CN1320004C - Low polydispersity poly-HEMA compositions - Google Patents

Abstract

The present invention relates to compositions comprising poly-HEMA having a peak molecular weight between about 25,000 and about 100,000, preferably between 25,000 and 80,000 and a polydispersity of less than about 2 to less than about 3.8 respectively and covalently bonded thereon, at least one cross-linkable functional group. The present invention further relates to low polydispersity poly-HEMA suitable for making the crosslinkable prepolymers, processes for functionalizing and purifying said poly-HEMA to form said crosslinkable prepolymers, viscous solutions made from said crosslinkable prepolymers, hydrogels made from said viscous solutions and articles made from said crosslinkable polymers, hydrogels and viscous solutions.

Description

Low polydispersity poly(2-hydroxyethyl methacrylate) composition

Related application information

This patent application claims priority to Provisional Application US Serial No. 60/363,639 filed on 2002-03-11.

technical field

The present invention relates to poly-2-hydroxyethyl methacrylate (herein referred to as polyHEMA) compositions having a specific molecular weight range and polydispersity. Also disclosed are methods of making contact lenses from the polyHEMA and contact lenses made therefrom.

Background technique

Contact lenses have been commercially available to improve vision since the 1950s. Most current contact lenses are made from hydrogels, which are made by polymerizing hydrophilic monomers such as HEMA (hydroxyethyl methacrylate) and vinylpyrrolidone in the presence of small amounts of cross-linking agents. Shrinkage due to polymerization of this monomer may be as high as 20% by volume.

Prepolymers having a PVA backbone and acrylic acid groups as reactive groups have been disclosed. The reactive prepolymer is dissolved in water and cross-linked in a mold by UV irradiation to form a contact lens. Although there was little shrinkage during curing, the mechanical properties exhibited by the hydrogels thus produced proved only marginal for use as contact lenses.

US Patents 4,495,313, 4,889,664 and 5,039,459 disclose the formation of conventional hydrogels.

Brief description of the drawings

Figure 1 shows the Hansen solubility parameter spheres for the compositions prepared in the examples.

Detailed description of the invention

The present invention relates to a composition comprising polyHEMA having a peak molecular weight of from about 25,000 to about 100,000, preferably 25,000 to 80,000 and a polydispersity of less than about 2 to less than about 3.8, and covalently bonded Bonded thereto, at least one crosslinkable functional group.

The present invention also relates to low polydispersity polyHEMA suitable for the manufacture of the crosslinkable prepolymers of the present invention, methods of functionalizing and purifying said polyHEMA to form said crosslinkable prepolymers, from said viscous solutions Fabricated hydrogels and articles made from the crosslinkable polymers, hydrogels and viscous solutions. Furthermore, the present invention relates to methods of making said viscous solutions, hydrogels and articles. Preferred articles of manufacture include medical devices, particularly contact lenses.

We have found that the uncore shrinkage, swelling and related problems of polyHEMA hydrogels can be overcome by preparing the hydrogels from a lower molecular weight and low polydispersity crosslinkable prepolymer. We have also found that polyHEMA with lower molecular weight and low polydispersity can be prepared by new practical methods and has many uses in itself. In addition, the polyHEMA of the present invention can be converted into crosslinkable prepolymers useful in the manufacture of a variety of articles, including hydrophilic coatings and contact lenses with improved mechanical properties. Finally, the crosslinkable prepolymers of the present invention enable the production of high precision molded articles.

As used herein, "polyHEMA" refers to a polymer comprising repeat units of 2-hydroxyethyl methacrylate. The polyHEMA of the present invention has a peak molecular weight ranging from about 25,000 with a polydispersity of less than about 2, to a peak molecular weight of about 100,0000 with a polydispersity of less than about 3.8. Preferably, the compositions of the present invention have a peak molecular weight of about 30,000 with a polydispersity of less than about 2 and a peak molecular weight of about 90,000 with a polydispersity of less than about 3.5. More preferably, the compositions of the present invention have a peak molecular weight of about 30,000 with a polydispersity of less than about 2, to a peak molecular weight of about 80,000 with a polydispersity of less than about 3.2. Suitable polyHEMA also have a peak molecular weight of less than about 100,000 and a polydispersity of less than about 2, preferably a peak molecular weight of between about 45,000 and 100,000 and a polydispersity of less than about 2.5. In certain embodiments, the polydispersity is less than about 2.5, preferably less than about 2, more preferably less than about 1.7, and in certain embodiments, less than about 1.5. The term polyHEMA, as used above, and throughout this specification, shall include polymers prepared solely from 2-hydroxyethyl methacrylate, as well as copolymers with other comonomers or co-reactants, as will be further described below .

The polyHEMA of the present invention should be substantially free of branched polymer chains and gel particles. Gel particles are insoluble polymer fragments believed to be polymer chains crosslinked by di- or polyfunctional monomers. By "essentially free" we mean less than about 0.1 wt% gel particles and/or branched polymer chains. It is therefore required to have a low crosslinker concentration in the HEMA monomer. Preferably, the amount of crosslinking agent is less than about 1%, more preferably less than about 0.5%, and in certain embodiments less than about 0.25%, based on all components present. All weight percentages are based on all components present unless otherwise indicated. Crosslinkers are compounds having two or more polymerizable functional groups. Examples of crosslinkers include TEGDMA (tetraethylene glycol dimethacrylate), TrEGDMA (triethylene glycol dimethacrylate), trimethylolpropane trimethacrylate (TMPTMA), and ethylene glycol dimethacrylate (EGDMA). EGDMA is often present in the commercially available 2-hydroxyethyl methacrylate monomer used to make the polyHEMA of the present invention. Care must therefore be taken to purchase HEMA monomers that have the low EGDMA concentrations specified herein. Suitable HEMA monomer grades are commercially available from the Rohm Chemical Company (D-64 293 Darmstadt, Germany).

Comonomers suitable for polymerization with HEMA monomers include hydrophilic monomers, such as vinyl-containing monomers, as well as hydrophobic monomers, and even tinting monomers that provide light absorbing capabilities at different wavelengths. The term "vinyl-type" or "vinyl-containing" monomer refers to a monomer containing a vinyl group (-CR=CR'R", where R, R' and R" are monovalent substituents), which have It is relatively easy to aggregate. Suitable vinyl-containing monomers include N,N-dimethylacrylamide (DMA), glyceryl methacrylate (GMA), 2-hydroxyethyl methacrylate, polyethylene glycol monomethacrylate, methyl Acrylic acid (MAA), acrylic acid, N-vinyllactam (e.g., N-vinylpyrrolidone, or NVP), N-vinyl-N-methylacetamide, N-vinyl-N-ethylacetamide , N-vinyl-N-ethyl formamide, N-vinyl formamide, vinyl carbonate monomer, vinyl carbamate monomer, oxazolone monomer and mixtures thereof.

Other examples are the hydrophilic vinyl carbonate or vinyl carbamate monomers disclosed in US Pat. Nos. 5,070,215, 4,711,943, and the hydrophilic oxazolone monomers disclosed in US Pat. No. 4,910,277, which are incorporated herein by reference. Other suitable hydrophilic monomers will be apparent to those skilled in the art.

More preferred hydrophilic monomers that can be incorporated into the polymers of the present invention include hydrophilic monomers such as DMA, GMA, 2-hydroxyethylmethacrylamide, NVP, polyethylene glycol monomethacrylate, MAA, Acrylic and its mixtures. DMA, GMA and MAA are most preferred in certain embodiments.

It is important that the selected hydrophobic monomer is polymerized with HEMA at a concentration and in such a manner that the resulting polyHEMA has sufficient solubility in the chosen diluent and does not interfere with the reactivity of the hydroxyl groups on the polyHEMA. Or the reactivity of the crosslinkable functional groups on the crosslinkable prepolymer.

Suitable hydrophobic monomers include silicone-containing monomers and macromers having polymerizable vinyl groups. Preferably, the vinyl groups are methacryloyloxy groups. Examples of suitable silicone-containing monomers and macromers include mPDMS-type monomers comprising at least two [-Si-O-] repeating units; SiGMA-type monomers comprising A polymerizable group, a hydroxyl group, and at least one "-Si-O-Si-"group; and a TRIS-type monomer containing at least one Si(OSi-) ₃ group.

Examples of suitable TRIS monomers include

Methacryloxypropyltris(trimethylsiloxy)silane,

Methacryloxypropylbis(trimethylsiloxy)methylsilane,

Methacryloxypropyl pentamethyldisiloxane, its mixture, etc.

Preferably, the mPDMS-type monomer comprises greater than 20 wt% total silicon and its attached oxygen, more preferably greater than 30 wt%, based on the molecular weight of the total siloxane-containing monomer. Suitable mPDMS monomers have the general formula

Examples of suitable linear mono-alkyl chain terminated polydimethylsiloxanes ("mPDMS") include:

Where b = 0 to 100, it is understood here that b is a distribution with a mode approximately equal to the stated value, preferably 4 to 16, more preferably 8 to 10; R ₅₈ comprises a polymerizable - A valent group, preferably a monovalent group containing a styryl, vinyl, (meth)acrylamide or (meth)acrylate moiety, more preferably a methacrylate moiety; each R is independently _monovalent Alkyl, or aryl group, can be further substituted on it alcohol, amine, ketone, carboxylic acid or ether group, preferably unsubstituted monovalent alkyl or aryl group, more preferably methyl; R ₆₀ is Monovalent alkyl, or aryl groups, which in turn may be further substituted with alcohol, amine, ketone, carboxylic acid or ether groups, preferably unsubstituted monovalent alkyl or aryl groups, preferably C _1-10 esters Aromatic or aromatic group, which itself can also include heteroatoms, more preferably C _3-8 alkyl group, most preferably butyl; R ₆₁ is independently alkyl or aryl, preferably ethyl, methyl, benzyl group, phenyl group or monovalent siloxane chain containing 1 to 100 repeating Si-O units.

Such mPDMS-type monomers are more fully disclosed in US 5,998,498, which is hereby incorporated by reference.

Preferably, in SiGMA-type monomers, silicon and its attached oxygen comprise about 10 wt%, more preferably greater than about 20 wt%, of the monomer. Examples of SiGMA-type monomers include monomers of the general formula I

Wherein the substituents are as specified in US 5,998,498, which is hereby incorporated by reference.

Specific examples of suitable SiGMA-type monomers include 2-acrylic acid, 2-methyl-2-hydroxy-3-[3-[1,3,3,3-tetramethyl-1-[trimethylsilyl ]oxy]disiloxanyl]propoxy]propyl ester

and (3-methacryloyloxy-2-hydroxypropoxy)propyltris(trimethylsiloxy)silane

Other suitable hydroxy-functional silicone-containing monomers are disclosed in US Pat. Nos. 4,235,985, 4,139,513 and 4,139,692, incorporated herein by reference.

Other examples of SiGMA-type monomers include, but are not limited to, (3-methacryloyloxy-2-hydroxypropoxy)propylbis(trimethylsiloxy)methylsilane.

It is important that the ratio between the hydrophilic and hydrophobic monomers is such that the functionalized crosslinkable prepolymer prepared from polyHEMA can be dissolved and cured in the hydrophilic diluent described below - a condition.

