Copolymers of poly(vinyl trifluoroacetate)or poly(vinyl alcohol)and manufacture of shaped articles therefrom

Copolymers of pdly(vinyl trifluoroacetate) of poly(vinyl alcohol) and manufacture of shaped articles therefrom

MINNESOTA MINING AND MANUFACTURING COMPANY

C:-,\ 64762

32889 I.SR 9A

Description

Copolymers of Poly(vinyl Trifluoroacetate) or P01y(vinyl

Alcohol) and Process for Thermoformed Articles Therefrom

Field of the Invention

This invention relates to non-crosslinked copolymers of poly(vinyl trifluoroacetate) with small amounts of either a vinyl ester or a disubstituted ethylene monomer and to novel copolymers derived therefrom by solvolysis. In another aspect, it relates to shaped articles, films, and coatings of both poly(vinyl trifluoroacetate) copolymers and poly(vinyl alcohol) copolymers, the latter being produced by solvolysis of poly(vinyl trifluoroacetate) copolymers. In a further aspect, it relates to hydrogel ocular devices formed from the poly(vinyl alcohol) copolymers of the invention.

Background of the Invention

Polymers of vinyl trifluoroacetate and vinyl alcohol are known in the art. Some polymers containing hydroxyl groups, such as poly(vinyl alcohol) form excellent hydrogels, i.e., they absorb large amounts of water without dissolving. Hydrogels have desirable physical, optical, and physiological properties and are useful, for example, as contact lens materials. However, in order to obtain properties of strength and structural integrity, these polymers are generally cross-linked. See, for example, U.S. Patent Nos. 3,220,960 and 3,361,858.

U.S. Patent No. 2,436,144 discloses copolymers of vinyl trifluoroacetate and.olefinic compounds useful as sheet materials for wrapping, for impregnating and coating materials, and in molding applications. It is noted that optimum properties are obtained when greater than 50 percent by weight of the polymerizable mixture is vinyl trifluoroacetate. The patent claims interpolymers containing 15 to 70 weight percent of vinyl trifluoroacetate. Example VIII discloses the hydrolysis of a vinyl trifluoroacetate homopolymer with sodium ethylate to provide a polymer which is soluble in water. No examples or suggestion of solvolysis of copolymers of poly(vinyl trifluoroacetate) are disclosed.

Harris, et al., J. Polymer Sci. A-l, 4 665-677 (1966) and Haas, et al., J. Polymer Sci,, 22 291 (1956), disclose the hydrolysis of poly(vinyl trifluoroacetate) homopolymers to poly(vinyl alcohol) homopolymers with syndiotactic properties (i.e., the stereochemical configurations of the tertiary carbon atoms are regularly alternating). U.S. Patents 3,220,960 and 3,361,858 teach that contact lenses can be made from cross-linked poly(vinyl alcohol) homopolymer hydrogels. It is known in the art that the strength of these polymers is generally related to the amount of cross-linking present.

Copolymers of vinyl alcohol are known and are reported, e.g., in Japanese Patent 78/91,995 and Japanese Patent 78/103,092; by L. A. Vol'f, et al., Khim. Volokna, 2, 14 (1979) and by J. Chernikov, et al., Nauchn. Tr,, Kuban Gos. Univ., 243, 141 (1977). The latter discloses cross-linked graft copolymers of poly(vinyl alcohol) and poly(acrylic) acid useful as biologically active man-made fibers.

None of the above-mentioned art discloses that non-crosslinked copolymers of vinyl trifluoroacetate with less than 5 weight percent of certain comonomers can provide, by solvolysis, syndiotactic polyivinyl alcohol) copolymers which surprisingly are insoluble in water and possess the desirable properties of very strong hydrogels. Further, it is known in the art that when cross-linked pply(vinyl alcohol) homopolymers are to be made into contact lenses they cannot be molded due to the infusibility of polyivinyl alcohol), but they must be mechanically cut or machined into the contact lens shape after cross-linking or curing, then hydrated to form the hydrogels.

In order to provide shaped articles having hydrogel properties from hydroxyl-containing monomers, the articles also possessing adequate strength and structural integrity, two processes are used in the art. One process requires forming a cross-linked polymer, cutting and machining the cross-linked polymer into the desired shape and configuration and then hydrating the article to provide a hydrogel article. This process utilizes labor-intensive cutting, machining, polishing, and the like. The other process, called spin casting is described, for example, in U.S. Patent No. 3,408,429 and requires that polymerization in the presence of a crosslinking agent be carried out in a rotating mold which approximates the shape of the desired article. After polymerization the article is further processed if necessary to attain the final shape. The shaped article is then hydrated to provide a hydrogel article.

An early attempt to hydrolyze vinyl trifluoroacetate polymers is disclosed in U.S. Patent No. 2,436,144 (see Example VIII), It is taught in the patent that the polymer obtained by hydrolysis is soluble in water, i.e., it is not a hydrogel. The polymers of poly(vinyl trifluoroacetate) obtained are described as colorless, transparent, tough and thermoplastic (col. 3, 11. 25-31). Further, the patent discloses molded articles of poly(vinyl trifluoroacetate) having softening temperatures of 70°C. Thus, the poly(vinyl trifluoroacetate) and its hydrolysis product of this patent are significantly different from that of the present invention.

