Compositions in the form of an injectable aqueous solution comprising amylin, an amylin receptor agonist or an amylin analog, and a co-polyamino acid

A Hydrophobic radical Hy having the following formula I:

• in which
• GpR is a radical of formula II or II′:
• GpA is a radical of formula III or III′:
• GpC is a radical of formula IV:
• the * indicate the sites of attachment of the different groups;
• a is a whole number equal to 0 or to 1;
• b is a whole number equal to 0 or to 1;
• p is a whole number equal to 1 or 2 and
• if p is equal to 1 then a is equal to 0 or to 1 and GpA is a radical of formula III′, and
• if p is equal to 2 then a is equal to 1, and GpA is a radical of formula III;
• c is a whole number equal to 0 or to 1, and if c is equal to 0 then d is equal to 1 or to 2;
• d is a whole number equal to 0, to 1 or to 2;
• r is a whole number equal to 0 or to 1, and
• if r is equal to 0 then the hydrophobic radical of formula I is attached to the co-polyamino acid via a covalent bond between a carbonyl of the hydrophobic radical and a nitrogen atom in N-terminal position of the co-polyamino acid, thus forming an amide function originating from the reaction of an amine function in N-terminal position of the precursor of the co-polyamino acid and an acid function borne by the precursor of the hydrophobic radical, and
• if r is equal to 1 then the hydrophobic radical of formula I is attached to the co-polyamino acid:
• via a covalent bond between a nitrogen atom of the hydrophobic radial and a carbonyl of the copolyamino acid, thus forming an amide function originating from the reaction of an amine function of the precursor of the hydrophobic radical and an acid function borne by the precursor of the co-polyamino acid, or
• via a covalent bond between a carbonyl of the hydrophobic radical and a nitrogen atom in N-terminal position of the co-polyamino acid, thus forming an amide function originating from the reaction of an acid function of the precursor of the hydrophobic radical and an amine function in N-terminal position borne by the precursor of the co-polyamino acid;
• R is a radical selected from the group consisting of:
• a linear or branched divalent alkyl radical comprising 2 to 12 carbon atoms if GpR is a radical of formula II or 1 to 11 carbon atoms if GpR is a radical of formula II′ or II″;
• a linear or branched divalent alkyl radical comprising 2 to 11 carbon atoms if GpR is a radical of formula II or 1 to 11 carbon atoms if GpR is a radical of formula II′ or II″, 1 to 11 carbon atoms, said alkyl radical bearing one or more —CONH2 functions, and
• an unsubstituted ether or polyether radical comprising 4 to 14 carbon atoms and 1 to 5 oxygen atoms;
• A is a linear or branched alkyl radical comprising 1 to 6 carbon atoms;
• B is a linear or branched alkyl radical, optionally comprising an aromatic ring, comprising 1 to 9 carbon atoms;
• Cx is a linear or branched monovalent alkyl radical, in which x indicates the number of carbon atoms and:
• if p is equal to 1, x is from 11 to 25 (11≤x≤25):
• if p is equal to 2, x is from 9 to 15(9≤x≤15),
• the ratio i between the number of hydrophobic radicals and the number of glutamic or aspartic units being from 0 to 0.5 (0<i≤0.5);
• when several hydrophobic radicals are borne by a co-polyamino acid, then they are identical or different,
• the degree of polymerization DP of glutamic or aspartic units is from 5 to 250;
• the free acid functions being in the form of a salt of an alkali cation selected from the group consisting of Na+ and K+.

A hydrophobic radical precursor Hy′ of the hydrophobic radical -Hy according to formula I′ as defined below:

• in which
• GpR is a radical of formula II or II′:
• GpA is a radical of formula III or III′:
• GpC is a radical of formula IV:
• the * indicate the sites of attachment of the different groups;
• a is a whole number equal to 0 or to 1;
• b is a whole number equal to 0 or to 1;
• p is a whole number equal to 1 or 2 and
• if p is equal to 1 then a is equal to 0 or to 1 and GpA is a radical of formula III′, and
• if p is equal to 2 then a is equal to 1, and GpA is a radical of formula III;
• c is a whole number equal to 0 or to 1, and if c is equal to 0 then d is equal to 1 or to 2;
• d is a whole number equal to 0, to 1 or to 2;
• r is a whole number equal to 0 or to 1, and
• if r is equal to 0 then the hydrophobic radical of formula I′ is attached to the co-polyamino acid via a covalent bond between a carbonyl of the hydrophobic radical and a nitrogen atom in N-terminal position of the co-polyamino acid, thus forming an amide function originating from the reaction of an amine function in N-terminal position of the precursor of the co-polyamino acid and an acid function borne by the precursor of the hydrophobic radical, and
• if r is equal to 1 then the hydrophobic radical of formula I′ is attached to the co-polyamino acid:
• via a covalent bond between a nitrogen atom of the hydrophobic radial and a carbonyl of the copolyamino acid, thus forming an amide function originating from the reaction of an amine function of the precursor of the hydrophobic radical and an acid function borne by the precursor of the co-polyamino acid, or
• via a covalent bond between a carbonyl of the hydrophobic radical and a nitrogen atom in N-terminal position of the co-polyamino acid, thus forming an amide function originating from the reaction of an acid function of the precursor of the hydrophobic radical and an amine function in N-terminal position borne by the precursor of the co-polyamino acid;
• R is a radical selected from the group consisting of:
• a linear or branched divalent alkyl radical comprising 2 to 12 carbon atoms if GpR is a radical of formula II or 1 to 11 carbon atoms if GpR is a radical of formula II′ or II″;
• a linear or branched divalent alkyl radical comprising 2 to 11 carbon atoms if GpR is a radical of formula II or 1 to 11 carbon atoms if GpR is a radical of formula II′ or II″, 1 to 11 carbon atoms, said alkyl radical bearing one or more —CONH2 functions, and
• an unsubstituted ether or polyether radical comprising 4 to 14 carbon atoms and 1 to 5 oxygen atoms;
• A is a linear or branched alkyl radical comprising 1 to 6 carbon atoms;
• B is a linear or branched alkyl radical, optionally comprising an aromatic ring, comprising 1 to 9 carbon atoms;
• Cx is a linear or branched monovalent alkyl radical, in which x indicates the number of carbon atoms and:
• if p is equal to 1, x is from 11 to 25 (11≤x≤25):
• if p is equal to 2, x is from 9 to 15 (9≤x≤15),
• the ratio i between the number of hydrophobic radicals and the number of glutamic or aspartic units being from 0 to 0.5 (0<i≤0.5);
• when several hydrophobic radicals are borne by a co-polyamino acid, then they are identical or different,
• the degree of polymerization DP of glutamic or aspartic units is from 5 to 250;
• the free acid functions being in the form of a salt of an alkali cation selected from the group consisting of Na+ and K+.