Also, hydrophobic monomers, like methyl methacrylate and ethyl methacrylate, can be incorporated into polyHEMA to modify water absorption, oxygen permeability, or other physical properties required for the intended use. The amount of comonomer used is generally less than about 50 wt%, preferably between about 0.5 and 40 wt%. More specific ranges will depend on the desired water content of the resulting hydrogel, the selected monomers and the solubility of the selected diluent. For example, when the comonomer comprises MMA, it is advantageously added in an amount of less than about 5 wt%, preferably between about 0.5 and about 5 wt%. In another embodiment, the comonomer comprises GMA in an amount up to about 50 wt%, preferably between about 25 and about 45 wt%. In another embodiment, the comonomer comprises DMA in an amount up to about 50 wt%, preferably between about 10 and about 40 wt%.

Initiators and chain transfer agents can also be used. Any satisfactory initiator may be used including, but not limited to, thermally activated initiators, ultraviolet and/or visible light photoinitiators, and the like, and combinations thereof. Suitable thermally activated initiators include lauryl peroxide, benzoyl peroxide, isopropyl percarbonate, azobisisobutyronitrile, 2,2-azobisisobutyronitrile, 2,2-azobis -2-Methylbutyronitrile, etc. Preferred initiators comprise 2,2-azobis-2-methylbutyronitrile (AMBM) and/or 2,2-azobisisobutyronitrile (AIBN).

The initiator is used in the reaction mixture in an effective amount, for example, from about 0.1 to about 5 weight percent, preferably from about 0.1 to about 2 parts by weight, per 100 parts of reactive monomers.

The polyHEMA of the present invention can be prepared in a variety of ways. In one embodiment, the HEMA monomer and any required comonomers are polymerized by free radical polymerization. The polymerization reaction is carried out in any solvent as long as the solvent can dissolve the HEMA monomer and the resulting polyHEMA during the polymerization. Solvents suitable for the polymerization of HEMA monomers include alcohols, diols, polyols, aromatic hydrocarbons, ethers, esters, ester alcohols, ketones, sulfoxides, pyrrolidones, amides and mixtures thereof, and the like. Specific solvents include methanol, ethanol, isopropanol, 1-propanol, methyl lactate, ethyl lactate, isopropyl lactate, glycol ethers like the Dowanol product line, ethoxylated propanol, DMF, DMSO, NMP, Cyclohexanone, mixtures thereof, etc. Preferred solvents include alcohols having 1 to 4 carbon atoms, more preferably ethanol, methanol and isopropanol. Sufficient solvent must be used to dissolve the monomer. A suitable concentration of the monomer in the solvent is generally from about 5 to about 25% by weight.

Free radical polymerization is carried out at a temperature between about 40°C and about 150°C. The upper limit will depend on the pressure limitations of the equipment available and the ability to handle the exotherm of polymerization. The lower limit will depend on the maximum acceptable reaction time and/or the properties of the initiator. In the case of polymerization at approximately ambient pressure, the preferred temperature range is from about 50°C to 110°C, more preferably from 60°C to about 90°C, and for the time necessary to provide the desired degree of conversion. Free radical polymerization proceeds relatively quickly. About 90 to about 98% of the monomer will react in about 1 to about 6 hours. If more complete conversion (greater than about 99%) is desired, the reaction can be carried out for about 12 to about 30 hours, more preferably about 16 to about 30 hours. Since the polyHEMA produced in the polymerization step will in many cases be subject to fractionation to remove low molecular weight species, it may not be required in all cases to run the polymerization process to high conversions. The pressure requirements are not strict, and it is more convenient to use normal pressure.

Chain transfer agents may optionally be included. Chain transfer agents useful in forming polyHEMA for use in the present invention have chain transfer constant values greater than about 0.001, preferably greater than about 0.2, more preferably greater than about 0.5. Suitable such chain transfer agents are well known and include, but are not limited to, aliphatic mercaptans of the general formula R-SH, where R is C ₁ -C ₁₂ aliphatic, benzyl, cycloaliphatic or CH ₃ (CH ₂ ) _x -SH, where x is 1 to 24, benzene, n-butyl chloride, tert-butyl chloride, n-butyl bromide, 2-mercaptoethanol, 1-dodecyl mercaptan, 2-chlorobutyl alkanes, acetone, acetic acid, chloroform, butylamine, triethylamine, di-n-butylsulfide and disulfide, tetrachloro- and bromo-carbons, etc., and combinations thereof. Generally, from about 0 to about 7 weight percent, based on the total weight of the monomer formulation, will be used. Preferably, dodecanethiol, decanethiol, octanethiol, mercaptoethanol or combinations thereof are used as chain transfer agents.

In certain embodiments, it is preferred that the polyHEMA is polymerized without the addition of a chain transfer agent. In this case, alcohols are used as solvents, preferably alcohols with 1 to 4 carbon atoms, preferred solvents are methanol, ethanol, isopropanol and mixtures thereof.

The polydispersity of the polyHEMA produced in free-radical polymerization is too high for direct use in the present invention. This is due to the reaction kinetics of this method, where the important termination reaction is the recombination of the two growing polymer chains. Therefore, when free radical polymerization is used to form the polyHEMA of the present invention, it is necessary to purify the polyHEMA either before or after functionalization to remove polymers whose molecular weight falls outside the desired range. Any method capable of separating materials based on molecular weight can be used.

Fractionation with solvent/non-solvent can be used. Purification of HEMA copolymers by precipitation is described in US 4,963,159 and is accomplished by adding HEMA copolymers dropwise to a non-solvent. The precipitated HEMA copolymer can then be dissolved in a solvent to obtain a solution substantially free of unpolymerized monomer.

PolyHEMA of the present invention can be formed by selecting solvents and non-solvents based on Hansen solubility parameters to remove undesirably high molecular weight polyHEMA. The Hansen solubility parameter describes the polymer-liquid interaction, so a set of three parameters δ _H , α _P , δ _D can be assigned to each solvent and polymer to describe the interaction between them. A description of the entire system can be found in "Handbook of Polymer-Liquid Interaction Parameters and Solubility Parameters," CRC Publishing Co., 1990, and "Handbook of Solubility Parameters and Other Cohesion Parameters," AFM Barton, CRC Publishing Co., 1985, Table 5. Each set of three parameters defines a point in the three-dimensional solubility space.

In the case of liquids as solvents for polymers, the parameters of the solvent must be chosen close to those of the polymer. The Hansen solubility parameter of polyHEMA can be determined from solubility tests in which samples of the polymer are stored in a number of different solvents. By observing whether the polymer dissolves, swells, or remains unchanged, the solubility sphere of a specific poly HEMA can be plotted in the solubility space, just as "Hansen Solubility Parameters"; "User's Manual" Charles M. Hansen, pp.43～53 , CRC Publishing Company 2000, and a computer program for CMH spherical calculations. Parameters of certain polyHEMA compositions are listed in Table 1 below and plotted in Figure 1 .

Table 1 MW(kDalton) D. P h R 75 16.9 18.1 20.1 8.3 55 17.2 16 17 10.4 35 18 15.2 15.4 11.7 twenty three 17 14.2 13.6 13.2 14 17 14.2 13.6 13.2 2 18 14 13.2 13.7 13 18 14 13.2 13.7

For fractionation, polyHEMA is dissolved in a solvent located inside the solubility sphere. Suitable _solvents have solubility parameters ranging from about 13 to about 20, from _about 5 to about 18, _and from about 10 to about 25. More preferably, the distance between the solvent and the polymer in the three-dimensional solubility space should not exceed the following values: _δD is between about 5 and about 10, _δP is between about 4 and about 12, and _δH is between about 10 and about 6.

Once the polyHEMA is dissolved, a non-solvent capable of reducing at least one of the solubility parameters of the resulting isolated mixture is gradually added to the dissolved polyHEMA solution until the desired degree of precipitation of high molecular weight material is obtained. It is not necessary to lower all three solubility parameters. In many embodiments, it is sufficient to lower only one parameter, eg, the delta _H parameter. In other embodiments, it may be advantageous to reduce two parameters, the _δH and _δP parameters. We have found that often a surprisingly small reduction in solvent parameter (as small as about 2 to about 5 units) will result in the desired separation.

The non-solvent must lower at least one parameter to ensure selective precipitation of polyHEMA having a peak molecular weight greater than about 90,000. If the non-solvent increases the solubility parameter of the separation mixture, the precipitation will vary with molecular weight to a much smaller extent and polyHEMA in the desired molecular weight range will be lost.

When adding non-solvents to polymer solutions, it may be difficult to avoid localized high concentrations of non-solvents. This will lead to local non-specific precipitation of the polymer. In such cases, it is useful to stop the addition until equilibrium is re-established. Non-specific precipitation can also be greatly reduced by increasing the temperature of the separation mixture until the mixture becomes clear, or by adding a non-solvent at a somewhat higher temperature and then reducing the temperature until the desired separation is obtained. The separation process can be facilitated by known means such as, but not limited to, centrifugation.

The amount and rate of precipitation will vary with the temperature at which the precipitation is carried out, the solubility parameters of the non-solvent, and the rate at which the non-solvent is added and whether the non-solvent is sufficiently mixed. Depending on the molecular weight of the polyHEMA formed by free radical polymerization, the amount of precipitated polymer can range from about 5 to about 50% of the total polyHEMA in solution to achieve the desired level of removal of high molecular weight polymer.

High molecular weight polyHEMA precipitates out of the solvent/non-solvent mixture and can be isolated by conventional means such as filtration, centrifugation, etc. If further separation is required, fractionation can be carried out iteratively by further reducing the solvent parameters, as described above. Again, mainly the highest molecular weight material will still be separated and removed from solution.

The high molecular weight polyHEMA to be selectively removed has a high viscosity in solution. This will in some cases make separations very difficult using the methods described above. Thus, the present invention provides an alternative fractionation method in which a homogeneous solution of polyHEMA is slightly cooled to separate the polymer solution into two liquid phases according to molecular weight. The method includes the following steps:

1. Prepare a solution of polyHEMA in a solvent using the Hasen solubility range and within the range specified above.

2. Determine the separation temperature T _s of the solution, which can be achieved by cooling a sample of the solution until the sample becomes heterogeneous and separates into two phases. The temperature at which separation or clouding tendencies are first observed is T _s .

3. Cool the solution to a temperature below T, at which point two phases will form,

4. Separate the two phases. The bottom phase will contain the highest molecular weight material.

Using the above method, high molecular weight poly-HEMA can be removed first, and then poly-HEMA with a molecular weight lower than the required range can be removed. At this point, for example, cool the polyHEMA/solvent mixture to a few degrees below Ts, wait for it to separate into two phases, siphon off the upper phase containing low and medium molecular weight polyHEMA, and cool it to a lower temperature to achieve the second phase. For the first separation, the second upper phase, the thin solution of the lower fraction, is siphoned away, while the second bottom phase, now containing mainly the desired low polydispersity polyHEMA, continues to be worked up. The polyHEMA in the second bottom phase has greatly reduced amounts of high and low molecular weight polyHEMA.

For many purposes, the polymer obtained from such a second bottom phase can be used directly. Further grading can be performed by repeating the process described above.

