University of South Florida

Natura Therapeutics, Inc.

Adam John Smith

Roland Douglas Shytle

Michael Zaworotko

Naga Duggirala

Jun Tan

R Douglas Shytle

Michael John Zaworotko

Padmini Kavuru

Cyndy Davis Sanberg

Tien Teng Ong

Brian Nelson Giunta

Ryan N Cantwell

Tranhha Nguyen

A cocrystal having the formula LiX·aM, or a solvate or hydrate thereof, wherein X is a conjugate base of an organic acid, M is a neutral organic molecule, and a is from 0.5 to 4, pharmaceutical compositions comprising such cocrystals, cocrystal solvates, or cocrystal hydrates, and methods of preparing such cocrystals, cocrystal solvates, or cocrystal hydrates, and such pharmaceutical compositions.

Organic anion lithium ionic cocrystal compounds and compositions

A cocrystal having the formula LiX.aM, or a solvate or hydrate thereof, wherein X is a conjugate base of an organic acid, M is a neutral organic molecule, and a is from 0.5 to 4, pharmaceutical compositions comprising such cocrystals, cocrystal solvates, or cocrystal hydrates, and methods of preparing such cocrystals, cocrystal solvates, or cocrystal hydrates, and such pharmaceutical compositions.

2:1 cocrystals of amino acids and Li+ salts crystallize from hot water to afford water stable cationic networks based upon tetrahedral lithium cations: bilayered square grids, a lithium zeolitic metal-organic material (LiZMOM) and several lithium diamondoid metal-organic materials (LiDMOMs). The compositions may be used as a pharmaceutical for the treatment of suicidality and other disorders that require lithium to penetrate the blood brain barrier and exert therapeutic effects in the CNS. Advantageously, the novel cocrystal forms described herein may be used to lower the oral dose required to achieve therapeutic concentrations of lithium in the brain, thus reducing the peripheral toxicity and potentially broadening the therapeutic index in comparison to conventional lithium forms.

Lithium cocrystal compositions

Lithium is regarded as the gold standard comparator and benchmark treatment for mania. One of the problems associated with Lithium is its narrow therapeutic window. Recent attempts to find new drugs with similar therapeutic activities have yielded new chemical entities. However, these potential new drugs have yet to match the many bioactivities attributable to lithium's efficacy for the treatment of neuropsychiatric diseases. Consequently, an intense effort for re-engineering lithium therapeutics using cocrystallization is currently underway. The evaluation of pharmacokinetics of previously unexplored lithium salts with organic anions (lithium salicylate and lithium lactate) has found that these lithium salts exhibit profoundly different pharmacokinetics compared to the more common FDA approved salt, lithium carbonate, in rats. Remarkably, lithium salicylate produced elevated blood and brain levels of lithium beyond 48 hours post-dose without the sharp peak that contributes to the toxicity problems of current lithium therapeutics.

Compositions of lithium salts and methods of use

Despite its narrow therapeutic window, lithium is regarded as the gold standard comparator and benchmark treatment for mania. Attempts to find new drugs with similar therapeutic activities have yielded new chemical entities. However, these new drugs have yet to match the many bioactivities attributable to lithium's efficacy for the treatment of neuropsychiatric diseases. Consequently, an intense effort for re-engineering lithium therapeutics using crystal engineering is underway. The evaluation of pharmacokinetics of previously unexplored lithium salts with organic anions (i.e. lithium salicylate) has found that these lithium salts exhibit profoundly different pharmacokinetics compared to the more common FDA approved salt, lithium carbonate, in rats. Remarkably, lithium salicylate produced elevated blood and brain levels of lithium beyond 48 hours post-dose without the sharp peak that contributes to the toxicity problems of current lithium therapeutics.

Plasma and brain pharmacokinetics of previously unexplored lithium salts

The invention concerns methods and compositions for treating a neuropsychiatric disorder, wherein the method comprises administering an effective amount of a co-crystal of lithium to a subject in need thereof, wherein the co-crystal comprises lithium, or a pharmaceutically acceptable salt thereof, and an amino acid.

Lithium co-crystals and an additional neuropsychiatric agent for treatment of neuropsychiatric disorders

Compositions and methods of increasing the bioavailability of catechins are presented. Compositions for increasing the bioavailability of catechins include compositions where the catechin is added to a solution of ethanol and water; compositions where the catechin is encapsulated within a nanoparticle; and compositions in which a nanoparticle complex is formed between the catechin and the nanoparticle. Each of these compositions was shown to increase bioavailability of EGCG and is useful in treating diseases such as Alzheimer's and HIV-associated dementia.

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Tampa, FL, United States of America

Adam John Smith