WO1998007055A1

WO1998007055A1 - Process for preparing an ocular device

Info

Publication number: WO1998007055A1
Application number: PCT/GB1997/002130
Authority: WO
Inventors: Barry Holdstock; Trevor Owen Glasbey; Jotinderpal Singh Sidhu
Original assignee: Hydron Limited
Priority date: 1996-08-13
Filing date: 1997-08-08
Publication date: 1998-02-19
Also published as: GB9903009D0; AU3704797A; GB9616959D0; GB2331990A

Abstract

A process of preparing an ocular device (such as a contact lens) consisting essentially of GMA and HEMA is described. The process comprising the following steps: a) copolymerising a second monomer and a first monomer having attached to it a modifier group, thereby to form a first polymer having associated with it the modifier group; and b) modifying all or some the modifier group associated with the first polymer to form a second polymer different from the first polymer thereby to form the ocular device consisting essentially of GMA and HEMA.

Description

PROCESS FOR PREPARING AN OCULAR DEVICE

The present invention relates to a process for preparing an ocular device (such as a contact lens). In addition, the present invention relates to the ocular device prepared by that process.

Polymers made from polymerisable monomers have wide spread applications. For example, polymers are used as additives for coating applications, such as paints and adhesives. Polymers are also used to prepare lenses, such as contact lenses.

Polymers are prepared by polymerising one or more types of polymerisable monomers, such as by emulsion polymerisation, solution polymerisation, suspension polymerisation or bulk polymerisation. The monomer(s) may be polymerised in the presence of optional ingredients such as any one of emulsifiers, stabilisers, surface active agents, initiators (such as photoinitiators), inhibitors, dispersants, oxidising agents, reducing agents, viscosity modifiers, catalysts, binders, activators, accelerators, tackifiers, plasticizers, saponification agents, chain transfer agents, cross-linking agents, surfactants, fillers, dyes, metal salts, and solvents.

There are numerous references on polymerisation of polymerisable monomers. For example, some teachings may be found in "Emulsion Polymerization: Theory and Practice" by D. C. Blackley (published by Wiley in 1975) and "Emulsion Polymerization" by F. A. Bovey et al. (published by Interscience Publishers in 1965). For example, a polymer can be prepared from monomers such as methyl acrylate, ethyl acrylate, butyl acrylate, 2-ethylhexyl acrylate, decyl acrylate, methyl methacrylate, ethyl methacrylate, butyl methacrylate, styrene, butadiene, ethylene, vinyl acetate, vinyl esters, C₉, C₁₀ and C_π tertiary monocarboxylic acids, vinyl chloride, vinyl pyridine, vinyl pyrrolidine, vinylidene chloride, acrylonitrile, chloroprene, acrylic acid, methacrylic acid, itaconic acid, maleic acid and fumaric acid. Examples of further teachings on polymerisation of polymerisable monomers may be found in "Vinyl and Related Polymers" by C.E. Schildknecht (New York: John Wiley & Sons 1952) and "Monomeric Acrylic Esters" by E.H. Riddle (New York: Reinhold Publishing Corp. 1954), and by A.G. Alexander (J Oil Colour Chemists' Association ( 1962] 45 12) and G.G. Greth and J.E. Wilson (J Appl Polymer Sci [1961] 5 135).

More recent teachings regarding polymerisation methods may be found in EP-A- 0622378, EP-A-0634428, EP-A-0623632, EP-A-0635522, EP-A-0633273, EP-A- 0632157, EP-A-0630908, EP- A-0630641 , EP-A-0628614, EP-A-0628610, EP-A- 0622449, EP-A-0626430 and EP-A-0625529.

