Tetracycline compositions
View Patent ↗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, comprising administering a therapeutically effective amount of a pharmaceutical composition to a subject in need thereof via topical administration to the eye of the subject, the pharmaceutical composition comprising an aqueous solution of tigecycline and a divalent or trivalent metal cation, wherein the pH of the solution is greater than 4 and less than 7 and the molar ratio of divalent or trivalent metal cation to tigecycline is greater than 6:1.
2. The method of claim 1 , wherein the molar ratio of divalent or trivalent metal cation to tigecycline is greater than 8:1.
3. The method of claim 1 , wherein the molar ratio of divalent or trivalent metal cation to tigecycline is greater than 10:1.
4. The method of claim 1 , wherein the molar ratio of divalent or trivalent metal cation to tigecycline is about 12:1.
5. The method of claim 1 , wherein the divalent or trivalent metal cation is a divalent metal cation.
6. The method of claim 1 , wherein the divalent or trivalent metal cation is calcium.
7. The method of claim 1 , wherein the solution comprises calcium chloride or calcium sulfate.
8. The method of claim 1 , wherein the divalent or trivalent metal cation is magnesium.
9. The method of claim 1 , wherein the solution comprises magnesium sulfate or magnesium chloride.
10. The method of claim 1 , wherein the concentration of tigecycline is at least 1 mg/ml.
11. The method of claim 1 , wherein the concentration of tigecycline is 5 mg/ml.
12. The method of claim 1 , wherein the solution comprises one or more additional constituents selected from the group consisting of hydrocortisone, dexamethasone, thonzonium bromide, tyloxapol, boric acid, and benzalkonium chloride.
13. The method of claim 1 , wherein the solution does not comprise a component selected from the group consisting of an antioxidant, a pyridine-containing compound, gluconate, an alcohol, glycerol, polyethylene glycol, a pyrrolidone-containing compound, a water-miscible local anaesthetic, urea, lactose, and a dehydrating agent.
14. The method of claim 1 , wherein the pharmaceutical composition is contained within a vial prior to administration.
15. The method of claim 14 , wherein the vial is a single-use vial.
16. A method of treating a bacterial infection, comprising:
reconstituting a water-soluble solid composition in a pharmaceutically acceptable diluent to form a solution; and
administering a therapeutically effective amount of the solution to a subject in need thereof via topical administration to the eye of the subject,
wherein the water-soluble solid composition comprises tigecycline and a divalent or trivalent metal cation, wherein the molar ratio of divalent or trivalent metal cation to tigecycline is greater than 6:1.
17. The method of claim 16 , wherein the molar ratio of divalent or trivalent metal cation to tigecycline is greater than 8:1.
18. The method of claim 16 , wherein the molar ratio of divalent or trivalent metal cation to tigecycline is greater than 10:1.
19. The method of claim 16 , wherein the molar ratio of divalent or trivalent metal cation to tigecycline is about 12:1.
20. The method of claim 16 , wherein the divalent or trivalent metal cation is a divalent metal cation.
21. The method of claim 16 , wherein the divalent or trivalent metal cation is calcium.
22. The method of claim 16 comprising calcium chloride or calcium sulfate.
23. The method of claim 16 , wherein the divalent or trivalent metal cation is magnesium.
24. The method of claim 16 comprising magnesium sulfate or magnesium chloride.
25. The method of claim 16 , wherein the water-soluble solid composition is in the form of a lyophile.
26. The method of claim 16 , wherein the water-soluble solid composition is contained within a vial.
27. The method of claim 26 , wherein the vial is a single-use vial.
28. The method of claim 26 , wherein the vial comprises greater than 30 mg and less than 100 mg of tigecycline.
29. The method of claim 26 , wherein the vial comprises at least 50 mg of tigecycline.
30. The method of claim 26 , wherein the vial comprises at least 200 μg of tigecycline.
31. The method of claim 26 , wherein the vial comprises at least 1 mg of tigecycline.
32. The method of claim 16 , wherein the pharmaceutically acceptable diluent is water.