Cross-linked and uncross-linked poly(vinyl alcohol) is known in the art. The properties of these forms of poly(vinyl alcohol) are known to differ as is disclosed in J. Polymer Sci., 14_, 441-457 (1976). Previous preparations of poly(vinyl alcohol) and shaped articles formed therefrom (see U.S. Patent No. 3,361,858) do not exhibit the improved properties obtained in the shaped poly(vinyl alcohol) articles of the present invention.

־4Summary of the Invention

Briefly, the present invention provides novel, non-crosslinked copolymers of vinyl trifluoroacetate (VTA) and up to 5 weight percent of the VTA of certain comonomers, such as vinyl esters or disubstituted ethylene monomers. Solvolysis of these copolymers provides novel water-insoluble, non-crosslinked, poly(vinyl alcohol) copolymers which can be hydrated to copolymers having controllably variable hydrogel properties and high strength. Such poly(vinyl alcohol) copolymers are particularly desirable as ocular devices such as contact lenses.

It has not previously been recognized that copolymers of poly(vinyl trifluoroacetate) could be used as a source of water-insoluble, non-crosslinked copolymers of poly(vinyl alcohol), or that such novel copolymers would give high tensile strength and high modulus hydrogel articles. The process comprises first casting or molding the poly.(vinyl trifluoroacetate) copolymer into ocular devices such as corneal transplants, corneal implants, or contact lens shaped articles in the presence of heat (i.e., thermoforming), then solvolyzing these shaped article copolymers to provide shaped articles of poly(vinyl alcohol) copolymers which can be hydrated to provide controllably variable hydrogel properties including structural integrity and high strength. This process is particularly advantageous for the purpose of providing surprisingly strong contact lenses, other articles, films, contact lens buttons, sheets and the like which have hydrogel properties, structural stability, and high strength can also be manufactured using this process.

In another aspect, in order to provide ocular devices and shaped articles of the invention having good structural stability, the solid poly(vinyl trifluoroacetate) copolymers (either in the form of the cast films or as solid polymer granules or powders) are placed in molds of various desired shapes, e.g., contact lens molds or pressed into sheets or films of various shapes. The polymer-filled molds of various shapes are then heated, generally slightly above (i.e., 10 to 20°C above) the melting point of the copolymer for 5 seconds to 15 minutes to thermoform the copolymer sample. Using this technique, shaped contact lenses and films, contact lens buttons, sheets and articles of various shapes can be obtained. Good retention of shape is observed if the molded poly(vinyl trifluoroacetate) copolymers are solvolyzed to poly(vinyl alcohol) copolymers. If the poly(vinyl alcohol) copolymers are then hydrated to form hydrogels, it is observed that the hydrogel articles retain their shape under normal room conditions of temperature and pressure and indeed have excellent and improved strength compared to alternative materials. Corneal implant and transplant lenses as well as contact lenses can also be molded or shaped from the copolymers of the invention. Solvent solutions may be used to form articles such as tubes by film coating on a suitable rod or mandrel.

Trihaloacetate-protected polymers are thermoplastic polymeric precursors to uncross-linked hydrogel polymers, and a solvolytic process followed by hydration transforms the molded precursor polymer into a shaped hydrogel polymer. Both strength and water sorbency in the absence of covalent cross-linking may be provided in certain examples by creating semicrystalline polymer hydrogels. These polymer hydrogels are suited for use as ocular devices because they have extraordinarily high strength, flexibility, transparency, and are capable of absorbing large amounts of water which give high rates of oxygen permeability needed for corneal health.

As mentioned above, cross-linked poly(vinyl alcohol), although having good strength and hydrogel properties, is non-thermoplastic and cannot be molded into shaped articles such as contact lenses. It has been discovered, surprisingly, that the polymeric compositions of this invention provide thermoplastic copolymeric I precursors to hydrogels which can be thermoprocessed to molded lens articles, then solvolyzed and subsequently hydrated to provide a molded hydrogel lens with high and controllable water sorbency characteristics.

It has not previously been recognized that the novel process of the present invention can provide articles with improved water absorption and in some instances improved strength even when compared to heavily cross-linked hydrogel polymers. The present process avoids both of the factors which can prevent thermal processability, i.e., hydrogen bonding by hydroxyl functional groups and cross-linking.

The present invention provides shaped hydrogels without using the step of machining or cutting a tough polymer, and thus provides a significant advantage in hydrogel processing.

The approach, materials, and processes described below are believed to represent a novel solution to achieving superior ocular devices giving a desirable and surprising combination of properties.

