1. A frozen pharmaceutical formulation suitable for administration to a subject parenterally, comprising a therapeutically effective amount of tigecycline and an agent selected from the group consisting of lactose, dextrose, glucose, mannose, sucrose, ribose, xylose and a combination thereof, wherein the formulation in a pre-frozen state at about 22\xb0 C. or in an unfrozen state at about 22\xb0 C. has a pH in the range of from 4.0 to 5.5.
2. The formulation of claim 1, wherein the agent is selected from the group consisting of lactose, dextrose, glucose, mannose, and a combination thereof.
3. The formulation of claim 1, wherein the concentration of tigecycline epimer in the formulation is at or below about 3% of the concentration of tigecycline.
4. The formulation of claim 3, wherein the agent is lactose.
5. The formulation of claim 1, wherein the therapeutically effective amount of tigecycline is about 150 mg.
6. The formulation of claim 1, wherein tigecycline is in a concentration within the range of about 0.1 mgml to about 2.0 mgml.
7. The formulation of claim 6, wherein tigecycline is in a concentration within the range of about 0.5 to about 1.5 mgml.
8. The formulation of claim 1, wherein the pH is from 4.5 to 5.1.
9. The formulation of claim 1, wherein the pH is from 4.8 to 5.1.
10. The formulation of claim 1, wherein the agent is lactose.
11. The formulation of claim 10, wherein lactose is in the form of lactose monohydrate.
12. The formulation of claim 10, wherein lactose is in a concentration within the range of about 40 mgml to about 80 mgml.
13. The formulation of claim 1, wherein the formulation contains at least about 98.0% tigecycline as a percentage of the initial weight of tigecycline in the composition after up to about 42 days at a temperature of about \u221220\xb0 C.
14. The formulation of claim 1, wherein the formulation contains at least about 90.0% tigecycline as a percentage of the initial weight of tigecycline in the composition after up to 36 months at a temperature of about \u221220\xb0 C. or lower than \u221220\xb0 C.
15. The formulation of claim 14, wherein the temperature is of about \u221220\xb0 C. to about \u221270\xb0 C.
16. The formulation of claim 15, wherein the formulation contains at least about 90.0% tigecycline as a percentage of the initial weight of tigecycline in the composition after up to 6 months.
17. The formulation of claim 13, wherein the pH is about 5.0.
18. The formulation of claim 1, wherein the agent is lactose and the formulation has a total impurity content equal to or less than about 0.7% after up to 26 months.
19. The formulation of claim 1, wherein the agent is dextrose and the formulation has a total impurity content equal to or less than about 0.9% after up to 26 months.
20. A process of making a frozen pharmaceutical formulation, comprising the steps of:
a. dissolving tigecycline and an agent selected from the group consisting of lactose, dextrose, glucose, mannose, sucrose, ribose, xylose and a combination thereof into a suitable liquid, forming a premixed solution;
b. adjusting the pH of the premixed solution to a range of 4.0-5.5;
c. filling one or more containers with the premixed solution; and
d. storing the one or more containers of premixed solution at a temperature below the freezing point of the liquid.
21. The process of claim 20, wherein the suitable liquid is water.
22. The process of claim 21, wherein the temperature below the freezing point of the liquid is about \u221220\xb0 C.
23. The process of claim 21, wherein the temperature below the freezing point of the liquid is about \u221220\xb0 C. to about \u221270\xb0 C.
24. The process of claim 20, wherein the pH of the premixed solution is from 4.5 to 5.1.
25. A pharmaceutical formulation made by the process of claim 20.
26. A process of making a frozen pharmaceutical formulation, comprising the steps of:
a. dissolving tigecycline and an agent selected from the group consisting of lactose, dextrose, glucose, mannose sucrose, fructose, ribose, xylose and a combination thereof into a suitable liquid having a freezing point above about \u221220\xb0 C., forming a premixed solution;
b. filling one or more containers with the premixed solution;
c. storing the one or more containers of premixed solution at a temperature below the freezing point of the liquid; and
d. adding an acidifying agent to form a mixture wherein the amount of acidifying agent is such that the pH of the resulting mixture when measured at a temperature of about 22\xb0 C. is 4.0-5.5.
