Colchicine drug-to-drug interactions

• US 10,383,820 B2
• Filed: 10/09/2018
• Issued: 08/20/2019
• Est. Priority Date: 12/20/2017
• Status: Active Grant

• Current Assignee: RxOMEG Therapeutics LLC
• Original Assignee: RxOMEG Therapeutics LLC
• Inventors: Muni, Indu, Vishnupad, Naomi
• Primary Examiner(s): Baek, Bong-Sook
• Application Number:
  US16/155,571
• Publication Number:
  US 20190183793A1
• Time in Patent Office: 315 Days
• Field of Search: None
• CPC Class Codes: A61K 31/165 having aromatic rings, e.g. colchicine, atenolol, progabide
• CPC Class Codes: A61K 31/403 condensed with carbocyclic rings, e.g. carbazole
• CPC Class Codes: A61K 31/4422 1,4-Dihydropyridines, e.g. nifedipine, nicardipine
• CPC Class Codes: A61K 31/4709 Non-condensed quinolines and containing further heterocyclic rings
• CPC Class Codes: A61K 31/496 Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
• CPC Class Codes: A61K 47/02 Inorganic compounds
• CPC Class Codes: A61K 47/10 Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
• CPC Class Codes: A61K 47/12 Carboxylic acids; Salts or anhydrides thereof
• CPC Class Codes: A61K 47/26 Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
• CPC Class Codes: A61K 47/36 Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
• CPC Class Codes: A61K 9/0053 Mouth and digestive tract, i.e. intraoral and peroral administration rectal administration A61K9/0031
• CPC Class Codes: A61K 9/0095 Drinks; Beverages; Syrups; Compositions for reconstitution thereof, e.g. powders or tablets to be dispersed in a glass of water; Veterinary drenches A61K9/0007 takes precedence; eatable gels or foams A61K9/0056; oral mucosa adhesive forms A61K9/006
• CPC Class Codes: A61K 9/08 Solutions composition of solutions A61K47/00
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 31/00 Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics

Abstract

The use of oral colchicine solutions in combination with other therapeutics, while minimizing toxic drug to drug interactions are described herein. Related compositions are also provided.

Claims

1. A method of treating a colchicine sensitive disorder, comprising orally administering a liquid colchicine solution to a human subject having a colchicine sensitive disorder in an effective amount to treat the disorder, wherein the colchicine sensitive disorder is selected from gout, familial Mediterranean fever (FMF), pericarditis, Behç

et'"'"'s disease, atrial fibrillation, amyloidosis, calcium pyrophosphate deposition disease (pseudogout), cirrhosis of the liver, or sarcoid arthritis,

wherein the liquid colchicine solution comprises a concentration of colchicine of 0.01-1.0 mg/ml, 0.1-0.3% w/v of anhydrous citric acid, 0.8-1.6% w/v of dibasic sodium phosphate heptahydrate, 0.1-0.2% w/v of a thickening agent, a preservative, glycols, and water, and wherein the liquid colchicine solution is stable for at least one month at refrigerated and ambient temperature conditions.

2. The method of claim 1, wherein the liquid colchicine solution further comprises one or more agents selected from the group consisting of propylene glycol, glycerin, benzyl alcohol, xanthan gum, sucralose, a dye, and a flavoring agent and/or taste enhancing agent.

3. The method of claim 1, wherein the liquid colchicine solution has a stable pH.

4. The method of claim 1, wherein the liquid colchicine solution has a viscosity in the range of 40-800 cps.

5. The method of claim 1, wherein the liquid colchicine solution has less than 5% of total impurities.

6. The method of claim 1, wherein the liquid colchicine solution has less than 0.5% of degradants.

7. The method of claim 6, wherein the degradants comprise β

-lumicolchicine, γ

-lumicolchicine, and/or colchiceine.

8. The method of claim 1, wherein the liquid colchicine solution is a 0.12 mg/ml solution.

9. A method of treating gout, comprising orally administering a liquid colchicine solution to a human subject in an effective amount to treat gout, wherein the liquid colchicine solution comprises a concentration of colchicine of 0.01-1.0 mg/ml, 0.1-0.3% w/v of anhydrous citric acid, 0.8-1.6% w/v of dibasic sodium phosphate heptahydrate, 0.1-0.2% w/v of a thickening agent, a preservative, glycols, and water, and wherein the liquid colchicine solution is stable for at least one month at refrigerated and ambient temperature conditions.

10. The method of claim 9, wherein the liquid colchicine solution is a 0.12 mg/ml solution.