Process for producing antithrombogenic vinyl acetate polymer or hydrolyzate thereof

A process for producing an antithrombogenic hydrolyzed ethylene-vinyl acetate copolymer containing about 3 to 45 weight % vinyl acetate and about 97 to 55 weight % ethylene which comprises treating a water-insoluble hydrolyzed ethylene-vinyl acetate copolymer containing about 3 to 45 weight % vinyl acetate and about 97 to 55 weight % ethylene in the form of a shaped article with a solution of a fibrinolytic enzyme so as to fix the enzyme to the copolymer wherein the hydrolyzed ethylene-vinyl acetate copolymer contains a reactive functional group capable of forming a covalent bond with the fibronolytic enzyme and the enzyme is fixed to the polymer through covalent bonding,

• said reactive functional group being selected from the group consisting of an isocyanate group, an epoxy group, a formyl group, an acid chloride group, a carboxylic acid anhydride group and the reactive functional group having been introduced thereinto by treating the hydrolyzed ethylene-vinyl acetate copolymer having an amino group with a polyfunctional reagent, selected from the group consisting of a polyisocyanate, a polyepoxide, a polyaldehyde, a polyacid chloride and a polycarboxylic acid anhydride, having at least two of the reactive functional groups capable of reacting with an amino group, and
• the fibrinolytic enzyme is fixed to the polymer through covalent bonding, wherein said amino group has been introduced:
• (A) by treating the hydrolyzed ethylene-vinyl acetate copolymer with an amino acetal;
• or
• (B) by first treating the hydrolyzed ethylenevinyl acetate copolymer with a polyfunctional reagent having at least two functional groups capable of reacting with a hydroxy group and amino group and then treating the copolymer with a polyamine, said polyfunctional reagent being selected from the group consisting of a polyisocyanate, a polyepoxide, a polycarboxylic acid anhydride, a polyaldehyde and a polyacid chloride.

An antithrombogenic hydrolyzed ethylenevinyl acetate copolymer article, comprising:

• a shaped article of a water-insoluble hydrolyzed ethylene-vinyl acetate copolymer containing about 3 to 45 weight % vinyl acetate and about 97 to 55 weight % ethylene, to the surface of which is fixed a fibrinolytic enzyme, wherein the hydrolyzed ethylene-vinyl acetate copolymer contains a reactive functional group capable of forming a covalent bond with said fibrinolytic enzyme and said enzyme is fixed to the polymer through covalent bonding, said reactive functional group being selected from the group consisting of:
• (A) an isocyanate group which has been introduced thereinto by treating the hydrolyzed ethylene-vinyl acetate copolymer with a polyisocyanate,
• (B) an epoxy group which has been introduced thereinto by treating the hydrolyzed ethylene-vinyl acetate copolymer with a polyepoxide,
• (C) a formyl group which has been introduced thereinto by treating the hydrolyzed ethylene-vinyl acetate copolymer with a polyaldehyde,
• (D) an acid chloride group which has been introduced thereinto by treating the hydrolyzed ethylene-vinyl acetate copolymer with an acid chloride,
• (E) a carboxylic acid anhydride group which has been introduced thereinto by treating the hydrolyzed ethylene-vinyl acetate copolymer with a polycarboxylic acid anhydride,
• (F) an amino group which has been introduced thereinto by treating the hydrolyzed ethylene-vinyl acetate copolymer with an amino acetal, and
• (G) an amino group which has been introduced thereinto by first treating the hydrolyzed ethylene-vinyl acetate copolymer with a polyfunctional reagent having at least two functional groups capable of reacting with both a hydroxy group and amino group and then treating the copolymer with a polyamine, said polyfunctional reagent being selected from the group consisting of a polyisocyanate, a polyepoxide, a polycarboxylic acid anhydride, a polyaldehyde and a polyacid chloride.

A water-insoluble hydrolyzed ethylene-vinyl acetate copolymer containing about 3 to 45 weight % vinyl acetate and about 97 to 55 weight % ethylene having an antithrombogenic property, comprising:

• a water-insoluble hydrolyzed ethylene-vinyl acetate copolymer containing about 3 to 45 weight % vinyl acetate and about 97 to 55 weight % ethylene having fixed thereto a fibrinolytic enzyme, wherein the water-insoluble hydrolyzed ethylene-vinyl acetate copolymer contains a reactive functional group capable of forming a covalent bond with said fibrinolytic enzyme and said enzyme is fixed to said copolymer through covalent bonding, and
• said reactive functional group being selected from the group consisting of an isocyanate group, an epoxy group, a formyl group, an acid chloride group, a carboxylic acid anhydride group and the reactive functional group having been introduced thereinto by treating the hydrolyzed ethylene-vinyl acetate copolymer having an amino group with a polyfunctional reagent selected from the group consisting of a polyisocyanate, a polyepoxide, a polyaldehyde, a polyacid chloride and a polycarboxylic acid anhydride, having at least two of the reactive functional groups capable of reacting with an amino group, and
• the fibrinolytic enzyme is fixed to the polymer through covalent bonding, wherein said amino group has been introduced:
• (A) by treating the hydrolyzed ethylene-vinyl acetate copolymer with an amino acetal;
• or
• (B) by first treating the hydrolyzed ethylene-vinyl acetate copolymer with a polyfunctional reagent having at least two functional groups capable of reacting with a hydroxy group and amino group and then treating the copolymer with a polyamine, said polyfunctional reagent being selected from the group consisting of a polyisocyanate, a polyepoxide, a polycarboxylic acid anhydride, a polyaldehyde and a polyacid chloride.