The present invention provides a monomeric insulin analog formulation stabilized against aggregation in which the buffering agent is either TRIS or arginine. The stable formulations of the present invention are useful for treating diabetes, and are particularly advantageous in treatment regimes requiring lengthy chemical and physical stability, such as, in continuous infusion systems.

Stable insulin formulations

A mixture of conjugates in which each conjugate in the mixture comprises an insulin drug coupled to an oligomer that includes a polyalkylene glycol moiety is disclosed. The mixture may exhibit higher in vivo activity than a polydispersed mixture of similar conjugates. The mixture may also be more effective at surviving an in vitro model of intestinal digestion than polydispersed mixtures of similar conjugates. The mixture may also result in less inter-subject variability than polydispersed mixtures of similar conjugates.

Mixtures of insulin drug-oligomer conjugates comprising polyalkylene glycol, uses thereof, and methods of making same

Pharmaceutical compositions that include an insulin drug-oligomer conjugate, a fatty acid component, and a bile salt component are described. The insulin drug is covalently coupled to an oligomeric moiety. The fatty acid component and the bile salt component are present in a weight-to-weight ratio of between 1:5 and 5:1. Methods of treating an insulin deficiency in a subject in need of such treatment using such pharmaceutical compositions are also provided, as are methods of providing such pharmaceutical compositions.

Pharmaceutical compositions of insulin drug-oligomer conjugates and methods of treating diseases therewith

The present invention provides means to improve the chemical stability of aqueous, parenteral pharmaceutical compositions comprising a polypeptide and glycerin. Reactive aldehydes are identified in commercial glycerins, and means for reducing such are provided. Convenient means are provided to assay for reactive aldehydes in glycerin, and a strong linear correlation between the level of reactive aldehydes in glycerin and chemical stability of compositions comprising a polypeptide and glycerin is demonstrated. The invention includes aqueous compositions comprising a polypeptide and glycerin having improved chemical stability compared to compositions previously known.

Polypeptide compositions with improved stability

The present invention relates to the field of diabetes. More particularly, the invention relates to PEGylated insulin lispro compounds that are PEGylated with high molecular weight poly(ethylene glycol), are highly soluble at physiological pH, have an extended duration of action, and characterized by pharmacokinetic, pharmacodynamic, and/or activity peak-trough ratios of less than 2. The invention also relates to methods of providing such molecules, to pharmaceutical compositions containing them, and to their therapeutic uses.

Pegylated insulin lispro compounds

Insulin preparations of superior chemical stability, comprising human insulin or an analogue or derivative thereof, glycerol and/or mannitol, and 5 to 100 mM of the halogenide are disclosed.

INSULIN PREPARATIONS CONTAINING NaCl

An aqueous insulin composition with improved chemical and physical stability comprising human insulin or an analogue or derivative thereof, a buffer selected from glycylglycine, citrate or TRIS, in particular glycylglycine, and metal ions, in particular calcium or magnesium ions

Stabilised insulin compositions

In the present invention, there are disclosed aqueous insulin preparations of superior chemical stability, comprising human insulin or an analogue or derivative thereof, glycerol and/or mannitol, and 5 to 100 mM of halide, a mixture of 0.5 to 4.0 mg/ml of m-cresol and 0.5 to 4.0 mg/ml of phenol, wherein the halide is selected from the group consisting of alkali element or alkaline earth element halide.

Aqueous insulin preparation containing sodium chloride, method and use thereof

PROBLEM TO BE SOLVED: To provide an insulin preparation having superior chemical stability SOLUTION: The insulin preparation comprises human insulin, an analog or derivative thereof, glycerol and/or mannitol, and 5-100 mM of a halide Wherein, the halide is an alkali or alkaline earth halide, preferably chloride, more preferably sodium chloride, and it comprises 100-250 mM of, more preferably 140-250 mM of, and most preferably 160-200 mM of glycerol and/or mannitol COPYRIGHT: (C)2010,JPO&INPIT

Elsebeth Norup

Papers

INSULIN PREPARATIONS CONTAINING NaCl

Stabilised insulin compositions

Aqueous insulin preparation containing sodium chloride, method and use thereof

INSULIN PREPARATION CONTAINING NaCl

Insulin preparations containing a halogenide