As used in the present application:

ocular device means a corneal transplant, corneal implant or contact lens;

solvolysis means the reaction of an ester group capable of cleaving into a carboxyl-containing compound (e.g., amide, ester, or acid) and an alcohol in the presence of a nucleophile such as water (at room temperature), ammonium hydroxide or an organic amine or in the presence of a lower (C! to C4) alkanol (at temperatures up to 60°C) in one hour or less;

thermoformable (thermoprocessable) polymer means a polymer which may be heated to a temperature in the range of 150 to 300°C, and preferably at about 200°C, and most preferably from 10 to 20°C above the crystalline melting point (T_m) of the poly(vinyl trifluoroacetate) copolymer, maintained at that temperature for 5 sec. to 15 min. and then cooled to provide a shaped article of the polymer which will retain its shape under ambient conditions;

ambient conditions means room temperature and pressure;

hydrogel means a material which absorbs water in the range of 10 to 95 percent by weight, without itself dissolving;

high tensile strength means having a tensile strength greater than 6.9 kg/cm² (100 psi); and contact lens button means a cylindrical-shaped article which is machinable into a contact lens.

Detailed Description

The present invention provides a copolymer comprising the non-crosslinked reaction product of:

1) at least 95 weight percent, preferably 95 to 99.99 weight percent, of vinyl trifluoroacetate monomer, and

2) at least 0.01 weight percent, preferably 0.01 to 5 weight percent, of a comonomer selected from vinyl esters and disubstituted ethylenes.

in another aspect, the present invention provides a process for preparing shaped articles comprising the steps:

a. preparing the above-described copolymer of poly(vinyl)trifluoroacetate;

b. thermoforming said copolymer by heating in a mold or in sheet-form at a temperature in the range of 100 to 400״C for about 5 sec. to 15 min., and then cooling said polymer, to provide a shaped article;

c. optionally, solvolyzing the resulting shaped article to provide a hydroxy-substituted polymeric shaped article; and

d. optionally, hydrating said hydroxy-substituted polymeric shaped /article to provide a shaped hydrogel article,

Copolymers of the present invention are prepared by copolymerizing small amounts of selected comonomers with vinyl trifluoroacetate. The amounts of comonomer used will depend to a certain extent on the comonomer chosen, but 5 will generally be less than about 5 percent by weight of the vinyl trifluoroacetate. The amount of comonomer will also depend upon which properties of the polymer and the hydrolyzed polymer optionally derived therefrom are chosen to be maximized.

The comonomer selected will desirably have a reactivity similar to that of vinyl trifluoroacetate in order to obtain relatively uniform copolymerization. Any comonomer chosen preferably polymerizes at a rate comparable to vinyl trifluoroacetate, although polymerization rates from one-half to twice as fast are acceptable. For this reason, other vinyl esters having up to 6 carbon atoms in the alcohol portion of the ester, such as vinyl acetate, vinyl perfluoro-n-butyrate, vinyl formate and the like, are useful. Vinyl ethers having up to 8 carbon atoms, such as vinyl tertiary-butyl ether may also be used. Another class of comonomers which are particularly useful are disubstituted ethylenes, e.g,, esters or anhydrides of lower alkyl (C! to C₄)-substituted or unsubstituted dicarboxylic acids having up to 8 carbon atoms, such as derivatives of maleic, 25 fumaric, itaconic and citraconic acid, e.g., maleic anhydride, dimethyl itaconate, monoethyl fumarate, and the like. Preferred comonomers are maleic anhydride and vinyl acetate. They have the advantages of ready availability and relatively good solubility in vinyl trifluoroacetate monomer as well as good copolymerizability.

The process for the preparation of copolymers of vinyl trifluoroacetate is preferably a bulk polymerization process carried out in a conventional manner induced, for example, by relatively mild heating or irradiation in the 35 presence of a free-radical initiator in a relatively inert atmosphere, e.g., in a sealed ampoule or other container after degassing.

Included among free-radical initiators are the conventional thermally activated initiators such as organic peroxides, hydroperoxides, and azo compounds. Representative examples of such initiators include benzoyl peroxide, tertiary-butyl perbenzoate, di isopropyl peroxydicarbonate, cumene hydroperoxide, azobis(isobutyronitrile), methyl tricapryl ammonium persulfate, and diacyl peroxides such as decanoyl peroxide and the like. Generally, from about 0.05 to 5 percent by weight of a thermal initiator 'is used. These thermally activated initiators are preferred.

Photoinitiators may also be employed to initiate polymerization. Such initiators are well known and have been described, for example, in polymerization art, e.g. Chapter II of Photochemistry by Calvert and Pitts, John Wiley and Sons (1966). The preferred initiators are photoinitiators which facilitate polymerization when the composition is irradiated. Representative examples of such initiators include acyloin and derivatives thereof, such as benzoin, benzoin methyl ether, benzoin ethyl ether, benzoin isopropyl ether, benzoin isobutyl ether, and a-methylbenzoin; diketones such as benzil and diacetyl, etc.; ketones such as acetophenone, a,a,a-trichloroacetophenone, a, a, a-tribromoacetophenone, a, a-diethoxyacetophenone (DEAP), 2-hydroxy-2-methyl-l-phenyl-l-propanone, o-nitro-a, a, a-tribromoacetophenone, benzophenone and p,p¹ -tetramethyldiaminobenzophenone; a-acyloxime esters such as benzil-(Q-ethoxycarbonyl)-a-monoxime; ketone/amine combinations such as benzophenone/N-methyldiethanolamine, benzophenone/tributylamine, and benzophenone/Michler's ketone; and benzilketals such as benzildiethylketal and

2,5-dichlorobenzildimethylketal. Normally, the photoinitiator is used in amounts ranging from about 0.01 to 5 percent by weight of the total monomeric composition. When the quantity is less than 0.01 percent by weight, the photopolymerization rate becomes extremely slow, if the photoinitiator is used in excess of 5 percent by weight, no correspondingly improved effect is observed. Preferably, about 0.05 to 1.0 percent of photoinitiator is used in the polymerizable compositions.

