Azlactone-functional substrates, corneal prostheses, and manufacture and use thereof

An azlactone-functional substrate, comprising a substrate having azlactone-reactive nucleophilic surfaces, said substrate selected from the group consisting of cellulose;

• modified cellulose derivatives;
• agarose, dextran;
• chitin;
• chitosan;
• polymers derived from hydroxyethyl methacrylate, hydroxypropyl acrylate, N-methylol acrylamide, allyl alcohol, allyl amine, or N-[3-(N'-isopropyl) aminopropyl] methacrylamide monomers;
• poly(vinyl alcohol) homopolymers;
• and poly(vinyl alcohol) copolymers, and a multi-functional azlactone composition covalently coupled thereto using at least one azlactone moiety in a manner such that at least one azlactone moiety remains available for further nucleophilic reaction;
• wherein the azlactone-functional substrate has the formula:
• ##STR6## wherein R.sup.1 and R.sup.2 independently can be an alkyl group having 1 to 14 carbon atoms, a cycloalkyl group having 3 to 14 carbon atoms, an aryl group having 5 to 12 ring atoms, an arenyl group having 6 to 26 carbon atoms and 0 to 3 S, N, and nonperoxidic O heteroatoms, or R.sup.1 and R.sup.2 taken together with the carbon to which they are joined can form a carbocyclic ring containing 4 to 12 ring atoms, and n is an integer 0 or 1;
• wherein y is at least one and is the number of azlactone moieties less at least one;
• wherein R.sup.3 is a bridging group capable of covalently connecting a plurality of azlactone moieties;
• and
• wherein B is the substrate having azlactone-reactive nucleophilic surfaces and A is a residue of a azlactone-reactive nucleophilic group on the surface on the substrate, the azlactone-reactive nucleophilic group comprising O, S, or NR.sup.4, and wherein R.sup.4 is hydrogen or an alkyl group containing from 1 to 4 carbon atoms.

An activated substrate having the formula:

• ##STR7## wherein R.sup.1 and R.sup.2 independently can be an alkyl group having 1 to 14 carbon atoms, a cycloalkyl group having 3 to 14 carbon atoms, an aryl group having 5 to 12 ring atoms, an arenyl group having 6 to 26 carbon atoms and 0 to 3 S, N, and nonperoxidic O heteroatoms, or R.sup.1 and R.sup.2 taken together with the carbon to which they are joined can form a carbocyclic ring containing 4 to 12 ring atoms, and n is an integer 0 or 1;
• wherein y is at least one and is the number of azlactone moieties less at least one;
• wherein R.sup.3 is a bridging group capable of covalently connecting a plurality of azlactone moieties;
• and
• wherein B is a substrate having azlactone-reactive nucleophilic surfaces and A is a residue of a azlactone-reactive nucleophilic group on the surface on the substrate, the azlactone-functional nucleophilic group comprising O, S, or NR.sup.4, wherein R.sup.4 is hydrogen or an alkyl group containing from 1 to 4 carbon atoms, and wherein the substrate is selected from the group consisting of cellulose;
• modified cellulose derivatives;
• agarose;
• dextran;
• chitin;
• chitosan;
• polymers derived from hydroxyethyl methacrylate, hydroxypropyl acrylate, N-methylol acrylamide, allyl alcohol, allyl amine, or N-[3-(N'-isopropyl) aminopropyl] methacrylamide monomers;
• poly(vinyl alcohol) homopolymers;
• and poly(vinyl alcohol) copolymers.

A method of making an azlactone-functional hydrogel, comprising the steps of:

• (a) forming a hydrogel in a dehydrated state comprising a composition having azlactone-reactive nucleophilic surfaces;
• (b) reacting a multi-functional azlactone composition with the azlactone-reactive nucleophilic surfaces of the hydrogel in a dehydrated state in a manner that retains at least one azlactone moiety remaining available for further nucleophilic reaction;
• wherein the azlactone-functional hydrogel has the formula:
• ##STR8## wherein R.sup.1 and R.sup.2 independently can be an alkyl group having 1 to 14 carbon atoms, a cycloalkyl group having 3 to 14 carbon atoms, an aryl group having 5 to 12 ring atoms, an arenyl group having 6 to 26 carbon atoms and 0 to 3 S, N, and nonperoxidic O heteroatoms, or R.sup.1 and R.sup.2 taken together with the carbon to which they are joined can form a carbocyclic ring containing 4 to 12 ring atoms, and n is an integer 0 or 1;
• wherein y is at least one and is the number of azlactone moieties less at least one;
• wherein R.sup.3 is a bridging group capable of covalently connecting a plurality of azlactone moieties;
• and
• wherein B is the hydrogel having azlactone-reactive nucleophilic surfaces and A is a residue of a azlactone-reactive nucleophilic group on the surface on the hydrogel, the azlactone-reactive nucleophilic group comprising, O, S, or NR.sup.4, and wherein R.sup.4 is hydrogen or an alkyl group containing from 1 to 4 carbon atoms.