Rapid-acting insulin formulation comprising a substituted anionic compound
Inventors
Soula, Gérard • Alluis, Bertrand
Assignees
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-10881716-B2
Publication Date
2021-01-05
Expiration Date
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 relates to a rapid acting insulin lispro pharmaceutical composition suitable for injection. The composition includes insulin lispro in hexameric form, has a pH of 7.4±0.4, and an insulin concentration between 100 to 200 IU/mL.
The formulation further includes a polyanionic compound, a preservative, and a tonicity agent. The polyanionic compound is citric acid or a salt of citric acid, including Na+, K+, Ca2+ or Mg2+, and is present in a concentration between 10 and 30 mM.
The composition has a circular dichroism signal at 251 nm at or below −300 deg cm2/dmol. The document states that citrate and compounds 1–11 do not appreciably affect the R6 hexamer signal, while EDTA and EDTA/citrate disrupt insulin hexamer stability.
Claims Coverage
One independent claim is identified, covering a rapid acting insulin lispro injectable formulation with three core inventive features: defined hexameric insulin lispro and pH/insulin concentration parameters, a citric-acid-based polyanionic compound within a specified concentration range, and formulation characterization by a circular dichroism signal at 251 nm, together with a preservative and a tonicity agent.
Hexameric insulin lispro composition with defined pH and insulin concentration
A rapid acting insulin lispro pharmaceutical composition suitable for injection having a pH of 7.4±0.4, comprising insulin lispro in hexameric form with an insulin concentration between 100 to 200 IU/mL.
Citric-acid-based polyanionic compound
The composition further comprises a polyanionic compound in a concentration between 10 and 30 mM, wherein the polyanionic compound is citric acid or the Na+, K+, Ca2+ or Mg2+ salt thereof.
Preservative, tonicity agent, and circular dichroism signal constraint
The composition includes a preservative and a tonicity agent, and the insulin pharmaceutical composition has a circular dichroism signal at 251 nm at or below −300 deg cm2/dmol.
Exclusion of EDTA
The composition is defined as excluding EDTA.
Selected tonicity agent options
The tonicity agent is selected from glycerol, sodium chloride, mannitol, or glycine.
m-cresol preservative
The preservative is m-cresol.
Zinc salts inclusion
The composition further comprises zinc salts.
Overall, the claim coverage centers on a rapid acting insulin lispro injectable formulation with hexameric insulin, defined pH and insulin concentration, a citric-acid-based polyanionic component, and a circular dichroism signal constraint at 251 nm, with dependent refinements excluding EDTA and specifying preservative and tonicity agent selections and possible inclusion of zinc salts.
Stated Advantages
Faster pharmacodynamics in pig studies, indicated by lower glucose Tmin versus commercial controls.
Faster pharmacokinetics in pig studies, indicated by lower insulin Tmax versus commercial controls.
Accelerates blood entry and glycemia reduction compared with reference formulations lacking the substituted anionic compound/NPP.
Preservation of the hexameric state indicated by circular dichroism results showing citrate and compounds 1–11 do not appreciably affect the R6 hexamer signal.
Preserves hexamer stability, supported by circular dichroism references.
Documented Applications
Rapid acting insulin lispro pharmaceutical compositions suitable for injection.
Pig pharmacology studies of lispro or human insulin formulations using the described polyanionic/citrate-containing compositions.
Interested in licensing this patent?