T _s can be influenced by proper choice of solvent. For example, the T _s of a solution of polyHEMA in isopropanol is higher than that of a solution with ethanol as solvent. Using a mixture of solvents allows fine-tuning of the temperature for optimal separation. Solvents suitable for fractionation based on _Ts include solvents with low _δH and _δP parameters, and preferably _δH is less than about 4 and _δP is less than about 6. Specific examples include hexane and heptane. This may be useful for the purpose of removing low end material from a solution in which high molecular weight polyHEMA has been removed. To achieve re-isolation, it is often desirable to employ temperatures well below room temperature, for example from about 5 to about 10°C. In such cases, it may be practical to add a small amount of solvent that raises the separation temperature to a more practical level, eg, to keep the polyHEMA solution in a liquid state, eg, from room temperature to about 50°C.

T _s is also affected by the concentration and polydispersity of polyHEMA in solution. For example, removal of high and low molecular weight polyHEMA may result in the polyHEMA remaining in solution exhibiting a _Ts higher than the original, more polydisperse material. Likewise, dilution to lower concentrations can also result in separation at higher temperatures. The reason for this may be that a certain concentration of low molecular weight polyHEMA chains may help keep longer chains in solution.

The volume ratio between the two phases and the concentration of polyHEMA in each phase can be affected by the adjustment of polymer parameters, the choice of solvent and separation temperature.

Suitable fractionation temperature ranges include those ranging from about 5 to about 50°C. Suitable rest times include between about 1 hour and about 7 days.

The amount of polyHEMA drained with the high molecular weight material should be between about 10% and about 50% by weight of the polyHEMA. With the low molecular weight fraction being removed from about 5 to about 40 wt% is usually practical, while the yield of polyHEMA with low polydispersity after removal of the high and low molecular weight material can range from about 10 to about 10% of the original amount. 90%, preferably about 30 to about 80%. However, harvest reduction is a minor concern, since polyHEMA produced by free-radical polymerization is relatively cheap, while fractionated materials are of high value in many fields.

In preferred polyHEMA, the number of polymer molecules having a molecular weight of less than about 15,000 is less than about 10%, preferably less than about 5%, more preferably less than about 2%.

It is clear from this description and examples that this fractionation method is flexible and can be tailored to suit the properties of a particular polymer. The conditions required to obtain the desired degree of polydispersity can be readily determined by simple small-scale experiments using the above disclosure.

Suitable temperature ranges include about 5 to about 50°C. Suitable rest times include between about 1 hour and about 7 days.

An important advantage of polyHEMA prepared by free radical polymerization followed by fractionation is that the initiators and other additives used in the polymerization have been used for many years and their toxicology is well known and well described. This is important when polyHEMA, crosslinkable prepolymers or the resulting hydrogels are used in the medical field.

In one embodiment, only the low molecular weight fraction is removed from the polyHEMA. This can be accomplished using the solvent/non-solvent method described above. In a preferred embodiment, low molecular weight material is removed during washing after functionalization of the polyHEMA.

The polyHEMA of the present invention can also be produced directly by anionic polymerization or controlled free radical polymerization, for example by TEMPO type polymerization, ATRP (atom transfer radical polymerization), GTP (group transfer polymerization) and RAFT (reversible addition-fragmentation chain transfer aggregation).

The general conditions of the above method are well known and are published in Controlled Radical Polymerization; Krzysztof Matyjaszewski, ed.; ACS Proceedings Series 685; American Chemical Society, Washington DC; 1998. For example, to carry out anionic polymerization, the desired silyl-protected monomer is dissolved in a suitable solvent, eg THF solution. The reaction is carried out at low temperature between about -60°C and about -90°C using well-known initiators such as 1,1-diphenylhexyllithium as the initiator. Polymerization can be terminated by conventional means such as, but not limited to, defatted methanol.

PolyHEMA compositions with specific molecular weight ranges and polydispersities can be used to make crosslinkable prepolymers with precisely defined polydispersities and molecular weights. As just one example, a crosslinkable prepolymer may have acrylic groups which can be crosslinked by ultraviolet light in a very short time to form contact lenses with very desirable properties heretofore never obtained by conventional methods.

PolyHEMA is functionalized into a crosslinkable prepolymer by adding crosslinkable functional groups thereon. In general, this functional group provides the prepolymer with the ability to crosslink and form crosslinked polymers or hydrogels. Reactants suitable for providing crosslinkable functional groups have the structure A-S-F, where A is a linking group capable of forming a covalent bond with hydroxyl groups in polyHEMA; S is a spacer and F is a functional group containing ethylenically unsaturated moieties . Suitable linking groups, A, include chloride, isocyanate, acid, anhydride, acid chloride, epoxy, azalide, combinations thereof, and the like. Preferred linking groups include anhydrides.

The spacer can be a direct bond, a linear, branched or cyclic alkyl or aryl group with 1 to 8 carbon atoms, preferably 1 to 4 carbon atoms, or the general formula -(CH ₂ -CH ₂ -O) _n -polyether chains, wherein n is between 1-8, preferably between 1-4.

Suitable functional groups include free radically polymerizable ethylenically unsaturated moieties. Suitable ethylenically unsaturated groups have the general formula

-C(R ¹⁰ )=CR ¹¹ R ¹²

Wherein R ¹⁰ , R ¹¹ and R ¹² are independently selected from H, C _1-6 alkyl, carbonyl, aryl and halogen. Preferably, R ¹⁰ , R ¹¹ and R ¹² are independently selected from H, methyl, aryl and carbonyl, more preferably in certain embodiments from H and methyl.

Preferred reactants include methacryloyl chloride, 2-isocyanatoethyl acrylate, isocyanatoethyl methacrylate (IEM), glycidyl methacrylate, cinnamoyl chloride, methacrylic anhydride, Acrylic anhydride and 2-vinyl-4-dimethylazalactone. Methacrylic anhydride is preferred.

A suitable amount of crosslinkable functional groups attached to polyHEMA is from about 1 to about 20%, preferably from about 1.5 to about 10%, most preferably from about 2 to about 5%, based on the available hydroxyl groups of the polyHEMA ester. stoichiometric meter. The degree of functionalization can be determined according to known methods, for example, by measuring unsaturated groups, or by hydrolysis of the direct bond of the functional reactant to the polymer, followed by determination of the evolved acid by HPLC.

Depending on the linking group chosen, functionalization can be performed with or without the presence of traditional catalysts. Suitable solvents include polar, aprotic solvents capable of dissolving polyHEMA under the selected reaction conditions. Examples of suitable solvents include dimethylformamide (DMF), hexamethylphosphoric triamide (HMPT), dimethylsulfoxide (DMSO), pyridine, nitromethane, acetonitrile, dioxane, tetrahydrofuran (THF) and N-methylpyrrolidone (NMP). Preferred solvents include formamide, DMF, DMSO, pyridine, NMP and THF. When an IEM is used, the catalyst is a tin catalyst, preferably dibutyltin dilaurate.

The functionalization reaction mixture may also contain a scavenger capable of reacting with the moieties produced by the functionalization reaction. For example, when using an anhydride as the linking group, it may be advantageous to include at least one tertiary amine, heterocyclic compound with an aprotic nitrogen, or other Lewis base to react with the resulting carboxyl group. Suitable tertiary amines include pyridine triethylenediamine and triethylamine, with triethylamine being preferred. If included, the tertiary amine may be added in a slight molar excess (about 10%). In a preferred embodiment, the solvent is NMP, the reactants are methacrylic anhydride, acrylic anhydride or mixtures thereof and triethylamine is present. The most preferred reactant is methacrylic anhydride.

The reaction takes place near room temperature. Each functional group will require a specific temperature range, as will be understood by those skilled in the art. A range of about 0°C to 50°C, preferably about 5°C to about 45°C is suitable. Atmospheric pressure can be used. For example, when the crosslinkable functional group is an anhydride, the functionalization is performed at a temperature between about 5°C and about 45°C for a period of about 20 to about 80 hours. Those skilled in the art understand that ranges outside the stated ranges can be tolerated by balancing the time and temperature chosen.

The reaction was carried out to produce a crosslinkable prepolymer having a polyHEMA backbone of the molecular weight and polydispersity specified above.

In addition to attaching crosslinkable side groups, other side groups can provide additional functionality, including but not limited to, photoinitiators for crosslinking, pharmaceutical activity, and the like. Still other functional groups may contain moieties that can bond and/or react with specific compounds when the crosslinked gel is used in the field of analytical diagnostics.

Once the crosslinkable prepolymer is formed, substantially all unreacted reactants and by-products should be removed. By "substantially all" we mean here that less than about 0.1 wt% remains after washing. This can be done by conventional means, eg ultrafiltration. However, in the present invention, substantially all unwanted components, including monomeric, oligomeric or polymeric raw materials used to prepare HEMA, can be removed by swelling the crosslinkable prepolymer with water and washing with water. Compounds and catalysts, as well as by-products generated during the preparation of crosslinkable prepolymers. Washing is carried out with deionized water under conditions chosen to provide a high surface/volume ratio to the crosslinkable prepolymer particles. This can be achieved by freeze-drying the crosslinkable prepolymer, forming a film from the crosslinkable prepolymer, extruding the crosslinkable prepolymer into rods, spraying the crosslinkable prepolymer solution into deionized water, and other similar methods known to those skilled in the art.

Washing can be performed intermittently with 3-5 changes of room temperature water, the equilibration time between each water change being shortened by performing the wash (extraction) at an elevated temperature below about 50°C.

This method has many advantages over prior art methods. The water washes away impurities that may be leached during storage and use, thereby ensuring the production of a pure material suitable for end use.

In one embodiment, unfractionated polyHEMA with a polydispersity outside the preferred range or polyHEMA from which only high molecular weight material has been removed is functionalized, followed by repeated washing of the functionalized material with copious amounts of water to remove reactive polyHEMA. and low molecular weight poly HEMA. Using this method, very pure functionalized polyHEMA can be obtained with a polydispersity as low as, for example, below 2.0, preferably below 1.7, more preferably below 1.5. The functionalized crosslinkable polyHEMA obtained in this way comprises less than 10%, preferably less than 5%, more preferably less than 2% polyHEMA having a molecular weight of less than about 15,000.

The degree of clearance of small molecules depends on the degree of functionalization and intended use. It is preferred that, during curing, all polyHEMA molecules are converted to a state where they are bound by at least two covalent bonds into the polymer network. Due to the statistical nature of functionalization and curing, the probability of a polyHEMA molecule being incorporated into the polymer network via only one covalent bond, or no covalent bonding at all, will scale with decreasing peak molecular weight and decreasing degree of functionalization. Increase.

In the case of lower functionalization, more low molecular weight material should be removed. The exact amount can easily be determined experimentally comparing the relationship between removal and mechanical properties.

Once the crosslinkable prepolymer has been purified, it is dissolved in a water-displaceable diluent to form a viscous solution. The diluent should act as a medium in which the crosslinkable functionalized polyHEMA prepolymer dissolves and in which the crosslinking reaction or cure takes place. In all other respects the diluent should be inactive. Suitable diluents include those capable of dissolving from about 30% to about 60% by weight of the crosslinkable prepolymer, based on the total weight of the viscous solution, at or below 65°C. Specific examples include alcohols having 1 to 4 carbon atoms, preferably methanol, ethanol, propanol and mixtures thereof. Water may be used in small amounts, as a co-diluent, for example in an amount less than about 50% of the total diluent. To prepare a hydrogel, a diluent should be added to the crosslinkable prepolymer in an amount approximately or equal to the amount of water present in the final hydrogel. Amounts of diluent ranging from about 40 to about 70% by weight of the resulting viscous solution are acceptable.

