Cation complexes of insulin compound conjugates, formulations and uses thereof

摘要

An insulin compound coupled to a modifying moiety having a formula:
—X—R1—Y-PAG-Z—R2  (Formula VI)where,X, Y and Z are independently selected linking groups and each is optionally present, and X, when present, is coupled to the insulin compound by a covalent bond,either R1 or R2 is a lower alkyl, optionally including a carbonyl group, and when R1 is a lower alkyl, R2 is a capping group, andPAG is a linear or branched carbon chain incorporating one or more alkalene glycol moieties, and optionally incorporating one or more additional moieties selected from the group consisting of —S—, —O—, —N—, and —C(O)—.

主权项

1. A solid complex comprising:
an insulin compound conjugate comprising an insulin compound conjugated to at least one modifying moiety, wherein the insulin compound is human insulin or an analog thereof, wherein said analog is a peptide that comprises an A chain and a B chain and wherein the B chain contains at least 29 amino acid residues, wherein the modifying moiety comprises from 2 to 10 PEG subunits (OCH2—CH2) forming a PEG component coupled to a lipophilic component, where the lipophilic component is an alkyl group, and either the PEG component or the lipophilic component is coupled to the insulin compound on at least the B29 amino acid residue; and a cation, wherein the cation is a divalent cation selected from the group consisting of Zn++, Mn++, Ca++, Fe++, Ni++, Cu++, Co++ and Mg++; where the insulin compound conjugate is complexed with the cation, and wherein the solid complex is a crystalline solid or a rod shaped crystal.