Lithium cocrystal compositions

Patent metadata

Field	Value
Publication number	US-10130708-B2
Application number	US-201214007023-A
Country	US
Kind code	B2
Filing date	Mar 26, 2012
Priority date	Mar 24, 2011
Publication date	Nov 20, 2018
Grant date	Nov 20, 2018

Abstract

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.

First claim

What is claimed is:

1. A pharmaceutical composition comprising a lithium cocrystal solid composition and one or more of pharmaceutically acceptable pharmaceutically acceptable carriers, diluents, adjuvants, excipients, or vehicles,
wherein the lithium cocrystal composition comprises a lithium salt and a neutral organic molecule in a stoichiometric ratio;
wherein the lithium solid cocrystal composition has the formula LiX.aM or LiX.aM.bS wherein X is a halide or a pharmaceutically acceptable oxyanion, M is a neutral organic molecule, a is 1 or 2, b is 0, 0.5, 1.0, 1.5, 2.0, 2.5 or 3.0, and S is solvent or water; and wherein M is leucine and X is chloride.

2. A pharmaceutical composition comprising an active agent and one or more of pharmaceutically acceptable carriers, diluents, adjuvants, excipients, or vehicles,
wherein the active agent is a solid lithium cocrystal composition comprising a lithium salt and a neutral organic molecule in a stoichiometric ratio;
wherein the lithium solid cocrystal composition has the formula LiX.aM or LiX.aM.bS wherein X is a chloride, M is leucine, a is 1 or 2, b is 0, 0.5, 1.0, 1.5, 2.0, 2.5 or 3.0, and S is solvent or water; and
wherein the pharmaceutical composition is in a dosage unit form comprising a predetermined amount of the active agent.

3. The pharmaceutical composition of claim 2 , wherein the active agent is in a therapeutic amount effective to treat mood disorders or suicidality in a subject in need thereof.

4. The pharmaceutical composition of claim 2 wherein the dosage unit form is a tablet or capsule for oral administration.

Assignees

• Zaworotko Michael John
• Shytle Roland D
• Ong Tien Teng
• Cantwell Ryan N
• Nguyen Tranhha
• Smith Adam John
• Kavuru Padmini
• Univ South Florida

Inventors

• Zaworotko Michael John
• Shytle Roland D
• Ong Tien Teng
• Cantwell Ryan N
• Nguyen Tranhha
• Smith Adam John
• Kavuru Padmini

Classifications

• A61K9/145

  with organic compounds · CPC title

• A61P25/20

  Hypnotics; Sedatives · CPC title

• A61P25/22

  Anxiolytics · CPC title

• A61P25/24

  Antidepressants · CPC title

• A61K47/22

  Heterocyclic compounds, e.g. ascorbic acid, tocopherol or pyrrolidones · CPC title