NZ280963A - Use of photo differential scanning calorimeter to determine utility of composition for use as a diluent in a process for producing contact lenses - Google Patents

Description

New Zealand Paient Spedficaiion for Paient Number £80963 New Zealand No. International No. 280963 PCT/ TO BE ENTERED AFTER ACCEPTANCE AND PUBLICATION Priority dates: 22.07.1993; Complete Specification Filed: 09.02.1996 Classification:^) G01N25/48; G02C7/04; B29D11/00 Publication date: 24 November 1997 Journal No.: 1422 NEW ZEALAND PATENTS ACT 1953 COMPLETE SPECIFICATION Title of Invention: A test to determine the utility of a composition for use as an inert, displaceable diluent a process for producing a contact lens Name, address and nationality of applicant(s) as in international application form: JOHNSON & JOHNSON VISION PRODUCTS, INC, a company organised under the laws of the United States of America of 4500 Salisbury Road, Suite 300, Jacksonville, Florida 32216-0995, United States of America 280963 PATENTS FORM 5 Number PATENTS ACT 1953 Dated COMPLETE SPECIFICATION A TEST TO DETERMINE THE UTILITY OF A COMPOSITION FOR USE AS AN INERT, DISPLACEABLE DILUENT IN A PROCESS FOR PRODUCING A CONTACT LENS We, JOHNSON & JOHNSON VISION PRODUCTS, INC of 4500 Salisbury Road, Suite 300, Jacksonville, Florida 32216-0995, USA, a company incorporated in the State of Florida, USA do hereby declare the invention for which we pray that a patent may be granted to us, and the method by which it is to be performed, to be particularly described in and by the following statement.

VTN-71 280963 This application is a divisional application of New Zealand Patent Application No 264008.

The invention relates to the production of shaped hydrogel articles including soft contact lenses, and more particularly to a method for the direct molding of such articles using a new class of inert, displaceable diluents. In particular this divisional application relates to testing of compositions for use as diluents in the process.

Background of the Invention Until recently, soft contact lenses of the hydrogel type have been manufactured either by lathe cutting or spin casting. In the lathe cutting method, a lens blank or button of a substantially anhydrous hydrophilic polymer (xerogel) is mechanically cut and polished to a lens shape on a fine lathe, and thereafter is contacted with water or saline to hydrate the polymer and form the desired hydrogel lens. The mechanical steps utilized in the lathe cutting operation are similar to those used in the manufacture of hard contact lenses, except that allowance must be made for swelling of the lens during hydration of the polymer.

In the spin casting method, a small quantity of hydrophilic monomer mixture is placed in a concave, optically polished mold, and the mold is rotated while the monomers are polymerized to form a xerogel lens. The two optical surfaces of the lens are formed simultaneously during polymerization, the outer surface being formed by the concave mold surface and the inner surface being shaped by the joint actions of centrifugal force generated by the rotating mold and surface tension of the polymerization mixture. The lens produced thereby is contacted with water or saline to hydrate the polymer and form a hydrogel lens as in the case of the lathe cut lens.

More recently, an improved process for producing hydrogel contact lenses has been developed, which method is not only more economical than either the lathe cut method or the spin casting -la- VTN-71 280963 method, but it has the advantage of enabling a more precise control over the final shape of the hydrated lens. This new method comprises the direct molding of a monomer mixture wherein said mixture is dissolved in a non-aqueous, displaceable solvent, the mixture is placed in a mold having the precise shape of the final desired hydrogel (i. e., water-swollen) lens, and the monomer/solvent mixture is subjected to conditions whereby the monomer(s) polymerize, to thereby produce a polymer/solvent mixture in the shape of the final desired hydrogel lens. (The polymerization is preferably carried out in a non-aqueous medium because water can interfere with the polymerization reaction and adversely affect the properties of the resulting polymer.) After the polymerization is complete, the solvent is displaced with water to produce a hydrated lens whose final size and shape are quite similar to the size and shape of the original molded polymer/solvent article. Such direct molding of hydrogel contact lenses is disclosed in Larsen, U. S. Patent No. 4,495,313 and in Larsen et al., U. S. Patent Kos. 4,680,336, 4,889,664 and 5,039,459.

In Larsen, U. S. Patent No. 4,495,313 and in Larsen et al., U. S. Patent Nos. 4,889,664 and 5,039,459, the displaceable diluents disclosed are water-displaceable boric acid esters of polyhydric alcohols. In Larsen et al., U.S. Patent No. 4,680,336, the displaceable diluents disclosed are water-displaceable organic compounds selected on the basis of their viscosity and their Hansen cohesion parameters relative to the cohesion parameters of the polymeric component of the hydrogel to be prepared.

The present invention is based on the discovery of a new test for utility of compositions that can be used as displaceable diluents in the direct molding of shaped hydrogel articles such as soft contact lenses. 280963 SUMMARY OF THE INVENTION In accordance with the invention of this divisional application there is provided a test to determine the utility of a composition for use as an inert, displaceable diluent in a process for producing a contact lens, which process comprises molding or casting in a predetermined shape a polymerization mixture comprising: (a) a monomer mixture comprising a major proportion of one or more hydrophilic monomers, and one or more cross-linking monomers; and (b) an inert, displaceable, non-aqueous diluent under conditions to polymerize said monomer mixture to produce a gel of a copolymer of said monomers and said diluent; which test comprises carrying out the polymerization of said monomers in said polymerisation mixture in a photo differential scanning calorimeter wherein said polymerization is induced by ultraviolet irradiation at a light intensity of from about 2.5 to 3 mW/cm2, determining the time to maximum exotherm of said polymerization and comparing said time with a standard time of from about 0.2 to about 3.5 minutes, and determining the percent conversion of said monomer mixture to polymer and comparing said percent conversion with a standard of at least 40 percent.

Preferably the test comprises carrying out the polymerization of said monomers in said polymerization mixture in a photo differential scanning calorimeter wherein said polymerization is induced by ultraviolet irradiation at a light intensity of from about 2.5 to 3 mW/cm2, determining the time to maximum exotherm of said polymerization and -2a- 280963 comparing said time with a standard time of from about 0.4 to about 2.5 minutes, and determining the percent conversion of said monomer mixture to polymer and comparing said percent conversion with a standard of at least 50 percent -2b- VTN-71 280963 Brief Summary of the Invention of New Zealand Patent Application No 26»008 Shaped hydrogel articles such as soft contact lenses are prepared by the steps of: (1) molding or casting a polymerization mixture comprising: (a) a monomer mixture comprising a major proportion of one or more hydrophilic monomers such as 2-hydroxyethyl methacrylate, and one or more cross-linking monomers; and (b) an inert, displaceable non-aqueous diluent selected from the group consisting of: (i) ethoxylated alkyl glucoside; (ii) ethoxylated bisphenol A; (iii) polyethylene glycol; (iv) mixture of propoxylated and ethoxylated alkyl glucoside; (v) single phase mixture of ethoxylated or propoxylated. alkyl glucoside and dihydric alcohol of up to 12 carbon atoms; (vi) adduct of c-caprolactone and C^alkanediols and triols; (vii) ethoxylated Gj^alkanetriol; and (viii) mixtures of one or more of (i) through (vii), under conoitions to polymerize said monomer mixture to produce a shaped gel of a copolymer of said monomers and said diluent; and (2) thereafter replacing said diluent with water. , 280963 VTN-71 The Prior Art In addition to the Larsen and Larsen et al. patents cited above, other relevant prior art includes the following: Larsen, U.S. Patent No. 4,565,348; Ohkada et al., U.S. Patent No. 4,347,198; Shepherd, U.S. Patent No. 4,208,364; Mueller et al., EP-A-0 493 320 A2; and Wichterle et al., Re. 27,401 (U.S. Patent No. 3,220,960).

Detailed Description of the Invention of New Zealand Patent Application No 26»008 The inert, displaceable, non-aqueous diluents employed in the process of that invention are selected from the following group: (i) ethoxylated al'-yl glucoside; (ii) ethoxylated bisphenol A; (iii) polyethylene glycol; (iv) mixture of propoxylated and ethoxylated alkyl glucoside; (v) single phase mixture of ethoxylated or propoxylated alkyl glucoside and dihydric alcohol of up to 12 carbon atoms; (vi) adduct of e-caprolactone and C2^alkanediols and triols; (vii) ethoxylated Cj^alkanetriol; and (viii) mixtures of one or more of (i) through (vii).

The diluents employed are ultimately water-displaceable. That is, the shaped gel of a copolymer of said monomers and said diluent is treated with a solvent to remove the diluent and ultimately replace it with water. In most cases, the solvent used to remove the inert diluent will be water (or an aqueous solution such as physiological saline). However, if desired, and depending on the solubility characteristics of the inert diluent used in the process VTN-71 260963 of the invention, the solvent initially used to replace the inert diluent can be an organic liquid such as ethanol, methanol, acetone, glycerol, mixtures thereof, or the like, or a mixture of one or more such organic liquids with water, followed by extraction with pure water (or physiological saline) to produce a shaped gel comprising a copolymer of said monomers swollen with water.