As mentioned above, one particular application of polymers is in the preparation of lenses, especially contact lenses or intraocular lenses. Examples of teachings for the preparation of contact lenses may be found in EP-A-0359539, which discloses a method of forming a soft contact lens. Other documents that describe the preparation of contact lenses include WO-A-9502617 which discloses a contact lens made from a vinyl polymer bearing phosphonium groups, JP-A-06313009 which discloses a contact lens made from a polymer having a terminal phosphoryl-choline group, WO- A-9429756 which discloses a gas permeable ocular lens made from a block copolymer and a second polymer component, WO-A-9409042 which discloses a contact lens comprising polymer and a UV absorbing constituent, and WO-A-9211407 which discloses a tinted contact lens comprising a polymer and a dye wherein the lens is prepared by incorporating a dye into a hydrophilic polymer while the polymer is being formed. Further documents describing preparing contact lenses and the like frompolymerisablemonomersincludeEP-A-0574352, EP-A-0439394, EP-A-0378511 and EP-A-0424520.

Whilst polymers can be fairly easily prepared from polymerisable monomers there can be a problem in reliably and cheaply obtaining suitable monomers in a satisfactory pure form. In this regard, many desired polymerisable monomers are supplied with impurities. These impurities can be detrimental to the final product and so they have to be eliminated before the polymerisation reaction to form the desired polymer.

An example of such a monomer is glycidyl methacrylate (GYMA) which is fairly toxic. According to US-A-5380884, GYMA is usually contaminated with epichlorohydrin. The presence of epichlorohydrin is undesirable as it is also toxic in that it can cause intense skin irritation. According to US-A-5380884 GYMA can be purified by reacting an alkali metal salt in the presence of a quaternary ammonium salt and a polymerisation inhibitor in order to remove the epichlorohydrin.

Another example of such a monomer is glyceryl methacrylate (GMA) which is a preferred monomer for preparing contact lenses. Examples of documents mentioning the use of such a monomer include US-A-5236969, JP-A-04335007, GB-A-2180243 and EP-A-0100381. There are two major problems with GMA. First, the impurities often vary from batch to batch and so make it difficult to have a standard purification protocol. Second, GMA is a very expensive monomer.

There have been attempts to prepare GMA from other monomers, such as isopropylideneglyceryl methacrylate (IPGMA). One such process for preparing GMA is disclosed in US-A-4056496 wherein the process includes reacting IPGMA with sulphuric acid and hydroquinone for a period of 16 hours.

Another process for preparing GMA, also mentioned in US-A-4056496, includes the hydrolysis of GYMA by treating GYMA with concentrated sulphuric acid for 6 days (M.F. Refojo [1965] Journal of Polymer Science 9 pp 3161-3170).

Clearly these prior art methods are very labour intensive and include the use of hazardous chemicals and process steps.

Further prior art methods for preparing GMA polymers are disclosed in US 4338419, FR 8207595, WO 93/03841 and Ezrielev et al, Vysokomol. Soedin, Ser. B, 20(10), 777-9, Hild, Makromol. Chem, 177, 1947-1972 (1976) and Beinert et al, Die Makromolekulare Chemie, 175, 2069-2077 (1974)

US-A-5532289 discloses a process for forming a soft contact lens. According to the claims of this patent the lens is formed from a copolymer consisting essentially of 2,3-dihdroxypropyl methacrylate and 2-hydroxyethyl methacrylate. Hydroxyethyl methacrylate is sometimes referred to as HEMA. However, the examples teach the presence of at least one other co-monomer - that being ethylene glycol dimethacrylate. It is also noted that the copolymers of the Examples have an excess of GMA to HEMA. For example, in Example 2 a six fold excess of GMA is required to achieve a contact lens having a water content of 67% . The process of US-A-5532289 also requires a pre-distillation step wherein GMA is distilled. Hence, the process of US- A-5532289 is laborious and costly.

The present invention seeks to overcome the problems associated with the known processes for preparing polymers.

In this regard, we have now recognised that the conversion step of converting a comonomer derivative (such as GYMA) to the desired comonomer (such as GMA) before the copolymerisation process is time consuming, costly and not necessary.

Furthermore, we have now recognised that by copolymerising at least two specific monomers to form a first polymer and modifying the first polymer to form an ocular device (such as a contact lens) consisting essentially of GMA and HEMA, better consistency of hydration may be achieved and more control over the swell factor of the lens is possible.

