Macrocyclic polymorphs, compositions comprising such polymorphs and methods of use and manufacture thereof
View Patent ↗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.
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:
characterized by a powder x-ray diffraction pattern comprising peaks at diffraction angles 2θ of 7.6°, 15.4°, and 18.8°±0.1.
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 a compound of Formula I is present in at least about 75% to about 99.99% of the total weight.
6. The method of claim 1 , wherein the polymorphic form of a compound of Formula I is present in at least about 85% of the total weight.
7. The method of claim 1 , wherein the polymorphic form of a compound of Formula I is present in at least about 90% of the total weight.
8. The method of claim 1 , wherein the polymorphic form of a compound of Formula I is present in at least about 95% of the total weight.
9. The method of claim 1 , wherein the polymorphic form of a compound of Formula I is present in at least about 99% of the total weight.
10. The method of claim 1 , wherein the bacterial infection is caused by enterococci, vancomycin resistant enterococci, clostridia, Clostridium perfringen, or Clostridium difficile.
11. The method of claim 10 , wherein the bacterial infection is caused by Clostridium difficile.
12. A method of treating a gastrointestinal 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:
characterized by a powder x-ray diffraction pattern comprising peaks at diffraction angles 2θ of 7.6°, 15.4°, and 18.8°±0.1.
13. The method of claim 12 , wherein the administration is oral.
14. The method of claim 12 , wherein the amount is from about 0.001 mg to about 1000 mg.
15. The method of claim 12 , wherein the composition comprising a polymorphic form of a compound of Formula I is a solid dosage form.
16. The method of claim 12 , wherein the polymorphic form of a compound of Formula I is present in at least about 75% to about 99.99% of the total weight.
17. The method of claim 12 , wherein the polymorphic form of a compound of Formula I is present in at least about 85% of the total weight.
18. The method of claim 12 , wherein the polymorphic form of a compound of Formula I is present in at least about 90% of the total weight.
19. The method of claim 12 , wherein the polymorphic form of a compound of Formula I is present in at least about 95% of the total weight.
20. The method of claim 12 , wherein the polymorphic form of a compound of Formula I is present in at least about 99% of the total weight.
21. The method of claim 12 , wherein the gastrointestinal infection is caused by enterococci, vancomycin resistant enterococci, clostridia, Clostridium perfringen, or Clostridium difficile.
22. The method of claim 21 , wherein the gastrointestinal infection is caused by Clostridium difficile.
23. The method of claim 12 , wherein the gastrointestinal infection is C. difficile infection.
24. A method of treating C. difficile 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:
characterized by a powder x-ray diffraction pattern comprising peaks at diffraction angles 2θ of 7.6°, 15.4°, and 18.8°±0.1 as set forth in FIG. 2 .