Tetracycline compositions
The present invention relates to compositions, pharmaceutical compositions, and methods for preparing the same, comprising a tetracycline with improved stability and solubility. Some embodiments include a tetracycline with an excess of a divalent or trivalent cation.
1. A method of treating a bacterial infection in a subject, wherein the method consists of:
administering a therapeutically effective amount of a composition to a subject in need thereof via an intravenous route of administration,
wherein the composition consists of an aqueous solution consisting of minocycline or a salt thereof, a salt that comprises a magnesium cation, and a base,
wherein the molar ratio of magnesium cation to minocycline is greater than about 4:1, and
wherein the composition has a pH that is no less than 4 and no greater than 6,
whereby injection site hemolysis of red blood cells is reduced relative to intravenous administration of a composition that does not include magnesium.
2. The method of claim 1 , wherein the concentration of minocycline in the composition is at least 0.1 mg/ml.
3. The method of claim 1 , wherein the concentration of minocycline in the composition is at least 1 mg/ml.
4. The method of claim 1 , wherein the concentration of minocycline in the composition is at least 5 mg/ml.
5. The method of claim 1 , wherein the concentration of minocycline in the composition is at least 10 mg/ml.
6. The method of claim 1 , wherein the composition has a pH between about 4.5 to about 6.
7. The method of claim 1 , wherein the composition has a pH between about 4.5 to about 5.5.
8. The method of claim 1 , wherein the molar ratio of magnesium cation to minocycline is greater than or equal to 5:1.
9. The method of claim 1 , wherein the molar ratio of magnesium cation to minocycline is from 5:1 to 10:1.
10. The method of claim 1 , wherein the osmolality of the solution is less than 500 mOsm/kg.
11. The method of claim 1 , wherein the osmolality of the solution is less than 400 mOsm/kg.
12. The method of claim 1 , wherein the osmolality of the solution is less than 350 mOsm/kg.
13. The method of claim 1 , wherein the salt that comprises a magnesium cation is magnesium sulfate.
14. The method of claim 1 , wherein the salt that comprises a magnesium cation is magnesium acetate.
15. The method of claim 1 , wherein the salt that comprises a magnesium cation is magnesium chloride.
16. The method of claim 1 , wherein the base is NaOH.
17. The method of claim 1 , wherein the total volume of the composition administered is less than 1000 ml.
18. The method of claim 1 , wherein the total volume of the composition administered is less than 500 ml.
19. The method of claim 1 , wherein the total volume of the composition administered is less than 200 ml.
20. The method of claim 1 , wherein the total volume of the composition administered is less than 110 ml.
21. The method of claim 1 , wherein the composition is administered in less than 60 minutes.
22. The method of claim 1 , wherein the composition is administered in less than 40 minutes.
23. The method of claim 1 , wherein the composition is administered in less than 20 minutes.
24. The method of claim 1 , wherein the amount of minocycline in the composition is at least 80 mg.
25. The method of claim 1 , wherein the amount of minocycline in the composition is at least 100 mg.
26. The method of claim 1 , wherein the amount of minocycline in the composition is about 100 mg.
27. The method of claim 1 , wherein the amount of minocycline in the composition is at least 130 mg.
28. The method of claim 1 , wherein the amount of minocycline in the composition is at least 200 mg.
29. The method of claim 1 , wherein the amount of minocycline in the composition is at least 300 mg.
30. The method of claim 1 , wherein the amount of minocycline in the composition is at least 400 mg.
31. The method of claim 1 , wherein the amount of minocycline in the composition is at least 500 mg.