Injectable solution at pH 7 comprising at least one basal insulin the pI of which is from 5.8 to 8.5 and a co-polyamino acid bearing carboxylate charges and hydrophobic radicals
Inventors
GEISSLER, Alexandre • Laage, Ségolène • Charvet, Richard • Soula, Olivier
Assignees
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Publication Number
US-10383920-B2
Publication Date
2019-08-20
Expiration Date
Abstract
A physically stable compositions in the form of an injectable aqueous solution, the pH of which is from 6.0 to 8.0, including at least: a basal insulin of which the isoelectric point (pI) is from 5.8 to 8.5, and a co-polyamino acid bearing carboxylate charges and at least one hydrophobic radical.
Core Innovation
The invention relates to an injectable aqueous solution having a pH from 6.0 to 8.0, comprising at least one basal insulin having an isoelectric point from 5.8 to 8.5. The composition further comprises a co-polyamino acid consisting of glutamic or aspartic units bearing carboxylate charges and hydrophobic radicals Hy of formula I, with attachment of different groups bound by amide functions defined by parameters a, b, c, d, p and r.
Hy comprises more than 30 carbon atoms, and the ratio i between the number of hydrophobic radicals and the number of glutamic or aspartic units is between 0<i≤0.5. The co-polyamino acid degree of polymerization DP in glutamic or aspartic units is from 5 to 250, and the free acid functions are in the form of a salt of an alkaline cation selected from Na+ and K+.
The core structural definition includes GpR, GpA and GpC radicals and the conditional relationships between p, a and the type of GpA radical. The patent states that the defined hydrophobic radical Hy together with the glutamic/aspartic co-polyamino acid improves physical stability for the injectable aqueous insulin composition, increases insulin affinity at reduced excipient levels, and maintains precipitation propensity and compatibility with mixing with prandial insulin and/or GLP-1 receptor agonist co-therapy.
Claims Coverage
The provided material centers on one independent claim for an injectable aqueous solution combining basal insulin with a specifically structured co-polyamino acid. The inventive features are the pH-defined insulin composition and the detailed hydrophobic radical and co-polyamino acid structural constraints.
Injectable aqueous solution with pH-defined basal insulin system
An injectable aqueous solution with pH 6.0 to 8.0 comprising at least one basal insulin having an isoelectric point from 5.8 to 8.5, and a co-polyamino acid consisting of glutamic or aspartic units bearing carboxylate charges and hydrophobic radicals Hy.
Hydrophobic radicals defined by formula I with parameterized attachment and amide function
Hydrophobic radicals Hy are radicals of formula I, with GpR, GpA and GpC defined by formula II/II′, formula III/III′ and formula IV, respectively, and attachment parameters a, b, p, c, d and r specifying the formation of amide functions between the hydrophobic radical and the co-polyamino acid.
Hydrophobic radical size and grafting density constraints (i and DP) with alkaline salt form
Hy comprises more than 30 carbon atoms; the ratio i between the number of hydrophobic radicals and the number of glutamic or aspartic units is between 0<i≤0.5; the degree of polymerization DP in glutamic or aspartic units is from 5 to 250; and the free acid functions are in the form of a salt of an alkaline cation selected from Na+ and K+.
Across the provided material, the claim coverage is anchored by an injectable aqueous solution with a defined pH, basal insulin with a specified pI range, and a co-polyamino acid carrying carboxylate charges and hydrophobic radicals of formula I, further constrained by the statistical grafting ratio i, the degree of polymerization DP, and alkaline-cation salt forms.
Stated Advantages
Improves physical stability of neutral-pH insulin compositions.
Increases insulin affinity at reduced excipient levels.
Maintains precipitation propensity and compatibility with mixing with prandial insulin and/or GLP-1 receptor agonist co-therapy.
Documented Applications
Compatible with mixing with prandial insulin and/or GLP-1 receptor agonist co-therapy.
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