Ethoxylated and propoxylated alkyl glucosides are compositions of Formula (I) : wherein Rl represents a C^alkyl group (preferably methyl), each R individually represents -CH2-CH2- or -CH2-CH(CH3)and the sum of w, x, y, and z is a number within the range of from about 5 to 50 (preferably from 5 to 30) , and represents the total number of ethylene or propylene oxide units in the composition. The diluent represented by Formula (I) can be (i) an ethoxylated alkyl glucoside, (ii) a propoxylated alkyl glucoside, (iii) a mixed ethoxylated/propoxylated alkyl glucoside, or mixture of two or three of (i), (ii), and (iii), provided that a major proportion of the R groups in the mixture of compositions represented by Formula (I) represent groups. Ethoxylated and propoxylated alkyl glucosides are commercially available products that are prepared by reacting ethylene oxide or propylene oxide with an alkyl glucoside.

Ethoxylated or propoxylated glucoside can also be employed in a mixture with a dihydric alcohol of up to 12 carbon atoms, and preferably of up to 6 carbon atoms. The mixture of the two materials should be in such proportions that the mixture is single phase. Illustrative dihydric alcohols t' " ' * elude 0(RQ)yH VTN-71 280963 ethylene glycol, propylene glycol, 1,4-butanediol, 1,6-hexanediol, and the like.

Ethoxylated bisphenol A is a compound of Formula (II): wherein R2 represents -CHj-CHj-, and m + n is a number within --the range of from about 2 to about 100 (preferably from about 4 to about 20), and represents the total number of ethylene oxide units in the composition. Ethoxylated bisphenol A is a commercially available product that is prepared by reacting ethylene oxide with bisphenol A.

Polyethylene glycols are compounds that can be represented by Formula (III): H0-(CH2-CH2O)n-H wherein n represents a number such that the molecular weight of the polyethylene glycol is within the range of from about 300 to about 10,000, and preferably from about 400 to 5000. Such polyethylene glycols are commercially available products.

Adducts of e-caprolactone with C2^ alkanediols and triols, are prepared by reacting e-caprolactone with the C2-6 alkanediol or triol in the presence of a suitable catalyst. Such adducts having molecular weights within the range of from about 300 to about 500 are preferred for use in the invention, Adducts of e-caprolactone and alkanediols and triols are commercially available products.

Ethoxylated triols such as ethoxylated trimethylolpropane, ethoxylated glycerol, ethoxylated 1,2,6-hexanetriol, and the like can also be used as the inert diluent. The molecular weights of VTN-71 28096 such materials will usually be within the range of from about 200 to about 1000.

Mixtures of one or more of the above can also be used in the invention. Preferred examples include mixtures of polyethylene glycol and ethoxylated bisphenol A, mixtures of polyethylene glycol and ethoxylated alkyl glucoside, mixtures of ethoxylated and/or propoxylated alkyl glucoside with ethoxylated bisphenol A, and mixtures of ethoxylated alkyl glucoside with ethoxylated triols.

The monomer mixture used in the process of the invention contains a major proportion of a hydrophilic monomer such as 2-hydroxyethyl methacrylate ("HEMA") as the major component, one or more cross-linking monomers, and optionally small amounts of other monomers such as methacrylic acid. HEMA is one preferred hydrophilic monomer. Other hydrophilic monomers that can be employed include 2-hydroxyethyl acrylate, 2-hydroxypropyl methacrylate, 2-hydroxypropyl acrylate, 3-hydroxypropyl methacrylate, N-vinyl pyrrolidone, glycerol mono-methacrylate, glycerol mono-acrylate, and the like.

Other hydrophilic monomers that can be employed in the invention include polyoxyethylene polyols having one o more of the terminal hydroxyl groups replaced with a functional group containing a polymerizable double bond. Examples include polyethylene glycol, ethoxylated alkyl glucoside, and ethoxylated bisphenol A reacted with one or more molar equivalents of an end-capping group such as isocyanatoethyl methacrylate ("IEM"), methacrylic anhydride, methacroyl chloride, vinylbenzoyl chloride, pr the like, to produce a polyethylene polyol having one or more terminal polymerizable olefinic groups bonded to the polyethylene polyol through linking moieties such as carbamate or ester groups. The Examples below include several representative preparations of such "end-capped" polyoxyethylene polyols.

VTN-71 28096 The cross-linking monomers that can be employed, either singly or in combination, include ethylene glycol dimethacrylate ("EGDMA") , trimethylolpropane trimethacrylate ("TMPTMA") , glycerol trimethacrylate, polyethylene glycol dimethacrylate (wherein the polyethylene glycol has a molecular weight up to, e. g., about 5000), and other polyacrylate and polymethacrylate esters, such as the end-capped polyoxyethylene polyols described above containing two or more terminal methacrylate moieties. The cross-linking monomer is used in the usual amounts, e. g., from about 0.000415 to about 0.0156 mol per 100 grams of reactive monomer mixture. The cross-linking monomer can be a hydrophilic monomer.

Other monomers that can be used include methacrylic acid, which is used to influence the amount of water that the hydrogel will absorb at equilibrium. Methacrylic acid is usually employed in amounts of from about 0.2 to about 8 parts, by weight, per 100 parts of hydrophilic monomer. Other monomers that can be present in the polymerization mixture include methoxyethyl methacrylate, acrylic acid, ultra-violet absorbing monomers, and the like.

A polymerization catalyst is included in the monomer mixture. The polymerization catalyst can be a compound such as lauroyl peroxide, benzoyl peroxide, isopropyl percarbonate, azobisiso-butyronitrile, or the like, that generates free radicals at moderately elevated temperatures, or the polymerization catalyst can be a photo initiator system such as an aromatic a-hydroxy ketone or a tertiary amine plus a diketone. Illustrative examples of photoinitiator systems are 2-hydroxy-2-methyl-l-phenyl-propan-l-one and a combination of camphorquinone and ethyl 4-(f/,N-dimethyl-amino) benzoate. The catalyst is used in the polymerization reaction mixture in catalytically effective amounts, e. g., from about 0.1 to about 2 parts by weight per 100 parts of hydrophilic monomer such as HEMA.

VTN-71 28096 The Examples below illustrate the practice of the invention. Some of the materials that are employed in the Examples are identified as follows: Ethoxylated Bisphenol A [ethoxylated 2,2-bis(4-hydroxy-phenyl) propane] - "Photonol 7025" [m + n in Formula (II) = 8] and "Photonol 7028" [m + n in Formula (II) =4); Ethoxylated trimethylolpropane - "Photonol 7158" [m.w. » 730); 4-Methoxyphenol [hydroquinone monomethyl ether) - "MEHQ"; Isocyanatoethyl methacrylate - "IEM"; N,N-dimethylacrylamide - "DMA"; Polyethylene glycol - "PEG nnnn" wherein the "nnnn" refers to the molecular weight; Ethoxylated (or propoxylated) methyl glucoside - "GLUCAM's E-5, P-10, E-10 and E—20" - [ME-5" signifies a total of 5 ethylene oxide units added to methyl glucoside, "P-io" signifies a total of 10 propylene oxide units added to methyl glucoside, etc.]; Isophorone diisocyanate [ 5-isocyanato-l- (isocyanatomethyl) -1,3,3,-trimethylcyclohexane] - "IPDI"; Polyethylene glycol nnn boric acid ester - "PEG nnn BAE"; l,4-Butanediol boric acid ester - "1,4-BDBAE"; Hydroxyethyl methacrylate - "HEMA"; Methacrylic acid - WMAA"; VTN-71 280963 Ethylene glycol diinethacrylate - "EGDMA"; Trimethylolpropane trimethacrylate - "TMPTHA"; 2-hydroxy-2-methyl-l-phenyl-propan-l-one - "DAROCURE 1173M; Polycaprolactone triol = reaction product (ester) of e-caprolactone with glycerol, m.w. about 300 - "PCLTSOO"; 1,2,6-trihydroxyhexane - Hl,2,6-THH"; Diethylene glycol - "DEGM; Ethylene glycol - "EG"; 1,4-Butane diol - Ml,4-BuDiolM; 1,4-Butane diol/boric acid ester - "l^-BOBAE" 1,2-Propane diol - Ml,2-ProDiolM; Boric acid/glycerol ester - "BAGE" Test Methods The following test methods are employed in the Examples: Test Method 1: PhotoDSC Determinations. (Preferred methods of the present divisional application).

All photocalorimetric measurements were carried out on a DuPont DSC model 910 unit equipped with an 830 photocalorimeter attachment and Omnitherm software. Sample size was 4.5-6.0 mg in every case. Operating conditions were as follows: temperature 45°C, N2 atmosphere (10 min purge at 40 mL/min prior to irradiation), intensity of the UV lamp source was 2.5-3.0 mW/cm2.

