CA1080888A - Hydrophilic copolymers - Google Patents

Abstract

ABSTRACT OF THE DISCLOSURE

A hydrophilic copolymer suitable for contact lenses consisting essentially of copolymerised N-vinyl-2-pyrrolidone and methyl methacrylate in a molar ratio of from about 6:1 to about 1:1 and including (i) a minor amount of at least one cross-linking agent containing at least two olefinic bonds per molecule and (ii) a minor amount of an ethylene oxide - propylene oxide block copolymer having a molecular weight of not more than about 6,000.

Description

The in~entiorl re].atcs to hydrophilic copolymers, Ollr Cnnadian Patent Application No. 140 194 discloses and claims ~ hydrophilic copolymer consisting essentially of (i) units derived from at least one o$ an N-~inyl pyrrolidone and a vinyl pyridine, preferably N-~inyl-2-pyrrolidone, (ii) units derived rrom an olefinically unsaturated monomer, pre~erably methyl mcthacrylate, and (iii) a minor amount o~ units derived from on~ or more cross-linking agents each containing at least two olei~lnic bonds in the molecu?e, at least some of the units being d~rlved from a dimethylacr~ylate of a monomeric alkylene glycol, divinyl benzene, diethylene glycol bis(allyl carbonate) or allyl methacrylate. ..
Ao¢ording to the invention there is provided a hydrophilic copolymer consisting essentially of copolymerised N-vinyl-2-pyrrolidone and methyl methacrylate in a molar ratio o~ ~rom ~`~
about 6:1 to about i:1 and including (i) a minor amount:of at ~.
.least two olefinic bonds per molecule and (ii) a minor~amount of an ethylene oxide - propylene oxide block copolymer having :
a molecular weight of not more than about 6,ooo~ Such a co- :-~
polymer has the aapacity to absorb large quantities o~ water ~:
whilst 9~ill remaining transparent, and the change of shape du- :
ring wator absorption is reliably predictable. Moreover, the : .:
copolym~r is, in General~ relatively resistant to bacterial . I :
contamination. .
It will be appreciated that the N-vinyl-2-pyrrolidone is :

a hydro~hilic comonomer and the methyl methacrylate is a hydro-,' ~ ~ ., - ._ 2 - 3~

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phobic co~llollomer, these comonolllers providing r~spectively hyd rophilic alld hydrophobic uni-ts in the hydrophilic copolymer.
The hydrophilic copolymcr preferably comprises up to 40%
by reight, of units derived from the hydrophobic comonomer, na~ ely the methyl methacrylate. The molar ratio o~ hydrophilic uni ts to hydrophobic units in the copolymer may vary over a wide range, ~or example from 8:1 to 1:2, suitably 4:1 to 1:1.
Copolymers of these compositions are easily moulded and machi~ed an~ have high mechanical strength.
The hydrophilic copolymer is cross-linked. The copolymer includes, as a cross-linking agent, a molecular species having at least two ole~inic bonds per molecule. Suitable cross-link-ing agents include alkylene glycol dimethacrylate, particularly ethylene glycol dimethacrylate, divinyl benzene, diethylene glycol bis(allyl carbonate), and allyl methacrylate. Two or more such agents can be used together. The degree o~ cross-.
linking may be varied widely but is suitably such that the cross- ~: :
.
linking agent is present in an amount ~ot more than 10%J pre~
erably not more than 60/o~ by weight o~ the monomers. Cross-link-ed copolymers have greater mechanical strength than otherwise slmilar non-cross-linked copolymers. ~ ~ ~
The copolymers suitably contain up tQ.60/o~ preferably 1 to : -5%~ by weight o~ the cross-linking agent, for e~ample divinyl -.:~
benzene or ethylene glycol dimethacrylate, based on the combin- ~`
ed weight o~ the two comonomers N-vinyl-2-pyrrolidone and methyl methacrylate. The molar ratio of the N-vinyl, pyrrolidone units .

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8~il to the methyl methacl~late in the copolymer may be ~rom 6:1 to 1:2 but is ad~antageollsly from ~:1 to 1:1 and preferably ~rom 4:1 to 2:1. Such copolymers have high gas and liquid permea-bility.
The N-vinyl pyrrolidone copolym~rs are hard, clear and colourless so]ids in the non-hydrated condition and remain clear and colourless when hydrated. They have good machining properties and satisfactory mechanical strength They are also readily prepared - The water absorptivity of the hydrophilic copolymers di~
ers from copolymer to copolymer and may be varied by varying the degree of cross-linking and by varying the molar ratio oY the hydrophilic to the hydrophobic units. The polymers may absorb more than their own dry weight of water upon being immersed in water fro 24 hours. ;~
The hydrophilic copolymers according to the lnvention have many uses. In particular, they are very suitable for use in contact with living tissue. Thus, for example, many of the hydrophilic copolymers are particularly suitable for~machining into contact lenses. Many of the copolymers are suitable for prosthetic use, for example as heart valves or inserts in the ", inner ear cavity, and also as dialysis membranes or members in artificial kidney machlnes. The polymers also have properties suitable for use in reverse osmosis applications.
The invention further provides a protective corneal or eye fitting or membrane which comprises a hydrated hydrophilic _ 4 -;

