Polymer-modified peptide drugs having enhanced biological and pharmacological activities
First Claim
1. A method for enhancing biological or pharmacological activity of a biologically active peptide comprising preparing an aqueous solution of a liquid polymer-modified version of said peptide by covalently binding said peptide to a biocompatible prepolymer under aqueous conditions, wherein said prepolymer is a triol or higher polyol made up of at least 75% oxyethylene monomers, said polyol having a molecular weight of about 7,000 to about 30,000, said polyol having essentially all of the hydroxyl groups capped with aliphatic or cycloaliphatic polyisocyanates, wherein said covalent bond is between an isocyanate group of said prepolymer and an amino, sulfhydryl, carboxyl or hydroxyl group of said peptide, wherein the amount of chain extended insoluble material is reduced.
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Abstract
Biocompatible polymers derived from isocyanate-capped high molecular weight triols and higher polyols are covalently linked to drugs. These polymer-modified drugs have one or more of the following advantages over the unmodified drug: reduction of immunogenicity of the drug, increased circulating half-life of the drug due to longer residence time in circulation, ability to administer multiple drugs together, and enhanced potency of the drug.
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Citations
28 Claims
- 1. A method for enhancing biological or pharmacological activity of a biologically active peptide comprising preparing an aqueous solution of a liquid polymer-modified version of said peptide by covalently binding said peptide to a biocompatible prepolymer under aqueous conditions, wherein said prepolymer is a triol or higher polyol made up of at least 75% oxyethylene monomers, said polyol having a molecular weight of about 7,000 to about 30,000, said polyol having essentially all of the hydroxyl groups capped with aliphatic or cycloaliphatic polyisocyanates, wherein said covalent bond is between an isocyanate group of said prepolymer and an amino, sulfhydryl, carboxyl or hydroxyl group of said peptide, wherein the amount of chain extended insoluble material is reduced.
- 7. An improved method of producing a biological or pharmacological response in a human being or animal by administration of a biologically active peptide, the improvement comprising administering an aqueous solution of a liquid polymer-modified version of said peptide prepared by covalently binding said peptide to a biocompatible prepolymer under aqueous conditions, wherein said prepolymer is a triol or higher polyol made up of at least 75% oxyethylene monomers, said polyol having a molecular weight of about 7,000 to about 30,000, said polyol having essentially all of the hydroxyl groups capped with aliphatic or cycloaliphatic polyisocyanates, wherein said covalent bond is between an isocyanate group of said prepolymer and an amino, sulfhydryl, carboxyl or hydroxyl group of said peptide, wherein the amount of chain extended insoluble material is reduced.
- 19. A method of treating a disease state or condition comprising administration of an aqueous solution of a pharmaceutically active amount of a liquid polymer-modified biologically active peptide, wherein said polymer-modified peptide is prepared by covalently binding said peptide to a biocompatible prepolymer under aqueous conditions, wherein said prepolymer is a triol or higher polyol made up of at least 75% oxyethylene monomers, said polyol having a molecular weight of about 7,000 to about 30,000, said polyol having essentially all of the hydroxyl groups capped with aliphatic or cycloaliphatic polyisocyanates, wherein said covalent bond is between an isocyanate group of said prepolymer and an amino, sulfhydryl, carboxyl or hydroxyl group of said peptide, wherein the amount of chain extended insoluble material is reduced.
Specification