The viscous solution of the present invention has a viscosity of about 50,000 cP to 1×10 ⁷ cP at 25°C, preferably about 100,000 cP to about 1,000,000 cP at 25°C, more preferably about 100,000 cP to about 500,000 cP at 25°C.

Preferably, the diluent is also safe for the intended end use of the article. Thus, for example, when the article of manufacture is a contact lens, the solvent should preferably be safe and compatible with the eye. This is especially important in those cases where the solvent is not or only partially removed prior to use. A diluent that does not evaporate from the finished product should be able to adjust the Tg of the viscous solution below about room temperature (preferably, Tg below about -50°C) and have a low vapor pressure (boiling point above about 180°C) . Examples of biocompatible diluents include polyethylene glycol, glycerin, propylene glycol, dipropylene glycol, mixtures thereof, and the like. Preferred polyethylene glycols have a molecular weight of about 200-600. The use of a biocompatible diluent allows omission of a separate wash/evaporation step to remove the diluent.

Low boiling point diluents may also be used, but an evaporation step may be required to remove diluents that are incompatible with the intended environment of use. The low boiling point diluent is polar and generally has a low boiling point (below about 150°C), which makes its removal by evaporation convenient. Suitable low boiling point diluents include alcohols, ethers, esters, glycols, mixtures thereof, and the like. Preferred low boiling point diluents include alcohols, ether alcohols, mixtures thereof, and the like. Specific examples of low-boiling point diluents include 3-methoxy-1-butanone, methyl lactate, 1-methoxy-2-propanol, 1-ethoxy-2-propanol, ethyl lactate, lactic acid Isopropyl esters, mixtures thereof, and the like.

A polymerization initiator may also be added. The initiator can be any initiator that is active under the processing conditions. Suitable initiators include thermal-activated-, photo-initiators (including ultraviolet and visible light initiators), and the like. Suitable thermally activated initiators include lauryl peroxide, benzoyl peroxide, isopropyl percarbonate, azobisisobutyronitrile, 2,2-azobisisobutyronitrile, 2,2-azobis -2-Methylbutyronitrile, etc. Suitable photoinitiators include aromatic alpha-hydroxy ketones or tertiary amines plus diketones. Illustrative examples of photoinitiator systems are 1-hydroxycyclohexylphenyl ketone, 2-hydroxy-methyl-1-phenyl-propan-1-one, benzophenone, thioxanth-9-one, camphorquinone and Combinations of ethyl 4-(N,N-dimethylamino)benzoate or N-methyldiethanolamine, hydroxycyclohexylphenyl ketone, bis(2,4,6-trimethylbenzoyl)-benzene phosphine oxide and bis(2,6-dimethoxybenzoyl)-2,4,4-trimethylpentylphosphine oxide, (2,4,6-trimethylbenzoyl)diphenyl Phosphine oxides and combinations thereof and the like. Photoinitiation is the preferred method, while bis(2,6-dimethoxybenzoyl)-2,4,4-trimethylphenylphosphine oxide, bis(2,4,6-trimethylbenzoyl Acyl)-phenylphosphine oxide and 2-hydroxy-methyl-1-phenyl-propan-1-one are preferred photoinitiators. Other initiators are known in the art, for example, those disclosed in US Pat. No. 5,849,841, column 16, the disclosure of which is incorporated herein by reference.

Other additives that can be incorporated into the prepolymer or viscous solution include, but are not limited to, UV absorbing compounds, reactive dyes, organic or inorganic pigments, dyes, photochromic compounds, mold release agents, antimicrobial compounds, pharmaceuticals, mold lubricants , wetting agents, other desirable additives for maintaining product specification consistency (such as, but not limited to, TMPTMA), combinations thereof, and the like. These compositions can be added at almost any stage and can be copolymeric, sequential or associative or dispersed.

The viscous solution should preferably be free of compounds such as free monomers that could form polymers that are not bound to the network during curing and/or would contribute to residual extractable material.

In solutions of polymers, the rheological properties depend largely on the longest molecule. The polyHEMAs of the present invention have a low content of very high molecular weight molecules which impart many desirable properties to their solutions.

Viscous solutions according to the invention advantageously have a short relaxation time. The relaxation time is less than about 10 s, preferably less than about 5 s, more preferably less than about 1 s. Short relaxation times are advantageous because prepolymers with short relaxation times are able to relax flow-induced stresses prior to curing so that the cured polymer network does not contain frozen stresses. This allows the viscous solution of the present invention to be processed without requiring long "dwell" times between closing the mold and curing the viscous solution.

The polyHEMA of the present invention can be used as a raw material for the manufacture of functionalized polyHEMA prepolymers and hydrogels, base materials for toners in contact lenses, base materials for tampo and inkjet printing inks, and the like.

The viscous solutions of the present invention can be used to form a wide variety of articles. For example, molded articles, profiles, preforms, billets, films, fibers, hoses, sheets, coatings, etc. More specifically, suitable articles include biomedical devices, medical grade coatings, polymers having reactive groups or bioassay markers bonded to the polymer, and the like.

The term "biomedical device" as used herein is any article intended for use in or on mammalian tissue or body fluids. Examples of such devices include, but are not limited to, prostheses, implants, molds, bodily fluid collection bags, sensitive elements, hydrogel bandages, tubing, coatings for any of the foregoing, carriers of antibody diagnostic and therapeutic agents, and ophthalmic devices . A preferred class of biomedical devices includes ophthalmic devices, particularly contact lenses.

As used herein, the terms "lens" and "ophthalmic device" refer to devices that are placed in or on the eye. These devices may provide optical correction, wound care, drug delivery, diagnostic functions, or possibly cosmetic functions. The term lens includes, but is not limited to, soft contact lenses, hard contact lenses, intraocular lenses, superimposed lenses, ocular inlays, optical insert lenses, and spectacle lenses.

There are many methods that can be used to form articles of the invention, including injection molding, extrusion molding, spin casting, extrusion coating, closed molding, casting, combinations thereof, and the like. This forming method will be followed by the curing step described below.

In one embodiment of the invention, a prepolymer solution is used to form a lens. The preferred method of producing lenses from the viscous solutions of the present invention is direct molding. A lens forming quantity of the prepolymer solution is dispensed into a mold having the final desired hydrogel shape. The mold can be fabricated from any suitable material including, but not limited to, polypropylene, polystyrene, and cyclic polyolefins.

The so-called "lens forming capacity" refers to the quantity sufficient to produce a lens of the required size and thickness. Typically, about 10 to about 50 μL of viscous solution is used per contact lens. Next, the mold halves (upper and lower mold parts) are assembled so that the viscous solution fills the mold cavity. An advantage of the invention is that the required dwell time between the assembly of the mold halves and curing is very short.

We have found that the viscous solution must be kept in the closed mold for a period of 2-3 times the relaxation time of the viscous solution in order to avoid introducing undesirable stresses in the final article. The viscous solutions of the present invention advantageously have a short relaxation time (less than about 10 s, preferably less than about 5 s, more preferably less than about 1 s) at room temperature, which allows a dwell time of typically less than about 30 s, preferably less than about 10 s, more preferably Less than about 5s.

An added benefit of the short dwell times of the present invention is that they greatly reduce the diffusion of oxygen from the upper and lower mold halves into the crosslinkable prepolymer. Oxygen diffusion can hinder the curing process on the surface of the article. It can be seen that the viscous solution can be kept longer than specified in the low oxygen content mold with little or no negative impact other than protracted production time.

The mold containing the viscous solution is irradiated with ionizing or actinically active radiation, such as electron beams, X-rays, ultraviolet or visible light, ie, electromagnetic waves or particle radiation having a wavelength between about 280 and about 650 nm. Also suitable are UV lamps, HE/Cd, argon ions or nitrogen or metal vapors or NdYAG laser beams with frequency doubling. The choice of radiation source and initiator is known to those skilled in the art. Those skilled in the art also understand that the depth of radiation penetration into viscous solutions and the rate of crosslinking are proportional to the molecular absorption coefficient and the concentration of the selected photoinitiator. In preferred embodiments, the radiation source is selected from high intensity UVA (about 315 to about 400 nm), UVB (about 280 to about 315 nm), or visible light (about 400 to about 450 nm). As used herein, the term "high intensity" refers to an intensity between about 100 mW/cm ² and about 10,000 mW/cm ² . The curing time is short, generally less than about 30 seconds, preferably less than about 10 seconds. The curing temperature may range from about normal temperature to a high temperature of about 90°C. For convenience and simplicity, curing is preferably carried out at close to normal temperature. The exact conditions will depend on the composition of the lens material chosen and can be at the discretion of one skilled in the art.

The curing conditions must be sufficient to form a polymer network from the crosslinkable prepolymer. The resulting polymer network will be swollen by the diluent and take the form of mold cavities.

Once curing is complete, the mold is opened. In the present invention, a purification step after curing to remove unreacted components or by-products is either simplified or eliminated compared to conventional molding methods. If a biocompatible diluent is used, no washing or evaporation steps are required at this stage. An advantage of the present invention is that when biocompatible diluents are used, neither extraction nor diluent exchange steps after molding are required. If a low boiling point thinner is used, the thinner should be evaporated and the lens hydrated with water.

The resulting lens contains a polymer network that turns into a hydrogel when swollen with water. The hydrogels of the present invention may comprise from about 20 to about 75% by weight water, preferably from about 20 to about 65% by weight water. The hydrogel of the present invention has excellent mechanical properties, including modulus and elongation at break. The modulus is at least about 20 psi, preferably from about 20 to about 90 psi, more preferably from about 20 to about 70 psi.

The elongation at break is greater than about 100%, preferably greater than about 120%. Due to the absence of loose polymer chains, the hydrogel will return to its original shape after high relative deformation, eg, 100%, without leaving permanent deformation. The hydrogel of the present invention also has no visual turbidity and distortion. The above combination of properties makes the hydrogels of the present invention perfectly suitable for use as ophthalmic devices, especially soft contact lenses.

The lenses so produced can be transferred to individual lens packages containing buffered saline solution. The saline solution can be added to the package either before or after lens transfer. Lenses containing a biocompatible diluent, upon placement in a saline solution, will exchange the diluent for water to form the desired hydrogel. This, if desired, can also be done in a separate step. During storage in the package, the polymer network will absorb a defined amount of water determined by the hydrophilicity of the polymer. This equilibrium water content (expressed as wt% of the hydrated lens) can be higher or lower than the amount of diluent handled during curing. Typical hydrogels used to make contact lenses contain between about 20 and about 75% by weight water. Thus, when in equilibrium with water, the hydrogel will expand or contract. However, the essential feature is that the shape of the fully hydrated article will be a true replica of the shape of the mold cavity, notwithstanding possible dimensional variations.

In a preferred embodiment, careful selection of the amount of diluent produces a lens that will neither expand nor contract when in equilibrium with water, and is therefore a 1:1 replica of the mold cavity, which is critical for predicting the finished lens. The optical parameters are an advantage.

Suitable packaging styles and materials are known in the art. The plastic package is releasably sealed with a film. Suitable sealing films are known in the art and include foils, polymer films and mixtures thereof.