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copolym~r. As a Illelllbrane 1 - 2mm thick, such a membrane is flexible and soft. Such protective membranes or soft lenses are suitable ~or use, for example, when an eye has been injured or in need o-f protection for any other reason. The membrane may be made opaque. The protecti~e corneal membrane can in many, if not most, cases replace the swathes o~ bandages whioh are comm-only used when an eye has suffered injury or has undergone surgical treatment.
The hydrophilic copolymers and articles made from them may include medicinally or therapeutically active ingredients, for example, antibiotics, bactericides, fungicides, steroids, hormone preparations or other drugs, for example mydriacyl, cetamide, dendrid, tropicamide, idoxuridine or sulphacetamide sodium. Such ingredients may be incorporated in the polymer-isation or by absorption from solutions when ~irst hydrating the copolymer. Thus the non-optical, corneal proteotive mem-brane may include an antibiotic or other drug and so ~unction not only as a protective membrane for the eye but also as a vehicle for the installation o~ a drug into the eye.
~ he hydrophilic solid copolymers may be produced by sub-jecting monomers to an initiation process. Where the initia-tion process is carried out by means o~ a chemical initiator a cross-linking agent may also be provided. In addition polymerisation, the initiator may, for example, be an organic pero~ide or hydroperoxide, a percarbonate such as isopropyl percar~onate, a redox system, or an azo compound. The pre-. , .. . , . : :.
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f ferr~d initiator is azodiisobutyronitrile. Tho amount of ini-tiator present may be 0.01 to O.lOC/o by weight of the monomers.
The polymerisation is preferably ef~ecte~ in -the suhstan-tia ly comple-te absence of oxygcn, under a gas iner-t to the polymerisation e.g nitrogen, or a rare gas, or in vacuo. The polymerisation is preferably begun at a relatively low temp-erature, for example 35-50 C, until the monomers have gelled.
However, gellation may be effected at any temperature below the boiling point of the monomers used~ The temperature is later raised, for example to 50-60C, to complete the polymer-isation, but polymerisation could also be completed at any temperature below the decomposition temperature of the copoly-mer Substantially uniform bubble-free copolymers may there-fore be obtained. The period for completing polymerisation may vary from 1 to 16 days or more.
The ratios of comonomers may be varied as hereinbefore indicated as may be the proportion of cross-linking agent when used.
Cross-linked hydrophilic copolymers according to the invention may be produced by effecting copolymerisation prior to, or concurrently with the formation of cross-linkages.
Of the following Examples~ Examples 1 to 15 are compar-ati~e examples and Examples 16 to 24 illustrate the invention.
Unless otherwise stated, a similar procedure was used in each example. The monomers were placed in a glass tube, azo-diisobutyronitrile (AZDN) was added as initiator in an amount ..

Of 0~1% l~/W ol monomer, ~nd the mixtwre was pur~ed ~ith oxygen-free nitrogen, the nitrogen being bubbled through the liquid for 5~10 mins. In some o~ the examples, a cross-linkin~ agent andjor water were also added before the purging step. ~he tube was then sealed, either under vacuum or under nitrogen, and placed in a thermostatically controlled water bath. The tube was maintained initially at 40C for a period at least suffi-cient for the monomers to gel, after which the temperature was gradually raised to 60C and the polymerisation was completed at that tempe~ature.
The solid copolymer was removed from the tube and the top surface layer (1 - 2mm thick) was removed on a lathe and a imm thick disc was cut from the next layer of the rod of copolymer which had a diameter of approximately 20 mm. This disc, whlch is hereinafter identified as "the 1 mm thick disc" of the co~
polymer was used to determine the water absorptivity of the copolymer. The disc was weighed under anhydrous conditions and then immersed in distilled water (p~ 6.5) and its uptake o~
water after immersion for 1 day, 4 days and li days was deter- -mined by reweighing after carefully blotting off all the sur-face water. The water absorbed is given as a percentage cal-culated as follows--% water absorbed = (Wl Wo) 100 :, Wo , "
where Wo is the weight of the disc before immersion and Wl its weight after immersion.

