Antibiotic macrocycle compounds and methods of manufacture and use thereof
View Patent ↗The invention encompasses an active metabolite of the 18-membered macrocyclic antimicrobial agents, specifically, a metabolite of tiacumicin B and in certain embodiments, R-Tiacumicin B or and its related compounds. In particular, the invention encompasses a compound that acts as a potent antibiotic agent for the treatment of bacterial infections, specifically GI infections caused by toxin producing strains of Clostridium difficile ( C. difficile ) and Clostridium perfringens ( C. perfringens ).
1. A pharmaceutical composition comprising a compound of formula II
in free form or in the form of its pharmaceutically acceptable salts.
2. The pharmaceutical composition of claim 1 , wherein the compound of Formula II is stereomerically pure.
3. The pharmaceutical composition of claim 1 in the form of an oral dosage form.
4. The pharmaceutical composition of claim 3 , wherein the oral dosage form is a tablet, capsule, gel cap, solution, syrup, or elixir.
5. The pharmaceutical composition of claim 1 , wherein the compound of Formula II is present in an amount of about 0.001 mg to about 4000 mg.
6. The pharmaceutical composition of claim 1 , wherein the compound of Formula II is present in an amount of about 0.01 mg to about 2000 mg.
7. The pharmaceutical composition of claim 1 , wherein the compound of Formula II is present in an amount of about 0.1 mg to about 1000 mg.
8. The pharmaceutical composition of claim 1 , wherein the compound of Formula II is present in an amount of about 1 mg to about 800 mg.
9. The pharmaceutical composition of claim 1 , wherein the compound of Formula II is an alkaline metal or tertiary alkyl ammonium salt.
10. The pharmaceutical composition of claim 1 , wherein the compound of Formula II is a Na + , K + , Mg 2+ , Ca 2+ , Zn 2+ salt.
11. The pharmaceutical composition of claim 1 , further comprising a pharmaceutically acceptable carrier or vehicle.
12. A method for treating bacterial infections in a mammal, which comprises administering to said mammal a composition comprising a therapeutically or prophylactically effective amount of a compound of Formula II:
in free form or in the form of its pharmaceutically acceptable salts.
13. The method of claim 12 , wherein the therapeutically effective amount is from about 0.001 mg/kg to about 2000 mg/kg.
14. The method of claim 12 , wherein the mammal is human.
15. The method of claim 12 , wherein the route of administration is oral or parenteral.
16. The method of claim 12 , wherein the route of administration is intravenous, intradermal, intramuscular, intraperitoneal, subcutaneous, epidural, intracerebral, or intravaginal.
17. The method of claim 12 , wherein the dosage is 0.001 milligram to 200 milligrams per kilogram of the subject's body weight.
18. The method of claim 12 , wherein the dosage is 0.01 milligrams to 100 milligrams per kilogram of the subject's body weight.
19. The method of claim 12 , wherein the dosage is 0.1 milligrams to 50 milligrams per kilogram of the subject's body weight.
20. A method for treating bacterial infections in a mammal, which comprises contacting the gastrointestinal tract of said mammal with a compound of Formula II:
in free form or in the form of its pharmaceutically acceptable salts.