Rapid-acting insulin formulation comprising a substituted anionic compound

Inventors

Soula, Gérard • Alluis, Bertrand

Assignees

Adocia SAS

Abstract

A composition in aqueous solution includes insulin and at least one substituted anionic compound chosen from substituted anionic compounds consisting of a backbone formed from a discrete number u of between 1 and 8 (1≤u≤8) of identical or different saccharide units, linked via identical or different glycoside bonds, the saccharide units being chosen from the group consisting of hexoses, in cyclic form or in open reduced form, said compound comprising partially substituted carboxyl functional groups, the unsubstituted carboxyl functional groups being salifiable. A pharmaceutical formulation including the composition is also set forth.

Core Innovation

The invention provides a rapid-acting insulin formulation that includes insulin in hexameric form together with a non-polymeric polyanionic compound. The non-polymeric polyanionic compound is described as citric acid or citrate salts, tartaric acid or tartrate salts, triphosphates or triphosphoric acid salts, and defined saccharide-based carboxylated oligomers, and the insulin may be insulin lispro, insulin aspart, or insulin glulisine.

The invention also provides an insulin lispro pharmaceutical composition having a pH of 7.4±0.4 and an insulin concentration between 100 to 200 IU/mL, in which the insulin is in hexameric form in the presence of zinc. The composition includes a polyanionic compound in a concentration between 9.3 mM and 30 mM, wherein the polyanionic compound is citric acid or the Na+, K+, Ca2+ or Mg2+ salt thereof, and a tonicity agent, and is characterized by a circular dichroism signal at 251 nm at or below −300 deg cm2/dmol.

The disclosure positions the formulation as using substituted anionic compounds and non-polymeric polyanionic compounds to accelerate insulin dissociation and action while maintaining hexamer stability. The rationale is contrasted against EDTA/citric systems, and circular dichroism signals and in vivo glucose and insulin kinetics are referenced in support of hexamer stability and rapid action behavior.

Claims Coverage

The consolidated claim coverage identifies three independent claims centered on injectable rapid acting insulin lispro formulations and a treatment method. The inventive features concentrate on hexameric lispro with zinc, a specified pH and insulin concentration, a citric-acid polyanionic component concentration range, inclusion of a tonicity agent, and a bounded circular dichroism signal at 251 nm (≤ −300 deg·cm2·dmol−1).

Across the independent claims, the coverage centers on injectable rapid acting insulin lispro formulations where lispro is maintained in hexameric form in the presence of zinc, under a specified pH (7.4±0.4), specified insulin concentration (100–200 IU/mL), and a citric-acid polyanionic compound (9.3–30 mM or 10–30 mM) with a tonicity agent, while requiring a circular dichroism signal at 251 nm at or below −300 deg·cm2·dmol−1.

Stated Advantages

Documented Applications

No documented applications found