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w The copolymer was also e~amined in respect of i-ts clar-ity and mechanical strength, and its machining properties in a non-hydrated s-tate were observed.
EXAMP~E i A mixture of 4.i9g freshly distilled acrylic acid, 5.81g methyl methacrylate, i ml water and O.Olg ~ZDN was, in a glass tube, purged with nitrogen and the tube was sealed under nitrogen. The tube was held for 13 days at 40C (gelation occurred in 12 days), raised gradually to 60C and maintained at 60C ~or 48 hours. The 1 mm thick disc of the polymer was hazy in appearance and the water absorption of the disc~ deter-mined as hereinbefore described, was 39~0% after 1 day, 40~4%
after 4 days and 41~4% after 11 days immersion. The disc was, after immersion, soft, pliable, swollen and ha~y.

A mixture of 5.26g N-viny1-2-pyrrolldone7 4.74g freshly distilled methyl methacrylate, 0.5g divlnyl benzene and 0.01g AZDN in a glass tube was purged ~rith nitrogen and sealed in - the tube under nitrogen. The tube was then maintained for 10 days at 40C, followed by 4 days at 50C and finally 4 days at 60C. Gellation occurred within 3 days and the solid co- ~
. .
polymer produced was hard, clear and colourless. The water absorption o~ the copolymer, determined on the lmm thick disc as hereinbe~ore described~ was 19.7%~ i6.9C/o9 and 16.9% a~ter 1 day, 4 days and 11 days respectively. The disc, after 11 days immersion, was clear, faily flexible and slightly distorted.

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,, ' , ,, ' ', ", ' ' ' To produce a contact lens from this material~ polymer-isalion was carried out in a circular section mould provided Wit~l removable plugs having convex and concave spheroidal sur Caces complementary to the surfaces of the lens.
A similar -technique was ~Ised to make a protective corneal fit ting except that a dye such as phtha~ocyaninine blue, phtha-Iocyaninine green, benzidine yellow anlide, iron oxide, or titanium oxide was added to the constituents prior to polymer is~tion. Another suitable dye is that sold by Imperial Chem-icll Industries Limited under the trade name SW polymon green GN 500.

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Example 2 was repeated but with the addition of 1 ml water to the initial mixture. The gellation time was 7 days and the copolymer produced was hard, clear and colourless.
The water absorption o~ the copolymer, determined as herein-before described, was 25.4%~ 23.5% and 23.9% after 1 day, 4days and 11 days respectively. The discg after the 11 days immersion, was clear, fairly flexible and slightly distorted.
A membrane of this material was obtained by pouring the constituents into a shallow tray prior to polymerisation. ~, Example 2 was repeated except that 0.5g o~ ethylene glycol dimethacrylate was used as the cross-linking agent in place of the 0.5g of divinyl benzene. The monomers gelled in 3 days and the copolymer produced was hard, clear and colour-" 5 ' ' : ' _. ,, ' , .' ' ' ': '` :' ' ' ,;' ' "
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' ' ' ' . . : ' , less. The l~at~r absolption of tho copol~rmer, determined asher~inbefore described, was 19. 60/o~ 19 . 4%~ 17 . 8% after immer~
sio~ ~or 1 day, ~ days and 11 days respectively. The hydrated disl ~ was, after 11 days immersion, fairly ~lexible, clear and -sli rhtly distorted.
A sleeve for an artificial heart valve was machined ~roma cylindrical workpiece of this material in a lathe.
EXAMPLE $
¦ A mixture o~ 7.0g N-winyl-2-pyrrolidone, 3.0g of ~reshly disltilled methyl methacrylate, 0.5g of ethylene glycol dimeth-~crylate and 0 Olg AZDN was purged with nitrogen ln a glass tube, sealed in the tube under nitrogen and then polymerised by being held for 7 days at 40C, 3 days at 50C and 4 days at 60C. The gellation time was less than 3 days and the cross-linked copolymer obtained was a hard, very clear solid. The -water absorption of the copolymer upon 1 day, 4 days and 11 days immersion in distilled water was found to be 45.2C/o~ 45.5%
and 47.4% respectively. The hydrated disc containing 47.4%
was ~ery flexible and very clear.
A metallic prosthetic device was coated in this materlal by immersion in liquid formed by melting this material.

Example 5 was repeated with two midifications, namely (i) 0.2g of ethylene glycol dimethacrylate was used instead of 0.5g and (ii) the mixture was held at 40C ~or 6 days and not 7 days. The gellation time was less $han 3 days and the cross-:.

