Pharmaceutical preparations comprising acid-stabilised insulin

A pharmaceutical preparation comprising

• Acid-stabilised insulin
• Zinc ions
• A zinc-binding ligand of Formula (i):
• CGr-Lnk-Frg1-Frg2-X Formula (I)
• wherein,
• CGr is a chemical group which reversibly binds to a HiSBIO Zn2+ site of an insulin hexamer;
• Lnk is a linker selected from
• a valence bond
• a chemical group GB of the formula —B1—B2—C(O)—, —B1—B2—SO2—, —B1—B2—CH2—, or —B1B2-NH—;
• wherein B1 is a valence bond, —O—, —S—, or —NR6B—,
• B2 is a valence bond, C1-C18-alkylene, C2-C18-alkenylene, C2-C18-alkynylene, arylene, heteroarylene, -C1-C18-alkyl-aryl-, —C2-C18-alkenyl-aryl-, —C2-C18-alkynyl-aryl-, —C(═O)—C1-C18-alkyl-C(═O)—, —C(═O)-C1-C18-alkenyl-C(═O)—, —C(═O)-C1-C18-alkyl-O-C1-C18-alkyl-C(═O)—, —C(═O)-C1-C18-alkyl-S-C1-C18-alkyl-C(═O)—, —C(═O)-C1-C18-alkyl-NR6-C1-C18-alkyl-C(═O)—, —C(═O)-aryl-C(═O)—, —C(═O)-heteroaryl-C(═O)—;
• wherein the alkylene, alkenylene, and alkynylene moieties are optionally substituted by —CN, —CF3, —OCF3, —OR6B, or NR6BR7B and the arylene and heteroarylene moieties are optionally substituted by halogen, —C(O)OR6B, —C(O)H, OCOR6B, —SO2, —CN, —CF3, —OCF3, —NO2, —OR6B, —NR6BR7B, C1-C18-alkyl, or C1-C18-alkanoyl;
• R6B and R7B are independently H, C1-C4-alkyl;
• Frg1 is a fragment consisting of 0 to 5 neutral α- or β-amino acids
• Frg2 is a fragment comprising 1 to 20 positively charged groups independently selected from amino or guanidino groups;
• and
• X is —OH, —NH2 or a diamino group,
• or a salt thereof with a pharmaceutically acceptable acid or base, or any optical isomer or mixture of optical isomers, racemic mixture, or any tautomeric forms: