Amphiphilic drug-oligomer conjugates with hydroyzable lipophile components and methods for making and using the same

US6309633A · kind A · utility

Assignee

• Nobex Corporation · US

Inventors

• Nnochiri Ekwuribe · Cary, US
• Muthukumar Ramaswamy · Cary, US
• Jayanthi Rajagopalan · Cary, US

Key dates

• Filing date: Jun 19, 1999
• Grant date: Oct 30, 2001
• Expiry date: Jun 19, 2019

Classification

• Technology area (CPC Y): Emerging Cross-Sectional Technologies
• CPC primary: Y02A50/30
• WIPO field: Pharmaceuticals
• WIPO sector: Chemistry

Abstract

The invention provides a drug-oligomer conjugate having the following general formula: ##STR1## wherein D is a therapeutic drug moiety; H and H' are each a hydrophilic moiety, independently selected from the group consisting of straight or branched PEG polymers having from 2 to 130 PEG subunits, and sugars; L is a lipophilic moiety selected from the group consisting of alkyl groups having 2-26 carbon atoms, cholesterol, adamantane and fatty acids; o is a number from 1 to the maximum number of covalent bonding sites on H; m+n+p together have a value of at least one and not exceeding the total number of covalent bonding sites on D for the --H', --L and --H--L substituents; the H--L bond(s) are hydrolyzable and the D--L' bond(s), when present, are hydrolyzable; the conjugate being further characterized by one of the following: (i) m is 0 and p is at least 1; (ii) n is 0 and p is at least 1; (iii) m and n are each 0 and p is at least 1; (iv) p is 0 and m and n are each at least 1. The therapeutic drug moiety is preferably a therapeutic protein or peptide, preferably insulin or a functional equivalent thereof.