Macrocyclic polymorphs, compositions comprising such polymorphs, and methods of use and manufacture thereof

• US 8,859,510 B2
• Filed: 01/22/2008
• Issued: 10/14/2014
• Est. Priority Date: 01/22/2007
• Status: Active Grant

• Current Assignee: Merck Sharp & Dohme LLC (Merck & Co., Inc.)
• Original Assignee: Optimer Pharmaceuticals LLC (Merck & Co., Inc.)
• Inventors: Chiu, Yu-Hung, Che, Tessie Mary, Romero, Alex, Ichikawa, Yoshi, Shue, Youe-Kong
• Primary Examiner(s): Jiang, Shaojia Anna
• Assistant Examiner(s): Lau, Jonathan S
• Application Number:
  US12/523,790
• Publication Number:
  US 20100081800A1
• Time in Patent Office: 2,457 Days
• Field of Search: 514/28
• US Class Current: 514/28
• CPC Class Codes: A61K 31/351 not condensed with another ring
• CPC Class Codes: A61P 31/04 Antibacterial agents
• CPC Class Codes: C07D 407/14 containing three or more hetero rings
• CPC Class Codes: C07H 17/08 Hetero rings containing eight or more ring members, e.g. erythromycins

Abstract

The invention relates to novel forms of compounds displaying broad spectrum antibiotic activity, especially crystalline polymorphic forms and amorphous forms of such compounds, compositions comprising such crystalline polymorphic forms and amorphous forms of such compounds, processes for manufacture and use thereof. The compounds and compositions of the invention are useful in the pharmaceutical industry, for example, in the treatment or prevention of diseases or disorders associated with the use of antibiotics, chemotherapies, or antiviral therapies, including, but not limited to, colitis, for example, pseudo-membranous colitis; antibiotic associated diarrhea; and infections due to Clostridium difficile (“C. difficile”), Clostridium perfringens (“C. perfringens”), Staphylococcus species, for example, methicillin-resistant Staphylococcus, or Enterococcus including Vancomycin-resistant enterococci.

Claims

1. A method of treating a bacterial infection in a subject in need thereof comprising administering to said subject a therapeutically effective amount of a composition comprising a polymorphic form of a compound of Formula I:

2. The method of claim 1, wherein the administration is oral.

3. The method of claim 1, wherein the amount is from about 0.001 mg to about 1000 mg.

4. The method of claim 1, wherein the composition comprising a polymorphic form of a compound of Formula I is a solid dosage form.

5. The method of claim 1, wherein the polymorphic form of the compound of Formula I is present in the composition with at least about 85% of the total weight of tiacumicins.

6. The method of claim 1, wherein the polymorphic form of the compound of Formula I is present in the composition with at least about 90% of the total weight of tiacumicins.

7. The method of claim 1, wherein the polymorphic form of the compound of Formula I is present in the composition in at least about 93% of the total weight of tiacumicins.

8. The method of claim 1, wherein the polymorphic form of the compound of Formula I is present in the composition in at least about 95% of the total weight of tiacumicins.

9. The method of claim 1, wherein the polymorphic form of the compound of Formula I is present in the composition in at least about 99% of the total weight of tiacumicins.

10. The method of claim 1, wherein the bacterial infection is caused by Clostridia.

11. The method of claim 10, wherein the bacterial infection is caused by Clostridium difficile.

12. The method of claim 1, wherein the bacterial infection is a gastrointestinal infection.

13. The method of claim 1, wherein the bacterial infection is Clostridium difficile infection.