizable siloxanes (18.13 parts FMM, 30.38 parts M5A and 0.49 parts X-22-1622), and • 1 part by weight of other agents including a thermal initiator (VAZO-64) and a crosslinker (triallyl isocyanate).

[0109] Base polymerizable silicone hydrogel contact lens formulation 4 was prepared containing: • 9 parts by weight hydrophobic monomers (2 parts isobornyl methacrylate (IBM) and 7 parts hydroxybutyl methacrylate (HOB)), • 39 parts by weight hydrophilic A-vinyl amide monomers (A-vinyl A-methyl acetamide (VMA)), • 49 parts by weight of polymerizable siloxanes (18.04 parts FMM, 30.23 parts M5A and 0.49 parts X-22-1622), and • 1 part by weight of other agents including a thermal initiator (VAZO-64) and a crosslinker (triallyl isocyanate).

[0110] Base formulation 5 was prepared containing: • 13 parts by weight hydrophobic monomers (methyl methacrylate (MMA)), • 42 parts by weight hydrophilic A-vinyl amide monomers (A-vinyl A-methyl acetamide (VMA), • 6 parts by weight hydrophilic acrylate monomers (ethylene glycol methacrylate (EGMA)), • 35 parts by weight of polymerizable siloxanes (8.83 parts M5A and 26.48 parts X-22-1622), and • 2 parts by weight of other agents including a thermal initiator (VAZO-64) and a crosslinker (0.09 parts Tri ethylene glycol divinyl ether (TEGDVE) and 0.44 parts ethylene glycol dimethacrylate (EGDMA)).

[0111] The monomers were obtained from commercially available sources and are believed to include trace amounts of polymerisation inhibitors which require oxygen to function. Assessment of surface rippling

[0112] Rippling severity was assessed visually based on zonometer or SAG optimec images of the lens and rated from 0 to 5, using the following scale: • 0 - no visible ripples. • 1 - very minor, faint ripples. • 2 - minor ripples. • 3 - moderate ripples. • 4 - severe ripples. • 5 - very severe, long and deep ripples. Surface rippling without TPP

[0113] The following examples illustrate the severity of surface rippling that occurs in the PP moulds for the formulation, and how this can be mitigated by the inclusion of the oxygen scavenger TPP.

[0114] The severity of surface ripples was investigated using polymerizable mixtures that combine base formulation 1, with a 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 to the monomer formulations were made. All formulations were cast in identical PP moulds. The results are summarized in Table 1 below. The table shows that the severity of rippling increases with increased loading of M5A, with the most severe surface rippling exhibited by mixture 6, containing 75:25 M5A : FMM. Table 1. Mixture Base Silicone Mixture Viscosity (25 °C) Severity of rippling 1 1 M5A : KF-1622 (25:75) 1 2 1 M5A : KF-1622 (50:50) 2 3 1 M5A : KF-1622 (75:25) 3 4 1 M5A : FMM (25:75) 12 cP 2 5 1 M5A : FMM (50:50) 18 cP 4 6 1 M5A : FMM (75:25) 5 7 1 M3U : FMM (81:19) 5

[0115] Severe rippling was also observed for lenses made from mixture 7 containing 81:19 M3U : FMM.

[0116] In comparison lenses made from a UV-curing a formulation comprising -49% (wt / wt) of a siloxane component and having a viscosity of approximately 40 cP at 25 °C showed no ripples (0).

[0117] The severity of rippling appears to corelate to the viscosity of the thermally-curable formulations. M5A has a Mn of 8000 to 11000 and a viscosity of 350 to 450 mm2 / s and M3U has a Mn of 12000 to 20000 and a viscosity of 450 to 750 mm2 / s, whereas KF-1622 has a Mn of less than 1000 and a viscosity of 5.6 to 6.3 mm2 / s and FMM has a Mn of 1200 to 2000 and a viscosity of 35 to 45 mm2 / s. Replacing lower viscosity / lower Mn siloxanes such as FMM with higher molecular weight / higher viscosity siloxanes such as M5A has been shown to adversely affect the level of rippling. Thus, there is a particular need for a means of alleviating rippling of formulations that include significant amounts of higher molecular weight / higher viscosity siloxanes. Effect of TPP on surface rippling

[0118] Addition of TPP to the monomer formulation enabled contact lenses to be manufactured that are free from surface rippling. As the TPP loading is increased the degree of rippling observed is reduced.