Thus, according to a first aspect of the present invention there is provided a process of preparing an ocular device (such as a contact lens) consisting essentially of GMA and HEMA, the process comprising the following steps: a) copolymerising a second monomer and a first monomer having attached to it a modifier group, thereby to form a first polymer having associated with it the modifier group; and b) modifying all or some the modifier group associated with the first polymer to form a second polymer different from the first polymer thereby to form the ocular device consisting essentially of GMA and HEMA.

According to a second aspect of the present invention there is provided an ocular device (such as a contact lens) prepared by the process according to the present invention.

According to a third aspect of the present invention there is provided an ocular device (such as a contact lens) preparation reaction system, wherein the ocular device consists essentially of GMA and HEMA, the reaction system comprising: i) a first polymer having associated with it a modifier group, wherein the first polymer is obtainable by copolymerising a second monomer and a first monomer having attached to it a modifier group; and ii) a treatment medium for modifying all or some of the modifier group associated with the first polymer thereby to form a second polymer different from the first polymer and thereby to form the ocular device consisting essentially of GMA and HEMA.

The present invention also provides an ocular device (such as a contact lens) obtained by the method of the present invention wherein the ocular device comprises HEMA in amounts of from 80-20% ; GMA in amounts of from 20-80% by weight; and optionally a cross-linking polymerised monomer in an amount of 5% or less; and wherein the ocular device contains less than 0.01 % methacrylic acid.

By using a modified monomer for copolymerisation, the present invention provides major benefits.

In this regard, the modified monomer is often more easily purified and/or less expensive and/or purer than the desired monomer itself. A further important advantage is that there is no need to convert a monomer derivative to a desired monomer before the copolymerisation step.

The present invention is also advantageous because it is possible to tailor the resultant properties or characteristics of the desired second polymer by appropriate selection of any one of the first monomer, the second monomer, the modifier group or the modifying step, or combinations thereof. By way of example, all of the modifier group can be modified or only some of the modifier group can be modified, such as in a localised area in or on the resultant polymer.

The present invention is further advantageous because it can be used for preparing ocular devices having a broad range of properties through appropriate selection of any one of the first monomer, the second monomer, the modifier group or the modifying step, or combinations thereof.

Further advantages include: easier preparation of the resultant ocular device; more control over shrinkage during the polymerisation step; in some applications a reduced shrinkage of the polymer during the polymerisation step; in some applications easy removal of the modifier group; more control over the dimensional consistency of the resultant polymer; in some applications better dimensional consistency of the resultant polymer; more control over swell on hydration; in some applications reduced swell on hydration; and in some applications more control over the water sensitivity of polymer. The present invention also enables useful volatile monomers to be used in the ultimate formation of the second polymer as a modifier group can be attached to such monomers and thereby reduce their volatility to enable the first polymer to be prepared in a consistent manner and/or a safe manner.

Especially with regard to lenses which are sensitive to humidity, by use of the present invention it is possible to prepare a polymer in button form (i.e. for subsequent lathing or the like to form the resultant contact lens) wherein the polymer is sufficiently hydrophobic to allow long term storage and processing in unconditioned air, i.e. no special precautions against humid air are required. The present invention also enables the desired polymer (such as a contact lens or a button for same) to be prepared by means of a simple modification step which modifies the modifier group, which modification step need not be carried out immediately after formation of the first polymer. Instead, the first polymer can be stored before conversion to the second polymer. Also, with regard to volatile monomer starting products, by reducing their volatility the present invention enables such modified monomers to be used in processes such as spin casting which until now have had to limited to the use of low volatile monomers such as hydroxy ethyl methacrylate. An additional advantage is that localised areas of the blank or button can be modified thus allowing easier preparation of more specialist lenses. For example, if the modifier group can impart a colour after the modification step then, for example, a tint or iris pattern can be imparted on to the blank or the lens. A further advantage is that one mould could be used to prepare different lenses having different properties simply by controlling the degree of modification, such as shrinkage etc.

With further regard to shrinkage, the composition of the first polymer can be tailored so that a large amount of shrinkage occurs on modification to the second polymer. This would minimise any defects that may be present on the lens surface.