VTN-71 280963 Maximum polymerization rates (Rpmax) were calculated from the following equation: ([M]0/Q00) (dQ/dt) raax (1) where Q,,,, and (M]0 denote the total heat evolved by the sample and the methacrylate double bond concentration, respectively, and (dQ/dt) max is the maximum rate of heat evolution observed (at t=Tmax) [Tmax = time to peak exotherm, which coincides with the time at which the polymerization reaches its maximum rate of reaction]. Note that Q,,,, is obtained from the DSC trace by integrating the area under the exotherm (total heat evolved per sample unit mass, i.e. Qm) and multiplying this quantity by the sample mass. [M]0 is obtained by simply calculating the double bond concentration in the formulation, including diluent. The density of the RMM ["Reactive Monomer Mixture"] needs to be determined in order to calculate (M]0 in moles of methacrylate group per unit volume of RMM.

It has been found that T^^ will normally be within the range of from about 0.2 to about 3.5 minutes, and preferably from about 0.4 to about 2.5 minutes, for those inert, displaceable diluents that can be employed successfully in the particular reactive monomer mixture employed. Therefore, a convenient test to determine whether any proposed inert, displaceable diluent can be employed with any given reactive monomer mixture to produce a shaped gel (any shape will do - it need not be in the 5hape of a contact lens for the test) of a copolymer of said monomers that is useful for use as a contact lens, is to determine the Tmax by the PhotoDSC test given above. The useful inert, displaceable diluents for that particular RMM will yield a Tmax within the ranges given above.

VTH-71 280963 It: has also been found that, in most cases, a % conversion of the reactive monomer mix (as determined by dividing the area under the DSC trace up to Tmax by the total area under the DSC trace), in the Photo DSC test given above, of at least 40% at Tmax, and preferably at least 50%, is required in order to produce an optically clear gel.

Test Method 2: RMM and Diluent Density Measurements.

All liquid densities were measured by a method based on Archimedes principle. A Sartorius Research balance fitted with a liquid density kit (available from the manufacturer) was used to carry out all measurements. The method consists in weighing a glass bob in and out of the liquid being tested. The volume of the glass bob 15 is predetermined using a liquid of known density (e.g. water).

The densities of high viscosity liquids (e.g. boric acid esters) were determined with the use of an aluminum pyenometer whose volume had been measured using deionized water at a given temperature.

Test Method 3. Tensile Properties (Modulus, Elongation and Strength).

The lens to be tested is cut to the desired specimen size and 2 5 shape, and the cross sectional area measured. The sample is then attached into the upper grip of a crosshead movement type of testing instrument equipped with a load cell. The crosshead is lowered to the initial gauge length and the sample specimen attached to the fixed grip. The sample is then elongated at a 3 0 constant rate of strain and the resulting stress-strain curve is recorded. The elongation is expressed in percent and the tensile modulus and strength is expressed in psi (lbs/in2) . It has been found that for a shaped gel to be useful as a contact lens, the modulus of the shaped gel should be at least about 20 psi, and 3 5 preferably at least about 25 psi. 28096 VTN-71 Test Method 4. Gravimetric Water Content.

Samples for gravimetric water content measurements were prepared as follows: A number of 20 mm diameter x 3 mm deep cylindrical polystyrene cavities were hand filled with degassed HEMA-based formulations and cured for approximately 20 minutes under fluorescent tubes in a N2 atmosphere. The total measured energy dose was 1.2-1.6 Joules/cm2. The polymer/diluent disks were demolded from the polystyrene cavities using a hot plate. The disk were then cut with a no.7 cork bore to obtain a 9-10 mm diameter disk. Typically, the polystyrene cavities are filled with sufficient reactive monomer mix to obtain a 1-1.5 mm thick disk. The diluent swollen polymer disks are hydrated in deionized water for 3 hrs at 70°C, and subsequently allowed to remain for an additional 3 days at room temperature. The disks are then removed from the DI (de-ionized) water bath, air dried for 10-15 hrs, and subsequently vacuum dried (< 1.5 mm Hg) at 100°C for 2 hrs. The weight of each disk is taken, and the disk are then placed in physiological saline for 2 days. The polymer disks are then removed from the saline solution, blotted carefully to remove surface water, and weighed again. The water content is then calculated as follows: % Water = 100 (m^, - m^J/m^, (2) Where mdry and m^ denote the weight of the polymer disks before and after hydration, respectively.

Test Method 5. Oxygen Permeability (Dk) The oxygen permeability was measured by the method of Fatt et al., "Measurement of Oxygen Transmissibility and Permeability of Hydrogel Lenses and Materials", International Contact Lens Clinic, Vol. 9/No.2, March/April 1982, p 76. A polarographic oxygen sensor 280963 VTN-71 consisting of a 4 mm diameter gold cathode and a silver-silver chloride ring anode is used in this method. The measured oxygen permeability is denoted by Dk, where D represents the diffusion coefficient for oxygen in the material being tested, and k is the solubility of oxygen in the material. The permeability (Dk) units are (cm2/s) (mL 02/ mL • mm Hg) .

The following six examples illustrate the preparation of reactive cross-linkers (Examples 1-4) , and two prior art diluents 10 (Examples 5 and 6) : Example 1 Synthesis of dicapped ethoxylated Bisphenol A (BPA 890) To a 5L three neck round bottom flask are added 728g (1.255 mol) of dried Photonol 7025 (molecular weight = 580g/mol) , 1.5L of dry acetonitrile, l.Og of 4-methcxy phenol (MEHQ) and 0.5g of stannous octoate (approximately 0.1 mol % relative to diol). After these 2 0 components are added, the resulting solution is purged with dry 02 ^ for 30-45 minutes (a gas diffuser is used for this purpose). After the 02 purge is completed, 365g (2.35 mol) of isocyanatoethyl methacrylate (IEM) and 730g of acetonitrile are charged to a 1L addition funnel (this operation is preferably carried out under 25 N.,) .

The contents of the addition funnel (i.e. the IEM solution) are then added, dropwise with vigorous stirring, to the 5L round bottom flask. The addition should take about 2-3 hours to complete. 3 0 After the IEM addition is complete, the addition funnel is rinsed with 50-100 mL of acetonitrile. The progress of the reaction is followed monitored by following the disappearance of the NCO absorption at 2270 cm'1 in the infrared spectra. The acetonitrile is removed under reduced pressure and the resultant viscous liquid 3 5 dicapped bisphenol A 890 is used as prepared. 280963 VTN-71 Example 2 Synthesis of dicapped polyethylene glycol (PEG) 4000 A total of 200g (0.05 mol) of dry PEG 4000 is placed into a 1L three neck round bottom flask equipped with mechanical agitation, and a gas-inlet tube. A dry nitrogen blanket is established in the reaction vessel. To this flask is added 375g of dry acetonitrile and the PEG 4000 is allowed to sit until it has completely dissolved. Subsequently, two drops of stannous octoate and 500 ppm of MEHO, are added. To a 100 mL addition funnel are added 15.52g (0.100 mol) of IEM and 50 mL of acetonitrile. After the addition of the IEM is completed, the reaction progress is monitored by following the disappearance of the NCO absorption at 2270"1 in the infrared spectra. After the reaction is completed, the acetonitrile is removed under reduced pressure and the resultant white waxy dicapped PEG 4 000 is used as is.

Example 3 Synthesis of dicapped polyethylene glycol (PEG) 4500 A total of 22534 g (0.05 mol) of dry PEG 4500 is placed into a 1L three neck round bottom flask equipped with mechanical agitation and a gas inlet-tube. The system is flushed successively with dry nitrogen and dry oxygen. To this flask are added 375g of dry acetonitrile and the PEG 4500 is allowed to sit until it has completely dissolved. Subsequently, 2 drops of stannous octoate and 500 ppm MEHQ are added. To a 100 mL addition funnel are added 15.52g (0.100 mol) of IEM, and 50 mL of acetonitrile. After addition of the IEM is completed, the reaction progress is monitored by following the disappearance of the NCO absorption at 2270 cm*1, After the reaction is completed, the acetonitrile is removed under reduced VTN-71 280963 pressure and the resultant white waxy dicapped PEG 4500 is used as is.

