insulin composition, method for treating diabetes mellitus in a human patient or mammal, insulin analogue and use thereof

摘要

An insulin composition comprises an insulin analog and a polymer mixture. the insulin analogue contains b4 and a10 cysteine substitutions (to form b4-a10 cystine) and one or more additional substitutions selected from the group consisting of: a 5 to 11 amino acid connecting domain between insulin a and b domains ; a beta unbranched amino acid substitution at position a8; a beta unbranched acidic or polar side chain at the a14 position; a halogen modification of pheb24 in the ortho position; and replacing lysine at position b29 with glu, ala, val, ile, leu, amino propionic acid, amino butyric acid or norleucine. The insulin analog is compatible with a manufacturing process that includes one or more steps within the temperature range of 90 to 120 ° C. the encapsulated insulin analog may optionally contain free peg or be pegylated. The insulin analog-encapsulated polymer mixture may be shaped as a microneedle patch for topical administration or as micropellets for subcutaneous injection.