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The water absorp tion oi the copolymer, determined as herein-before described, ~as 82.60~o after 4 days and 51.3% after 11 days The hydra-ted disc was very clear, swollen, so~t and very flexible.
By loading this material witkl a therapeutic agent prior to polymerisation tablets were obtained which were suitable for implantation in the human body after surgery or for oral administration. When these tablets are lodged in human tissue or in the stomach, the therapeutic agent is released into the surroundings in a gradual manner, as a result of trans~er of body liquids into and from the tablet material ' EXAMPLE 7 A mixture of 7.5g N-vinyl-2-pyrrolidone, 2.5g methyl methacrylate, 0.5g ethylene glycol dimethacrylate and O.Olg AZDN was purged with nitrogen, sealed in a gIass tube under nitrogen and polymerised by being held at 40C for 6 days, 50C for 8 days and 60C for 2 days, the gellation time bein~
less than 1 day The cross-linked copolymer obtained was a hard solid of great clarity. The water absorption of the copolymer, determlned on the 1 mm thick disc as hereinbefore described, was 5007% in 1 day and 47.9% in 4 days. The disc had broken into pieces when it was examined after being ~ -immersed ~or 11 days in distilled water. The hydrated disc was clear, very fle~lble and fairly soft.

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Exanlple 7 lYas repeated bllt ~.~ith the use of 0.2g instead of 0.5g of ethylene glycol dimethacrylate. The gellation time ~as less than 1 day and the cross-Linked vinyl pyrrolidone/
met hyl methacrylate copolymer produced was a hard, very clear so] id. Its water absorption was 105.5% after 1 day, 79.9%
afl er 4 days and 65.40/o after 11 days. The 11 day hydrated disc was very clear, very flexible and very soft.
j EXAMPLE ~
~ A mixture of 7.5g N-vinyl-2-pyrrolidone, 2.5g methyl me hacrylate, 0.070g allyl methacrylate, 0 005g ethylene glycol dimethacrylate, O.Olg AZDN and 0.005g isopropyl percarbonate was purged with nitrogen in a glass tube and then sealed under nitrogen in the tube and polymerised by being held at 40C for 6 days, 50C for 8 days and 60C for 2 days, the gellation time being less than 1 day. The cross-linked copolymer obtained was a hard solid of great clarity. The water absorption of the copolymer, determined on the 1 mm thiok disc as hereinbefore described, was 70% in one day. The hydrated disc was transpar-ent, very flexible and soft.

- A mixture o~ 7.0g N-vinyl-2-pyrrolidone, 3.0g methyl methacrylate~ O.lg ethylene glycol dimethacrylate and O.Olg.
AZDN was purged with nitrogen, sealed under nitrogen in a glass tube and maintained at 40C for 4 days, 50C for 5 days and 60C for 2 days. The solid, cross-linked copolymer so obtained was hard, colourless and of great clarity. The water absorption .

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o~ the copolymer, determined on the 1 mm thick disc a~ herein-before clescribed, ~as 70.0Q/o aftcr 1 day and 1~9.2% after 2~
days. The 21l days - hydrated disc was clear and very Llexible EX~MPLE il A mixture o~ 8.0g N-vinyl-2-pyrrolidone, 2 0g methyl methacryl~te, O.lg ethylene glycol dimethacrylate and O.Olg AZDN was purged with nitrogen and polymerised under nitrogen as described in Example 10. The cross-linked copolymer so produc-ed was a clear, colourless, hard solid. The water absorption of the copolymer determined as hereinbefore described, was 123.0% after 1 day and 67.oo/o after 24 dayx. The hydrated disc was very clear, extremely flexible and so~t.

A m~xture of 4.62g freshly distilled methacrylic acid, 5 5~g methyl methacrylate, 0.5g divinyl benzene and O.Olg ~DN was purged with nitrogen and sealed in a glass tube undèr ~itr~gen~ The mixture was held for 14 days at 40C and then ~or ~8 hours at 60C, the gellation time being 7 days. The 1 ~m thiok disc was clear and the water absorption, determined as ~rain~efore described was 2 ~1%~ 5 ~ 9% and 7. 9/0 after 1, 4 and ~ days respectively. The hydrated copolymer was clear bat brittle. `;~

~ ~i~ture of 3.3g of each of N-vinyl-2-pyrrolidone, methyl met~ac~late and 2-hydroxethyl methacrylate and 0.2g ethylene glycol dimethacrylate and O.Olg AZDN was purged with nitrogen .