Example 4 Synthesis of GLUCAM E-20/polyethylene glycol (PEG) 4500 Derivative A total of lOOg of dry PEG 4500 (0.022 mol) is placed into a three-neck 1L round bottom flask equipped with mechanical agitation and a gas-inlet tube. The system is then flushed successively with dry nitrogen and dry oxygen. To this flask is then added 375g of dry acetonitrile and the PEG 4 500 is allowed to sit until it has completely dissolved. Subsequently, 2 drops of stannous octoate and 500 ppm of MEHQ are added. To an addition funnel are added 3.41g (0.022 mol) of IEM and 10 mL of acetonitrile. After the addition of the IEM is completed, the reaction progress is followed by monitoring the disappearance of the NCO absorption at 2270 cm"1 in the infrared spectra. When this peak has completely disappeared, the above reaction mixture is transferred to a 500 mL addition funnel. The contents of the addition funnel are slowly added to a three necked round bottom 2L flask containing a solution of 200g of dry acetonitrile and 4.89g (0.022 mol) of isophorone diisocyanate (IPDI). Provisions should be made for efficient mechanical agitation throughout the addition. After the addition is completed, the reaction is followed by monitoring the disappearance of the PEG hydroxy 1 peak centered at 3400 cm*1 in the infrared spectrum. To the above mixture are then added 6.0g (0.006 mol) of GLUCAM E-20 in 50 mL of acetonitrile. After the NCO absorption at 2270 cm'1 has disappeared, the acetonitrile is removed under reduced pressure and the resultant white powder GLUCAM E-20/PEG 4500 solid is used as is. 28096 VTN-71 Example 5 Synthesis of PEG 400 Boric Acid Ester Diluent (PEG 400 BAE) A total of 400g (1 mol) of polyethylene glycol 400 (PEG 400) is placed into a 2L rotary evaporator flask. To this flask are added 123.7g (2.0 mols) of boric acid. The flask is placed on a rotary evaporator and the pressure is slowly reduced to 0.5-1.0 mm Hg. After full vacuum is established, the temperature of the bath is slowly raised to 92°C. Water is recovered from the reaction as the boric acid ester is formed. The clear viscous liquid PEG 400 BAE is used as is. (This diluent is illustrative of the prior art diluents disclosed by Larsen et al., U.S. Patent Nos. 5,039,459 and 4,889,664. ] Example 6 Synthesis of 1,4-Butanediol Boric Acid Ester (1,4-BDBAE) A total of 277.7g (4.5 mols) of boric acid was placed into a 3L rotary evaporator flask. To this flask was added l,223g of 1,4-butanediol (13.6 mols). The flask is then placed on a rotary evaporator and the pressure is slowly reduced to 0.5-1.0 mm Hg. After full vacuum is established, the temperature of the bath is slowly raised to 85°C at approximately 5°C per 20 minutes. Water is recovered from the reaction as the boric acid ester is formed. The clear viscous liquid 1,4-BDBAE is used as is. [This diluent is illustrative of the prior art diluents disclosed by Larsen et al., U.S. Patent Nos. 5,039,459 and 4,889,664.] Examples 7-35 In these examples, various diluents were employed to prepare soft contact lenses from the following reactive monomer mixture: 280963 VTN-71 A blend is prepared using 96.8% by weight of HEMA, 1.97% methacrylic acid, 0.78% ethylene glycol dimethacrylate (EGDMA), 0.1% of trirnethylolpropane trimethacrylate (TMPTMA) and 0.34% of DAROCUR 1173. To this monomer mix is added the inert, displaceable diluent being evaluated. After thoroughly mixing the formulation at ambient temperature, the mixture is allowed to stir under reduced pressure (40 mm Hg) for 30 min (at 25°C) and subsequently transferred to contact lens molds. The filled molds are exposed to UV light (wavelength = 300-380 nm, dose = 1.2-1.6 Joules/cm2) for 20 minutes at approximately 50°C. The molds are then separated, and placed in physiological saline for 3.0 hrs at 70°C to remove the inert diluent and any residual unreacted monomers. After this initial hydration period the lenses are allowed to equilibrate to room temperature in a fresh bath of physiological saline. The lenses are then tested according to Test Methods 3, 4 and 5.

The Tables below display the diluents evaluated, the monomer/diluent ratios, and the results of the tests made in accordance with Test Methods 3', 4 and 5, for Examples 7-35: VTN-71 280963 Example 7 Example 8 Example 9 | Composition (%): HEMA 96.8 96.8 96.8 MAA 1.97 1.97 1.97 EGDMA 0.78 0.78 0.78 TMPTMA 0.1 0.1 0.1 Darocur 1173 C.34 0.34 0.34 1 Diluent: GLUCAM E20 GLUCAM E10 GLUCAM E5 Mon./Dil. Ratio 48:52 48:52 48: 52 Properties: Modulus (psi) 34+4 36±3 33±4 1 * Elongatiion 149+50 148±63 174146 Tens. Strength (psi) 40+10 40+12 46+9 Water Content (%) 57 . 4 ±. 7 54.4±.2 59.9±.3 Hydrogel Clear Clear Clear Kinetic Parameters: Tmax (min) 1.75 1.65 1.48 Conv. @ Tmax (%) 64 . 5 64.7 61.4 VTN-71 280963 Example 10 Control (Prior art) Example 11 Control (Prior art) Example 12 | Composition (%): HEMA 96.8 96.8 96.8 I MAA 1. 97 1.97 1.97 1 EGDMA 0.78 0.78 0,78 1 TMPTMA 0.1 0.1 0.1 Darocur 1173 0.34 0.34 0.34 Diluent: 1,2,6-THH Glycerol Phot 7158 Mon./Dil. Ratio 48:52 48:52 48:52 | Properties: Modulus (psi) ±2 40±3 27±2 V Elongation 183±53 119±33 174+49 Tens. Strength (psi) 36±80 37±72 3 7 ±7 Water Content (%) 59.9±.1 60.6±.6 59.5±.3 Hydrogel Clear Clear Clear Kinetic Parameters: Tmax (min) 1.80 1.53 2.15 Conv. @ Tmax (%) 73.4 70.9 65.1 TN—7 1 280963 Example 13 Example 14 Example 15 1 Composition (%): HEMA 96.8 96.8 96.8 1 MAA 1.97 1.97 1.97 I EGDMA 0.78 0.78 0.78 1 TMPTMA 0.1 0.1 0,1 I Darocur 1173 0.34 0.34 0.34 Diluent: Phot 7025 Phot 7028 PCLT300 Mon./Dil. Ratio 48:52 48:52 48:52 I Properties: Modulus (psi) 33±3 34+3 29+3 % Elongation 200+76 191+48 179+55 | Tens. Strength 1 (Psi) 48115 4719 4019 | Water Content (%) 62.21.2 59.31.5 61.01.6 Hydrogel Clear Clear Clear Kinetic Parameters: Tmax (min) 1.52 1.47 1.72 Conv. @ Tmax (%) 62.2 61.2 69.0 VTN-71 280963 Example 16 Control (Prior art) Example 17 Control (Opaque) Example 18 8 Control 8 (Prior 8 art) 8 Composition (%) : HEMA 96.8 96.8 96.8 1 MAA 1.97 1.97 1.97 | EGDMA 0.78 0.78 0.78 TMPTMA 0.1 0. 1 0.1 Darocur 1173 0.34 0.34 0.34 Diluent: 1,4-BDBAE GLUCAM P10 DEG | | Mon./Dil. Ratio 48:52 48:52 48:52 I Properties: Modulus (psi) 27+2 16±4 j 14+3 % Elongation 124+20 266±35 203+56 a Tens. Strength (psi) 28±35 48±12 +4 Water Content (%) 62.6±.6 63.5±.5 CO • +1 • in VO Hydrogel Clear Opaque Clear Kinetic Parameters: 1 Tmax (min) 1.08 0.87 4.83 U Conv. @ Tmax (%) 59.5 31.5 83. 3 280 ^TN-71 Example 19 Control (Prior art) Example 20 Control (Prior art) Example 21 1 Composition (%): I HEMA 96.8 96.8 96.8 | MAA 1.97 1.97 i.97 1 EG DMA 0.78 0. 78 0.78 B TMPTMA 0.1 0.1 0.1 8 Darocur 1173 0.34 0. 34 0.24 Diluent: PEG 400BAE BAGE PEG 400 I Mon./Dil. Ratio 48:52 48:52 48:52 8 Properties: Modulus (psi) 33+2 34+2 +3 8 % Elongation 134±29 114±42 179+35 | Tens. Strength (psi) ±5 34±8 3.9+2 I Water Content (%) 60.4±.2 62.7±.3 62.7±.8 Hydrogel Clear Clear Clear Kinetic Parameters: Tmax (min) 0.52 1.37 3 .61 Conv. e Tmax (%) 34.8 68.8 68.9 280963 VTN-71 • Example 22 (Low modulus) Example 23 Control (Prior art) Example 24 Control (Prior art) Composition (%): • HEMA 96.8 96.8 96.8 MAA 1.97 1.97 1.9*7 I EGDMA 0.78 0.78 0.78 1 TMPTMA 0.1 0.1 0.1 Darocur 1173 0.34 0.34 0. 34 | Diluent: 1,4-BuDiol 1,2-ProDiol EG | Mon./Dil. Ratio 48:52 48:52 48:52 I • Properties: Modulus (psi) 13+1 16+1 23±2 1 % Elongation 215+66 215+53 168±30 | • Tens. Strength (psi) 23±6 28±6 27+4 8 Water Content (%) 66.4±.6 — 59.91.2 Hydrogel Clear Clear Clear Kinetic Parameters: Tmax (min) 3.42 .48 4.80 Conv. § Tmax (%) 65.4 71.5 75.0 28 0 9 6 3 VTN-71 Example 25 Control (Opaque) Example 26 Control (Opaque) Example 27 | Control | (Opaque) 1 Composition (%): HEMA 96.8 96.8 96.8 1 MAA 1.97 1.97 1.97 | EGDMA 0.78 0.78 0.78 1 TMPTMA 0.1 0.1 0.1 j Darocur 1173 0.34 0.34 0.34 Diluent (%) : GLUCAM P-10 95 85 70 GLUCAM E-10 I Mon./Dil. Ratio 48:52 48:52 48:52 | Properties: Modulus (psi) 12±1 1712 2112 1 % Elongation 282±56 233+45 192142 Tens. Str. (psi) 4 3 ±9 4418 40111 Water Content (%) 68.71.4 69.81.6 68.91.4 Hydrogel Opaque Opaque Opaque B Kinetic Parameters: Tmax (min) 0.85 0.98 1.14 8 Conv. § Tmax (%) 28.8 38. 5 49.1 VTN-71 Example 28 Example 29 | Composition (%): HEMA 96.8 96.8 MAA 1.97 1.97 EGDMA 0.78 0.78 TMPTMA 0.1 0.1 Darocur 1173 0.34 0.34 Diluent (%) : GLUCAM P-10 40 GLUCAM E-10 60 80 Mon./Dil. Ratio 48:52 48:52 Properties: Modulus (psi) 38±3 38±4 % Elongation 162+32 199±55 Tens. Strength (psi) 4 4 ±9 49±11 Water Content (%) 59.5±.2 58.4±.5 Hydrogel Clear Clear Kinetic Parameters: Tmax (min) 1.47 1.56 Conv. @ Tmax (%) 62.2 64. 1 VTN-71 280963 • Example 30 Control (Opaque) Example 31 Control (Opaque) Example 32 I Composit ion (%): A HEMA 96.8 96.8 96.8 w MAA 1.97 1.97 1.97 EGDMA 0.78 0.78 0.78 TMPTMA 0.1 0.1 0.1 Darocur 1173 0.34 0.34 0.34 Diluent (%): GLUCAM P-10 95 85 . 70 1,4-BuDiol Mon./Dil. Ratio 48:52 48:52 48:52 • Properties: Modulus (psi) 14±1 21±3 ±4 j % Elongation 209±49 194+43 175±59 | Tens. Str. (psi) 3 5±9 41±10 31±10 | Water Content (%) 69.3±.6 70.1+.3 62.2±.3 | Hydrogel Opaque Opaque Clear | Kinetic Parameters: Tmax (min) 0.96 1.21 2.24 1 Conv. § Tmax (%) 37.5 51.6 66.2 VTN-71 280963 • Example 33 (Modulus borderline) Example 34 (Modulus borderline) Example 35 8 (Modulus tt border- 1 line) I Compos it ion (%): • HEMA 96.8 96.8 96.8 1 MAA 1.97 1.97 1,97 1 EGDMA 0.78 0.78 0.78 | TMPTMA 0.1 0.1 0. 1 1 Darocur 1173 0.34 0. 34 0.34 I Diluent (*): GLUCAM P-10 50 40 [ 1,4—BuDiol 50 60 80 1 Mon./Dil. Ratio 48:52 48:52 48:52 | — Properties: Modulus (psi) ±3 21±2 i9±l I % Elongation 160±41 201±63 258±80 > Tens. Str. (psi) 23±7 31+60 36+90 Water Content (%) 62.2±.3 62.4±.4 62.9±.1 Hydrogel Clear Clear Clear Kinetic Parameters: Tmax (min) 2.81 3.23 3.43 Conv. § Tmax (%) 69. 4 68.9 60. 2 280963 VTN-71 Examples 3 6-39 In these examples, Photonol 7025 was employed as the diluent in conjunction with a reactive monomer mix containing HEMA, the reactive cross-linker of Example 4, and Darocur 1173, in various proportions. The following is an illustrative preparation: A monomer mixture containing of 25% by weight of the PEG 4500-GLUCAM E-20 derivative described in Example 4, 0.35% DAROCUR 1173, 10 and 74.7% of HEMA was mixed with Photonol 7025, an inert, displaceable diluent in such amounts as to make up a 48% monomer, 52% diluent blend. After thoroughly mixing the above formulation at 65°C, the mixture is allowed to stir under reduced pressure (40 mm Hg) for 30 min (at 65°C) and subsequently transferred to contact 15 lens molds. The filled molds are exposed to UV light (wavelength = 300-380 nm, dose = 1.2-1.6 Joules/cnu) for 20 minutes at approximately 65°c. The molds are then separated, and placed in physiological saline for 3.0 hrs at 70°C to remove the inert diluent and any residual unreacted monomers. After this initial 20 hydration period the lenses are allowed to equilibrate to room temperature in a fresh bath of physiological saline. The lenses are then tested according to Test Methods 3, 4 and 5.