The present invention is very advantageous for preparing ocular devices, such as contact lenses (both hard and soft contact lenses), intraocular lenses, interocular lenses and intercorneal implants, as well as prostheses and hydrogel articles. In this regard, the present invention not only enables the ocular devices to be made more easily but also it allows a greater control over any one of the shrinkage, the dimensional consistency, the swell, the water sensitivity, the hydrophobicity or the hydrophilicity, or combinations thereof, of the resultant polymer.

With regard to the control over the swell, a reduction in the swell factor compared to what is normally observed can be achieved when the modifying group is modified

(e.g. removed) after the polymerisation step to form the first polymer. It is believed 07055

8

that the reduction in swell is due to the presence of less hydrophilic material than if the same mass of unmodified monomer had been polymerised. This is because there is a contrived loss of the modifier group. In addition, the modifier group dilutes the concentration of the polymerisable group of the monomer. It is believed that this dilution reduces the level of contraction during polymerisation. This is of particular benefit for cast moulding of contact lenses.

The present invention has the advantage that because of the low initial cross-linker concentration in the monomer mixture, controlled additions of further cross-linker to achieve the desired/optimum level are possible. In contrast, if preformed first monomer eg. GMA is used, the level of cross-linker is often already too high to allow further additions without detriment to the mechanical properties of the final lens. This advantage of the present invention is demonstrated if GMAC is polymerized and then hydrolysed. The resultant hydrolysed polymer will simply dissolve.

Table 1 below demonstrates the effect of the addition of cross-linker to a GMAC/2- HEMA copolymer. Copolymer 1 , made without the addition of cross-linker is insoluble. This is due to the presence of 0.3 % ethylene glycol dimethacrylate in the 2-HEMA.

TABLE 1

Copolymer No. Glycero! Dimethacrylate Swell Factor Addition (%) (wet lens diameter/ dry lens diameter)

1 0 1.67

2 0.1 1.60

3 0.3 1.45

4 0.5 1.40 5 1.0 1.34

6 2.0 1.28

7 5.0 1.18

The polymerisable first monomers consist of GMA, hydroxy ethyl methacrylate (HEMA), and combinations thereof.

The polymerisable second monomers consist of GMA, HEMA, and combinations thereof.

Preferably, HEMA is 2-HEMA.

The first and second monomers are selected so that the ocular device consists essentially of GMA and HEMA.

Examples of preferred modifier groups that can be used in the present invention include any one of tert-butoxy carbonyl (t-BOC), ketais (for example acetone), acetals (for example acetaldehyde), trimethyl silyl (TMS), glycidyl, N-hydroxy succinimide and carbonate ester, and combinations thereof.

Examples of preferred modification steps that can be used in the present invention include one of base hydrolysis, acid hydrolysis, neutral hydrolysis reactions, cleavage with F , and combinations thereof. Naturally, depending on the type of the modifier group(s), a suitable modification step would be selected, such as acid hydrolysis treatment if the modifier group were t-Boc and base hydrolysis treatment if the modifier group were a carbonate.

For use in the present invention there can be two different types of first monomers and/or two different types of second monomers and/or at least two different types of modifier groups and/or at least two different types of modifying steps. Furthermore, the first monomer(s) and/or the second monomer(s) and/or the modifier group(s) can be homogenously or heterogeneously distributed in the first polymer and/or the second polymer.

The modifying step(s) can be applied to all or a part or parts of the first polymer.

A preferred aspect of the present invention is the use of GMA with a modifier group as the first monomer to form the first polymer rather than the use of the monomer itself. As mentioned above, GMA is available commercially in an impure state and the concentration of the impurities may vary and affect the properties of the resulting polymer. Furthermore, pure GMA is expensive. It is also very difficult to purify. However, by using a derivative such as (2,2 dimethyl-l,3-dioxolan-4-yl) methyl methacrylate (GMAC) in the process of the present invention enables a first polymer to be prepared easily and efficiently. GMAC can be prepared following the teachings of Mori et al ([1994] Macromolecules 27 pp 35-39) and Oguchi et al Polym Eng. Sci. ([1990] 30 449). Moreover, modification of, for example, GMAC in such a first polymer by a suitable modification step converts the GMAC to GMA, thus forming the desired second polymer. This process does not require a pre-polymerisation conversion step to convert GMAC monomer to GMA monomer, which is laborious, expensive and unnecessary. This preferred process of the present invention is also of particular interest as GMAC can be readily synthesised from cheap, commercially available materials and it can be prepared in a pure state, i.e. free from the substances normally present in commercial GMA, especially cross-linking substances. Moreover, GMAC is readily co-polymerised with other suitable monomers, eg 2- HEMA.