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and then polym~rised under nitrogen by being held at 40C for 6 dlys follo~ed by 8 days at 50C and 2 days at 60C. The cro~s-linked copolymer ~as a very clear, hard solid. The water absorption of the copolymer, determined as hereinbefore des~ribe~, was 19.8%~ 16.1% and 1~.3% after 1, 4 and 11 days imm~rsion respectively. The hydrated disc was very clear and slightly flexible, EX~MPLE 14 The procedure of Example 13 was repeated with one mod ification, namely that 0.2g instead of 0.5g of ethylene glycol dimethacrylate was used, The ~opolymer was a very clear hard solid and its water absorptlon was 2~.60/o~ 20.60/o and 19.7%
after i, 4 and 11 days immersion respectively. The hydrated disc was very clear, distorted and fairly rigid.

A mixture of 8.0g N-vinyl-2-pyrrolidone and 2.0g of freshly distilled diethylene glycol bis(allyl carbonate) and O.Olg AZDN were purged with nitrogen and then polymerised under nitrogen, the polymerisation being effected by holding the mixture at 50C for 1 day followed by 3 days at 60C.
The mec~anical properties of the hydrophilic copolymer are modified by the inclusion of a minor amount of an ethylene oxide - propylene oxide block copolymer and this feature forms an integral and important part of the invention.
A preferred hydrophilic copolymer consists essentially of copolymerised N-vinyl-2-pyrrolidone and methyl methacrylate~

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a minor amount of at least one cross-linking agcnt containing two olefinic bonds in thc molecule, and a minor amount o~ an ethylene oxide-propylene oxide block copolymer which has a molecular weight o~ not more than about 6,ooo.
The ethylene oxide - propylene oxide block copolymer may contain one or more ethylene oxide polymer blocks and one or more propylene oxide polymer blocks. The block copolymer suitably has a molecular weight of at least about 1,000 and advantageously a molecular weight of from about 1,500 to about 5000. The preferred ethylene o~ide - propylene oxide copolymer has a molecular weight of from about 3000 to about 4000; such a block copolymer is available on the market under the name Monolan PB and is manufactured by Lankro Chemicals Limited.
The amount of the ethylene oxids -propylene oxide block copolymer used is suitably not more than 10% w!w, advantageous-1~ not more than about 5% w/w and preferably not more than about 3% w/w based on the remainder of the hydrophilic copolymer which is pre~erably constituted essentially by N-vinyl-2-pyrrolidone units, methyl methacrylate units and units of a cross-linking agent. The minimum amount of the block copolymer used may be about 0~25% w/w or about 0~5% w/w~ Generally, the amount o~ the modifier or block copolymer used is preferably not more than about 2% w/w and about 1! w/w of the modifier is ;~
frequently an appropriate amount.
~he molar ratio of the N-vinyl-2-pyrrolidone to the methyl methacrylate is suitably from about 6-1 to about 1:1 i . ,:
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and is pref~rably ~rom about ll:l to about l:i.
Suitable cross-linking agents include allyl methacrylate, divinyl benzene, dimcthacrylates and bis(allyl carbonates) of alkylene glycols and polyalkylene glycols, ~or example, ethylene glycol dimethacrylate and diethylene glycol bis~allyl car~onate).
The preferred cross-linking agent is allyl methacrylate. The amount of cross-linking agent is allyl methacrylate. The amount of cross-linking agent present may be, for example, frpm about 0.2% to about 5%, suitably not more than 20h, by weight of the copolymerised N-vinylpyrrolidone and methyl methacrylate.
Inter alia, the tensile strength, elongation at break and resistance to fracture upon flexure of the hydrated copolymer are improved by the ethylene oxide - propylene oxide block copolymer, particularly the block copolymer having a molecular -~weight of ~rom a bout 3000 to about 4000 such as that sold under the name Monolan PB.

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- To 4 parts by weight (hereinba~ter abbreviated to pbw) o~ N-vinyl-2-pyrrolidone, 1 pbw methyl methacrylate and 0.50 pbw of a cross-linking mix consisting of a mixture o~ 900 pbw methyl methacrylate and 120 pbw allyl methacrylate were added i~o W/W (that is, 0.055 pbw) of the ethylene oxide - propylene o~ide block copolymer of about 3000 - 4000 molecular weight ~: .
aYailable under the name Monolan PB followed by 0.01 pbw AZDN ~;
and 0.005 pbw isopropyl percarbonate. The whole mi~ture was disposed in ~ glass tube, purged with nitrogen and then sealed I Y O~ 1 0~ ~

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undol nitro~en in the tube a~ter l~hich the mixture l~as po]ymer-i~ed at 40C for 6 days, 50C for 8 days and 60C ~or 2 days.
T~lo oopolymer (hereinaIter designated as copolymer A) obtained w~ a }lard, clear solid. The equilibrium water absorption or molsture content o~ copolymer A, determined on the 1 mm thick dl~c as hereinbe:eore described but using isotonic saline solu-tlon rather than distilled water, was 70%. The hydrated disc wuY transparent, flexible and soft.

