Compositions and methods of treating metabolic disorders

• US 9,211,263 B2
• Filed: 01/05/2013
• Issued: 12/15/2015
• Est. Priority Date: 01/06/2012
• Status: Active Grant

• Current Assignee: Anji Pharmaceuticals, Inc.
• Original Assignee: Elcelyx Therapeutics, Inc.
• Inventors: Baron, Alain D., Fineman, Mark S., Beeley, Nigel R. A.
• Primary Examiner(s): Park, H. Sarah
• Application Number:
  US13/734,966
• Publication Number:
  US 20130177604A1
• Time in Patent Office: 1,074 Days
• Field of Search: None
• US Class Current: 1/1
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/155 Amidines (), e.g. guanidine (H2N—C(=NH)—NH2), isourea (N=C(OH)—NH2), isothiourea (—N=C(SH)—NH2)
• CPC Class Codes: A61K 31/36 Compounds containing methylenedioxyphenyl groups, e.g. sesamin
• CPC Class Codes: A61K 31/4196 1,2,4-Triazoles
• CPC Class Codes: A61K 31/53 having six-membered rings with three nitrogens as the only ring hetero atoms, e.g. chlorazanil, melamine melarsoprol A61K31/555 ; with four nitrogen atoms A61K31/495
• CPC Class Codes: A61K 31/55 having seven-membered rings, e.g. azelastine, pentylenetetrazole
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 9/0053 Mouth and digestive tract, i.e. intraoral and peroral administration rectal administration A61K9/0031
• CPC Class Codes: A61K 9/2054 Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
• CPC Class Codes: A61K 9/2813 Inorganic compounds
• CPC Class Codes: A61K 9/282 Organic compounds, e.g. fats
• CPC Class Codes: A61K 9/2846 Poly(meth)acrylates
• CPC Class Codes: A61K 9/2866 Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: C07D 249/14 Nitrogen atoms
• CPC Class Codes: C07D 251/10 having two double bonds between ring members or between ring members and non-ring members
• CPC Class Codes: C07D 251/18 with nitrogen atoms directly attached to the two other ring carbon atoms, e.g. guanamines
• CPC Class Codes: C07D 255/02 not condensed with other rings
• CPC Class Codes: C07D 307/52 Radicals substituted by nitrogen atoms not forming part of a nitro radical
• CPC Class Codes: C07D 317/58 Radicals substituted by nitrogen atoms nitro radicals C07D317/52
• CPC Class Codes: C07D 405/12 : linked by a chain containing hetero atoms as chain links

Abstract

Methods for improving the gastrointestinal tolerability of biguanide compounds and for treating metabolic disorders and/or inducing weight loss in patients in need thereof, particularly in individuals having a contraindication for treatment with biguanide compounds, are provided comprising administering delayed release formulations of such biguanide compounds, including metformin, targeted to the small intestine.

Claims

1. A method of treating a renally impaired subject having diabetes, comprising administering a therapeutically effective amount of metformin or a salt thereof to said subject in a formulation targeted for delivery to the distal small intestine, wherein said formulation comprises an oral dosage form enterically coated at a pH at or above 6.0 or 6.5, and wherein the metformin has a reduced relative average bioavailability of about 40, 50 or 60% in said formulation in comparison with an immediate-release formulation having the same amount of metformin or salt thereof.

2. The method according to claim 1, wherein the administration produces a mean plasma AUC_0-36 less than about 14,000, 13,000 or 12,000 ng*h/mL when said formulation is administered at 500 mg twice daily.

3. The method according to claim 1, wherein the administration produces a mean C_max less than about 800, 700 or 600 ng/mL when said formulation is administered at 500 mg twice daily.

4. The method according to claim 1, wherein said oral dosage form further comprises a modified release component for at least a portion of said metformin or a salt thereof.

5. The method according to claim 1, wherein the oral dosage form comprises less than 500 mg of metformin or a salt thereof.

6. A method according to claim 1, further comprising administration of a DPP-IV inhibitor.

7. A method according to claim 1, further comprising administration of an anti-obesity or anti-diabetes agent.

8. The method according to claim 1, wherein said metformin or a salt thereof is metformin hydrochloride.