Modified release pharmaceutical compositions of huperzine and methods of using the same

Abstract

The present application discloses pharmaceutical compositions for modified release of huperzine. The pharmaceutical compositions and methods described herein, allow for dosing of huperzine at higher therapeutic thresholds, while avoiding rapid serum peak plasma levels, thereby avoiding the adverse nausea and vomiting associated with the immediate release pharmaceutical compositions. Methods of treating neurological disorders and/or seizure disorders with the modified release compositions is also described.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS[0001]The present application claims benefit of and priority to U.S. Provisional No. 62 / 508,554 entitled “EXTENDED RELEASE FORMULATIONS OF HUPERZINE AND METHODS OF USING THE SAME,” filed May 19, 2017, the contents of which is hereby incorporated by reference in its entirety.SUMMARY OF THE INVENTION[0002]Huperzine A is a naturally occurring sesquiterpene alkaloid compound found in the firmoss Huperzia serrata. It is a potent inhibitor of acetylcholinesterase. In several countries, Huperzine A is sold as a dietary supplement for memory support. In China, huperzine A is State Food and Drug Administration (SFDA) approved for the treatment of dementia.[0003]Huperzine A has been administered to healthy volunteers and patients in numerous trials, many in China, demonstrating acceptable safety and tolerability as well as efficacy in Alzheimer's disease, benign senescent forgetfulness, vascular dementia, myasthenia gravis, schizophrenia, and cocaine dep...

AI Technical Summary

Benefits of technology

[0027]Some embodiments describe a method of treating a disorder selected from the group consisting of a neurological disorder and / or a seizure disorder, to a patient in need thereof, wherein the patient experiences a better side effect profile, comprising administering a modified release pharmaceutical composition of huperzine A, wherein the modified release pharmaceutical composition of huperzine A is characterized by a Css of huperzine A in plasma selected from the group consisting of: about 0.52 to about 0.82 ng / mL at a 0.25 mg dose; about 1.91 to about 2.99 ng / mL at a 0.50 mg dose; about 3.56 to about 5.55 ng / mL at a 0.75 mg dose; about 5.58 to about 8.72 ng / mL at a 1 mg dose; about 8.22 to about 12.84 ng / mL at a 1.25 mg dose; about 9.02 to about 14.09 ng / mL at a 1.5 mg dose; about 10.04 to about 15.69 ng / mL at a 1.75 mg dose; about 16 to about 25 ng / mL at a 2.0 mg dose; and about 18.48 to about 28.88 ng / mL at a 2.5 mg dose. In some embodiments, the modified release pharmaceutical composition is according to any embodiment described herein.

[0028]Some embodiments describe a method of treating a disorder selected from the group consisting of a neurological disorder and / or a seizure disorder, in a patient in need thereof, wherein the patient experiences a better side effect profile, comprising administering a modified release pharmaceutical composition of huperzine A, wherein the modified release pharmaceutical composition of huperzine A is characterized by a Css of huperzine A in plasma of at least 8 ng / mL when administered at a therapeutically effective dose

Problems solved by technology

While these studies showed a favorable safety profile, in some studies, transient dose related nausea occurred at the higher dose levels.

There are no available published data on the efficacy of huperzine A in patients with epilepsy in the medical or patent literature.

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