When the activating energy is ultraviolet light, the irradiation is typically carried out at a temperature of about 0 to 50°C for 30 seconds to 5 hours or more. Following ultraviolet irradiation, the composition may be heated at 50 to 100°C to complete the polymerization, provided the free-radical initiator is thermally activatable.

Heating to effect polymerization is generally at 20 to 100°C, and preferably at 30 to 70°C. The precise temperature range depends somewhat on the temperature necessary to activate the free-radical initiator. For example, when azobisisobutyronitrile is used as the initiator the temperature is preferably about 45 to 50°C.

The actual polymerization reaction may be run by combining the vinyl trifluoroacetate, the comonomer and the initiator in a glass ampoule, freezing the reactants with a cold bath such as liquid nitrogen, degassing the ampoule by use of vacuum, and then sealing it. Heating the ampoule, e.g., in a constant temperature bath provides the heat necessary for the initiation of the polymerization reaction. Irradiation generally uses an ultraviolet lamp. The reaction time is generally several hours, and has conveniently been carried out overnight, i.e., for about 12 to 20 hours, to provide essentially complete conversion of the monomers to copolymers.

Vinyl trifluoroacetate is preferably purified i.e., trace amounts of acetaldehyde, trifluoroacetic anhydride and trifluoroacetic acid are removed from the vinyl trifluoroacetate for best results. The copolymer product is a white to off-white solid which is soluble in Ν,Ν-dimethylformamide, ethyl acetate, acetonitrile, warm acetone, and the like. Differential thermal analyses show glass transition temperatures of about 50 to 100°C and crystalline melt transitions of about 150 to 200°C.

Molecular weights of the poly(vinyl trifluoroacetate) copolymers are typically greater than ,000, and preferably in the range of 400,000 to

4,000,000, for the weight average molecular weight; such high molecular weights are preferred since approximately

2/3 of the polymer mass is lost in the subsequent solvolysis step which provides poly(vinyl alcohol) copolymers. Molecular weights of the corresponding poly(vinyl alcohol) copolymers obtained through solvolysis are about 1/3 of the value for poly(vinyl trifluoroacetate) copolymers due to loss of mass of the trifluoroacetate groups from the poly(vinyl trifluoroacetate) copolymer. In the present invention the molecular weights of the preferred embodiments generally are characterized by having a polydispersity (P) of less than 2.0. This indicates a relatively narrow molecular weight distribution. P is a generally recognized measurement of the overall sharpness or breadth of the range of the molecular weights of polymer chains and is equal to weight average molecular weight number average molecular weight

2θ Solvolysis of the trifluoroacetyl group of the above-described poly(vinyl trifluoroacetate) copolymers provides novel poly(vinyl alcohol) copolymers. It is indeed surprising that the poly(vinyl alcohol) copolymers of the present invention have greatly improved hydrogel ²⁵ properties when compared to known hydrogels of comparable water absorption capacity. In particular, it has been observed that very small amounts of comonomer, typically less than 5 percent, provide two or more times the weight of water absorption than the homopolymer does. This ³⁰ increased water absorption is particularly important in the preparation of contact lenses, since increased water absorption is known to correlate well with increased oxygen permeability, a property essential to extended wear of contact lenses. As little as 0.25 percent of maleic ³⁵ anhydride in a copolymer was observed to more than double the oxygen permeability of a contact lens prepared according to the present invention. Similarly, only 0.5 percent of maleic anhydride in a copolymer was found to increase the oxygen permeability of a contact lens about four times, and with one percent the increase was about 5.5 times. After solvolysis, the poly(vinyl alcohol) copolymers of the invention comprise 85 to 99.97 weight percent of vinyl alcohol monomer units and 0.03 to 15 weight percent of comonomer units derived from vinyl esters and disubstituted ethylenes.

Solvolysis is typically carried out under relatively mild conditions, for example, using methanolic ammonium hydroxide at approximately 20°C. The base used is preferably a mild base, including (in addition to ammonium hydroxide) the organic amines such as piperidine, morpholine, ethylamine, di(n-propyl)amine, and di(n-butyl)amine, in a diluent. The base chosen may influence the ionic character of the polymer. The diluent used is preferably a non-aqueous liquid which will not dissolve either the poly(vinyl trifluoroacetate) copolymer or the copolymeric poly(vinyl alcohol) solvolysis product. The diluent can be a lower alkanol (C| to C₄) or an ether such as tetrahydrofuran or diethyl ether. The solvolysis is preferably complete, and it is very rapid. For example, using 9:1 methanol^ammonium hydroxide as the solvolysis reagent, solvolysis is essentially complete in 15 minutes. The reaction time may be monitored analytically, e.g., chromatographically to determine both the rate and the completion of the solvolysis.

