Stabilization of epinephrine formulations

Abstract

The disclosure herein relates to the innovative epinephrine formulations in aqueous solution of medicinal products that enhance the physicochemical stabilities of epinephrine and extend the product shelf life. In some instances, the formulations comprise epinephrine or a salt thereof, a complexing agent, and a “non-sulfite” antioxidant. The epinephrine formulations substantially demonstrated the superior physicochemical stabilities to conventional sulfite formulation of commercial medications currently available. In some instances, sulfite-free formulations further provide further benefit (e.g., safety benefits) to sulfite-sensitive patients. The compositions, methods for preparing the formulations, and methods of using the same (e.g., in the treatment of anaphylaxis) are also provided.

Description

CROSS-REFERENCE[0001]This application claims the benefit of U.S. Provisional Application Nos. 62 / 351,462 filed on 17 Jun. 2016, and 62 / 476,852 filed on 26 Mar. 2017, both entitled “Stabilization of Epinephrine Formulations,” and each of which are incorporated herein by reference in their entireties.FIELD OF THE INVENTION[0002]The invention generally relates to epinephrine formulations, particularly the physicochemical stability enhancement of epinephrine formulations (e.g., injection formulations (1:1000) in aqueous solution, such as for anaphylaxis treatment of anaphylactic shock).BACKGROUND OF THE INVENTION[0003]Epinephrine, more commonly known as adrenaline, is a hormone secreted by the medulla of the adrenal glands. Strong emotions such as fear or anger cause epinephrine to be released into the bloodstream, which causes an increase in heart rate, muscle strength, blood pressure, and sugar metabolism. This reaction, known as the “Flight or Fight Response”, prepares the body for s...

AI Technical Summary

Benefits of technology

The patent text describes a new formulation of epinephrine that has good stability and minimal degradation. The formulation uses a combination of antioxidants, complexing agents, and pH buffering agents to protect the epinephrine from degradation. The formulation also includes a chelating agent to prevent the formation of degradation products. The formulation has been found to have good potency retention, visual characteristics, and low formation of degradation products even at rigorous storage conditions. The formulation can be used for injection and has been found to have a shelf life of at least two years. Overall, the new formulation provides a more stable and effective form of epinephrine for use in various medical applications.

Problems solved by technology

Anaphylaxis is a sudden, severe, systemic allergic reaction that can be fatal, in many cases, if left untreated.

Contact with anaphylaxis-inducing agents, and the severity of the resulting anaphylactic reaction, can be extremely unpredictable.

The modification or degradation of the catechol amines is undesirable for a number of reasons.

Modification of the catechol amine results in loss of titer of the active ingredient, formation of compounds which may have undesirable physiological effects, and the appearance of a dark color, which makes the solution offensive and unmarketable.

The safety and / or toxicity of ESA in commercial epinephrine products for anaphylactic treatment are still not well understood.

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