The following table displays the proportions used in the 25 reactive monomer mixtures and the results of the tests made in accordance with Test Methods 3, 4 and 5 for Examples 36-39: 280963 VTN-71 Example 36 (Modulus borderline) Example 37 (Modulus borderline) Example 38 (Modulus borderline) Example 39 (Modulus borderline) 1 Composition (%): 1 HEMA 74.7 64.7 49.7 39.7 | PEG4500-GLUE20 50 60 B Darocur 1173 0.35 0. 35 0.35 0.35 Diluent: Pho 7025 Pho 7025 Pho 7025 Pho 7025 Mon./Dil. Ratio 48:52 48:52 48:52 48:52 1 Properties: I 8 Modulus (psi) 22±1 19±1 22±8 2013 | 1 % Elongation 266±42 218±44 180±76 160±41 | I Tens. Str. (psi) ±5 ±5 ±2 23±7 | 1 | Water Content (\) 55±2 69±1 70±1 80+2 1 1 Hydrogel Clear Clear Clear Clear 1 1 Dk 31.5 40.3 60.5 4!.3 I 280963 VTN-71 Examples 40-44 In these examples, Photonol 7025 was used as the diluent in conjunction with a reactive monomer mixture ot HEMA, MAA, PEG 4500XL (Example 3), BPA890XL (Example l), and Darocur 1173, in various proportions. The following is an illustrative preparation: A reactive monomer blend made up of 5.78% by weight of the PEG 4500 cross-linker described in Example 3, 11.1% of the ethoxylated bisphenol A cross-linker described in Example 1, 0.34% DAROCUR 1173, 1.98% methacrylic acid, and 80.8% HEMA was mixed with enough Photonol 7025 to make up a 48% monomer mix and 52% diluent. Aft£r thoroughly mixing the above blend at 65°C, the mixture is allowed to stir under reduced pressure (40 mm Hg) for 30 min (at 65°C) and subsequently transferred to contact lens molds. The filled molds are exposed to UV light (wavelength = 300-380 nm, dose = 1.2-1.6 Joules/cnw) for 20 minutes at approximately 65°C. The molds are then separated, and placed in physiological saline for 3.0 hrs at 70°C to remove the inert diluent and any residual unreacted monomers. After this initial hydration period the lenses are allowed to equilibrate to room temperature in a fresh bath of physiological saline. The lenses are then tested according to Test Methods 3, 4 and 5.

The following table displays the proportions of the monomers and the results of the tests made in accordance with Test Methods 3, 4 and 5 for Examples 40-44: VTN-71 280963 Example 40 Example 41 Example 42 1 Composition (%): HEMA 80.8 75.3 64.5 1 MAA 1.98 1.98 1.98 J PEG 4 500XL .78 11. 1 22.1 1 BPA890XL 11.1 11.1 11.1 I Darocur 1173 0.34 0.34 0.34 I Diluent: Phot 7025 Phot 7025 Phot 7025 I Mon./Dil. Ratio 48:52 48:52 48:52 1 Properties: Modulus (psi) 68±6 84±9 80±9 % Elongation 57±16 59 + 13 90+27 I Tens. Strength (psi) 48 + 12 51±9 7 6±19 I Water Content (%) 36±1 41±1 52±1 j Hydrogel Clear Clear Clear | Dk .5 23.0 28.8 VTN-71 280963 Composition (%) HEMA MAA Example 43 53.9 1.98 PEG 4500XL BPA890XL Darocur 1173 Diluent: Mon./Dil. Ratio Properties: Modulus (psi) % Elongation Tens. Strength (psi) 32.7 11.1 0.34 Phot 7025 48:52 84±8 84±22 73+16 water Content (%) Hydrogel Dk 59+1 Clear .7 Example 44 41.9 1.98 44.7 11.1 0. 34 Phot 7025 48:52 81+9 80+32 78+34 63±1 Clear 39.7 280963 VTN-71 Examples 45-59 In these examples, Photonol 7025 was used as the diluent in conjunction with a reactive monomer mixture of HEMA, MAA, PEG 4000XL (Example 2), diglycidyl bisphenol A dimethacrylate (Example l), and Darocur 1173, in various proportions. The following is an illustrative preparation: A reactive monomer blend made up of 90.6% by weight of HEMA, 1.98% 10 by weight of MAA, 5% by weight of the PEG 4000XL cross-linker described in Example 2, 2.04% by weight of the diglycidyl bisphenol A dimethacrylate cross-linker of Example 1, and 0.34% DAROCUR 1173, was mixed with enough Photonol 7025 to make up a 48% monomer mix and 52% diluent. After thoroughly mixing the above blend at 65°C, 15 the mixture is allowed to stir under reduced pressure (40 mm Hg) for 30 min (at 65°C) and subsequently transferred to contact lens molds. The filled molds are exposed to UV light (wavelength - 300-380 nm, dose = 1.2-1.6 Joules/cn^) for 20 minutes at approximately 65°C. The molds are then separated, and placed in physiological 20 saline for 3.0 hrs at 70*C to remove the inert diluent and any residual unreacted monomers. After this initial hydration period the lenses are allowed to equilibrate to room temperature in a fresh bath of physiological saline. The lenses are then tested according to Test Methods 3, 4 and 5.