Although amounts of comonomer up to 5 percent of the vinyl trifluoroacetate copolymers can be used for some purposes to provide desirable copolymers, the amount of comonomer must be carefully selected in order to provide good ocular devices such as contact lenses. The amount of comonomer will be less than about 5 weight percent in general, but in order to form ocular devices with maleic anhydride as the comonomer, it has been found that an amount in the range of 0.01 to 2 weight percent is preferred, and 0.01 to 1 weight percent is most preferred.

Copolymers with less than 1 percent maleic anhydride appear to provide, after solvolysis, hydrogel copolymers having high strength, excellent oxygen permeability and good optical clarity. Copolymers with greater than 1 weight percent maleic anhydride become increasingly hazy.

Copolymers which have been solvolyzed and which contain maleic anhydride as the comonomer contain solvolyzed anhydride units. For example, when ammonium hydroxide is used for solvolysis, the solvolyzed comonomer unit becomes: -fCH—CH—CH₂—CHh

O=C C=O OH νη₂ Οθ nh₄ ® For this reason, the copolymers are very slightly charged at pH 7.

Copolymers with non-solvolyzable comonomer units (e.g,, dimethyl itaconate), units much less readily solvolyzed than anhydrides (such as vinyl acetate), or with units (such as vinyl esters) which would not solvolyze to ionic reaction products under the conditions used in the present invention would, of course, yield hydrogels with no associated ionic charge. This characteristic (i.e., no ionic charge) has been found to be of great utility in preparing hydrogel articles with low tendency to absorb proteins from biological fluids such as the tear fluids of the eye.

Although it is clear that strength is a desirable characteristic of shaped polymeric articles of the present invention, it also has been found that various copolymers will maximize various aspects of strength to allow selection of different copolymers of the invention for varying applications. That is, the copolymer with a good tensile strength and modulus but less ideal elongation might be preferred under bending stress in applications such as contact lenses. For applications where a pulling stress will be applied to the article, such as vascular grafts, a combination of all three properties is desirable.

The tensile strength, elongation and modulus are all measurements of the relative mechanical properties of a material. Samples of shaped polymeric articles of both poly(vinyl trifluoroacetate) copolymers and poly(vinyl alcohol) copolymers of the present invention were evaluated using fully hydrated samples at ambient (i.e,. room, e.g., 20°C) temperature. Tensile strength testing was done in accordance with ASTM D412-80. A commercially available tensile tester (MTS Tensile Tester, MTS Inc., Minneapolis, MN) which was modified to accept sample rings rather than strips was used. The rings were held over pegs on a sample holder rather than in conventional jaws, with the object of avoiding sample slippage. Measurements were carried out with samples immersed in water to prevent drying of the samples during testing. It was found that tensile strengths of 6.9 kg/cm² and greater were obtained. Preferred materials exhibited tensile strengths of greater than 13.8 kg/cm² and most preferred materials had tensile strengths of greater than 20.7 kg/cm². By way of comparison hydrogel materials suitable for use as contact lens materials because of high water content typically have tensile strengths of 0.7 kg/cm² or less. Measuring another aspect of strength, the percent elongation before breaking of samples made from the polymers and copolymers was determined. Preferred materials showed elongation of at least 70 percent, and most preferred materials showed elongation over 150 percent. As noted in TABLE V below, a commercially available contact lens had elongation of 110 percent.

Another aspect of strength, the modulus of elasticity, was also measured. The preferred materials of the invention showed a modulus of greater than 6.9 kg/cm². Most preferred materials showed a modulus greater than 10.4 kg/cm². As noted in TABLE V below, a commercially available contact lens exhibited a modulus of elasticity of

3.2 kg/cm².

Surprisingly, polymer hydrogels of poly(vinyl alcohol) copolymers prepared by the process of the present invention show two distinct improvements oyer related .J materials previously known. The strength of these hydrogels of the invention is much greater than that of known, conventional poly(vinyl alcohol) materials such as commercially available poly(vinyl alcohol) derived from poly(vinyl acetate) by alkaline hydrolysis. When films of the poly(vinyl alcohol) copolymers of the present invention are compared to films of commercially available poly(vinyl alcohol) in stress-strain measurements, the total energies to failure, i.e., the areas under the stress-strain curves show distinct differences between the polymer films. Over twice as much energy is required to cause failure of the poly(vinyl alcohol) copolymer films of the present invention. It is hypothesized that this difference in mechanical strength is related to differing intermolecular forces associated with the more highly syndiotactic stereochemical structure (i.e., the stereochemical configurations of the tertiary carbon atoms are regularly alternating) associated with the polymers of the invention. Commercially available poly(vinyl alcohol) has a more atactic structure (tertiary carbon atoms possessing a random stereochemical configuration) and its crystallinity properties are distinctly different i.e., the poly(vinyl alcohol) of the prior art has a lower crystalline melting temperature than the poly(vinyl alcohol) copolymers of the present invention.

