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US 12,708,659 B2Granted
Polyphenolic insulin
AssigneeKimball Westward LLC
InventorRobert R. Reddy
Life of this patent
Estimating the term…
Abstract
Insulin complexes are stabilized using a ligand that increases binding interactions between the insulin monomers, and particularly between the B-chains of two adjacent insulin monomers. Particularly preferred ligands are polyphenols, and insulin complexes are typically in the R-state and may therefore also include metal cations and a small phenolic compound in a binding site that is distinct from the polyphenol binding site.
Claims20
A pharmaceutical composition, comprising:
- an insulin complex comprising a plurality of insulin monomers, each insulin monomer comprising an A-chain and a B-chain coupled together via disulfide bonds;
- a polyphenol non-covalently bound to an apical area of an interface formed by respective B-chains of a first and a second insulin monomer in the complex;
- and
- wherein at least part of the apical area is solvent exposed.
1 more element
A method of producing a pharmaceutical composition comprising insulin, comprising:
- providing an insulin complex comprising a plurality of insulin monomers, each insulin monomer comprising an A-chain and a B-chain coupled together via disulfide bonds;
- combining the insulin complex with a polyphenol to produce a stabilized insulin complex, wherein the polyphenol in the stabilized insulin complex is non-covalently bound to an apical area of an interface formed by respective B-chains of a first and a second insulin monomer in the insulin complex;
- and
- wherein at least part of the apical area is solvent exposed.
1 more element
A method of increasing storage stability of an insulin complex, comprising:
- providing an insulin complex comprising a plurality of insulin monomers, each insulin monomer comprising an A-chain and a B-chain coupled together via disulfide bonds;
- combining the insulin complex with a polyphenol to produce a stabilized insulin complex, wherein the polyphenol in the stabilized insulin complex is non-covalently bound to an apical area of an interface formed by respective B-chains of a first and a second insulin monomer in the insulin complex, and wherein the stabilized insulin complex has a storage stability that is greater than that of the insulin complex without the polyphenol;
- and
- wherein at least part of the apical area is solvent exposed.
1 more element
Dependencies are inferred from the claim text.