The sealed package containing the lenses is then subjected to product sterilization (the original manuscript is missing). Suitable sterilization apparatus and conditions are known in the art and include, for example, autoclave steaming.

It will be apparent to those skilled in the art that other steps may also be included in the molding and packaging process described above. These other steps may include coating the formed lens, surface treatment of the lens during forming (e.g., by mold transfer), inspecting the lens, removing defective lenses, cleaning the mold halves, reusing the mold halves, combining them, etc. Methods and coating compositions are disclosed in US Patent Nos. 3,854,982; 3,916,033; 4,920,184; and 5,002,794; 5,779,943; 6,087,415;

The shaped articles of the invention have very low or no tendency to distort after removal from the mould. Distortion has been an inherent problem in molded articles formed from high molecular weight functionalized prepolymers. The presence of prepolymer chains having a molecular weight above the range specified by the invention will impart a slow relaxation time to the functionalized prepolymer. During curing, the stresses caused by the unrelaxed long chains are frozen in the cured polymer network. When removed from the mold, the stress causes the molded article to distort so that its shape is no longer a true replica of the mold. The crosslinkable prepolymers of the present invention have a short relaxation time, which eliminates the occurrence of distortion after molding.

As used herein, the term "hydrogel" refers to a hydrated crosslinked polymer system containing water in equilibrium. Typical hydrogels are oxygen permeable and biocompatible, thus making them a preferred material for the production of biomedical devices, especially contact lenses or intraocular lenses.

In the present invention, all molecular weights are to be understood as molecular weights determined according to Gel Permeation Chromatography (GPC) analysis (also known as Size Exclusion Chromatography) using K. Almdal of Risφ National Laboratory (Denmark). Method developed by (K.Almdal K., Determination of absolute molecular weight distribution by size-exclusion chromatography. Synthesis of narrow molecular weight distribution polymers. Poly(formazan) by size-exclusion chromatography coupled with refractive index and low-angle laser light scattering detection. Identification of the molecular weight distribution of 2-hydroxyethyl acrylate), Risφ-M-2787 (v.1) (1989) 141p).

In this method, a series of polyethylene glycols and polyethylene oxides of precisely defined molecular weights are used to calibrate the equipment. These standards used for polyHEMA provided more accurate peak molecular weight and Pd (polydispersity) than previous methods developed for more hydrophobic polymers. This method will be described below.

Molecular weight can be determined as described below. The SEC equipment consisted of: column oven, 40°C, PELC-410 pump, autosampler with PE Nelson 900A/D and series 200: detector was RI Merck L7490.

The column set consisted of two TSK-Gel columns (manufactured by TosoHaas) (G4000PW+G2500PW) and a guard column.

The eluent consisted of methanol-water (75/25 weight ratio) adjusted to 50 mM sodium chloride (NaCl).

The flow rate was 0.5 mL/min. The injection volume was 150 μL and the flow time was 60 min.

The calibration curve was obtained by third-order regression using PEG and PEO with peak molecular weights ranging from 96,000 to 194 as standard reference substances. These polymer standards were purchased from Polymer Laboratories Inc., Amherst MA (calibration kit PEG-10 part number 2070-0100; PEO-10 part number 2080-0101). A standard reference with a peak molecular weight of 194 was added to give a flow signal at a precisely defined location, used as an internal standard or fixed point. Added sodium chloride does the same and gives a second fixed point.

Peak integration was done manually. Integration start and end points were manually determined based on significant differences from the overall baseline. Results are reported giving Mz, Mw, Mn and Mpeak in PEG, PEO units. The relevant values for HEMA units are reported according to the standard and calculated according to the following mathematical function:

M _HEMA = ^{10.1,362+0,7854*logM, PBG/PBO}

Injection solutions were prepared from methanol-water in a 75/25 weight ratio, adjusted to 60 mM NaCl to give a polymer concentration of 2 mg/mL. Tetraethylene glycol was added to the samples at a concentration of 1 mg/mL to give a reference value for the peak flow rate. The solution was filtered on a 0.5 μm disposable filter before reinjection.

In the present invention, the polydispersity Pd of a polymer sample is defined as

Pd= _Mw / _Mn . The peak molecular weight Mp is the molecular weight of the highest peak in the molecular weight distribution curve.

Tensile properties (elongation and tensile modulus) were measured using a mobile tensile testing machine equipped with a load cell descending to the height of the initial scale, sliding the crosshead at a constant rate. Suitable testing machines include Instron, Model 1122. A dogbone-shaped sample, 0.522 inches long, 0.276 inches wide "ear" and 0.213 inches wide "neck," was mounted on a grip and stretched at a constant strain rate of 2 in/min until fracture. Measure the initial scale length (Lo) and the fracture length (Lf) of the sample. Twelve samples of each composition were measured and averaged. Percent elongation = [(Lf-Lo)/Lo] x 100.

Tensile modulus is measured from the initial linear portion of the stress/strain curve.

Viscosity was measured using a Haake RS100 RheoSress equipped with a Haake circulating bath and temperature controller. The complex viscosity measurement procedure is to scan the frequency from 40Hz to 1mHz, then increase to 40Hz again, take 3 frequencies for each decade, repeat each frequency 3 times (measurement) and wait for a period between each measurement . The assay employed a parallel plate geometry at 25°C+1 with a diameter of 20 mm and a gap size (sample thickness) of 0.7 mm, corresponding to a sample volume of approximately 0.22 mL. Referring to the Cox-Mertz law (John Ferry, Viscoelastic Properties of Polymers, 3rd ed., McGray-Hill Books, Inc., 1980.), the reported viscosity value (η) is the low frequency value of the complex viscosity (η ^* ).

The relaxation time was determined using the Haake RS100 RheoStress described above and using a shear stress of 400 Pa. The relaxation time is obtained by plotting G' and G" against frequency, the two intersect each other at frequency f, so that at frequencies below f G" > G', and above f, G' > G ". Relaxation time = 1/f.

The actual degree of functionality was determined by hydrolysis of the product and detection of released methacrylic acid by HPLC. Hydrolyzed samples were prepared from aliquots of methanol solution and 1 mL NaOH 1M. Hydrolysis was performed at room temperature for at least 12 h. The amount of methacrylic acid detected is compared to the amount of dry polymer contained in the sample, giving the actual degree of functionalization.

Specifically, the HPLC equipment included: a column oven at 25°C, a Merck L6000 pump, and a Perkin Elmer LC290 UV detector. The combination of columns consisted of a Merck RP18 column (125mm/4mm) and a guard column.

The mobile phase was an acetonitrile-water mixture (1/9 weight ratio), pH adjusted to 2.5 with trifluoroacetic acid. The flow rate was fixed at 1 mL/min and the injection volume was 10 μL.

Detection is performed at a wavelength of 230 nm. Data acquisition time is 8min. A series of calibration solutions are produced by diluting solutions of methacrylic acid in the mobile phase at concentrations ranging from 5 to 25 ppm.

Injection solutions were made from hydrolyzed samples and 10 mL HCl, 1M, diluted in mobile phase. The solution was filtered on a 13 mmGD/X0, 45 μm Whatmann filter before injection.

The following examples are not intended to limit the present invention. They serve only to give a way of practicing the invention. Those skilled in contact lenses, as well as other specialties, will be able to find other ways to practice the invention. However, those methods are also considered to be within the scope of the present invention.

The following abbreviations will be used in the examples.

AIBM 2,2'-azobis(2-methylbutyronitrile)

DABCO Triethylenediamine

DMAP N,N-Dimethylaminopyridine

DMF N,N-Dimethylformamide

DMSO Dimethyl Sulfoxide

EOH ethanol

GMA Glyceryl Methacrylate

HEMA 2-Hydroxyethyl Methacrylate

IPA 2-propanol

MAA Methacrylic acid

MAACl Methacryloyl Chloride

MAAH Methacrylic Anhydride

NMP 1-methyl-2-pyrrolidone

PEG Polyethylene glycol

p(TMS-HEMA) Poly(trimethylsiloxyethyl-methacrylate)

Py Pyridine

TEA Triethylamine

TMS-HEMA Trimethylsiloxyethyl-methacrylate

TEG Tetraethylene glycol

Example 1

1911.6 g ethanol, 1056.6 g HEMA monomer, 3.00 g dodecyl mercaptan and 21.00 g methacrylic acid were mixed at 25°C. The mixture was poured into a 5 L stainless steel reactor with a three-blade stirrer, temperature controller, and cooling and heating jackets.

The mixture was heated to 68°C and 7.50 g of 2.2'-azobis(2-methylbutyronitrile) (AMBN) was added. The AMBN dissolved rapidly and the reactor was covered with a slow flow of nitrogen. The temperature was maintained at 68 °C for 18 h to complete the conversion. The reactor was heated to 80 °C and held at this temperature for 22 h to destroy residual initiator and mercaptan. After cooling to room temperature, samples were withdrawn and the solids content was determined by evaporation at 125°C, 3-4 mm Hg for 24 h. Solids content = 37.2%, Mp = 76.6 kilodaltons, Pd = 3.75.

The polyHEMA solution was diluted with ethanol to give a 10% solution of polyHEMA in ethanol. At 24°C the solution became cloudy. The solution was heated to 40°C to render it homogeneous, then allowed to stand at about 21°C.

After 3 days the solution had separated into two clear phases.

The two phases were separated and analyzed:

Table 2 Rating ID Quantity Vol.% Solid w% Mpk Dalton PD top 80 8.6 64.0 2.8 end 20 15.6 144 3.34

The bottom fraction rich in high molecular weight polymer was discarded.

The upper fraction was isolated and left at 8°C for further fractionation. After 24 h, the solution separated into two phases. The upper fraction comprised 85% by volume of the total and contained 2.5% by weight polyHEMA. The bottom phase comprised 15% by volume of the total solution and contained 35.7% by weight polyHEMA. Mp 83.8 kilodaltons, Pd = 2.18. This fraction was isolated for functionalization.

Example 2

HEMA monomer (impurity level lower than 0.8% purchased from Rohm) was mixed with triethylamine (≥99.5% pure, supplied by Fluka) and petroleum ether (boiling point 40-60°C) fed through alumina, And reaction with trimethylchlorosilane (>99.0% pure, supplied by Fluka) results in trimethylsiloxyethyl-methacrylate (TMS-HEMA). TMS-HEMA was purified by distillation from calcium hydride (once) and triethylaluminum (electronic grade, supplied by Aldrich) (twice).

TMS-HEMA was polymerized in THF (absolutely pure) solution (Fluka) at -78°C with 1,1-diphenylhexyllithium as an initiator to obtain the polymerized product quantitatively. Polymerization was terminated with degassed methanol. The polymer was isolated by adding a THF solution of poly(trimethylsiloxyethyl-methacrylate)p(TMS-HEMA) to a large excess of water.

The polymer has a peak molecular weight of 63 kilodaltons, Mw=75 kilodaltons and a polydispersity equal to 1.6.

Example 3

1619 g ethanol, 176.5 g HEMA monomer and 3.60 g methacrylic acid (MAA) were blended at 25°C. The mixture was poured into a 3 L glass reactor equipped with a stirrer, temperature controller and cooling and heating jacket.