A second major improvement is in the hydrogel properties of the polymers. Commercially available poly(vinyl alcohol) derived from poly(vinyl acetate) generally displays water absorption levels of about 40 weight percent or less, depending on drying time and temperature of the polymer film used for hydration. Poly(vinyl alcohol) copolymers of the present invention, and especially copolymers of poly(vinyl alcohol) containing as little as 1 percent or less by weight of various comonomers have water absorption values which may be controllably varied to give hydrogels which absorb much more water than these commercially available poly(vinyl alcohol) materials. Aqueous liquid absorption (e.g., swelled in water or normal saline) levels of 10 to 90, and preferably 60 to 70 or more weight percent, are obtained with polymers of the present invention. It is believed that ionic comonomers can lead to enhanced aqueous liquid absorption by affecting the crystallinity of the poly(vinyl alcohol) copolymer and by increasing the inherent absorptivity of the amorphous regions of the polymers. Non-ionic comonomers may exert their surprisingly large effects principally by affecting polymer crystallinity.

Once the shaped polymeric article has been thermoformed it is optionally, and in most cases preferably, hydrolyzed or solvolyzed to provide a shaped article of different chemical composition. The hydrolysis or solvolysis reaction is carried out under relatively mild conditions (i.e,, less than 60°C) using a nucleophile capable of displacing the trihaloacetyl group from the polymer. The nucleophile used is preferably a mild base, such as methanolic ammonium hydroxide or an organic amine (such as di-n-butylamine, morpholine or diethylamine). Ammonium hydroxide is the preferred nucleophilic reagent for the solvolysis step of this process. The base chosen will regulate the ionic character of the polymer when the polymer contains a carboxylic comonomer such as maleic anhydride.

The solvolysis reaction is carried out in a diluent which is not a solvent for the trihaloacetylated polymer, for example a diluent such as water, a lower alkanol e.g., ethanol or methanol, an ether e.g,, diethyl ether or tetrahydrofuran, and the like.

The reaction time may be monitored analytically, e.g., chromatographically to determine both rate and completion of reaction. The solvolysis is preferably complete, and it is very rapid. For example, using 9:1 methanol:ammonium hydroxide as the solvolysis reagent, solvolysis is essentially complete in 15 minutes for most of the polymeric articles.

It is believed that in the cases of the poly(vinyl alcohol) polymers the improved properties of the shaped hydrogel articles in the absence of cross—linking may be the result of the formation of semicrystalline polymer hydrogels. In other materials other forces may be involved.

In addition to hydrogel contact lenses (soft lenses), corneal transplants, corneal implants, molded tubes, e.g., as vascular prostheses and hydrogel coatings, may be prepared by the process of this invention.

In addition, articles of the invention may be prepared by any type of molding, casting, vacuum forming, or extrusion process known in the art. For example, hydrogel films or sheets of these copolymers can be prepared by solvent casting a sample of dissolved polymer into a thin film, drying to evaporate the solvent, treating the film for a relatively short time with a solvolysis reagent and then placing the sample in water. The product is the desired hydrogel of poly(vinyl alcohol) copolymer. While various solvents for solvent casting may be used, solvents such as acetone, ethyl acetate or acetonitrile are preferred since their relatively high volatility permits an essentially complete removal from cast films.

Injection molding is an alternative method of molding which is useful to prepare shaped articles from the copolymers of the present invention.

Objects and advantages of this invention are further illustrated by the following examples, but the particular materials and amounts thereof recited in these examples, as well as other conditions and details, should not be construed to unduly limit this invention,

EXAMPLE 1

A mixture of 5 g of vinyl trifluoroacetate, 0.030 g of maleic anhydride and 0,025 g of azobisisobutyronitrile was placed in an ampoule, the contents of which were then frozen with liquid nitrogen. The ampoule was then degassed under a vacuum and sealed. The ampoule was heated in a bath at about 47°C for about 16 hours. The contents of the ampoule were found to be white solid poly(vinyl trifluoroacetate-maleic anhydride) copolymer. The nuclear magnetic resonance spectrum of the copolymer was consistent with the assigned structure.

EXAMPLE 2

One gram of the product of EXAMPLE 1 was pressed 10 between two polyester sheets at 191 °C for about 45 seconds.

After cooling the polymer film was placed in a flask and about 20 ml of 10 weight percent concentrated ammonium hydroxide in methanol was added. After standing for 15 minutes, the polymer was separated by decanting the 15 liquids, then dried in air to provide a copolymer of vinyl alcohol and maleic anhydride solvolyzed by ammonium hydroxide. The copolymer was found to form a hydrogel when water was added. Water absorption provided a clear, strong elastic film without dissolving the polymer sample.