[0119] The effect of adding TPP to base formulation 2, with an overall silicone content of 54 parts by weight made up of a 62:38 ratio of difunctional : monofunctional siloxanes, is shown in Table 2 below. Table 2. Mixture Base Weight percentage TPP Severity of rippling 8 2 0.000% 3 9 2 0.091% 3 10 2 0.181% 2 11 2 0.271% 1 12 2 0.404% 0

[0120] The data in Table 2 shows that the severity of rippling decreases with increased loading of TPP oxygen scavenger. When no TPP is included (mix 8), the rippling is at its most prominent. When 0.404% TPP is included (mix 12), the rippling is mitigated to such an extent that it can no longer be observed visually. Comparison of TPP and TPPO

[0121] The following formulations were prepared to confirm that the oxygen scavenging properties of TPP were responsible for the lack of rippling observed. Three formulations were prepared that were identical except that either no TPP was present, 0.448 parts by weight of TPP and 0.475 by weight of TPPO, i.e. the same molar equivalent as 0.448 parts by weight of TPP. Table 3. Rippling observed without TPP, with TPP and with TPPO Mixture Base TPP / TPPO (parts by weight) Rippling 13 4 Zero Yes 14 4 0.448 TPP No 15 4 0.475 TPPO Yes Effect of TPP on Gelation

[0122] The following examples illustrate the effects of TPP on the formulation gelation.

[0123] Polymerizable mixtures that combine base formulation 3 and formulation 5 with either no TPP or TPP in the amounts shown in Table 4 were freshly prepared and either 25 g or 12.5 g of the mixture was placed into closed 37 ml vials to mimic a small or large air headspace, respectively, above the monomer mixture surface. These were then placed into a water bath at 17 °C and the mixtures visually assessed for gelation at intervals each day. Table 4. Gelation onset times with and without TPP Mixture Base TPP (parts by weight) Viscosity (25 °C) Time to gelation 12.5 g formulation 25 g formulation 16 3 Zero >9 days >9 days 17 5 Zero >9 days >8 days 18 3 0.41 19 cP <1 day <1 day 19 5 0.44 3 cP >9 days <1 day

[0124] No gelation was observed for comparative mixture 16 and comparative mixture 17 comprising base formulation 3 or base formulation 5 respectively that lack TPP in either the large or small headspace samples after storage in the water bath for 8 days.

[0125] Comparative mixtures 18 and 19 containing base formulations 3 and 5 respectively together with approximately 0.4 parts by weight TPP were seen to gel rapidly in small headspace samples. Low viscosity comparative mixture 19 could be stored for 8 days in large headspace vessels without gelation occurring, whereas higher viscosity mixture 18 gelled within one day even in large headspace vessels.

[0126] These results demonstrate that lower viscosity mixtures based on formulation 5, which includes higher amounts of hydrophilic monomers and lower amounts of siloxanes than formulation 3, can tolerate the inclusion of TPP when oxygen is present, i.e. in large headspace vessels. However, when oxygen is largely excluded, i.e. in small headspace vessels, the presence of TPP leads to rapid gelation of the mixture within a day. Higher viscosity mixtures based on formulation 3, which includes lower amounts of hydrophilic monomers and higher amounts of siloxanes than formulation 5, cannot tolerate the inclusion of TPP even when oxygen is present, i.e. in large headspace vessels.

[0127] The above results indicate that the oxygen scavenging properties of TPP and the viscosity of the formulation are linked to gelation. Effect of Tints and UV / HEVL blockers

[0128] It was observed that the nature of the tint and UV / HEVL blockers present in the mixture influenced the stability of mixtures comprising base formulation 3 / 4. Table 5. Gelation onset times with TPP and various tints / UV / HEVL blockers Mixture Base Tint (parts by weight) U V / HEVL blockers (parts by weight) TPP (parts by weight) Time to gelation 12.5 g formulation 25 g formulation 18 3 RB246 (0.0082) Norbloc (1.36) 0.41 <1 day <1 day 20 4 RB247 (0.0135) UV416 (0.27) UV13 (1.08%) UV28 (0.05%) 0.40 >9 days >4 days

[0129] Referring to Table 5, comparing the stability of comparative mixture 18 comprising base formulation 3 together with 0.41 parts TPP, 0.0082 parts RB246 and 1.36 parts Norbloc, and mixture 20 comprising base formulation 4 together with 0.40 parts TPP, 0.0135 parts RB247 and a combination of 0.27 parts benzophenone UV absorbing agent and 1.58 parts of benzotriazole HEVL absorbers, a significant difference in gelation onset times is observed. The base formulations 3 and 4 are very similar and thus principal difference between comparative mixture 18 and mixture 19 of the disclosure is the presence of a tint and UV / HEVL blockers that act as polymerisation inhibitors. Mixture 18 that contains RB246 and Norbloc, exhibits a lower stability than mixture 20 that contains RB247 and UV416.