The mixture was heated to 68°C and 1.26 g of AMBN was added. The AMBN dissolved rapidly and the reactor was covered with a slow flow of nitrogen. The temperature was maintained at 68 °C for 20 h to complete the conversion. After cooling to room temperature, the polymer solution was diluted with ethanol to give a 10% solution of polyHEMA in ethanol. Before classification, Mp was 70 kilodaltons and Pd was 3.33. After adding 2% hexane, the solution had a fog point of 31°C. The polymer was fractionated in Example 10.

Example 4

1625g ethanol, 108.4g HEMA monomer and 72.8g glyceryl methacrylate were blended at 25°C. The mixture was poured into a 3 L glass reactor equipped with a stirrer, temperature controller and cooling and heating jacket.

The mixture was heated to 74°C, and 1.29 g of AMBN was added, and the reactor was covered with a slow flow of nitrogen. The temperature was maintained at 74 °C for 20 h to complete the conversion. After cooling to room temperature, the polymer solution was diluted with ethanol to give a 10% solution of poly-(HEMA-co-GMA) in ethanol. Mp is 56 kilodaltons and Pd is 2.35. The solution had a fog point of 35°C and was left at 33°C for 3 days to be graded. The upper fraction is siphoned out while the lower fraction is discarded. 2% heptane was added to the upper fraction. This produces a fog point of 49°C. After standing at 29° C. for 3 days, a new upper fraction formed and was discarded. A lower fraction was isolated containing 64% of the original polymer, which was determined to have a Mp of 66 kilodaltons and a Pd of 2.1. This polymer was functionalized in Example 21.

Example 5-9

The polymerization reaction of Example 3 was repeated at different temperatures and with the solvents shown in Table 3 below. The results are presented in Table 3 and show that good control of molecular weight can be achieved using this method.

table 3 example T(°C) solvent Mp(kD) PD 5 82 2-propanol 35 3.4 6 78 2-propanol 40 3.4 7 74 ethanol 50 2.6 8 72 ethanol 60 3.6 9 68 ethanol 70 3.3

Example 10

800 g of the solution prepared in Example 3 were heated to 40°C to render it homogeneous and then allowed to stand at 28°C. After 5 days, the solution separated into two clear phases. The upper phase containing 77.1% polymer was siphoned off and the bottom phase was discarded.

The hexane content in the upper phase was adjusted to 7%, resulting in a fog point of 54°C. The solution was heated to 57°C to render it homogeneous, then allowed to stand at 29°C. After 4 days, the solution separated into two clear phases. The upper phase containing the low molecular weight polymer fraction was siphoned off and the bottom phase was fractionated a third time. This time, the concentration of hexane was adjusted to 8%, and the solution was allowed to stand at 30°C for 4 days. The upper phase containing the low molecular weight polymer fraction is siphoned off and the polymer in the lower phase is isolated for functionalization. The results of the functionalization are shown in Table 4 below.

Table 4 MwK Dalton M _p K Dalton PD Unfractionated p-HEMA 98 70 3.33 fractionated p-HEMA 97 76 1.51

Example 11

PolyHEMA with nominal 2% MAA was prepared as in Example 3 and fractionated as described in Example 10. The content of MAA in the un-fractionated and fractionated material was determined as described in the ISO standard (3682-1983(E)) and is reported in Table 5 below.

table 5 M _w (kD) M _p (kD) PD %MAA Unfractionated p-HEMA 98 70 3.33 1.8 fractionated p-HEMA 97 76 1.51 1.8

The MAA content in the unfractionated copolymer was equal to the MAA content measured in the fractionated copolymer. This suggests that the fractionation process only separates polymers based on molecular weight, not composition.

Example 12

9.09 g of polyHEMA prepared and isolated in Example 2 were dried by evaporation at 125° C., 3 mm Hg for 24 h, and subsequently dissolved by slight heating in pyridine, resulting in a 10 wt % solution. The solution was cooled in an ice bath, and 400 μL of methacryloyl chloride (corresponding to a target value of 6 mol% esterification of hydroxyl groups in polyHEMA was added. Subsequently, most of the pyridine was removed under vacuum at 25–30 °C, and the functionalized The deionized copolymer was contacted with deionized water to dissolve residual pyridine and other low molecular weight materials. The water was decanted and washed repeatedly until the HPLC system could no longer pick up residual pyridine.

The functionalized polymer has a Mp of 62 kilodaltons and a Pd of 1.6.

Example 13

110 mL of anhydrous 1-methyl-2-pyrrolidone (NMP) (water≤0.01%) was added to a total of 13.6 g of dry poly(HEMA-co-MAA) from Example 1 previously dried under vacuum at 100° C. for 12 h. The reaction flask, equipped with a magnetic stirrer bar, was maintained under an atmosphere of dry nitrogen. A solution of 2% methacrylic anhydride in 94% anhydrous NMP (24.7 mL, 0.003 mol) was added dropwise over 2-3 min. Triethylamine (0.45 mL, 0.003 mol) was added, and the contents of the flask were heated at 35° C. with stirring for 48 h.

The temperature was lowered to 25 °C, and then 200 mL of deionized water was added. Subsequently, the crude reaction product was poured into 400 mL of aqueous HCl (0.1 M, pH=1.5). 4 L of deionized water was added and precipitation was induced immediately. After the precipitate was washed with water, it was dissolved in 100 mL of ethanol. A second precipitation was performed with 1 L of water and HCl (pH=1.5). The precipitate is soaked in excess water for several hours to remove residual acid.

Finally, the precipitate was dissolved in methanol to obtain a clear solution.

Example 14

4.38 g of unfractionated HEMA-MAA copolymer were dried by evaporation at 125°C, 3 mm Hg for 24 h, then dissolved in DMF (99+%, < 0.1% H ₂ O) to obtain a 20 wt% solution. To obtain esterification of about 3% of the hydroxyl groups of the copolymer, 1.08 mmol of methacrylic anhydride (94% pure) was mixed with 8 mL of DMF and then added to the polymer solution. Triethylamine (1.08 mmol, > 99.5% pure, ex Fluka) was then added. The mixture was allowed to react at 30 °C for 20 h, then quenched by adding 2 mL of water. Glycerol (10 g) was added to the polymer solution, then DMF was distilled off (30° C., 0.5 mbar, 2 h).

Contact the functionalized copolymer with water to dissolve residual DMF and other low molecular weight materials. Decant off and wash repeatedly until no trace of DMF is left. The degree of functionalization was determined to be 2.2%, Mpeak = 41 kilodaltons, Pd = 2.8. When molded into a hydrogel using a method similar to Example 22, the following mechanical properties were measured: Modulus: 11 ± 2 psi, elongation 120 ± 25. Due to the higher Pd, the performance is relatively poor.

Examples 15-20

PolyHEMA (unfractionated) prepared according to Example 1 was functionalized using the method described in Example 13 (Examples 15 and 16). PolyHEMA prepared according to Example 1 was fractionated using the method described in Example 10 and then functionalized using the method described in Example 13 (Examples 17 and 18). Lenses were prepared from graded and unfractionated functionalized polyHEMA using the method of Example 22 with 61% tetraethylene glycol as diluent. The viscous solution was solidified as in Example 22. The results are presented in Table 6 below.

Table 6 example HEMA/MAA polymer functionalized polymer Lens properties MpkD PD MP PD Modulus psl elongation% 15 40 3.48 48 1.67 32 76 16 53 3.59 62 1.88 33 90 17 44 1.35 45 1.4 37 109 16 64 1.7 70 1.59 40 106

It can be seen that this method of functionalization reduces the polydispersity to acceptable values. In general, washing steps remove the smallest polyHEMA molecules. Lens properties indicate that functionalized polymers with lower polydispersity exhibit better mechanical properties.

Example 21

3.22 g of the GMA-HEMA copolymer produced and isolated in Example 4 were dried by evaporation at 125° C., 3 mm Hg for 24 h, and subsequently dissolved in DMF (99+%, ≤0.1% H ₂ O) to obtain 20 wt % solution. To obtain an average degree of esterification of about 2.4 units per 100 units, 0.74 mmol of methacrylic anhydride (94% pure from Fluka) was mixed with 6 mL of DMF and then added to the polymer solution. Triethylamine (0.74 mmol, > 99.5% pure, ex Fluka) was then added to the polymer solution. The mixture was allowed to react at 30 °C for 20 h, then quenched by adding 2 mL of water. Glycerol (10 g) was added to the polymer solution, then DMF was distilled off (30° C., 0.5 mbar, 2 h).

Contact the functionalized copolymer with deionized water to dissolve residual DMF and other low molecular weight materials. After cooling to below about 5°C, the functionalized polymer precipitated and the aqueous phase was decanted. Methanol was added to dissolve the functionalized polymer. The degree of functionalization was determined to be 2.3, corresponding to 90% of the target value. The functionalized polymer was dissolved in tetraethylene glycol using the method of Example 22 to make a molding solution containing 39 wt% solids. The produced hydrogel lens has the following mechanical properties (equilibrium water content 65%) modulus 18±1 psi. Elongation 120±25%.

Example 22

A solution of HEMA-2% MAA copolymer from Example 13 was transferred through a 25mm GD/×0.45mm Whatmann filter into a syringe and mixed with tetraethylene glycol (99+% pure from Fluka) to contain 39 wt% interpolymer, 60.5 % tetraethylene glycol molding solution, and then add 0.5wt% Darocur 1173 photoinitiator. The blend is mixed. Low boiling point solvents were removed by applying a controlled vacuum to the syringe. Centrifuge the cylinder so that all solution flows down to the outlet port. Insert the sleeve into the cylinder and push down until it touches the molding solution, maintaining a temporary air escape path. The barrel containing the molding solution is placed in a fixture where a controlled force is applied to the barrel and injects approximately 50 mg of the solution into the lower half of a polystyrene contact lens mold. The top half is seated, the mold is closed and the two parts are held together for 5 s with a 10 kg load.

The closed mold is placed on a conveyor belt moving at 1 m/s and the mold is passed under a high intensity UV lamp focused 20 mm above the conveyor belt for less than about 10 s. The maximum intensity is 5W/cm ² , and the closed mold is irradiated with a total of 15J/cm ² , according to the test results in the ultraviolet range of a PowerPuck_UV spectrophotometer placed next to the closed mold.

After curing, remove the cover by hand and soak the lens in deionized water for 10 minutes. The resulting hydrogel lenses maintained their shape and size when the tetraethylene glycol diluent was replaced with saline. A 1:1 replica of the mold surface was then made. The 14.00mm diameter mold produced a 14.00mm diameter hydrogel lens.

Example 23

Example 1 was repeated except that the polyHEMA was diluted with ethanol to a 36 wt% solution in ethanol. The molecular weight and polydispersity of the polyHEMA produced are reported in Table 7 below.

Example 24

Example 1 was repeated except that polyHEMA was diluted with ethanol to a 36 wt% solution in ethanol and octyl mercaptan was used as the chain transfer agent instead of dodecyl mercaptan. The obtained polymer solution was fractionated as described in Example 10. The molecular weight and polydispersity of the polyHEMA produced are reported in Table 7 below.

Table 7 example Graded Mw(kD) Mp(kD) PD twenty three none 67 48 2.56 twenty four Ex10 47 40 1.26

Examples 25-28

Example 3 was repeated except that the polymerization temperature (Examples 25-27) and solvent (Example 28) were changed as shown in Table 8 below. Example 27 was not graded. All other examples in this group were graded according to Example 10. Molecular weights and polydispersities are reported in Table 8 below.