EXAMPLE 3

Using the method of EXAMPLE 1, vinyl trifluoroacetate was copolymer!zed (99/1 weight ratio) with various monomers to provide the copolymers shown in TABLE I:

TABLE

Sample Comonomer Copolymer a dimethyl itaconate poly(vinyl trifluoroacetate-co-dimethyl itaconate) b monoethyl fumarate poly(vinyl trifluoroacetate-co-monoethyl fumarate) c vinyl perfluorobutyrate poly(vinyl trifluoroacetate-co-vinyl perfluorobutyrate)

Using the method of EXAMPLE 2, the copolymers of the above examples were thermoformed, then solvolyzed to provide the copolymers of TABLE II:

TABLE II

Copolymeric

Sample starting material a poly(vinyl trifluoroacetate-co-dimethyl itaconate) b poly(vinyl trifluoroace tate-co-monoethyl fumarate) c poly(vinyl trifluoroacetate-co-vinyl perfluorobutyrate)

Copolymeric Writer sorption* product (weight percent) poly(vinyl alcohol-co- 47 dimethyl itaconate) poly( vinyl alcohol-co- 58 monoethyl fumarate) poly(vinyl alcohol-co- 42 vinyl perfluorobutyrate *The water sorption of the polymers (percent H2O) of Tables

II, III, and IV was a weight percent determination using the formula percent H₂O ־־ [(w₂ - W!)/W₂] x 100 J where W₂ is a water-swollen sample weight and W! is dry sample weight.

EXAMPLE 4

A mixture of 50 g vinyl trifluoroacetate, 0.75 g vinyl acetate and 0.25 g of decanoyl peroxide was placed in an ampoule. The ampoule was sealed and maintained at 47°C for about 16 hours, then at 57°C for two hours. The product, poly(vinyl trifluoroacetate-polyvinylacetate) copolymer, was removed from the ampoule, pressed at 191 °C for about one minute into sheets and solvolyzed by treating with 10 percent ammonium hydroxide in methanol. The product was poly(vinyl alcohol-polyvinyl acetate) copolymer as confirmed by nmr spectroscopy. The polymer can be used for making a corneal implant or transplant.

EXAMPLE 5

A mixture of 50 g vinyl trifluoroacetate, 0.75 g vinyl acetate, and 0.05 g 2-hydroxy-2-methyl-l-phenyl-lpropanone was placed in an ampoule. The ampoule was sealed and then rotated under a ultraviolet sunlamp for about three hours. Air was blown over the ampoule during the irradiation to cool it. The product, poly(vinyltrifluoroacetate-polyvinyl acetate) copolymer, was removed from the ampoule and pressed into sheets at 191 °C for two minutes. The sheets were solvolyzed in 10 percent ammonium hydroxide in methanol for thirty minutes to provide poly(vinyl alcoholpolyvinyl acetate) copolymer. The polymer can be used for making a corneal implant or transplant.

EXAMPLE 6

The poly(vinyl alcohol-polyvinyl acetate) copolymers (each containing 1.5 percent by weight (calculated) polyvinyl acetate) from EXAMPLE 4 and 5 were evaluated for various properties. The results are shown in TABLE III below:

TABLE III

<td></td><td></td><td> Oxygen</td><td> Tensile</td><td></td><td> Elonga-</td><td> Protein bound</td>

<td></td><td> Weight</td><td> perme-</td><td> strength</td><td> Modulus</td><td> tion</td><td> (micrograms/cm^)</td>

<td> Sample</td><td> % water</td><td> ability*</td><td> (kg/cm^)</td><td> (kg/cm²)</td><td> ' %</td><td> albumin/globulin/lysozyme</td>

<td> a</td><td> 66</td><td> 32</td><td> 50</td><td> 7.2</td><td> 620</td><td> 2.4 0.4 4.8</td>

<td> (thermally</td><td></td><td></td><td></td><td></td><td></td><td></td>

<td> polymerized)</td><td></td><td></td><td></td><td></td><td></td><td></td>

<td> b (DV polymerized)</td><td> 69</td><td> 26</td><td> 55</td><td> 6.9</td><td> 515</td><td> 0.5</td><td> 0.25</td><td> 2.4</td>

*gas phase oxygen permeability

The data of TABLE III show the excellent physical properties of the poly(vinyl alcohol) copolymers of the invention.

EXAMPLE 7

In order to compare the effect of varying levels of vinyl acetate comonomer, the following general procedure was followed to prepare four copolymers. Vinyl trifluoroacetate and vinyl acetate, quantities as indicated in TABLE V below, and 0.05 g of decanoyl peroxide were sealed in ampoules and maintained at 47°C for sixteen hours. The polymer was removed from each ampoule and pressed into sheets at 191°C for about two minutes. Each sample was solvolyzed in 10 percent ammonium hydroxide in methanol for thirty minutes, dried and weighed dry, then allowed to absorb water and weighed to determine the

<td></td><td> percent</td><td> water absorbed as</td><td> shown below:</td><td></td>

<td></td><td></td><td></td><td> TABLE IV</td><td></td>

<td> 15</td><td></td><td> Vinyl</td><td></td><td></td>

<td></td><td> Sample</td><td> ־ trifluoroacetate</td><td> Vinyl acetate</td><td> Water absorbed</td>

<td></td><td> no.</td><td> -....&lt; g) '</td><td> (g)' ־</td><td> (weight percent)</td>

<td></td><td> a</td><td> 9.9</td><td> 0.05</td><td> 42</td>

<td></td><td> b</td><td> 9.875</td><td> 0.075</td><td> 57</td>

<td> 20</td><td> c</td><td> 9.85</td><td> 0.10</td><td> 68</td>

<td></td><td> d</td><td> 9.82</td><td> 0.13</td><td> 69</td>

The data of TABLE IV show that very small amounts of comonomers significantly improve the water absorption of poly(vinyl alcohol) copolymers.