For the present invention, any typical, suitable polymerisation method may be used. The preferred method is free radical polymerisation, thermal or UV initiated.

The copolymer material (i.e. the first polymer) may be fabricated as buttons or cast moulded or spun cast lenses. The modifier group can be any suitable modifier group.

For example, the modifier group can make the monomer more stable. The modifier group can make the monomer more or less polar. If the monomer becomes less polar (or non-polar) then the monomer can be used to prepare lenses by spin casting methods by use of polypropylene casts, which are advantageous. A preferred example of such a non-polar monomer is GMAC.

The modifier group can even make the monomer hydrophobic or hydrophilic, or even make the monomer more hydrophobic or more hydrophilic. Examples of modifier groups include: an anhydride group which can be modified to the respective acid group or an epoxide group which can be modified to the respective 1 ,2 diol group.

The modifier group can hydrophobic or hydrophilic. Preferably the modifier group is hydrophilic. This is particularly advantageous as the modification step can utilise an aqueous modification medium to modify the modifier group.

Preferably, the modifier group is a cleavable group and wherein the modifying step b) comprises dissociating the modifier group from the first polymer to form a second polymer containing less or no modifier group. This is advantageous if it is desired for the modifier group to be removed easily after the modification step.

Preferably the first polymer is formed from a mixture of first monomers having attached thereto different modifier groups. This aspect of the present invention allows different areas of the formed first polymer to be modified at different rates or times.

Preferably the first monomer is GMA.

Preferably the first monomer with the attached modifier group is GMAC. The use of GMAC is advantageous as it can be readily polymerised and it can be readily converted to GMA by the process of the present invention. In addition, it may be more readily obtained in a relatively pure form and at a more acceptable cost than GMA.

Preferably the second monomer is 2-HEMA.

Preferably the first polymer is prepared by cast moulding or spin casting techniques.

Additionally the present invention also covers the first polymer and/or the second polymer for use as a blank for a lens.