Table 8 example T(°C) Reagent Mw(kD) Mp(kD) PD 25 72 EOH 95 64 1.7 26 68 EOH 94 70 1.56 27 75 EOH 67 49 2.6 28 74 IPA 52 45 1.39

Examples 29-37

The polymers of Examples 23-28 were functionalized in a manner similar to that of Example 13, with the changes shown in Table 9 below. The percent functionalization, molecular weight and polydispersity are listed in Table 9.

Table 9 example Prepolymer Ex.# %f target %f actual Reagent alkali Acylating agent Mw(kD) Mp(kD) PD 29 twenty three 10 2.3 DMSO Python MAACl 83 56 2.18 30 26 8 2.2 NMP TEA MAACl 89 67 1.42 31 28 6 2.9 NMP DMAP MAAH 56 48 1.21 32 28 3.4 2.1 NMP TEA ^* MAACl 63 48 1.30 33 25 3 1.4 NMP Python MAAH 89 68 1.43 34 27 10 2.2 NMP DABCO MAACl 82 55 1.79 35 26 3.3 2.9 NMP TEA MAAH 81 111 1.61 36 26 3 2.2 NMP TEA MAAH 84 114 1.66 37 twenty four 3 2.4 NMP TEA MAAH 43 50 1.25

Carried out at 57°C.

Examples 38-41

The functionalized prepolymers prepared in Examples 33 and 35-37 were molded into lenses according to Example 22. Modulus, elongation and equilibrium water content are reported in Table 10 below.

Table 10 example Functionalized PP example Modulus (psi) elongation(%) % _H2O 38 33 4 462 62 39 35 50 107 58 40 36 20 150 59 41 37 25 160 59

Example 42

In a syringe, a polymer solution containing 19.5 wt% prepolymer from Example 33 and 19.5 wt% prepolymer from Example 35 was mixed with TEG (99+% pure, supplied by Fluka) and photoinitiator Darocur 1173. After evaporation of the alcohol, the viscous solution contained 0.5 wt% Darocur 1173, 60.5 wt% TEG and 19.5 wt% of each prepolymer. Hydrogels fabricated and cured with this molding solution according to Example 22 exhibited the following mechanical properties: Modulus: 27±2 psi, elongation 186±14%.

Example 43

In a syringe, a solution of the functionalized prepolymer from Example 30 was mixed with tetraethylene glycol (99+% pure, supplied by Fluka) and the photoinitiator Darocur 1173. After evaporating off the low boiling point solvent, the viscous solution contained 0.5 wt% Darocur 1173, 50 wt% tetraethylene glycol and 49.5 wt% functionalized prepolymer from Example 30. Addition of degassed water resulted in a viscous solution containing 0.4 wt% Darocur 1173, 39 wt% tetraethylene glycol and 38.6 wt% prepolymer and 22% water as co-diluent. The hydrogel made from this molding solution was cured according to Example 22 and obtained the following mechanical properties: Modulus: 34±7 psi, elongation 136±20%.

Example 45

The bottom fraction of the prepolymer in Example 1 enriched in the high molecular weight polymer fraction (described in Table 2) was functionalized using the method described in Example 9. Subsequently, the functionalized and washed prepolymer was mixed with TEG using the method described in Example 22 to obtain a viscous solution containing 50 wt% solids. The relaxation time of this viscous solution was determined to be 400 s at 20°C.

About 50 mg of this solution was molded into contact lenses according to Example 22 at 20°C with dwell times of 200, 400 and 800 s.

After curing, remove the cover by hand and soak the lens in deionized water for 10 minutes. Lenses prepared with dwell times of 200 s and 400 s were distorted and out of shape from the mold cavity. Lenses prepared with a dwell time of 800 s maintained the spherical shape of the mold without distortion.

Claims (112)