EXAMPLE 8

A mixture of 50 g of vinyl trifluoroacetate, 0.75 g of vinyl acetate and 0.05 g of 2-hydroxy-2-methyl-lphenyl-l-propanone was placed in a reactor and covered with a layer of 500 ml of ice-water. The reactor was irradiated under an ultraviolet sunlamp for 3 hours. The product copolymer was separated, rinsed with methanol and dried. The copolymer wa^ then melt-processed according to the procedure of EXAMPLE 2 into film samples and solvolyzed in percent ammonium hydroxide in methanol for 30 minutes to provide poly(vinyl alcohol-co-vinyl acetate) films which when swollen in water gave transparent high strength hydrogel materials.

EXAMPLE 9

Poly(vinyl trifluoroacetate-co-vinyl acetate) from EXAMPLE 8 was purified by dissolving the polymeric product in acetone to provide a 25 percent by weight solution, followed by precipitation into heptane (a non-solvent for the polymer) resulting in the formation of fibrous polymer. This polymer was dried, then thermally processed by pressing at 191 °C for two minutes into sheets. Thermal stability was measured by standard thermogravimetric analysis techniques (using a Mettler Thermogravimetric Analyzer, Mettler Instruments, Chicago, IL), comparing weight loss at various temperatures. These polymer sheets showed better thermal stability than sheets which had not been purified before melt processing.

EXAMPLE 10

TABLE V shows how percent water absorbed, estimated gas phase oxygen permeability and various measures of strength can be varied by varying the amount of comonomer present in copolymer hydrogels derived from appropriate vinyl trifluoroacetate copolymers prepared according to the method of EXAMPLE 1 and solvolyzed according to the method of EXAMPLE 2.

Variation of Properties of Polyvinyl Alcohol-Maleic Anhydride Copolymers

TABLE V

<td rowspan="2"> 5</td><td rowspan="2"> Sample a</td><td rowspan="2"> Polymer (¾ is by weight) . Polyvinyl alcohol; 0% maleic anhydride</td><td rowspan="2"> Weight percent water absorbed 41</td><td rowspan="2"> Oxygen perrne- ability 5.4</td><td rowspan="2"> Tensile strength (kg/cm²) 162</td><td colspan="2"> Percent Modulus elonga-</td>

<td> (kg/cm²) 115</td><td> tion 750</td>

<td> 10</td><td> b</td><td> Polyvinyl alcohol plus 0.25% maleic anhydride</td><td> 54</td><td> 12</td><td> 90</td><td> 44</td><td> 680</td>

<td></td><td> c</td><td> Polyvinyl alcohol plus 0.5% maleic anhydride</td><td> 65</td><td> 20</td><td> 48</td><td> 23</td><td> 530</td>

<td> 15</td><td> d</td><td> Polyvinyl alcohol plus 1.0% maleic anhydride</td><td> 72</td><td> 30</td><td> 26</td><td> 17</td><td> 440</td>

<td> 20</td><td> e</td><td> Commercially available lens</td><td> 55</td><td> 12</td><td> 1.6</td><td> 3.2</td><td> 110</td>

<td></td><td></td><td colspan="3"> *The opthalmic devices of the present</td><td> invention</td><td colspan="2"> preferably exhibit</td>

an oxygen permeability CpC>2) of at least 10 Barters when measured in accordance with the polarographic oxygen electrode method described by M. F, Refojo et al, Permeability of Dissolved Oxygen Through Contact

Lenses - 1. Cellulose Acetate Butyrate, Cont. Intraocular Lens Med, J♦ 3.(4), 27 (1977). More preferably the devices of the invention exhibit an oxygen permeability of at least 20 Barters.

The estimated ρθ£ was determined by the method of Refojo referenced above. The units are 10”H ml of 02.cm/sec.cm² .mmHg.

EXAMPLE 11

The copolymer of EXAMPLE 10, Sample c, of 99.5 weight percent vinyl trifluoroacetate and 0.5 weight percent maleic anhydride was dissolved in acetone to give a 20 weight percent solution. The solution was cast onto a clear polyester film in sufficient thickness to give, after solvent evaporation, a clear film of approximately 0.015 inches (about 0.4 mm) thickness. This film was placed in a metal mold designed to form a single contact lens, and the mold (heated at approximately 200°C) was closed under pressure (hydraulic ram pressure of approximately 1000 psi or 70 kg/cm²) for approximately two minutes.

The mold was cooled and the molded lens was removed and placed in a container with approximately 20 ml of 9/1 methanol-concentrated ammonium hydroxide for about 15 minutes. The solvolyzed contact lens was then air dried and placed in distilled water. Hydration provided a clear, flexible, very strong hydrogel lens.

Various modifications and alterations of this invention will become apparent to those skilled in the art without departing from the scope and spirit of this invention, and it should be understood that this invention is not to be unduly limited to the illustrative embodiments set forth herein.