In some applications trace or small amounts of other polymerisable monomers may be present. Examples of such other polymerisable monomers include one or more of: (alkyl and cycloalkyl) acrylates; (alkyl and cycloalkyl) methacrylates; free-radical polymerizable olefinic acids, including alkoxy-, alkylphenoxy-, alkylphenoxy- (polyethyleneoxide)-, vinyl ester-, amine substituted (including quaternary ammonium salts thereof), nitrile-, halo-, hydroxy-, and acid substituted (for example phospho- or sulpho-) derivatives thereof; and other suitable ethylenically unsaturated polymerisable monomers; including combinations thereof. Preferably the alkyl and cycloalkyl groups contain up to 20 carbon atoms, e.g. (C,-C₂₀ alkyl and C,-C₂₀ cycloalkyl) acrylates, and (C_rC₂₀ alkyl and C,-C₂o cycloalkyl) methacrylates. In more detail, typical polymerisable monomers for use as the first monomer or the second monomer include any one of methyl acrylate, ethyl acrylate, n-propyl acrylate, isopropyl acrylate, n-butyl acrylate, isobutyl acrylate, t-butyl acrylate, isobornyl acrylate, pentyl acrylate, hexyl acrylate, octyl acrylate, iso-octyl acrylate, nonyl acrylate, lauryl acrylate, stearyl acrylate, eicosyl acrylate, 2-ethylhexyl acrylate, cyclohexyl acrylate, cycloheptyl acrylate, methyl methacrylate, ethyl methacrylate, hydroxymethylacrylate, hydroxymethylmethacrylate, propyl methacrylate, n-butyl methacrylate, t-butyl methacrylate, isobutyl methacrylate, pentyl methacrylate, hexyl methacrylate, cyclohexyl methacrylate, 2-ethylhexyl methacrylate, isobornyl methacrylate, heptyl methacrylate, cycloheptyl methacrylate, octyl methacrylate, iso- octyl methacrylate, nonyl methacrylate. decyl methacrylate, lauryl methacrylate, eicosyl methacrylate, dodecyl acrylate, pentadecyl acrylate, cetyl acrylate, stearyl acrylate, eicosyl acrylate, isodecyl acrylate, vinyl stearate, nonylphenoxy- (ethyleneoxide),.₂₀ acrylate, octadecene, hexadecene, tetradecene, dodecene, dodecyl methacrylate, pentadecyl methacrylate, cetyl methacrylate, stearyl methacrylate, eicosyl methacrylate, isodecyl methacrylate, nonylphenoxy-(ethyleneoxide),-₂₀ methacrylate, acrylic acid, methacrylic acid, fumaric acid, crotonic acid, itaconic acid, fumaric anhydride, crotonic anhydride, itaconic anhydride, aleic acid, maleic anhydride, styrene, alpha-methyl styrene, vinyl toluene, acrylonitrile, methacrylonitrile, ethylene, vinyl acetate, vinyl chloride, vinylidene chloride, acrylamide, methacrylamide, methacrylamide 2-cyanoethyl acrylate, 2-cyanoethyl methacrylate, dimethylaminoethyl methacrylate, dimethylaminopropyl methacrylate t-butylaminoethyl methacrylate, glycidyl acrylate, glycidyl methacrylate, glyceryl acrylate, glyceryl methacrylate, benzyl acrylate, benzyl methacrylate, phenyl acrylate, phenyl methacrylate, vinyl pyridine, vinyl pyrrolidine, siloxanes, silanes and mixtures thereof. Other polymerisable monomers are disclosed in US-A-2879178, US-A- 3037006, US-A-3502627, US-A-3037969 and US-A-3497485.

Additional other such polymerisable monomers can methacrylic acid, acrylic acid, GYMA, N-vinyl pyrrolidone, alkyl methacrylates (such as C,.₂₀ alkyl methacrylates, more preferably C_M5 alkyl methacrylates, more preferably C ₀ alkyl methacrylates, more preferably C,.₅ alkyl methacrylates, such as methyl methacrylate), alkyl acrylates (such as C,.₂₀ alkyl acrylates, more preferably C,.₁₅ alkyl acrylates, more preferably C,.₁₀ alkyl acrylates, more preferably C,-₅ alkyl acrylates, such as methyl acrylate), aryl methacrylates, aryl acrylates, diacetone acrylamide, acrylamide, methacrylamide, N-alkyl acrylamides (such as C,.₂₀ N-alkyl acrylamides, more preferably C,.₁₅ N-alkyl acrylamides, more preferably C,.₁₀ N-alkyl acrylamides, more preferably C_{1 5} N-alkyl acrylamides, such as methyl acrylamide), N-alkyl methacrylamides (such as C^o N-alkyl methacrylamides, more preferably C,.,₅ N- alkyl methacrylamides, more preferably C,.₁₀ N-alkyl methacrylamides, more preferably C_{1 5} N-alkyl methacrylamides, such as methyl methacrylamide), vinyl acetate, vinyl esters, styrene, other substituted olefins, N-dialkyl acrylamides (such as C,.₂o N-dialkyl acrylamides, more preferably _1S N-dialkyl acrylamides, more preferably C, ₁₀ N-dialkyl acrylamides, more preferably C[ ₅ N-dialkyl acrylamides, such as N N dimethyl acrylamide), N-dialkyl methacrylamides (such as C, ₂₀ N-dialkyl methacrylamides, more preferably C,-₁₅ N-dialkyl methacrylamides, more preferably C_M0 N-dialkyl methacrylamides, more preferably N-dialkyl methacrylamides, such as N N dimethyl methacrylamide), 3-methacryloxypropyl tris (trimethysilyl siloxy) silane (TRIS monomer), fluoro substituted alkyl and aryl acrylates and methacrylates (preferably wherein the alkyl is C,-₂₀ alkyl, more preferably C,_.,, alkyl, more preferably C,.₁₀ alkyl, more preferably C,.₅ alkyl), and combinations thereof.