I Example 16 was repeated but using 2% w/w~ 3% w!w, 4% w/w and 5% w/w instead of 1% w/w Of the modifier, that is Monolan Pl3, to give four copolymers hereina~ter designated as copoly-mors B, C, D and E respectively. Copolymers B and C were hard and clear solids. Copolymers D and E were not as hard as COpolymers B and C and whilst copolymer D was clear, copolymer -~E showed some haze or cloudiness. The equilibrium water absorptions or moisture contents of copolymers B, C, D and E
determined, as in Example 16, with isotonic saline solution instead of distilled water, were 69.30/o~ 68.1%~ 67.30/D and 66.50/o re~pectively. ~he ~our hydrated discs were ~lexible, those of oopolymers B, C and D being clear and that of copolymer E being h~y or cloudy. ;~

Example 16 was repeated except that Monolan PB was omitt-e~, The copolymer (hereinafter designated as copolymer Z) obtained was a hard~ clear solid the equilibrium water absorp-'' ,', ..~ . .

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tion or moisturc content (detcrmined with isotonic salinesolution) oL ~hich l~as 71%. ~he hydrated disc was transparent, flexible and soft.
~X~~ 22 Example 16 was repeated except that 10% w/w instead o~
1~ w/w of the modi-fier, Monolan PB, was used.
_XAMPLE 23 Example 16 was repeated except that 3 pbw instead of 4 pbw of N-vinyl-2-pyrrolidone were used and that 1 pbw instead of 0.5 pbw of the cross-linking mix was used.

Example 16 was repeated except that there were used (a) 5 pbw instead of 4 pbw of N-vinyl-2-pyrrolidone~ (b) 0.20 pbw instead of 0.50 pbw of the cross-linking mix and (c) 2% w/w instead of 1% W/W Of Monolan PB.
Some of the advantageous effects of including the ethy-lene oxide - propylene oxide block copolymer as a modifier in - the hydrophilic copolymer composition are illustrated by way of example with reference to the accompanying drawings in which:-Figure 1 shows a plot of the linear expansion ratio against the percent w/w of modi~ier present;
Figure 2 shows a plot of the ratio of the tensile strengths of the hydrophilic copolymer containing the modifier and a similar plot for hydrophilic copolymer containing none of the bloc~ copolymeric modifier; and Figure 3 shows a plot of the percent e?ongation at break .

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~, ' ' : , . ' of the modi~ied hydrophilic copolymer and a si~ilar plot for the unlllodifiecl hydrophilic copolymer, The linear e~pansion ratio of a hydrophilic copolymer is thc ra-tio of a linear dimension o~ a specimen of the copolymer when the copolymer is ~ully hydratcd in isotonic saline to the ~rresponding linear dimension when the speciment is dry, This ratio is of critical importance to the success of a process of making lenses from the copolymer, since the lenses are cut with the dry copolymer to a complex formula ~hich provides the proper prescription after each cut lens has been hydrated, Thus any inaccuracy in the value of the ratio between batches of material will adversely affect the standard of the final lens. The lenses are cut to have a hydrated curvature which must be acc-urate to 0,05 mm on a base curve of 8.0 mm and thus the value of the linear expansion ratio must be accurate to a similar degree, that is, better than 5 in 800, The linear expansion ratios of copolymers Z, A, B, C, D
and E were determined and found to be 1.535, 1.529, 1,523, ~ ;
1.514, 1,508 and 1,502 respectively, A further copolymer ;~
prepared as in Eæample 16 but with 7% w/w instead of 1% W/W :
of ~onolan PB, was found to have alinear expansion ratio of .- -, . .. .
i.495. These results are-plotted in Figure 1 in which the error bars show the spread of the three determinations which were effected in each instance, Thus the modifier, Monolan PB, provides a valuable oontrol on the final properties of the copolymer, ,' ~;

