Salts of potassium atp channel openers and uses thereof
AssigneeEssentialis, Inc.
InventorsNeil Cowen, Kenneth Kashkin, Khaled Yamout
Life of this patent
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Abstract
Provided are immediate or prolonged administration of certain salts of KATP channel openers such as diazoxide to a subject to achieve novel pharmacodynamic, pharmacokinetic, therapeutic, physiological, metabolic and compositional outcomes in the treatment of diseases or conditions involving KATP channels. Also provided are pharmaceutical formulations, methods of administration and dosing of the salts that achieve these outcomes and reduce the incidence of adverse effects in treated individuals. Further provided are method of co-administering the salts with other drugs to treat diseases of humans and animals.
Claims35
1-129. (canceled)
A salt comprising:
- an anion of a KATP channel opener selected from the group consisting of Formula I, Formula II, Formula III and Formula IV;
- and
- a cation selected from the group consisting of an alkali metal and a compound comprising a tertiary amine or ammonium group,
- wherein when said salt comprises diazoxide as the anion and sodium as the cation, said salt is not in a form suitable for intravenous use.
A salt comprising an anion of a KATP channel opener selected from the group consisting of Formula V, Formula VI, Formula VII and Formula VIII.
A salt comprising a cation of a KATP channel opener selected from the group consisting of Formula V, Formula VI, Formula VII and Formula VIII, wherein at least one substituent comprises an amino group.
A method for the preparation of a salt of diazoxide comprising:
- reacting one equivalent of a cation source selected from the group consisting of sodium hydroxide, potassium hydroxide, choline hydroxide, and hexamethyl hexamethylene diammonium dihydroxide with diazoxide,
- wherein said diazoxide is dissolved in a solvent selected from the group consisting of acetonitrile, low molecular weight ketones, tetrahydrofuran, dimethylformamide and n-methyl pyrrolidinone, and
- removing the solvent.
A polymorph of a salt, said salt comprising:
- diazoxide, and
- a cation selected from the group consisting of an alkali metal and a compound comprising a tertiary amine or quaternary ammonium group.
A process for producing a diazoxide choline salt, said process comprising:
- suspending diazoxide in a solvent and mixing with a choline salt;
- adding a co-solvent to the suspension under conditions sufficient to cause formation and precipitation of said diazoxide choline salt;
- harvesting the precipitate to provide said diazoxide choline salt.
A method of treating obesity or obesity-related morbidity in an obese subject, said method comprising administering to a subject in need thereof an effective amount of a compound of Formulae I-VIII.
A method of treatment of a subject suffering from or at risk for Alzheimer's disease, said method comprising administering to said subject a therapeutically effective amount of a compound according to any of Formulae I-VIII.
A method of treatment of a subject suffering from or at risk for Alzheimer's disease, said method comprising administering to said subject a therapeutically effective amount of a formulation, said formulation comprising a salt of a compound according to any of Formulae I-VIII.
Dependencies are inferred from the claim text.