Stable formulation of modified GLP-1

Abstract

Pharmaceutical formulations of GLP-1 compounds and methods for preparation thereof.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS[0001]This application is a continuation of U.S. application Ser. No. 10 / 185,923 filed on Jun. 27, 2002 and claims priority under 35 U.S.C. 119 of Danish Application No. PA 2001 01010 filed Jun. 28, 2001; Danish Application No. PA 2001 01011 filed Jun. 28, 2001; Danish Application No. PA 2001 01052 filed Jul. 4, 2001; Danish Application No. PA 2001 01053 filed Jul. 4, 2001; and Danish Application No. PA 2002 00093 filed Jan. 18, 2002; and US Provisional Applications No. 60 / 308,325 filed Jul. 27, 2001 and 60 / 308,297 filed Jul. 27, 2001, the contents of which are fully incorporated herein by reference.FIELD OF THE INVENTION[0002]The present invention relates to pharmaceutical formulations comprising GLP-1 compounds, uses thereof and methods for preparing said formulations.BACKGROUND OF THE INVENTION[0003]Peptides are widely used in medical practice, and since they can be produced by recombinant DNA technology it can be expected that their importa...

AI Technical Summary

Benefits of technology

[0012]We have discovered that certain modified GLP-1 or analogues thereof when formulated in aqueous solution together with a buffer, are physically stable at high concentrations of the modified GLP-1 or analogues thereof, when kept in the pH range from about 7 to about 10. The present formulations are physically stable within a given shelf life period at the recommended storage temperature (typically 2-3 years at 2-8° C.). Furthermore, the present formulations are physically stable during in-use (typically 1 month at accelerated temperatures e.g. 25° C. or 37° C.). The formulations of the invention are also chemically stable thus rendering them shelf-stable and suitable for invasive (eg. injection, subcutaneous injection, intramuscular, intraveneous or infusion) as well as non-invasive (eg nasal or pulmonary, transdermal or transmucosal e.g. buccal) means of administration. When the inventive formulation comprising a GLP-1 compound was compared to the same formulation comprising GLP-1 (7-37) substituted for the GLP-1 compound, the physical stability was increased considerably, and typically the shelf-life was increased from a few seconds to several months in the tests used.

Problems solved by technology

Furthermore, as an insulinotropic hormone, GIP was found to be almost ineffective in NIDDM.

While much attention has been focused on the pharmacological properties of acylated GLP-1 compounds, hitherto little is known about their physico-chemical and solution structural properties.

It is an important technical challenge to ensure prolonged stability during storage (shelf life) of many protein based drug products due to the inherent lability of macromolecules.

GLP-1 is known to be prone to instability due to aggregation.

Both degradation pathways may ultimately lead to loss of biological activity of the protein drug.

However, solubility limitations and the low stability against the actions of endogenous diaminopeptidyl peptidase limits the usefulness of these compounds, and thus there still is a need for improvements in this field.