Salts of potassium ATP channel openers and uses thereof

• US 7,572,789 B2
• Filed: 02/24/2009
• Issued: 08/11/2009
• Est. Priority Date: 01/05/2006
• Status: Active Grant

• Current Assignee: Essentialis, Inc. (Soleno Therapeutics, Inc.)
• Original Assignee: Essentialis, Inc. (Soleno Therapeutics, Inc.)
• Inventors: Cowen, Neil M., Yamout, Khaled A., Kashkin, Kenneth B.
• Primary Examiner(s): CHANG, CELIA C
• Application Number:
  US12/391,990
• Publication Number:
  US 20090148526A1
• Time in Patent Office: 168 Days
• Field of Search: 514/223.2, 544/12
• US Class Current: 514/223.2
• CPC Class Codes: A61K 31/54 having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame
• CPC Class Codes: A61K 31/549 having two or more nitrogen atoms in the same ring, e.g. hydrochlorothiazide
• CPC Class Codes: A61K 38/27 Growth hormone [GH], i.e. somatotropin
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 9/2086 Layered tablets, e.g. bilayer tablets; Tablets of the type inert core-active coat active cores with a complete drug-free outer coat A61K9/28
• CPC Class Codes: A61P 25/18 Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
• CPC Class Codes: A61P 25/24 Antidepressants
• CPC Class Codes: A61P 25/28 for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• CPC Class Codes: A61P 3/00 Drugs for disorders of the metabolism of the blood or the extracellular fluid A61P7/00
• CPC Class Codes: A61P 3/04 Anorexiants; Antiobesity agents
• CPC Class Codes: A61P 3/08 for glucose homeostasis pancreatic hormones A61P5/48
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 5/50 for increasing or potentiating the activity of insulin
• CPC Class Codes: A61P 9/10 for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: A61P 9/12 Antihypertensives
• CPC Class Codes: C07C 209/68 from amines, by reactions not involving amino groups, e.g. reduction of unsaturated amines, aromatisation, or substitution of the carbon skeleton
• CPC Class Codes: C07C 213/08 by reactions not involving the formation of amino groups, hydroxy groups or etherified or esterified hydroxy groups
• CPC Class Codes: C07D 285/24 with oxygen atoms directly attached to the ring sulfur atom

Abstract

Provided are immediate or prolonged administration of certain salts of K_ATP 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 K_ATP 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.

Claims

1. A salt comprising:

a KATP channel opener selected from the group consisting of Formula III and Formula IV, and a counter ion as shown below

2. The salt according to claim 1 wherein said KATP channel opener is diazoxide.

3. The salt according to claim 1 wherein said KATP channel opener is diazoxide and said counter ion is choline.

4. The salt according to claim 1 wherein said KATP channel opener is diazoxide and said counter ion is hexamethyl hexamethylene diammonium.

5. A pharmaceutical formulation comprising the salt of claim 1 and at least one pharmaceutically acceptable excipient.

6. The formulation according to claim 5 wherein the pharmaceutical formulation is an oral dosage form.

7. The formulation according to claim 6 which is an enteric coated formulation.

8. The formulation according to claim 7 wherein the enteric coating is selected from the group consisting of:

(a) a compression coating on a tablet, (b) a thin film on a tablet, and (c) a coating on microparticles wherein the microparticles can be further encapsulated.

9. The formulation according to claim 6 wherein the formulation is a sustained release formulation.

10. The formulation according to claim 9 wherein the period of release is 8-24 hours following administration.

11. The formulation according to claim 9 wherein the formulation comprises a component selected from the group consisting of:

(a) a pH sensitive polymeric coating, (b) a hydrogel, (c) a film coating that controls the rate of diffusion of the salt from a coated matrix, (d) n erodable matrix that controls rate of salt release, (e) polymer coated pellets, granules or microparticles of salt which can be further encapsulated or compressed into a tablet, (f) an osmotic pump system containing the salt, (g) a compression coated tablet form of the salt, and (h) combinations thereof.

12. The formulation according to claim 5 for a single administration that contains between 10 and 2000 mg of the salt.

13. The formulation according to claim 5 for a single administration that contains between 300 and 500 mg of the salt.

14. The formulation according to claim 9 wherein the period of release is 2-30 hours following administration.