The following tables display the proportions of the monomers and the results of the tests made in accordance with Test Methods 3, 4 and 5 for Examples 45-59: 280963 VTN-71 1 Example 45 Example 46 Example 47 Example 48 1 Composition (*): | HEMA 90.6 85.6 75.6 65.6 | MAA 1.98 1.98 1.98 1.98 B PEG 4000XL "30 1 DGBPA510 2.04 2.04 2.04 2.04 | Darocur 1173 0.34 0. 34 0.34 .,9*34 Diluent: Phot 7025 Phot 7025 Phot 7025 Phot 7025 8 Mon./Dil. Ratio 48:52 48:52 48:52 48:52 | Properties: 8 Modulus (psi) 43±3 44±3 50±2 49±6 % Elongation 133±35 148±34 135±35 139±38 Tehs. Strength (psi) 44±11 46 + 10 | 49±9 i 53+13 Water Content (%) 42 + 1 45±1 52±1 56±1 Hydrogel Clear Clear Clear Clear Dk .3 33.6 39.4 42.7 Kinetic Parameters: Tmax (min) 1.52 1.19 1.26 Conv. 6 Tmax (%) 53.8 59. 3 49.2 " 1 280963 VTN-71 1 Example 49 Example 50 Example 51 Example 52 1 Composition (%) : HEMA 55.6 89.2 84.2 73.8 MAA 1.98 1.98 1.98 1.98 PEG 4000XL 40 DGBPA510 2.04 3.84 2.04 2.04 Darocur 1173 0.34 0.34 0.34 0.34 n B Diluent: Phot 7025 Phot 7025 Phot 7025 Phot 7025 1 Mon./Dil. Ratio 48:52 48:52 48: 52 48:52 1 Properties: 1 . Modulus (psi) 47+7 60+4 60±5 62+3 | \ Elongation 118+33 94+29 12 6±25 129+33 1 Tens. Strength J (psi) 44±12 48±11 64+15 64±15 8 Water Content (%) 61±1 37±1 40+1 47±1 J 1 Hydrogel Clear Clear Clear Clear | 8 Dk 49.5 .4 27.6 .1 280963 VTN-71 Example 53 Example 54 Example 55 Example 56 1 Composition (%): HEMA 63.8 53.8 91.6 86.6 MAA 1.98 1.98 0.98 0.98 PEG 4000XL 40 DGBPA510 2.04 2.04 2.04 2.04 8 Darocur 1173 0.34 0.34 0.34 0.34 I Diluent: Phot 7025 Phot 7025 Phot 7025 Phot 7025 | Mon./Dil. Ratio 48: 52 48:52 48:52 48:52 | Properties: Modulus (psi) 60±4 52 + 11 43+3 49+5 fl % Elongation 109141 108±27 124+37 131+37 | Tens. strength (psi) 50±15 52±13 42+9 48±10 I Water Content (%) 54+2 57±1 48±1 52±1 | Hydrogel Clear Clear Clear clear | Dk 41.4 46.3 .8 48.10 | Kinetic Parameters: Tmax (min) — — 1.18 1.13 Conv. ? Tmax (%) — 62.0 60. 0 VTN-71 2809 Example 57 Example 58 Example 59 | Composition (%): HEMA 76.6 66.6 56.6 n MAA 0.98 0.98 0.98 PEG 4000XL 40 DGBPA510 2.04 2.04 2.04 Darocur 1173 0.34 0.34 0.34 Diluent: Phot 7025 Phot 7025 Phot 7025 Mon./Dil. Ratio 48:52 48:52 48:52 Properties: Modulus (psi) 49± 3 48±5 46±2 % Elongation 141±35 123±43 130±51 | Tens. Strength (psi) 53±10 49±14 52±18 Water Content (%) 60±1 65±1 70±1 Hydrogel Clear Clear Clear Dk 31.1 40.2 44.0 Kinetic Parameters: Tmax (min) 0.89 0.82 0.68 Conv. § Tmax (%) 53. 4 52.7 46.4 28 OS VTN-71 Examples 60-69 > In these examples, GLUCAM E20 was used as the diluent in conjunction with a reactive monomer mixture of HEMA, MAA, PEG 5 4500XL (Example 3} , diglycidyl bisphenol A dimethacrylate (Example l) , and Darocur 1173, in various proportions. The following is an ^ illustrative preparation: A reactive monomer blend made up of 5.7% by weight of the PEG 4500 10 cross-linker described in Example 3, 4.98% of the ethoxylated bisphenol A described in Example 1, 0.35% DAROCUR 1173, 1.98% methacrylic acid, and 87.0% HEMA was mixed with enough GLUCAM E-20 to make up a 48% monomer mix and 52% diluent. After thoroughly mixing the above blend at 65°C, the mixture is allowed to stir 15 under reduced pressure (40 mm Hg) for 30 min (at 65°C) and subsequently transferred to contact lens molds. The filled molds are exposed to UV light (wavelength = 300-380 nm, dose = 1.2-1.6 Joules/cm2) for 20 minutes at approximately 65°C. The molds are then separated, aind placed in physiological saline for 3.0 hrs at 20 70 °C to remove the inert diluent and any residual unreacted ^ monomers. After this initial hydration period the lenses are allowed to equilibrate to room temperature in a fresh bath of physiological saline. The lenses are then tested according to Test Methods 3, 4 and 5.

I The following tables display the proportions of the monomers and the results of the tests made in accordance with Test Methods 3, 4 and 5 for Examples 60-69: 280963 VTN-71 Example 60 Example 61 Example 62 Example 63 B Composition (%): HEMA 87.0 81.8 73.7 59.4 MAA 1.98 1.98 1.98 1.98 PEG 4500XL .7 .9 19 33.3 BPA890XL 4.98 4 .98 4.98 4.98 8 Darocur 1173 0.35 0. 35 0.35 0.35 | Diluent: GLUCAM E20 GLUCAM E20 GLUCAM E20 GLUCAM E20 | Mon./Dil. Ratio 48:52 48:52 48:52 48:52 fl Properties: Modulus (psi) 63±7 63±5 6614 7015 % Elongation 119±23 120±3 3 142135 145134 Tens. Strength (psi) 33±12 34114 46118 51119 Water Content (%) 56±1 5811 6211 6811 Hydrogel Clear Clear Clear clear Dk .9 27.7 32.3 38.7 -4 0 — 280963 VTN-71 Composition (%) : HEMA MAA Example 64 48.5 1.98 Example 65 83.1 1.98 Example 66 77.9 1.98 PEG 4 500XL 44.2 .7 .9 BPA890XL 4.98 8.9 8.9 Darocur 1173 0.35 0. 35 0.35 Diluent: Mon./Dil. Ratio Properties: GLUCAM E20 GLUCAM E20 GLUCAM E20 48:52 48:52 48:52 Modulus (psi) % Elongation Tens. Strength (psi) Water Content (%) Hydrogel Dk 80±12 159+36 68±24 71+1 Clear 4S.0 86±8 89+4 114+14 120+30 40115 53±1 Clear 21.0 43 + 19 55+1 Clear 23 .4 VTN-71 280963 <§ 9 Composition (%) : HEMA MAA PEG 4500XL 69.8 1.98 19 BPA890XL Darocur 117 3 8.9 0.35 Diluent: Mon./Dil. Ratio Properties: Modulus (psi) % Elongation Tens. Strength (psi) Water Content (%) Hydrogel Dk GLUCAM E20 48:52 55.5 1.98 33. 3 8.9 0.35 GLUCAM E20 48:52 89±5 127±35 49±25 60±1 Clear 29.2 96±6 163±25 82±21 65±1 Clear 34 .5 44.6 1.98 44.2 8.9 0.35 GLUCAM E20 48:52 102±6 162+25 87±15 69±2 Clear 40.3 280963 VTN-71 Example 70 (Synthesis of monocapped polyethylene glycol 3350) "PEG 3350MC" A total of 200g (0.060 mol) of dry PEG 3350 is placed into a three neck flask equipped with mechanical agitation, and a gas inlet tube. The system is flushed with dry nitrogen and subsequently, dry oxygen. To the PEG 3350 are added 600g of dry acetonitrile and allowed to mix until all of the PEG 3350 has completely dissolved. Subsequently, 2 drops of stannous octoate and 500 ppm of MEHQ are added. Via a dropping funnel are added 8.69g (0.056 mol) of isocyanatoethyl methacrylate. The reaction is allowed to proceed at room temperature for 24-28 hours. The progress of the reaction is followed by the disappearance of the NCO absorption at 2270 cm"1 in the infrared spectra. The acetonitrile is then removed under reduced pressure and the white waxy monocapped PEG 3350 is used as is.