[0130] The dynamic viscosity at 25 °C of a 10 mL sample of mixture 20 increased from 18.4 cP to 19.5 cP after storage in a sealed 14 mL vial at 17 °C for 48 hours, i.e. an increase of 5.4%. The viscosity increase indicated that the formulation remains curable using a thermally-initiated curing mechanism, i.e. while the tint and UV- HEVL blockers are acting as polymerization inhibitors prolonging the pot life of the formulation, they do hinder the rapid and complete curing of the formulation when required.

[0131] In all cases light was excluded from the vessels containing the mixtures. Therefore, the difference in stability is not attributable to the light transmission characteristics imparted to the mixture by the tint and UV / HEVL blockers.

[0132] Comparative trials using mixtures comprising base formulation 3 together with 0.40 parts TPP using small headspace vessels (see Table 6) were conducted to investigate the effects of the tint and UV / HEVL blockers on stability. Table 6. Gelation state with various tints and UV / HEVL blockers. Mixture Tint (parts) UV blocker (parts) HEVL blocker (parts) Time to gelation (days) 21 None None None <0.5 22 None Norbloc (1.36) None <0.5 23 RB246 (0.0135) None None <1 24 None None UV13 (1.08) <1 25 None None UV28 (0.50) <1 26 None UV416 (0.27) None <1 27 RB247 (0.0135) None None 2 28 RB247 (0.0135) None UV13 (1.08) 3 29 RB247 (0.0135) None UV28 (0.50) 3 30 RB247 (0.0135) UV416 (0.27) None 3 -4 31 RB247 (0.0135) UV416 (0.27) UV13 (1.08) >8 32 RB247 (0.0135) UV416 (0.27) UV28 (0.50) >8

[0133] These results demonstrate that while the UV absorbing agent Norbloc did not delay the onset of polymerisation, each of RB246, UV416, UV13 and UV28 have a moderate stabilising effect. These results also demonstrate that the inclusion of the tint RB247 significantly delays the onset of polymerisation, with RB247 being more effective than RB246 at equivalent weight % loading. RB247 appears to have the most significant stabilising effect of all the tints and UV / HEVL blockers when used alone.

[0134] The stabilising effects were found to be synergistic, and the most improved monomer mixture stability was achieved with a combination of RB247 with UV416 and a benzotriazole HEVL absorber (Mixtures 20, 31 and 32).

[0135] The disclosure herein refers to certain illustrated examples, it is to be understood that these examples are presented by way of example and not by way of limitation. The intent of the foregoing detailed description, although discussing exemplary examples, is to be construed to cover all modifications, alternatives, and equivalents of the examples as may fall within the spirit and scope of the disclosure as defined by the additional disclosure.

[0136] The entire contents of all cited references in this disclosure, to the extent that they are not inconsistent with the present disclosure, are incorporated herein by reference.

[0137] Other embodiments of the present disclosure will be apparent to those skilled in the art from consideration of the present specification and practice of the present disclosure disclosed herein. It is intended that the present specification and examples be considered as exemplary only with a true scope and spirit of the disclosure being indicated by the following claims and equivalents thereof.

Claims

1. A batch of a thermally-curable, silicone hydrogel, contact lens formulation having a mass of at least 1 kg and a dynamic viscosity of greater than 15 cP at 25 °C, comprising:a. a thermally-activated radical polymerization initiator.b. one or more oxygen scavengers; andc. one or more polymerization inhibitors that are effective in the absence of oxygen.

2. The formulation of claim 1, wherein the amount of oxygen scavengers present in the formulation provides 1 kg of the formulation with a capacity to react with at least 3 mmol O2 (at 50% RH, 101,000 Pa and 20 °C).

3. The formulation or contact lens of claim 1 or claim 2, comprising triphenylphosphine (TPP) in an amount of from 0.2 to 2.0% (wt / wt).

4. The formulation of any preceding claim, wherein the one or more polymerization inhibitors are present in an amount that allows the dynamic viscosity of 10 mL the formulation to increase by at least 2% while preventing the formulation from solidifying, when stored at 17 °C for 48 hours in a 14 mL sealed container.