The lists of monomers also include substituted derivatives of those monomers, such as halogenated monomers, especially fluorinated monomer derivatives

The term "trace or small" means less than about 6%, preferably less than 1 % of the final composition, more preferably less than 0.5%, even more preferably less than 0.1 % .

In the polymerisation reaction medium there can be in small or trace amounts other suitable polymerisable monomers such as any one of those outlined above and/or suitable optional ingredients.

The emulsifiers, stabilisers, surface active agents, initiators (such as photoinitiators), inhibitors, dispersants, oxidising agents, reducing agents, viscosity modifiers, catalysts, binders, activators, accelerators, tackifiers, plasticizers, saponification agents, chain transfer agents, cross-linking agents, surfactants, fillers, dyes, metal salts, and solvents that can be used in the present invention can be any of those commonly used in the art.

By way of example, the surfactants and dispersants can be salts of fatty rosin and naphthenic acids, condensation products of naphthalene sulphonic acid and formaldehyde of low molecular weight, carboxylic polymers and copolymers of the appropriate hydrophile-lipophile balance, higher alkyl sulfates, such as sodium lauryl sulfate, alkyl aryl sulfonates, such as dodecyl benzene sulfonate, sodium or potassium isopropylbenzene sulfonates or isopropylnaphthalene sulfonates; sulfosuccinates, such as sodium dioctylsulfosuccinate alkali metal higher alkyl sulfosuccinates, e.g. sodium octyl sulfosuccinate, sodium N-methyl-N-palmitoyltaurate, sodium oleyl isethionate, alkali metal salts of alkylarylpolyethoxyethanol sulfates or sulfonates, e.g.. sodium t-octylphenoxy-polyethoxyethyl sulfate having 1 to 5 oxyethylene units. Typical polymerisation inhibitors that can be used include hydroquinone, monomethyl ether, benzoquinone, phenothiazine and methylene blue.

The present invention will now be described only by way of example.

1. Cast Moulding

3g of GMAC was blended with 2g of 2-HEMA. Benzoin methyl ether (0.1 %) was dissolved in the mixture which was then filtered. The mixture was charged into polypropylene moulds which were assembled and exposed to UV light (or, alternatively, heat). The cured lenses were ejected and exposed to IN hydrochloric acid. After equilibration in normal saline solution the resulting hydrogel lenses had a water content of 58% .

Lenses with water contents of between 40% and 63% were prepared. We found that the water content of the lenses depends on the initial GMAC content. In this regard, higher concentrations of GMAC in the copolymer gave higher water contents and that the hydration process became progressively slower with increasing GMAC concentration. The rate of hydrolysis can be increased by the addition of a water miscible/soluble substance, such as ethanol, to either the hydrolysis solution or the polymerisation reaction medium (i.e. the monomer mix). Furthermore, if the hydration is conducted in deionised water the equilibrium water content is very low, ie <20% but addition of acid invariably increased the water content to > 40%. The extractable content of the lenses is consistent with the loss of the appropriate quantity of acetone. Acetone could be detected in the hydrolysis solution by giving a precipitate of the 2,4 dinitro-phenyl hydrazone with 2,4 dinitrophenyl hydrazine.

2. Spin Casting

The mixture prepared in Example 1 was charged into PVC moulds designed for spin casting. After passage through a bank of UV lamps the cured lens were removed from the mould by exposure to IN hydrochloric acid.

Buttons

The monomer mixture prepared in Example 1 was initiated with 0.1 % isopropyl per dicarbonate (IPP) . The mixture was charged into polypropylene button moulds which were sealed and immersed in a water bath. After 16 hours at 32 °C the clear colourless buttons were ejected and further heated to 120°C for 1 hour and allowed to cool to 50°C at a rate of 17°C/hr. Lenses were lathed cut from the buttons and exposed to IN hydrochloric acid as previously described.