Examples 71-107 In these examples, various diluents and diluent mixtures were used in conjunction with a reactive monomer mixture of HEMA, DMA, PEG 4000XL (Example 2), diglycidyl bisphenol A dimethacrylate (Example 1), PEG 3350MC (Example 70), and Darocur 1173. The following is an illustrative preparation: A reactive monomer blend was prepared using 64.7% by weight HEMA, 20.0% AT,W-dimethyl acrylamide (DMA), the dicapped PEG 4000 cross-linker described in Example 2, 2.0% of the ethoxylated bisphenol A cross-linker described in Example l, 6.0% of the monocapped PEG 3 350 described in Example 70, and 0.34% of Darocur 1173. To 60% by weight of this monomer blend was added 40% of PEG 1000 as an inert, displaceable diluent. After thoroughly mixing the above blend at 60°C, the mixture is allowed to stir under reduced pressure (40 mm Hg) for 30 min (at 60°C) and subsequently transferred to contact lens molds. The filled molds are exposed to UV 28096 VTN-71 light (wavelength = 300-380 nm, dose = 1.2-1.6 Joules/cnw) for 20 minutes at approximately 60"C. The molds are then separated, and placed in physiological saline for 3.0 hrs at 70°C to remove the inert diluent and any residual unreacted monomers. After this initial hydration period the lenses are allowed to equilibrate to room temperature in a fresh bath of physiological saline. The lenses are then tested according to Test Methods 3, 4 and 5.

The following tables display the proportions of the monomers and the results of the tests made in accordance with Test Methods 3, 4 and 5 for Examples 71-107: e VTN-71 2809 1G Example 71 Example 72 Example 73 | (Modulus B border- 1 line) | Composition (%): HEMA 64.7 64.7 64.7 | DMA I PEG 4000XL 7 7 7 I PEG 3 350MC 6 6 6 BPA890XL 2 2 2 Darocur 117 3 0. 34 0.34 0. 34 Diluent: PEG 1000 PEG 750 PEG 600 1 Mon./Dil. Ratio 60:40 60:40 60:40 1 • Properties: Modulus (psi) 22 19 1 % Elongation 191 200 191 B Tens. Str. (psi) 27 21 24 | Water Content (%) 63.0 61.7 61.3 I Hydrogel Clear Clear Clear Kinetic Parameters: Tmax (min) 3.50 3 .90 4.00 Conv. at Tmax (%) 59.0 58.0 61. 0 VTN-71 • Example 74 (Modulus borderline) Example 75 8 Control | (Prior | art) | Composition (%): • HEMA 64.7 64.7 DMA PEG 4000XL 7 7 PEG 3350MC 6 6 BPA890XL 2 2 Darocur 1173 0.34 0. 34 Diluent: PEG 400 PEG 400BAE j Mon./Dil. Ratio 60:40 60:40 1 • j Properties: Modulus (psi) 18 51 -1 % Elongation 189 122 | • Tens. Strength (psi) 26 46 Water Content (%) 62.1 61.3 Hydrogel Clear Clear Kinetic Parameters: Tmax (min) 4.30 0.34 Conv. at Tmax (%) 63.0 39.0 280963 VTN-71 LO % Example 76 Example 77 Example 78 1 Coiaposition (%) : HEMA 64.7 64.7 64.7 1 DMA I PEG 4 000XL 7 7 7 PEG 3 350MC 6 6 6 1 BPA890XL 2 2 2 I Darocur 1173 0. 34 0.34 0.34 | j Diluent: GLUCAM E10 GLUCAM E20 Phot 7025 H Mon./Dii.. Ratio 60:40 60:40 60:40 Properties: 1 I Modulus (psi) 53 51 50 % Elongation 135 133 165 Tens. Strength (psi) 47 44 49 Water Content (%) 60.8 60.5 61.1 Hydrogel Clear Clear Clear Kinetic Parameters: Tmax (min) 1. 10 0.90 1.10 Conv. at Tmax (%) 42 . 0 44.0 39.0 280963 VTN-71 Example 79 Example 80 Example 81 Example 82 1 Composition (%): 1 HEMA 64.7 64.7 64.7 64.7 1 DMA 1 PEG 4000XL 7 7 7 ... 7 I BPA890 2 2 2 2 1 PEG 3350MC 6 6 6 6 1 Darocur 1173 0. 34 0. 34 0.34 0.34 Diluent; (%) : PEG 400 90 75 60 50 H Photonol 7025 40 50 8 Mon./Dil. Ratio 60:40 60:40 60:40 60:40 i Properties: B Modulus (psi) 27 31 39 | % Elongation 200 210 190 186 8 1 Tens. Strength I (psi) 28 31 29 | Water Content (%) 62.1 61.9 62.0 61.2 j 8 Hydrogel Clear Clear Clear Clear 1 J | Kinetic Parameters: | Tmax (min) 4.2 4.0 3.9 3.4 1 Conv. @ Tmax (%) 59.0 56.0 52 S3 VTN-71 280963 Example 83 Example 84 Example 85 8 Composition (%): HEMA 64.7 64.7 64.7 | DMA 1 | PEG 4000XL 7 7 7 8 I BPA890 2 2 2 1 I PEG 3350MC 6 6 6 I Darocur 1173 0.34 0.34 0.34 Diluent (%) : PEG 400 Photonol 7025 65 75 85 Mon./Dil. Ratio 60:40 60:40 60:40 Properties: Modulus (psi) 42 51 52 % Elongation 175 185 160 Tens. Strength (psi) 40 40 43 Water Content (%) 61.1 60.9 60.7 Hydrogel Clear Clear Clear Kinetic Parameters: Tmax (min) 2.1 1.6 1.2 Conv. @ Tmax (%) 51. 0 48.0 41.0 280963 VTN-71 Example 86 Example 87 Example 88 Example 89 Composit ion (*): HEMA 64.7 64 .7 64.7 64.7 | DMA 1 PEG 4000XL 7 7 7 - 7 BPA890 2 2 2 2 PEG 3350MC 6 6 6 ; 6 B Darocur 1173 0.34 0.34 0.34 0.34 Diluent: (%) : PEG 400 90 75 60 50 8 GLUCAM E20 40 50 | Mon./Dil. Ratio 60:40 60:40 60:40 60:40 1 Properties: 1 Modulus (psi) 24 29 37 | * Elongation 185 190 188 178 ! I Tens. Strength j (psi) 4 29 31 34 1 Water Content (%) 61.8 61.7 61.2 61.0 9 Hydrogel Clear Clear Clear Clear j H Kinetic Parameters: | Tmax (min) 4.1 3.7 3.2 2.1 I Conv. @ Tmax (*) u\ <0 • o 50.0 49.0 46.0 | € VTN-71 28096 * Example 90 Example 91 Example 92 Composition (%): HEMA 64.7 64.7 64.7 DMA PEG 4000XL 7 7 7 BPA890 2 2 2 PEG 3 350MC 6 6 6 Darocur 1173 0.34 0.34 0.34 I Diluent (%): PEG 4 00 90 75 60 GLUCAM E20 40 Mon./Dil. Ratio 60:40 60:40 60:40 Properties: Modulus (psi) 44 48 52 % Elongation 150 150 141 Tens. Strength (psi) 41 39 45 Water Content (%) 60.8 60.7 60.5 Hydrogel Clear Clear Clear Kinetic Parameters: Tmax (min) 1.4 1.0 0.9 Conv. @ Tmax (%) 48.0 44.0 47.0 280963 VTN-71 Example 93 Example 94 (Modulus borderline) Example 95 Example 96 Composition (%) : HEMA 64.7 54.7 64.7 64.7 DMA | PEG 4000XL 7 7 7 7 j BPA890 2 2 2 2 | PEG 3350MC 6 6 6 6 | Darocur 1173 0. 34 0.34 0.34 0.34 | Diluent (%): j PEG 1000 100 90 75 60 1 GJLUCAM E20 0 40 | Mon./Dil. Ratio 60:40 60:40 60:40 60:40 A Properties: Modulus (psi) 21 28 33 B % Elongation 191 190 175 184 | Tens. Str. (psi) 27 37 31 Water Content (\) 63.0 62.3 62.0 61.6 Hydrogel Clear Clear Clear Clear Kinetic Parameters: Tnax (min) 3.5 3.3 2.9 Conv. 9 Tmax (*) 59.0 55.0 53.0 54.0 | VTN-71 280963 Example 97 Example 98 Example 99 Examp.100 j Composition (%): HEMA 64.7 64.7 64.7 64.7 I DMA J PEG 4000XL 7 7 7 7 BPA890 2 2 2 2 PEG 3 3 50MC 6 6 6 6 Darocur 1173 0.34 0.34 0.34 0.34 Diluent (*) : PEG 1000 50 GLUCAM E20 50 65 75 85 Mon./Dil. Ratio 60:40 60:40 60:40 60:40 1 Properties: Modulus (psi) 34 33 47 49 8 % Elongation 141 132 122 111 1 Tens. Strength (psi) 42 41 49 41 Water Content (%) 61.0 61.3 60.8 61.0 Hydrogel Clear Clear Clear Clear B Kinetic Parameters: Tmax (min) 2.1 1.4 1.1 1.1 Conv. @ Tmax (%) 49.0 47 .0 46.0 41.0 28GSG3 VTN-71 Examp. 101 (Modulus borderline) Examp. 102 Examp. 103 Examp. 104 Composition (%): HEMA 64.7 64.7 64- 7 64.7 DMA PEG 4000XL 7 7 7 7 BPA890 2 2 2 -- 2 PEG 3350MC 6 6 6 6 Darocur 1173 0.34 0.34 0.34 0.34 LO j Diluent (%): 1 PEG 1000 90 75 60 50 1 Photonol 7025 40 50 R Mon./Dil. Ratio 60:40 60:40 60:40 60:40 U Properties: U Modulus (psi) 19 27 32 I k Elongation 183 175 181 177 1 Tens. Str. (psi) 36 28 31 33 1 Water Content (%) 61.1 62.8 62.5 62.1 1 Hydrogel Clear Clear Clear Clear | Kinetic Parameters: | Tnax (min) 3.6 3.4 3.1 2.7 B Conv. § Tmax (%) 49.0 51.0 45.0 350 1 VTN-71 280963 Examp. 105 Examp. 106 Examp. 107 Q Composition (%): HEMA 64.7 64.7 64.7 | DMA 1 PEG 4000XL 7 7 7 BPA890 2 2 2 PEG 3350MC 6 6 6 Darocur 1173 0. 34 0. 34 0.34 | Diluent (%) : PEG 1000 90 75 60 I Photonol 7025 40 | Mon./Dil. Ratio 60:40 60:40 60:40 I Properties: Modulus (psi) 39 45 46 % Elongation 131 125 130 Tens. Strength (psi) 41 41 47 Water Content (%) 61.5 60. 7 60.8 Hydrogel Clear Clear Clear Kinetic Parameters: Tmax (min) 1.4 1.1 1.1 Conv. @ Tmax (%) 41.0 42.0 44.0 VTN-71 Example 108 Synthesis of Isocyanatoethyl Methacrylate Capped PES 2000 Monomethyl Ether.