5. The formulation of any preceding claim, wherein the one or more polymerization inhibitors include one or more of an anthraquinone tinting agent, a benzophenone UV absorbing agent, and benzotriazole HEVL absorber, especially a combination of an anthraquinone tinting agent and one or both of a benzophenone UV absorbing agent and benzotriazole HEVL absorber.

6. The formulation of any preceding claim, comprising at least 40% (wt / wt) of a polymerizable siloxane component; and at least 30% (wt / wt) of hydrophilic 7V-vinyl amide monomer(s).

7. The formulation of any preceding claim, comprising a polymerizable siloxane component in an amount of at least 45% (wt / wt).19 09 258. The formulation of claim 6 or claim 7, wherein at least 40% (wt / wt) of the polymerizable siloxane content is di-functional siloxanes having a molecular weight of at least 8,000 daltons.

9. The formulation of any preceding claim, comprising a di-functional siloxane(s) having a molecular weight of at least 8,000 daltons, in an amount of from 20 to 40% (wt / wt).

10. The formulation of any preceding claim, comprising A-m ethyl A-vinyl acetamide in an amount of from 35 to 50% (wt / wt).

11. The formulation of any preceding claim, comprising an A-vinyl amide monomer component in an amount of at least 37% (wt / wt).

12. The formulation of any preceding claim, comprising at least 5% (wt / wt) of nonsiloxane hydrophobic monomers, especially hydrophobic methacrylate monomers.

13. The formulation of claim 12, wherein the hydrophobic monomers include hydroxybutyl methacrylate, isobornyl methacrylate or a combination of hydroxybutyl methacrylate and isobornyl methacrylate.

14. The formulation of any preceding claim, comprising a di-functional siloxane monomer represented by formula (III),ch3 ch3 R,ll m ch3 I 'b c«3” m 1 CHs Q \ QCH $CH$Q H j" (III)wherein Ri is selected from either hydrogen or a methyl group; R2 is selected from either hydrogen or a C1-4 hydrocarbon group; m represents an integer of from 0 to 10; n represents an integer of from 4 up to about 15, 25, or 100; a and b represent integers of 1 or more; a+b is equal to 20-500; b / (a+b) is equal to 0.01-0.22; and the configuration of siloxane units includes a random configuration.

15. The formulation of any preceding claim, comprising a mono-functional methacrylatecontaining siloxane monomer represented by formula (II),(II)19 09 25where n is an integer from about 10 to 15.

16. A silicone hydrogel contact lens, comprising a polymeric lens body which is the polymeric product of thermally curing a formulation comprising:a. a thermally-activated radical polymerization initiator;b. one or more oxygen scavengers; andc. one or more polymerization inhibitors that are effective in the absence of oxygen,wherein the silicone hydrogel contact lens is a daily disposable lens for use in correcting vision.

17. The silicone hydrogel contact lens of claim 16, wherein the lens (i) has a chord diameter from 13.8 to 14.9 mm, (ii) a base curve from 8.1 to 8.9 mm, and / or (iii) an optical power of from -14.0 diopter to +10.0 diopter.

18. The silicone hydrogel contact lens of claim 17, wherein the formulation has a dynamic viscosity of greater than 15 cP at 25 °C.

19. The silicone hydrogel contact lens of claim 16, 17 or 18, wherein the formulation is as further defined in any one of claims 2 to 15.

20. Use of one or more polymerization inhibitors that are effective in the absence of oxygen to stabilise a batch of a thermally-curable contact lens formulation having a mass of at least 1 kg and a dynamic viscosity of greater than 15 cP at 17 °C, comprising an oxygen scavenger and a thermally-activated radical polymerization initiator, wherein the one or more polymerisation inhibitors are present in an amount that allows the dynamic viscosity of the formulation to increase by at least 2% while preventing the formulation from solidifying, when 10 mL of the formulation is stored at 17 °C for 48 hours in a 14 mL sealed container.

21. The use of claim 20 wherein the batch of a thermally-curable contact lens formulation is as further defined in any one of claims 1 to 15.

22. Use of a combination of an oxygen scavenger and one or more polymerization inhibitors that are effective in the absence of oxygen, to prepare a thermally-cured, daily disposable, silicone hydrogel contact lens for use in correcting vision, with lower levels of undesirable of surface rippling compared to lenses prepared from identical formulations that lack the oxygen scavenger.

23. The use of claim 22 wherein the lens is as further defined in any one of claims 16 to 19.19 09 25