GB2088390A - Preparation of hydrogel materials - Google Patents

Abstract

A multi-stage process is described for the preparation of a copolymer of NVP and an alkyl acrylate or methacrylate which comprises the following steps:- (1) subjecting a monomeric mixture containing NVP and a lower alkyl acrylate or methacrylate to bulk polymerisation in the presence of a free radical catalyst and a minor amount of a cross-linking agent containing at least two olefinic centres of unsaturation, progressively increasing the temperature of the polymerisation mixture to a final temperature of not more than 70 DEG C whereby the resultant polymer contains between 10 and 30 per cent of unreacted monomer; (2) subjecting the polymer from step (1) to irradiation and (3) heating the irradiated polymer to a temperature greater than 70 DEG C whereby the final polymer is substantially free from unreacted monomer. The polymer has improved mechanical properties and a low residual content of water-extractable material and is used for contact lenses.

Description

SPECIFICATION Multi-stage preparation of hydrogel materials This invention relates to the preparation of polymeric materials suitable for contact lens manufacture.

U.S. Patent No. 3 532 679 (Steckler) describes the preparation of hydrophilic copolymers of an N-vinyl lactam, such as N-vinyl-2-pyrrolidone (NVP), with an alkyl acrylate or methacrylate, such as methyl methacrylate, cross-linked with a di-olefinic cross-linking agent by heating the monomer mixture in the presence of a free radical catalyst such as azobisisobutyronitrile (AZDN) to a temperature up to about 700 C. The resulting hard, clear copolymers may be machined to form lenses and then converted to hydrogels having a high water content and good oxygen permeability.

While the polymers obtained by the Steckler procedure can be used for lens production they do not possess optimum mechanical properties. One difficulty arising from the Steckler process is that the resulting polymers contain a substantial proportion of water-soluble material which is difficult to remove entirely from the hydrogel.

Consequently, when used as a contact lens, water-soluble material tends to be leached out by the tears in use. In addition, and perhaps more importantly, the presence of a variable amount of unbound water-soluble material in the final copolymer leads to the formation of voids in the final polymer network and makes it extremely difficult to produce lenses of predetermined, consistent mechanical properties or to achieve optimum tensile strength levels.

From a theoretical view point it can be seen that one reason for this situation is the unfavourable reactivity ratios of the main monomer pair, lower alkyl acrylate or methacrylate and NVP, the NVP being much less reactive than the acrylate or methacrylate. By calculation it can be shown that in the case of a monomer mixture comprising methyl methacrylate (MMA) and NVP in the molar ratio of about 2:3, respectively, substantially all the MMA will have polymerised at about 45 per cent conversion of the manomer mixture on a molal basis. Consequently more than 50 per cent of the repeating units in the final product will comprise essentially pure NVP sequences and much of this NVP will be extractable as water-soluble homopolymer or monomeric NVP.

It has now been found that copolymers of NVP and alkyl acrylates or methacrylates having improved mechanical properties and a lowresidual content of water-extractable material can be prepared using a multi-stage polymerisation procedure involving irradiation of a polymerisation mixture which is polymerised in an initial bulk polymerisation stage in the presence of a free radical generating catalyst.

In the initial bulk polymerisation stage the polymerisation mixture is prepared by thoroughly mixing NVP, the alkyl acrylate or methacrylate, e.g. MMA, olefinic cross-linking agent and free radical catalyst (e.g. at ambient temperature).The mixture is degassed to remove atmospheric oxygen by application of vacuum and filled into polymerisation containers and transferred to a water bath or a gas circulating oven. The polymerisation reaction is conducted at progressively increased temperatures in such a way and for an overall reaction time that a significant proportion of the monomer remains unreacted. Typically the conversion of monomer to polymer at this stage should be between 60 and 90 per cent complete, preferably 75 to 85 per cent.

The next stage in the polymerisation involves irradiation of the polymer with gamma radiation, UV light or electron beam radiation. Gamma radiation has been found to be the most effective.

This can be carried out without removing the polymer from the polymerisation container where this is transparent to the radiation. Moulds made from polythene, polypropylene or P.T.F.E. are suitable for this purpose. Irradiation of the polymer is preferably carried out over a period of several hours, typically 6 to 1 5 hours and the case of gamma radiation, a total dose of 2 to 4 Megarads has been found to be suitable.

After irradiation as discussed above, the polymer was heated in vacuo at a temperature higher than that reached in the initial bulk polymerisation stage. Typically the polymer is heated to a temperature of 90 to 1 200C for a period of 30 minutes to several hours. While a major effect of this heating step is to anneal the polymer and thereby remove stresses and strains therein, it is believed that it may also contribute to the completion of the polymerisation reaction. It is certainly apparent from examination of the polymer after the initial polymerisation stage, and comparing this with the polymer obtained after the final heating step, that the irradiation treatment and subsequent heating step significantly improves the tensile strength and machineability of the polymer.Furthermore, analysis shows that while the polymerisation had typically reached about 75 to 85 per cent at the end of the first polymerisation stage, the content of unpolymerised material present in the final product was less than 0.5 per cent.

