| 主权项 |
1. A composition in the form of an injectable aqueous solution, the pH of which is between 6.0 and 8.0, comprising at least:
a) a basal insulin, the isoelectric point pI of which is between 5.8 and 8.5; b) a co-polyamino acid bearing carboxylate charges and substituted with hydrophobic groups, chosen from the co-polyamino acids of formula I: in which:
A independently represents either a —CH2— group (aspartic unit) or a —CH2—CH2— group (glutamic unit),R1 is a radical chosen from the group consisting of an H, a linear C2 to C10 acyl group, a branched C3 to C10 acyl group, a benzyl, a terminal “amino acid” unit and a pyroglutamate,R2 is an —NR′R″ radical, R′ and R″, which may be identical or different, being chosen from the group consisting of H, linear or branched or cyclic C2 to C30 alkyls and benzyl, and said R′ and R″ alkyls being alkyls which can together form one or more saturated, unsaturated and/or aromatic rings which are carbon-based and/or which can comprise heteroatoms, chosen from the group consisting of O, N and S,R′3 is a radical chosen from the group consisting of the radicals of formulae —OR3, II or II′: in which * indicates the site of attachment of the co-polyamino acid
R3 and R″3, which may be identical or different, represent an H or a cationic entity chosen from the group comprising metal cations,R is a radical chosen from the group consisting of a saturated or unsaturated, linear or branched C8 to C30 radical which can comprise heteroatoms or a C8 to C30 radical which can form rings which are carbon-based or which can comprise heteroatoms, which are saturated, unsaturated and/or aromatic, said rings possibly being ortho-condensed or peri-condensed, or a radical of formula III or III′ as defined below: in which * indicates the site of attachment to the co-polyamino acid, and
R4 and R′4, which may be identical or different, represent an H, a cationic entity chosen from the group comprising metal cations, an R″4 radical or an R′″4 radical, and at least one of R4 and R′4 is equal to R″4.
R″4 represents a saturated or unsaturated, linear or branched C8 to C30 radical which can comprise heteroatoms or a C8 to C30 radical which can form rings which are carbon-based or which can comprise heteroatoms, which are saturated, unsaturated and/or aromatic, said rings possibly being ortho-condensed or peri-condensed,R′″4 represents a saturated or unsaturated, linear or branched C1 to C7 radical which can comprise heteroatoms or a C1 to C7 radical which can form rings which are carbon-based or which can comprise heteroatoms, which are saturated, unsaturated and/or aromatic, said rings possibly being ortho-condensed or peri-condensed, andB independently represents either a —CH2— group (aspartic unit) or a —CH2—CH2— group (glutamic unit),R5 is a radical chosen from the group consisting of an H, a linear or branched C1 to C4 alkyl or a benzyl group,n/(n+m) is defined as the molar degree of grafting with hydrophobic radical of the monomeric units and is between 1 and 50 mol %,n+m represents the degree of polymerization of the co-polyamino acid, i.e. the average number of monomeric units per chain of co-polyamino acid, and 5≦n+m≦1000. |
