Norepinephrine Compositions And Methods Therefor

What is this patent about?

’259 is related to the field of pharmaceutical formulations, specifically addressing the need for a stable, ready-to-inject norepinephrine composition. Norepinephrine is a crucial medication used in emergencies to treat hypotension and cardiac arrest. Existing formulations often require dilution before use, increasing the risk of contamination and dosage errors. Moreover, some formulations contain antioxidants like sodium metabisulfite, which can cause allergic reactions. Therefore, there is a need for a stable, pre-diluted, and antioxidant-free norepinephrine formulation.

The underlying idea behind ’259 is to create a ready-to-inject norepinephrine formulation that maintains its stability over an extended period without the need for antioxidants. This is achieved by carefully controlling the pH of the aqueous solution , incorporating a chelating agent to minimize degradation caused by metal ions, and including a pharmaceutically acceptable salt to adjust tonicity. The formulation is designed to minimize both degradation of the norepinephrine and its isomerization from the active R-isomer to the inactive S-isomer.

The claims of ’259 focus on a method of preparing and the resulting composition of a storage-stable, substantially antioxidant-free, ready-to-administer norepinephrine solution. The independent claims cover a formulation containing an R-isomer of norepinephrine bitartrate in an aqueous solution with a concentration of equal to or less than 100 μg/ml. This solution also includes a chelating agent (1-100 μg/ml) and a pharmaceutically acceptable salt (0.6-1.2 wt%), with the pH adjusted to between 3.7 and 5.0. The key feature is that the formulation exhibits less than 10% isomerization and less than 5% degradation after three months of storage.

In practice, the invention involves carefully mixing norepinephrine bitartrate with a solution containing a chelating agent (like EDTA) and a salt (like NaCl). The pH is then adjusted using an acid or base to fall within the specified range. The resulting solution can then be sterilized, such as by autoclaving, and packaged for immediate use. The use of deoxygenated water and oxygen scavengers in the packaging further enhances stability by minimizing oxidative degradation.

This approach differs from prior solutions by eliminating the need for antioxidants, which can cause adverse reactions. The specific combination of pH control, chelating agents, and tonicity adjustment provides a synergistic effect, resulting in a formulation that is both stable and safe for direct injection. The invention also addresses the problem of isomerization, which can reduce the efficacy of the drug over time. By minimizing both degradation and isomerization, the ’259 formulation offers a significant improvement over existing norepinephrine products.