Composition and method for treating metabolic disorders

Inventors

Cincotta, Anthony H.

Assignees

Veroscience LLC

Abstract

Bromocriptine citrate administered to a vertebrate, animal or human, can be used for any purpose including, e.g., the long-term modification and regulation of metabolic disorders, including prediabetes, obesity, insulin resistance, hyperinsulinemia, hyperglycemia and type 2 diabetes mellitus (T2DM) and/or, e.g., the treatment of other medical disorder(s) including immune or endocrine disorders or diseases. Bromocriptine citrate is administered over a limited or extended period at a time of day dependent on re-establishing the normal circadian rhythm of central dopaminergic activity of healthy members of a similar species and sex. Insulin resistance, hyperinsulinemia and hyperglycemia, T2DM, prediabetes, MS or all, can be controlled in humans on a long term basis by such treatment inasmuch as the daily administration of bromocriptine citrate resets neuronal activity timing in the neural centers of the brain to produce long term effects.

Core Innovation

The invention relates to bromocriptine citrate for long-term treatment of metabolic disorders, including non-alcoholic steatohepatitis (NASH), by resetting central dopaminergic circadian rhythms in a patient. The approach increases central dopaminergic activity at a time of day that corresponds to the circadian peak of central dopaminergic activity in a healthy individual of the same species and sex, and the treatment is described as timed to the healthy circadian peak to improve therapeutic performance over long-term use.

The disclosed subject matter emphasizes use of bromocriptine citrate rather than bromocriptine mesylate in the pharmaceutical compositions. It states that the citrate salt provides unexpectedly improved heat stability and aqueous stability, and that bromocriptine citrate has increased water solubility and absorption compared with bromocriptine mesylate. These properties contribute to improved formulation performance, long-term usability, and improved shelf life.

The document describes dosage timing windows linked to circadian physiology, including administration within a specified period after waking, within four hours of the circadian peak of central dopaminergic activity in a healthy individual, and oral dosing between 0400 and 1200 hours. It also includes co-administration with a dopamine D1 agonist in one independent claim and a stated daily dose range.

Claims Coverage

The provided claim set includes five independent claims that define treatment of non-alcoholic steatohepatitis (NASH) using bromocriptine citrate. Core inventive coverage centers on circadian-time dosing to increase central dopaminergic activity at a circadian peak, salt/formulation choice, and specific timing and co-administration limitations.

The independent claims provided cover methods of treating NASH by administering bromocriptine citrate at circadian-determined times intended to increase central dopaminergic activity at a circadian peak, including variants that require co-administration with a dopamine D1 agonist, specific timing relative to waking, and a specified oral dosing window with a stated daily dose range.

Stated Advantages

Documented Applications