CLAIMS 1. A composition comprising polyHEMA having a polydispersity of less than 2 from 25,000 peak molecular weight to 100,000 peak molecular weight with a polydispersity of less than 3.8. 2. The composition of claim 1, wherein the peak molecular weight is from 30,000 with a polydispersity of less than 2 to 90,000 with a polydispersity of less than 3.5. 3. The composition of claim 1, wherein the peak molecular weight is from 30,000 with a polydispersity of less than 2 to 80,000 with a polydispersity of less than 3.2. 4. The composition of claim 1, wherein the peak molecular weight is from 25,000 with a polydispersity of less than 1.5 to 80,000 with a polydispersity of less than 3.5. 5. The composition of claim 1, wherein said peak molecular weight is less than 100,000 and said polydispersity is less than 2. 6. The composition of claim 1, wherein said polydispersity is less than 1.7. 7. The composition of claim 1, wherein the polydispersity is less than 1.5. 8. The composition of claim 1, wherein the polyHEMA is substantially free of gel particles. 9. The composition of claim 1, wherein the polyHEMA is a copolymer comprising HEMA and at least one comonomer. 10. The composition of claim 9, wherein the comonomer comprises at least one hydrophilic monomer. 11. The composition of claim 10, wherein said at least one hydrophilic monomer is selected from vinyl-containing monomers. 12. The composition of claim 11, wherein said at least one vinyl-containing monomer is selected from the group consisting of N,N-dimethylacrylamide, glyceryl methacrylate, 2-hydroxyethyl methacrylate, polyethylene glycol Alcohol monomethacrylate, methacrylic acid, acrylic acid, N-vinyllactam, N-vinyl-N-methylacetamide, N-vinyl-N-ethylacetamide, N-vinyl-N - Ethylformamide, N-vinylformamide, vinyl carbonate monomers, vinyl carbamate monomers, oxazolone monomers and mixtures thereof. 13. The composition of claim 10, wherein said at least one hydrophilic monomer is selected from the group consisting of N,N-dimethylacrylamide, glyceryl methacrylate, 2-hydroxyethyl methacrylate, N-vinyl Pyrrolidone, polyethylene glycol monomethacrylate, methacrylic acid and acrylic acid and mixtures thereof. 14. The composition of claim 10, wherein said at least one hydrophilic monomer comprises N,N-dimethylacrylamide, methacrylic acid, and glyceryl methacrylate. 15. The composition of claim 10, wherein said at least one hydrophilic monomer is present in an amount of less than 50 wt%. 16. The composition of claim 10, wherein said at least one hydrophilic monomer is present in an amount ranging from 0.5 to 40 wt%. 17. The composition of claim 10, wherein said hydrophilic monomer comprises up to 50 wt% glyceryl methacrylate. 18. The composition of claim 10, wherein said hydrophilic monomer comprises between 25 to 45 wt% glyceryl methacrylate. 19. The composition of claim 10, wherein said hydrophilic monomer contains less than 5 wt% methacrylic acid. 20. The composition of claim 10, wherein said hydrophilic monomer contains between 0.5 to 5.0 wt% methacrylic acid. 21. The composition of claim 10, wherein said hydrophilic monomer contains up to 50 wt% N,N-dimethylacrylamide. 22. The composition of claim 10, wherein said hydrophilic monomer contains between 10-40 wt% N,N-dimethylacrylamide. 23. The composition of claim 1, wherein said polyHEMA is a homopolymer. 24. The composition of claim 9, wherein said copolymer contains at least one hydrophobic monomer. 25. The composition of claim 24, wherein the hydrophobic monomer comprises at least one silicone-containing monomer or macromonomer having at least one polymerizable vinyl group. 26. The composition of claim 25, wherein said polymerizable vinyl group contains 2-methacryloyloxy. 27. The composition of claim 9, wherein at least one comonomer is a tinting monomer that absorbs light in the visible and/or ultraviolet range. 28. The composition of claim 1, wherein less than 10 wt% of the polymer molecules in the polyHEMA have a peak molecular weight of less than 15,000. 29. A method comprising the steps of polymerizing by free radical polymerization HEMA monomers containing less than 0.5% by weight of a crosslinker and optionally at least one hydrophilic or hydrophobic comonomer to produce High polydispersity polyHEMA having polydispersities greater than 2.2 and 4, respectively, and purifying said high polydispersity polyHEMA to produce low polydispersity polyHEMA having a peak molecular weight of 25,000 to 100,000 and a polydispersity of less than 2 to less than 3.8 HEMA. 30. The method of claim 29, wherein said radical polymerization is carried out at a temperature between 40-150° C. for a period of 2-30 hours in a solvent capable of dissolving the monomer and polyHEMA during polymerization. 31. The method of claim 30, wherein the solvent is selected from the group consisting of alcohols, diols, polyols, aromatics, amides, sulfoxides, pyrrolidones, ethers, esters, ester alcohols, glycol ethers, ketones, and mixtures thereof. 32. The method of claim 30, wherein the solvent is selected from the group consisting of methanol, ethanol, isopropanol, 1-propanol, methyl lactate, ethyl lactate, isopropyl lactate, ethoxypropanol, glycol ethers, DMF, DMSO, NMP and cyclohexanone. 33. The method of claim 29, wherein said free radical polymerization is carried out at atmospheric pressure and a temperature between 60-90°C. 34. The method of claim 29, wherein said free radical polymerization is initiated by thermal initiation using at least one thermal initiator. 35. The method of claim 34, wherein the thermal initiator is selected from the group consisting of lauryl peroxide, benzoyl peroxide, isopropyl percarbonate, azobisisobutyronitrile, 2,2-azobisisobutyronitrile Nitrile, 2,2-azobis-2-methylbutyronitrile and mixtures thereof. 36. The method of claim 34, wherein the thermal initiator comprises 2,2-azobis-2-methylbutyronitrile, 2,2-azobis-isobutyronitrile, and mixtures thereof. 37. The method of claim 29, wherein said purification step is performed by temperature control and/or solvent/non-solvent fractionation using Hansen solubility parameters. 38. The method of claim 37, wherein said purifying step is carried out by temperature control comprising the steps of: a) dissolving the polyHEMA in a solvent having a Hansen solubility parameter within the solubility sphere of the polyHEMA to form a separation solution; b) cooling the separated solution to a temperature below T _s , thereby forming at least a lower phase and an upper phase comprising high molecular weight polyHEMA; and c) Remove the lower phase. 39. The method of claim 38, further comprising the steps of further purifying said upper phase by repeating steps (a) to (c); or adding at least one solvent capable of reducing said separation mixture to said upper phase. The amount of non-solvent should be sufficient to precipitate the low polydispersity polyHEMA from the separation mixture. 40. The method of claim 37, wherein said purification step is performed by solvent/non-solvent fractionation comprising: a) dissolving said polyHEMA in a solvent having a Hasen solubility parameter δ _D ranging from 13 to 20, δ _P ranging from 5 to 18 and δ _H ranging from 10 to 25 to form a separation solution; b) adding to said separation mixture a non-solvent capable of reducing at least one solubility parameter of said separation solution in an amount sufficient to precipitate high molecular weight polyHEMA from said separation solution; and c) Removal of the high molecular weight polyHEMA. 41. The method of claim 40, further comprising the steps of: further purifying the separated solution by repeating steps (a) to (c); or cooling the separated solution to a temperature lower than T _s , so as to form at least one containing a lower phase of high molecular weight polyHEMA and an upper phase; and removing the lower phase. 42. The method of claim 40, wherein said at least one solubility parameter comprises a delta _H parameter. 43. The method of claim 40, wherein the decrease in said at least one solubility parameter is between 2 and 5 units. 44. A method comprising the steps of attaching at least one crosslinkable functional group to polyHEMA having a peak molecular weight of 25,000 to 100,000 and a polydispersity of less than 2 to less than 3.8 to form a crosslinkable prepolymer, wherein the The conditions should be sufficient to covalently bind the crosslinkable functional groups to the polyHEMA chains. 45. The method of claim 44, wherein said crosslinkable functional groups are present in an amount ranging from 1 to 20 wt%, based on the stoichiometric amount of available hydroxyl groups in said polyHEMA. 46. The method of claim 44, wherein said crosslinkable functional groups are present in an amount ranging from 1.5 to 10 wt%, based on the stoichiometric amount of available hydroxyl groups in said polyHEMA. 47. The method of claim 44, wherein the crosslinkable functional group is derived from a reactant having the structure A-S-F, wherein A is a linking group capable of forming a covalent bond with a hydroxyl group in polyHEMA; S is a spacer; and F is a functional group containing ethylenic unsaturation. 48. The method of claim 47, wherein A is selected from the group consisting of chlorides, isocyanates, acids, anhydrides, acid chlorides, epoxies, azalides, and mixtures thereof. 49. The method of claim 47, wherein A comprises at least one anhydride. 50. The method of claim 47, wherein S is selected from direct bonds and linear, branched or cyclic alkyl or aryl groups of 1 to 8 carbon atoms and the general formula -(CH ₂ CH ₂ -O) _n - The polyether, wherein n is between 1-8. 51. The method of claim 47, wherein S is selected from direct bonds and linear, branched or cyclic alkyl groups of 1 to 4 carbon atoms and polymers of the general formula -(CH ₂ CH ₂ -O) _n - Ether, wherein n is between 1 and 4. 52. The method of claim 47, wherein F has the general formula -C(R ¹⁰ )=CR ¹¹ R ¹² And R ¹⁰ , R ¹¹ and R ¹² are independently selected from hydrogen and methyl. 53. The method of claim 47, wherein the reactant is selected from the group consisting of methacryloyl chloride, 2-isocyanatoethyl acrylate, isocyanatoethyl methacrylate, glycidyl methacrylate , cinnamoyl chloride, methacrylic anhydride, acrylic anhydride and 2-vinyl-4-dimethylazolactone. 54. The method of claim 44, wherein at least one functional group providing additional functionality other than crosslinking is attached to said crosslinkable prepolymer. 55. The method of claim 46, further comprising the step of: purifying said crosslinkable prepolymer comprising washing said prepolymer with water to remove substantially all undesired components and Residual by-products of the polymer step. 56. The method of claim 55, wherein said purifying step comprises the steps of: providing a high surface/volume ratio to the crosslinkable prepolymer, washing said crosslinkable prepolymer with deionized water at or above room temperature thing. 57. The method of claim 44, further comprising the step of mixing said purified crosslinkable prepolymer with a diluent to form a viscous solution having a viscosity at 25°C ranging from 50,000 cps to 1 x ¹⁰⁷ cps. 58. The method of claim 57, wherein said diluent is biocompatible, has a low Tg, low vapor pressure, and is capable of dissolving 30wt% to 60wt% of the crosslinkable prepolymer at or below 65°C, to The total weight of the viscous solution is based on the basis. 59. The method of claim 58, wherein the diluent is selected from the group consisting of polyethylene glycol, glycerin, propylene glycol, dipropylene glycol, and mixtures thereof. 60. The method of claim 59, wherein the diluent comprises polyethylene glycol having a molecular weight of 200-600. 61. The method of claim 58, wherein the diluent is polar and has a boiling point below 150°C. 62. The method of claim 61, wherein the diluent is selected from the group consisting of alcohols, ethers, esters, glycols, and mixtures thereof. 63. The method of claim 61, wherein the diluent is selected from the group consisting of alcohols, ether alcohols, and mixtures thereof. 64. The method of claim 61, wherein the diluent is selected from the group consisting of 3-methoxy-1-butanol, methyl lactate, 1-methoxy-2-propanol, 1-ethoxy-2-propanol Alcohol, Ethyl Lactate, Isopropyl Lactate and mixtures thereof. 65. The method of claim 61, further comprising the step of evaporating said diluent after forming and curing an article from said viscous solution. 66. The method of claim 57, wherein said viscous solution further comprises at least one initiator. 67. The method of claim 66, wherein the initiator comprises at least one of a photoinitiator, a thermally activated initiator, and mixtures thereof. 68. The method of claim 66, wherein the initiator is selected from the group consisting of bis(2,6-dimethoxybenzoyl)-2,4,4-trimethylpentylphosphine oxide and diketone, 1-hydroxy Cyclohexyl phenyl ketone. 69. The method of claim 57, wherein said viscous solution further comprises a compound selected from the group consisting of UV absorbing compounds, reactive dyes, organic or inorganic pigments, photochromic compounds, mold release agents, mold lubricants, antimicrobial compounds, drugs, wetting Agents and at least one additive for combinations thereof. 70. The method of claim 57, wherein the viscous solution has a relaxation time of less than 10 seconds. 71. The method of claim 57, wherein the viscous solution has a relaxation time of less than 5 seconds. 72. The method of claim 57, wherein the viscous solution has a relaxation time of less than 1 second. 73. The method of claim 44, wherein said polyHEMA is prepared by a polymerization process that directly produces a low polydispersity. 74. The method of claim 73, wherein said polymerization method is carried out by free radical living chain polymerization. 75. The method of claim 58, wherein said diluent further comprises water. 76. A method comprising the steps of: attaching at least one crosslinkable functional group to polyHEMA having a peak molecular weight of 25,000 to 100,000 and a polydispersity greater than 2.2 to greater than 4 to form a crosslinkable prepolymer, wherein conditions are sufficient to covalently incorporate said crosslinkable functional groups onto polyHEMA chains, and to treat said crosslinkable prepolymer to produce a crosslinkable prepolymer with a polydispersity of less than 2, wherein less than 10% by weight The molecular weight of the crosslinkable prepolymer is less than 15,000. 77. A composition comprising at least one crosslinkable prepolymer comprising polyHEMA having a peak molecular weight of 25,000 to 100,000 and a polydispersity of less than 2 to less than 3.8, and covalently bonded thereto At least one cross-linkable functional group on. 78. The composition of claim 77, wherein said crosslinkable functional groups are present in an amount ranging from 1 to 20%, based on the stoichiometric amount of available hydroxyl groups in said polyHEMA. 79. The composition of claim 77, wherein said crosslinkable functional groups are present in an amount ranging from 1.5 to 10 wt%, based on the stoichiometric amount of available hydroxyl groups in said polyHEMA. 80. The composition of claim 77, wherein said crosslinkable functional group is derived from a reactant having the structure A-S-F, wherein A is a linking group capable of forming a covalent bond with a hydroxyl group in polyHEMA; S is a spacer; and F is a functional group containing ethylenic unsaturation. 81. The composition of claim 80, wherein A is selected from the group consisting of Cl, isocyanates, acids, anhydrides, acid chlorides, epoxies, azalides, and mixtures thereof. 82. The composition of claim 80, wherein A comprises at least one anhydride. 83. The composition of claim 80, wherein S is selected from direct bonds and linear, branched or cyclic alkyl or aryl groups of ₁ to 8 carbon atoms and the general formula -( _CH2CH2 -O) _n -polyether, wherein n is between 1 and 8. 84. The composition of claim 80, wherein S is selected from direct bonds and linear, branched or cyclic alkyl groups of 1 to 4 carbon atoms and the general formula -(CH ₂ CH ₂ -O) _n - Polyether, wherein n is between 1-4. 85. The composition of claim 80, wherein F has the general formula -C(R ¹⁰ )=CR ¹¹ R ¹² wherein R ¹⁰ , R ¹¹ and R ¹² are independently selected from hydrogen and methyl. 86. The composition of claim 80, wherein said reactant is selected from the group consisting of methacryloyl chloride, methacrylic anhydride, acrylic anhydride and, 2-isocyanatoethyl acrylate, isocyanatoethyl formazan acrylate, glycidyl methacrylate, cinnamoyl chloride and 2-vinyl-4-dimethylazolactone. 87. The composition of claim 80, wherein the reactant comprises methacrylic anhydride. 88. The composition of claim 80, further comprising at least one covalently bonded functional group providing additional functionality other than crosslinking to said crosslinkable prepolymer. 89. A viscous solution comprising the crosslinkable prepolymer of claim 77, and a diluent in an amount sufficient to provide the viscous solution with a viscosity of 50,000 cps to 1 x ¹⁰⁷ cps at 25°C. 90. The viscous solution of claim 89, wherein said diluent is biocompatible, has a low Tg, low vapor pressure and is capable of dissolving 30 wt% to 60 wt% of the crosslinkable prepolymer at or below 65°C, Based on the total weight of the viscous solution. 91. The viscous solution of claim 90, wherein said diluent is selected from the group consisting of polyethylene glycol, glycerin, propylene glycol, dipropylene glycol, and mixtures thereof. 92. The viscous solution of claim 91, wherein said diluent comprises polyethylene glycol having a molecular weight of 200-600. 93. The viscous solution of claim 89, wherein the diluent is polar and has a boiling point below 150°C. 94. The viscous solution of claim 93, wherein said diluent is selected from the group consisting of alcohols, ether alcohols, and mixtures thereof. 95. The viscous solution of claim 93, wherein the diluent is selected from the group consisting of 3-methoxy-1-butanone, methyl lactate, 1-methoxy-2-propanol, 3-ethoxy-2 -Propanol, ethyl lactate, isopropyl lactate and mixtures thereof. 96. The viscous solution of claim 89, further comprising at least one initiator. 97. The viscous solution of claim 96, wherein said initiator comprises at least one of a photoinitiator, a thermally activated initiator, and mixtures thereof. 98. The viscous solution of claim 97, wherein the initiator is selected from the group consisting of bis(2,6-dimethoxybenzoyl)-2,4,4-trimethylpentylphosphine oxide and diketones, 1 -Hydroxycyclohexylphenyl ketone. 99. The viscous solution of claim 89, further having a relaxation time of less than 10 seconds. 100. The viscous solution of claim 89, further having a relaxation time of less than 5 seconds. 101. The viscous solution of claim 89, further having a relaxation time of less than 1 second. 102. The composition of claim 77, wherein the crosslinkable prepolymer comprises a bimodal molecular weight distribution. 103. A hydrogel comprising a polyHEMA network formed from the composition of claim 77. 104. The hydrogel of claim 103, wherein said hydrogel has a modulus of at least 20 psi. 105. The hydrogel of claim 103, wherein said modulus is between 20 and 90 psi. 106. The hydrogel of claim 103, wherein the hydrogel has an elongation at break greater than 100%. 107. The hydrogel of claim 103, wherein the hydrogel has an elongation at break greater than 120%. 108. An article comprising the hydrogel of claim 103. 109. The article of claim 108, wherein said article comprises a biomedical device. 110. The article of claim 108, wherein said article is an ophthalmic device. 111. The article of claim 110, wherein said ophthalmic device is a soft contact lens. 112. An article comprising a polymer network formed from the composition of claim 77.