27. The process of claim 25, wherein the suitable liquid is water.
28. The process of claim 26, wherein the temperature below the freezing point of the liquid is about \u221220\xb0 C.
29. The process of claim 26, wherein the temperature below the freezing point of the liquid is about \u221220\xb0 C. to about \u221270\xb0 C.
30. The process of claim 27, wherein the pH of the premixed solution is from 4.5 to 5.1.
31. A pharmaceutical formulation made by the process of claim 26.
32. A kit comprising (a) a flexible bag, and (b) the frozen pharmaceutical formulation of claim 1, wherein the frozen pharmaceutical formulation is contained in the bag.
33. A kit comprising (a) a vial, and (b) the frozen pharmaceutical formulation of claim 1, wherein the frozen pharmaceutical formulation is contained in the vial.
The claims below are in addition to those above.
All refrences to claim(s) which appear below refer to the numbering after this setence.
1. A method of improving exercise capacity of a human subject, the method comprising administering to the subject a composition comprising Salvia officinalis or an extract thereof, prior to commencement of the exercise.
2. The method of claim 1, wherein the composition is administered from about 15 minutes to 60 minutes prior to the commencement of the exercise.
3. The method of claim 2, wherein the composition further comprises a thermogenic substance.
4. The method of claim 3, wherein the thermogenic substance is caffeine.
5. The method of claim 4, wherein the caffeine is caffeine anhydrous or is from at least one of Coffee Arabica, Coffee canephora, Camellia sinensis, Ilex paraguariensis, Paullinia cupana, Theobroma cacao, or kola nut.
6. A method of improving the response of a human subject to a thermogenic substance, wherein the thermogenic substance is a component of a composition, the method comprising administering to the subject the composition that contains the thermogenic substance which composition also comprises Salvia officinalis or an extract thereof.
7. The method of claim 6, wherein the composition is administered prior to the commencement of exercise.
8. The method of claim 7, wherein the composition is administered from about 15 minutes to about 60 minutes prior the commencement of exercise.
9. The method of claim 8, wherein the thermogenic substance is caffeine.
10. The method of claim 9, wherein the caffeine is caffeine anhydrous or is from at least one of Coffea Arabica, Coffea canephora, Camellia sinensis, Ilex paraguariensis, Paullinia cupana, Theobroma cacao, or kola nut.
11. The method of claim 6, wherein the composition is administered prior to the consumption of a meal.
12. The method of claim 11, wherein the composition is administered from about 15 minutes to about 60 minutes prior the consumption of a meal.
13. The method of claim 12, wherein the thermogenic substance is caffeine.
14. The method of claim 13, wherein the caffeine is caffeine anhydrous or is from at least one of Coffea Arabica, Coffea canephora, Camellia sinensis, Ilex paraguariensis, Paullinia cupana, Theobroma cacao, or kola nut.
15. The method claim 3, wherein the improving exercise comprises improving at least one parameter of exercise capacity of the subject, the at least one parameter of exercise capacity is at least one of energy, cognitive focus, comfort, perceived exertion, or recovery of skeletal muscle contractility.
16. The method of claim 15, wherein the composition is administered from about 15 minutes to 60 minutes prior to the commencement of the exercise.
17. The method of claim 16, wherein the thermogenic substance is caffeine.
18. The method of claim 17, wherein the caffeine is caffeine anhydrous or is from at least one of Coffea Arabica, Coffea canephora, Camellia sinensis, Ilex paraguariensis, Paullinia cupana, Theobroma cacao, or kola nut.
19. A composition comprising Salvia officinalis or an extract thereof and a thermogenic substance, wherein the thermogenic substance is one of caffeine or sources of caffeine, yohimbine or sources of yohimbine, synephrine or sources of synerphrine, Green tea or Green tea extracts, forskolin or sources of forskolin, L-carnitine or salts of L-carnitine, and hydroxycitric acid or sources of hydroxycitric acid.