Experience with copolymers of NVP and alkyl acrylates or methacrylates has shown that polymers having properties which are very suitable for contact lens manufacture can be obtained by means of the multi-stage process of this invention. Polymers having the same advantageous properties are not obtained in a single step process, for example, by irradiating a monomeric mixture or by introducing the ester gradually to the reaction mixture.

While not wishing to be bound by any particular theory, our observations indicate that the improved mechanical properties of the polymers arise from the presence of reinforcing domains consisting essentially of hydrophobic acrylate or methacrylate distributed in a matrix of hydrophilic polymer of which the major component is NVP.

The effect of these domains is thought to be similar, to the separated styrene domains which are present in styrene -- butadiene -- styrene block copolymer thermoplastic rubbers and which have many physical properties which are superior to random copolymers of butadiene and styrene.

Thus it is believed that the copolymerised ester forms hydrophobic domains which have a higher modulus of elasticity than the remainder of the polymer. These hydrophobic domains, which can be seen with the electron microscope and appear to be about 500 Angstrom units in size, constitute a separate heterogeneous phase in the hydrophobic network of the copolymer. Provided that these hydrophobic domains or blocks are bonded to the hydrophobic network, the polymer is reinforced by their presence in an analogous way to particulate reinforcement of an elastomer.

Initiation of polymerisation of a similar monomer mixture by irradiation results in a more random distribution of the units derived from the hydrophobic monomer because the irradiation compensates to some extent for the lower reactivity of the NVP and the resulting copolymers do not possess the same advantageous properties as those prepared in accordance with the invention.

While the hydrophobic units of the copolymer may be derived from any lower alkyl acrylate or methacrylate, e.g. methyl, ethyl propyl or butyl, the preferred esters are methyl acrylate or methacrylate. Although in principle any crosslinking agent having at least two olefinic centres may be used to form the cross-linkages in the copolymer network, it is preferred to employ cross-linking agents having relatively low polymerisation reactivity compared with the MMA or other ester. In the case of MMA, the preferred cross-linking agents are allyl methacrylate, triallyl cyanurate and triallyl isocyanurate. The crosslinking agent should be present in the monomer mixture in a small amount, typically from 0.02 to 2 per cent of the initial monomer mixture.

The main constituents of the copolymer, i.e. the ester and the NVP, are preferably present in a molar ratio of NVP to ester of from 5:1 to 2:3, especially 2.7:1 to 2:3.

The following Example, in which parts are by weight, will illustrate the invention.

A homogeneous polymerisation mixture was prepared by thoroughly mixing 35 parts of purified NVP, 7 parts of purified MMA, 0.01 part of allyl methacrylate and 0.021 parts of AZDN. The liquid mixture was filtered, degassed by application of a vacuum (ca 5 mm.Hg) for 5 minutes and then filled into polythene tubes which were then sealed and transferred to a water bath. The tubes were then subjected to a heating programme in which they were maintained for 24 hour periods at 350, 400, 450 and 500 and finally for 48 hours at 6O0C. After this treatment the tubes were removed from the water bath and it was found that a hard rod of polymer had formed in the tubes.

Analysis of samples of discs cut from different parts of the tube indicated an average conversion of monomers to polymer of about 80 per cent.

The polymer rods were then exposed over a 12 hour period to a total dose of 2.5 Mrads of gamma radiation from a cobalt 60 radioisotope at a temperature between 30 and 40"C, preferably between 30 and 360C. The irradiated rods were cut into contact lens buttons (6 mm thick) which were then heated in vacuo for 45 minutes at 1200 C. Analysis of sample buttons indicated that the content of unpolymerised monomer was less than 0.5 per cent. Contact lenses were prepared from the buttons by conventional lathe turning and polishing techniques and were hydrated to equilibium in a 0.9 per cent saline solution. The resulting hydrated lenses were found to have a water content of 73 per cent w/w and possessed improved stiffness and strength compared with contact lenses which had been prepared in an identical manner except that the polymerisation had been carried out in a single stage.

Claims (3)

1. A multi-stage process for the preparation of a copolymer of NVP and an alkyl acrylate or methacrylate which comprises the following steps: (1) subjecting a monomeric mixture containing NVP and a lower alkyl acrylate or methacrylate to bulk polymerisation in the presence of a free radical catalyst and a minor amount of a crosslinking agent containing at least two olefinic centres of unsaturation, progressively increasing the temperature of the polymerisation mixture to a final temperature of not more than 700C whereby the resultant polymer contains between 10 and 30 per cent of unreacted monomer; (2) subjecting the polymer from step (1 ) to irradiation and (3) heating the irradiated polymer to a temperature greater than 700C whereby the final polymer is substantially free from unreacted monomer.

2.. A process according to claim 1 wherein the lower alkyl acrylate or methacrylate is methyl acrylate or methacrylate.

3. A process according to claim 1 or claim 2 wherein the cross-linking agent is allyl methacrylate, triallyl, cyanurate or triallyl isocyanurate.

.4. A process according to any one of the preceding claims wherein the polymer is irradiated with gamma radiation in Step (2).