Composition in injectable aqueous solution form with specific pH value, useful to treat diabetes, comprises basal insulin with specific isoelectric point and polyamino acid bearing carboxylate charges and substituted with hydrophobic group

摘要

Composition in the form of an injectable aqueous solution having a pH of 6-8, comprises a basal insulin having an isoelectric point of 5.8-8.5, and a polyamino acid bearing carboxylate charges and substituted with hydrophobic groups. Composition in the form of an injectable aqueous solution having a pH of 6-8, comprises a basal insulin having an isoelectric point of 5.8-8.5, and a polyamino acid bearing carboxylate charges and substituted with hydrophobic groups of formula (R1-[NH-CH(A-C(=O)-R)-C(=O)] n-[NH-CH(A-C(=O)-R3)-C(=O)] m-R2) (I). A, B1 : -CH 2- (aspartic unit) or -CH 2-CH 2- group (glutamic unit); R1 : H, linear 2-10C-acyl, branched 3-10C-acyl, benzyl, terminal amino acid unit or pyroglutamate unit; R2 : -NHR4, or benzyl or linear or branched 2-30C-acyl (both optionally include heteroatoms consisting of N, O or S); R4 : H, 2-30C-alkyl or branched 3-10C-acyl; R3 : H or a cationic entity comprising metal cations; R : monovalent radical of formula (-NH-CH(B1-C(=O)-O-R11)-C(=O)-O-R11) or (-NH-CH(R5)-C(=O)-O-R11), or R11; R11 : linear or branched 8-30C-radical (optionally saturated and optionally contains heteroatoms) or a radical capable of forming carbonaceous rings, which are optionally saturated and/or aromatic and optionally contain hetero atoms, where the rings are optionally ortho-condensed or peri-condensed; R5 : H, 1-4C-alkyl or a benzyl group; and n/(n+m) : 1-50 mole%, where n/(n+m) represents molar degree of grafting with hydrophobic radical of the monomeric units, n+m represents the degree of polymerization of the polyamino acid, i.e. the average number of monomeric units per chain of polyamino acid, and the n+m is 5-1000. Independent claims are included for single-dose formulations at a pH of between 7 and 7.8, comprising the basal insulin and a prandial insulin, or the basal insulin and a gut hormone, or the basal insulin, the prandial insulin and the gut hormone. ACTIVITY : Antidiabetic. MECHANISM OF ACTION : None given.