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The tensile strength of t'he hydrophilic copolynler in the hydrated state i9 a matter of great importance where the hydrat-ed co~olymer has to be handled dail,y as it does when it is used as a contact lens. The tensile strengths o~ copolymers A, B, C
and D in the equilibriulll hydrated state were determined.
Copolymers were prepared without Monolan PB (that is, ~rom N-vinyl-2-pyrrolidone, methyl methacrylate and allyl methacrylate only) in the manner described in Example 21 but the N-vinyl-2, pyrrolidone to methyl methacrylate molar ratios were varied to give four copolymers A~, B~, C~ and D~ having the same equilib-'rium moisture contents as copolymers A, B, C and D respectively, and the tensile strengths of copolymers A', B~, C' and Dl in that equilibrium hydrated state were also determined. The results were then presented as the following ~atios T.S. of copolymer A , ' T.S. of copol~mer B , T.S. of copolymer A~ T.S. of copolymer B !
T.S. of copol~mer C , and T.S. of copolymer D
T.S. of copolymer C' T,S. of copolymer D~
where T.S. denotes the tensile strength of the copolymer in, the equilibrium hydrated state. The results are presented in this manner in order to eliminate the separate effect of the - water content on the tensile strength and so clearly show the effect of the block copolymer modifier, i.e. Modolan PB5 on the tensile strength of the hydrated copolymer.
~ Figure 2 shows curve S which is a plot of the said ratios of the tensile strengths plotted against the percent block --' 20 - , .~ .

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' copolymeric modifier (Modolan ~B).
Curve T in ~igurc 2 is a plot of the ratios of the T.S. O:e copol~mer ~ or B~ or C~ or D~
T.S. of coyolyl~er ~
T,S. having the meaning hereinbefore given, l~ith copolymers A', B~, C~ and D~ being plotted on the same abscissae as copolymers A, B, C and D respectively. It is clear from Figure ~ that the addition of up to 3% of Monolan PB has a marked effect in improving the tensile strength of the hydrophilic copolymer in the hydrated state.
The percentage elongation at break of the hydrophilic copolymer in the hydrated state is an important parameter when the copolymer is used as a contact lens, for it is common prac-tice to fold the lens in half when removing it from the eye for hydration or storage in an appropriate solution and when remov-ing it from the solution and replacing it in the eye. This -folding in half produces strains of 100% or more at the outside ~-of the curve of the fold. -.. : .
As with tensile strength, the elongation to break of the copolymer at equilibrium hydration is a function of the water ,~-content of the hydrated copolymer and the water content at equilibrium hydration can be varied by varying the N-vinyl ~ ~`
pyrrolidone/methyl methacrylate molar ratio of the copolymer.
- The effect of Monolan PB should therefore be assessed separate-.. ~ . .
ly .
The elongations at break o~ copolymers Z, A, B, C, D and ,~ .

_ 21 : - ~ . :, , - .::.' ' : ~ :. :.
-:

E were detcrminec1 and the mean of six runs was taken. The results are shown in the following Tablc i:-TA~LE l CO POLYMEn ~ Z A -- C D E

MODIFIER O 1 2 3 _ _ 5 ~ BREAK 234 230 225 217 219 209 ¦ STANDAiD ~ ¦ 30'4 ¦ 22.3 31,1 27.l~ 3' MOISTURE CONTENT /0 71 7o 69.3 68.1 67.3 66.5 .. , - The elongation at break of copolymers A, B, C, D and E
is in Figure 3 plotted against the percentage content of the modifier, namely MONOLAN PB, giving curve U. Copolymer Z was modified solely by vary1ng its N-vinyl-2-pyrrolidone/methyl methacrylate molar ratio to provide five copolymers A~ Bl, C~, .
Dl and E~ having the same equilibrium water contents as copoly-.mers A, B, C, D and E. The percent elongations at break of copolymers A?, Bl, C~, Dl and Et were determined in the same manner as that used with copolymers A, B, C, D and E and the results plotted in Figure 3, curve V being thereby obtained.

In plotting curve V, the ordinate values were determined by the .
equilibrium water content of the particular copolymer so that the ordinate values for copolymers At, Bt, C'', Dl and E~ were .

, `1 . :
. - 22 .. , :
..
.: ; ~. . . - .
,: ` .'. ;' - "': ''" ':
~ ~ ' respectively -the same as lor copolymers A, B, C, D and E.
rrhus the equilibrium water content of the hydrophilic copolymer may b~ ~aried, lYhich variation alters the linear expansion ratio, (a) by ~arying the N-vin~l pyrrolidone/methyl methacry]ate or ~b) by incorporating Modolan PB in the copolymer.
As is evident from Figure 3, the latter method (b) results in a lesser degradative effect on the elongation at break of the copolymer.
The effect of repeated flexure upon the life of a contact lens made from the hydrophilic copolymer is also a matter of great important. The mechanism of the damage which occurs is presumed to be the formation of microcracks in the flexed sur-face as the surface begins to dry. Such microcracks are then -~
propagated when the lens is next hydrated.
Tests were carried out in a standard rig in which speci-mens of the hydrophilic copolymers~suitable for the pro~uction ;~
of contact lenses were subjected to repeated fle~ure for a period ~o 5 minutes after removal from a storage solution, the specimens being then rehydrated in the solution and the 5 minute flexing period repeated. In each 5 minute period, each specimen underwent 50 cycles of flexure. ; ,~
Specimens of copolymers Z, A, B and C were tested, five specimens of each copolymer being tested to breaking and the mean of the five numbers of fleæu~es to break calculated. The results are shown in the following Table 2:-, ,/

: . . .
-, , . ~ ,, ~::
.. ..
: . ~ .

