TREATMENTS OF GASTROINTESTINAL DISORDERS

• US 20140005128A1
• Filed: 08/11/2011
• Published: 01/02/2014
• Est. Priority Date: 08/11/2010
• Status: Abandoned Application

• Current Assignee: Ironwood Pharmaceuticals, Inc.
• Original Assignee: Forest Laboratories Holdings Limited (Abbvie Incorporated), Ironwood Pharmaceuticals, Inc.
• Inventors: Mo, Yun, Fretzen, Angelika, Cali, Brian, Dedhiya, Mahendra
• Application Number:
  US13/816,154
• Publication Number:
  US 20140005128A1
• Time in Patent Office: Days
• US Class Current: 514/21.5
• CPC Class Codes: A61K 38/10 Peptides having 12 to 20 amino acids A61K38/043 - A61K38/046 take precedence
• CPC Class Codes: A61K 38/12 Cyclic peptides , e.g. bacitracins; Polymyxins; Gramicidins S, C; Tyrocidins A, B or C A61K38/043 - A61K38/046 take precedence
• CPC Class Codes: A61K 47/18 Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
• CPC Class Codes: A61K 9/1611 Inorganic compounds
• CPC Class Codes: A61K 9/1641 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, poloxamers
• CPC Class Codes: A61K 9/1676 having a drug-free core with discrete complete coating layer containing drug adsorbates of liquid drug formulations on inert powders without simultaneous granulation step A61K9/141; with further drug-free outer coating A61K9/5078; drug conjugated to non-active particles A61K47/6921
• CPC Class Codes: A61P 1/00 Drugs for disorders of the alimentary tract or the digestive system
• CPC Class Codes: A61P 1/04 for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
• CPC Class Codes: A61P 1/10 Laxatives

Abstract

The present invention relates to stable pharmaceutical compositions comprising linaclotide or pharmaceutically acceptable salts thereof, as well as to various methods and processes for the preparation and use of the compositions.

Claims

1. A pharmaceutical composition comprising linaclotide, a cation or pharmaceutically acceptable salt thereof and an amine selected from meglumine or a mixture of meglumine and histidine.

2. The composition of claim 1, wherein the amine is meglumine.

4. The composition of claim 1 or claim 3, wherein the composition further comprises a polymer.

5. The composition of claim 4, wherein the polymer is selected from polyvinyl pyrrolidone (PVP), polyvinyl alcohol (PVA) or a mixture thereof.

6. A method of treating a gastrointestinal disorder comprising administering to a patient in need thereof, a therapeutically effective amount of the composition of claim 1 or claim 3.

7. The method of claim 6, wherein the gastrointestinal disorder is selected from the group consisting of irritable bowel syndrome, chronic constipation, opioid induced constipation and dyspepsia.

8. The method of claim 7, wherein the gastrointestinal disorder is chronic constipation.

9. The method of claim 7, wherein the gastrointestinal disorder is constipation-predominant irritable bowel syndrome.

10. A method of making the composition of claim 1, comprising combining linaclotide with a cation or pharmaceutically acceptable salt thereof and an amine selected from meglumine or a mixture of meglumine and histidine.

11. A composition prepared by the method of claim 10.

23. The composition of claim 1, wherein the composition comprises Ca²⁺ and an amino acid selected from meglumine or mixture of meglumine and histidine in a molar ratio of Ca²⁺:

amino acid between about 1.3;

1 and 0.7;

1.

24. The composition of claim 1, wherein the composition comprises Ca²⁺ and an amino acid selected from meglumine or mixture of meglumine and histidine in a molar ratio of Ca²⁺:

amino acid between about 1.1;

1 and 0.9;

1.

3. A pharmaceutical composition comprising linaclotide, a cation or pharmaceutically acceptable salt thereof and histidine, wherein the composition has a molar ratio of cation:

histidine of less than 2;

1.

12. A method of making the composition of claim 3, comprising combining linaclotide with a cation or pharmaceutically acceptable salt thereof and histidine, wherein the composition has a molar ratio of cation:

histidine of less than 2;

1.

13. A composition prepared by the method of claim 12.

25. The composition of claim 3, wherein the composition comprises Ca²⁺ and histidine in a molar ratio of Ca²⁺:

histidine between about 1.3;

1 and 0.7;

1.

26. The composition of claim 3, wherein the composition comprises Ca²⁺ and histidine in a molar ratio of Ca²⁺:

histidine between about 1.1;

1 and 0.9;

1.

14. A pharmaceutical composition comprising linaclotide, a cation or pharmaceutically acceptable salt thereof and a dipeptide selected from glycine-leucine, leucine-glycine, or a mixture thereof.

15. The composition of claim 14, wherein the composition further comprises a polymer.

16. The composition of claim 15, wherein the polymer is selected from polyvinyl pyrrolidone (PVP), polyvinyl alcohol (PVA) or a mixture thereof.

17. A method of treating a gastrointestinal disorder comprising administering to a patient in need thereof, a therapeutically effective amount of the composition of claim 14.

18. The method of claim 17, wherein the gastrointestinal disorder is selected from the group consisting of irritable bowel syndrome, chronic constipation, opioid induced constipation and dyspepsia.

19. The method of claim 18, wherein the gastrointestinal disorder is chronic constipation.

20. The method of claim 18, wherein the gastrointestinal disorder is constipation-predominant irritable bowel syndrome.

21. A method of making the composition of claim 14, comprising combining linaclotide with a cation or pharmaceutically acceptable salt thereof and a dipeptide selected from glycine-leucine, leucine-glycine, or a mixture thereof.

22. A composition prepared by the method of claim 21.