In summation, the present invention provides a process for preparing polymers for use as ocular devices (such as contact lenses), by a reliable and efficient process that obviates the need to prepare the desired monomer from a derivative thereof as a pre- polymerisation step.

In addition, the present invention provides a process wherein polymers can be prepared whose properties, such as swellability, hydrophobicity or hydrophilicity, can be altered after the preparation thereof.

Other modifications will be apparent to those skilled in the art without departing from the scope of the present invention. For example, in some instances, some (but not all) of the modifier group can be modified before the polymerisation step.

Claims

1. A process of preparing an ocular device (such as a contact lens) consisting essentially of GMA and HEMA, the process comprising the following steps:

a) copolymerising a second monomer and a first monomer having attached to it a modifier group, thereby to form a first polymer having associated with it the modifier group; and

b) modifying all or some the modifier group associated with the first polymer to form a second polymer different from the first polymer thereby to form the ocular device consisting essentially of GMA and HEMA.

2. A process according to claim 1 wherein the modifier group is a cleavable group and wherein the modifying step b) comprises dissociating the modifier group from the first polymer to form a second polymer containing less or no modifier group.

3. A process according to claim 1 or claim 2 wherein the modifier group is hydrophilic.

4. A process according to any one of the preceding claims wherein the first polymer is formed from a mixture of first monomers, preferably having attached thereto different modifier groups.

5. A process according to any one of the preceding claims wherein the first monomer is GMA.

6. A process according to claim 5 wherein the first monomer with the attached modifier group is GMAC.

7. A process according to claim 5 and 6 wherein the second monomer is 2- HEMA.

8. A process according to any one of the preceding claims wherein the first polymer and/or the second polymer are/is a blank for a lens.

9. A process according to any one of claims 1 to 7 wherein the first polymer and/or the second polymer are/ is in the form of a lens.

10. A process according to claim 8 or claim 9 wherein the lens is a contact lens.

11. A process according to any one of the preceding claims wherein the first polymer is prepared by cast moulding or spin casting techniques.

12. An ocular device (such as a contact lens) prepared by the process according to any one of the preceding claims.

13. An ocular device according to claim 12 wherein the ocular device is in the form of a lens, preferably a contact lens.

14. An ocular device according to claim 12 or 13 comprising HEMA in amounts of from 80-20% ; GMA in amounts of from 20-80% by weight; and optionally a cross-linking polymerised monomer in an amount of 5 % or less; and wherein the ocular device contains less than 0.01 % methacrylic acid.

15. An ocular device according to claim 12, 13 or 14 wherein the ocular device contains no methacrylic acid.

16. An ocular device according to claim 12, 13, 14 or 15 wherein the ocular device comprises HEMA in amounts of from 60-40%; and GMA in amounts of from 60-40% by weight.

17. An ocular device according to any one of claims 12 to 16 wherein the ocular device contains the cross-linking polymerised monomer which is in an amount of 5% or less.

18. An ocular device according to claim 17 wherein the ocular device contains a cross-linking polymerised monomer in an amount of from 0.1-5 % .

19. An ocular device according to claim 18 wherein the ocular device contains a cross-linking polymerised monomer in an amount of from 0.2-4% .

20. An ocular device according to claim 19 wherein the ocular device contains a cross-linking polymerised monomer in an amount of from 0.3-3% .

21. An ocular device (such as a contact lens) preparation reaction system, wherein the ocular device consists essentially of GMA and HEMA, the reaction system comprising:

i) a first polymer having associated with it a modifier group, wherein the first polymer is obtainable by copolymerising a second monomer and a first monomer having attached to it a modifier group; and

ii) a treatment medium for modifying all or some of the modifier group associated with the first polymer thereby to form a second polymer different from the first polymer and thereby to form the ocular device consisting essentially of GMA and HEMA.

22. An ocular device (such as a contact lens) formed from GMA and 2-HEMA wherein the ocular device is obtainable by the method according to any one of claims 1 to 11.

23. A process as substantially described herein with reference to claim 1.

24. An ocular device as substantially described herein with reference to claim 12.

25. A reaction system as substantially described herein with reference to claim 21.