.

~9~ ~ ~ 8 Copolylner B C

/0 Modi~ier 0 1 2 (Monolan PB) _. ___. 3 Mean o~
Flexures 1080.ll 13061107 1006 to break .

eandtirodn 90.6 115.694.6 82.1 ', : : .. - ,~ . :.

-. ,., ,.; . ~ : . , : . .

Claims (14)

The embodiments of the invention in which an exclusive property or privilege is claimed are defined as follows:-

1. A hydrophilic copolymer consisting essentially of copolymerised N-vinyl-2-pyrrolidene and methyl methacrylate in a molar ratio of from about 6:1 to about 1:1 and including (i) a minor amount of at least one cross-linking agent containing at least two olefinic bonds per molecule and (ii) a minor amount of an ethylene oxide - propylene oxide block copolymer having a molecular weight of not more than about 6,000.

2. A hydrophilic copolymer according to claim 1, in which the molar ratio of the N-vinyl-2-pyrrolidone units to the methyl methacrylate units is from about 4:1 to about 1:1.

3. A hydrophilic copolymer according to claim 1, in which the cross-linking agent is allyl methacrylate, divinyl benzene, ethylene glycol dimethacrylate or diethylene glycol bis(allyl carbonate).

4. A hydrophilic copolymer according to claim 2, in which said cross-linking agent is allyl methacrylate.

5. A hydrophilic copolymer according to claim 4, in which the said block copolymer is present in an amount of not more than about 5% by weight based on the weight of N-vinyl-2-pyrrolidone, methyl methacrylate and cross-linking agent.

6. A hydrophilic copolymer according to claim 5, in which said block copolymer has a molecular weight in the range 1,500 - 5,000.

7. A hydrophilic copolymer according to claim 6, in which said block copolymer has a molecular weight of from about 3,000 to about 4,000.

8. A hydrophilic copolymer according to claim 7, in which the said block copolymer constitutes from about 0.5% to about 3% by weight based on the total weight of N-vinyl-2-pyrrolidone methyl methacrylate and cross-linking agent.

9. A hydrophilic copolymer according to claim 1 and consisting essentially of (a) copolymerised N-vinyl-2-pyrro-lidone and methyl methacrylate in a molar ratio of from about 4:1 to about 1:1; (b) at least one cross-linking agent having two olefinic bonds in the molecule and constituting from about 0,2% to about 5% by weight of (a); and (c) an ethylene oxide -propylene oxide block copolymer having a molecular weight of from about 3,000 to about 4,000, said block copolymer constitu-ting from about 0,25% to about 2% by weight based on the combin-ed weight of (a) and (b).

10. A hydrophilic eopolymer according to claim 9, in which the cross-linking agent is allyl methaerylate, the cross-linking agent constituting not more than 2% by weight of (a).

11. A hydrophillc copolymer according to claim 1 and obtained by forming .alpha.-polymerisation reaction mixture consist-ing essentially of (A) N-vinyl-2-pyrrolidone, (B) methyl meth-aerylate, (C) at least one cross-linking agent having at least two double bonds in its molecule and (D) an ethylene oxide-propylene oxide block copolymer having a moleeular weight in the range of from at least about 1000 to not more than about 6000, the molar ratio of (A):(B) being from about 6:1 to about 1:1, the amount of (C) being Irom about 0.2% to about 5% by weight based on the weight of (A) plus (B), and the amount of (D) being from about 0.25% to not more than 10% by weight based on the sum of the weights of (A) plus (B) plus (C), polymeris-ing the polymerisation reaction mixture and obtaining the hydrophilic copolymer.

12. A hydrophilic copolymer according to claim 11, wherein the polymerisation is carried out at a temperature of from 35° to 50°C until the monomers have gelled, the temperature is then raised to 50° to 60°C and the polymerisation is completed at the latter temperature to thereby obtain the hydrophilic copolymer.

13. A hydrophilic copolymer according to claim 11, wherein the polymerisation is carried out by adding to the polymerisation reaction mixture from 0.01% to 0.10% by weight, based on the weight of (A) plus (B) plus (C) of a polymerisation initiator, then polymerising the polymerisation reaction mix-ture under an inert gas atmosphere, or in vacuo, until polymer-isation is completed.

14. A contact lens made from a hydrophilic copolymer according to claim 1, 9 or 11.