A total of 200g (0.10 mol) of dry PEG 2000 monomethyl ether is charged into a 1L three neck flask equipped with a mechanical stirrer and a gas inlet tube. A total of 600g of dry acetonitrile is added to the flask, and the monomethoxy PEG 2000 allowed to. dissolve completely. The system is then flushed with dry nitrogen and then dry oxygen. Subsequently, two drops of stannous octoate and 500 ppm of 4-methoxy hydroquinone (MEHQ) is added to the flask. Using a dropping funnel 15.51g (0.10 mol) of isocyanatoethyl methacrylate in 50g of acetonitrile are added dropwise to the contents of the 1L flask. The reaction is allowed to proceed at room temperature for 24-28 hrs. The progress of the reaction is followed by monitoring the disappearance of the NCO absorption at 2270 cm'1 in the infrared spectrum. After the reaction is deemed complete (no absorption at 2270*1), the solvent is removed under reduced pressure and the white, waxy monocapped monomethoxy PEG 2000 is used as is.

Examples 109-120 A reactive monomer blend was prepared using various amounts of HEMA, 20.0% N,N-dimethyl acrylamide (DMA), 16.0% of the dicapped PEG 4500 crosslinker described in Example 3 (PEG 4500XL), 8.0% of the ethoxylated bisphenol A crosslinker described in Example 1 (BPA890), various amounts of the monocapped monomethoxy PEG 2000 described in Example 108 (MC mPEG 2000), and 0.4% of Darocur 1173. To 55% by weight of this monomer blend was added 45% of an inert, displaceable diluent made up of 50% GLUCAM E-20 and 50% Photonol 7025. After thoroughly mixing the above blend at 60°c, the mixture is allowed to stir under reduced pressure (40 mm Hg) for 30 min (at 60°C) and subsequently transferred to contact lens molds. The -56 280963 VTN-71 filled molds are exposed to UV light (wavelength *= 300-380 nm, dose = 1.2-1.6 Joules/cnw) for 20 minutes at approximately 60°C. The molds are then separated, and placed in physiological saline for 3.0 hrs at 70°C to remove the inert diluent and any residual, unreacted monomers. After this initial hydration period the lenses are allowed to equilibrate to room temperature in a fresh bath of physiological saline. The lenses are then tested according to Test Methods 3, 4 and 5.

The reactive monomer mixture formulations and the results of the tests of the lenses prepared in accordance with Examples 109-120 are shown in the following tables: VTN-71 280963 Examp. 109 Examp. 110 Examp. ill Composition (%): HEMA 43.6 34.6 .6 DMA | PEG 4500XL 16 16 16 BPA890 8 8 8 MC mPEG 2000 12 21 Darocur 1173 0.4 0.4 0.4 1 Diluent (%) : Photonol 7025 50 50 50 GLUCAM E-20 50 50 50 | Mon./Dil. Ratio 55:45 55:45 55:45 1 1 Properties: I ■ Modulus (psi) 76 77 75 % Elongation 148 113 117 Dk 37 42 50 Water Content (%) 70.5 73.8 78.1 Hydrogel clear Clear Clear 280963 VTN-71 Examp. 112 Examp. 113 Examp. 114 fi Composition (%) : HEMA 43.6 34.6 .6 DMA I PEG 4500XL 16 16 16 | BPA890 8 8 8 1 MC mPEG 2000 12 21 | Darocur 1173 0.4 0.4 0.4 I Diluent (%): Photonol 7025 50 50 50 GLUCAM E-20 50 50 50 Mon./Dil. Ratio 45: 55 45:55 45:55 Properties: Modulus (psi) 51 44 47 % Elongation 142 119 128 DK 40 47 55 Water Content (%) 72. 9 76.6 80.3 Hydrogel Clear Clear Clear VTN-71 280963 Examp. 115 Examp. 116 Examp. 117 Composition (%): HEMA 36.6 27.6 13.6 DMA PEG 4500XL 16 16 16 BPA890 MC mPEG 2000 12 21 Darocur 1173 0.4 0.4 0.4 I I Diluent (%): I Photonol 7025 50 50 50 1 GLUCAM E-20 50 50 50 I j Mon./Dil. Ratio 55:45 55:45 55:45 Properties: | Modulus (psi) 130 126 125 1 % Elongation 96 81 68 1 I Dk 29 33 50 | Water Content (%) 64.7 68.2 78.i | Hydrogel Clear Clear Clear fl -60- VTN-71 280963 Examp. 118 Examp. 119 Examp. 120 D I Composition (%): | 1 HEMA 36.6 27.6 13 *6 1 | DMA ( | PEG 4500XL 16 16 16 1 BPA890 1 MC mPEG 2000 12 21 1 Darocur 1173 0.4 0.4 0.4 I Diluent (%) : Photonol 7025 50 50 50 GLUCAM E-20 50 50 50 j Mon./Dil. Ratio 45:55 45:55 45:55 I I Properties: j 1 1 | Modulus (psi) 37 ! 90 85 % Elongation 122 j 90 78 1 Dk 40 47 55 Water Content (%) 72.9 76.6 80.3 Hydrogel Clear Clear Clear

Claims (3)

WHAT WE CLAIM IS: 280 96 3

1. A test to determine the utility of a composition for use as an inert, displaceable diluent in a process for producing a contact lens, which process comprises molding or casting in a predetermined shape a polymerization mixture comprising: (a) a monomer mixture comprising a major proportion of one or more hydrophilic monomers, and one or more cross-linking monomers; and (b) an inert, displaceable, non-aqueous diluent under conditions to polymerize said monomer mixture to produce a gel of a copolymer of said monomers and said diluent; which test comprises carrying out the polymerization of said monomers in said polymerization mixture in a photo differential scanning calorimeter wherein said polymerization is induced by ultraviolet irradiation at a light intensity of from substantially 2.5 to 3 mW/cm2, determining the time to maximum exotherm of said polymerization and comparing said time with a desirable time of from substantially 0.2 to substantially 3.5 minutes, and determining the percent conversion of said monomer mixture to polymer and comparing said percent conversion with a standard of at least 40 percent.

2. The test of claim 1 wherein said test comprises carrying out the polymerization « NTPAJENT OFFICE _ 6? _ 2 OCT 1997 280 96 3 of said monomers in said polymerization mixture in a photo differential scanning calorimeter wherein said polymerization is induced by ultraviolet irradiation at a light intensity of from substantially 2.5 to 3 mW/cm2, determining the time to maximum exotherm of said polymerization and comparing said time with a desirable time of from substantially 0.4 to substantially 2.5 minutes, and determining the percent conversion of said monomer mixture to polymer and comparing said percent conversion with a standard of at least 50 percent.

3. A test of claim 1 or claim 2 substantially as hereinbefore described with reference to the Examples. ATTORNEYS FOR THE APPLICANT END OF CLAIMS N.Z. PATENT OFFICE -63- 2 OCT 199? REG£:vro