Therapeutic compositions comprising imidazole and imidazolium compounds
View Patent ↗Therapeutic compositions comprising substituted imidazole or imidazolium compounds may be used for a number of medical purposes, such as treatment of undesirable conditions or diseases, including disease or conditions related to bone, cancer, and/or pain.
1. A method of treating arthritis comprising orally administering a dosage form to a mammal in need thereof, wherein the dosage form comprises:
(Ion B) in a salt form, in an amount that is less than 0.1% w/w and greater than 0% w/w; or
(Ion C) in a salt form, in an amount that is less than 0.1% w/w and greater than 0% w/w;
wherein each A is independently an acidic functional group;
wherein, if present, the bioavailability of Compound A in the dosage form is from about 1.1% to about 4%.
2. The method of claim 1 , wherein the arthritis affects a knee, an elbow, a wrist, a shoulder, or a hip.
3. A method of treating arthritis comprising orally administering a dosage form to a human being suffering from arthritis, wherein the dosage form comprises:
a) zoledronic acid in a salt or an acid form; or
b) one of the following:
1) zoledronic acid in a salt or an acid form and
(Ion 1) in a salt form, in an amount that is less than 0.1% w/w and greater than 0% w/w; or
2) zoledronic acid in a salt or an acid form and
(Ion 2) in a salt form, in an amount that is less than 0.1% w/w and greater than 0% w/w; or
3) zoledronic acid in a salt or an acid form and a combination of Ion 1 in a salt form, in an amount that is less than 0.1% w/w and greater than 0% w/w, and Ion 2 in a salt form, in an amount that is less than 0.1% w/w and greater than 0% w/w;
wherein the dosage form is free of therapeutically active agents that are not zoledronic acid in a salt or an acid form, Ion 1 in a salt form, or Ion 2 in a salt form;
wherein any amount in % w/w is based upon the total weight of zoledronic acid in a salt or an acid form, Ion 1, Ion 2, and any corresponding counter ions; and
wherein the bioavailability of zoledronic acid in the dosage form is about 1.1% to about 4%.
4. The method of claim 3 , wherein the dosage form is orally administered in a manner that results in a bioavailability that is 1.3% to 3%.
5. The method of claim 4 , wherein the human being receives about 50 mg of zoledronic acid as a result of each administration of the dosage form.
6. The method of claim 3 , wherein the dosage form is orally administered in a manner that results in a bioavailability that is 1.3% to 4%.
7. The method of claim 3 , wherein the dosage form is orally administered in a manner that results in a bioavailability that is 1.4% to 3%.
8. The method of claim 3 , wherein the dosage form is orally administered in a manner that results in a bioavailability that is 1.4% to 4%.
9. The method of claim 3 , wherein the dosage form is orally administered in a manner that results in a bioavailability that is 1.5% to 3%.
10. The method of claim 3 , wherein the dosage form is orally administered in a manner that results in a bioavailability that is 1.6% to 3%.
11. The method of claim 3 , wherein the dosage form is orally administered in a manner that results in a bioavailability that is 1.6% to 4%.
12. The method of claim 3 , wherein the dosage form is orally administered in a manner that results in a bioavailability that is 1.8% to 3%.
13. The method of claim 3 , wherein the dosage form is orally administered in a manner that results in a bioavailability that is 1.8% to 4%.
14. The method of claim 3 , wherein the arthritis affects a knee, an elbow, a wrist, a shoulder, or a hip.
15. The method of claim 3 , wherein each dose of zoledronic acid is orally administered in a manner that provides an AUC of zoledronic acid of about 100 ng·h/mL to about 200 ng·h/mL.
16. The method of claim 3 , wherein the zoledronic acid is administered in a manner that results in a 24 hour sustained plasma factor that is about 10 to about 20.
17. The method of claim 3 , wherein the zoledronic acid is administered in a manner that results in a 24 hour sustained plasma factor that is about 10 to about 15.
18. The method of claim 3 , wherein the zoledronic acid is administered in a manner that results in a 24 hour sustained plasma factor that is about 12 to about 15.
19. The method of claim 3 , wherein the zoledronic acid is administered in a manner that results in a 24 hour sustained plasma factor that is at least twice that of 1 mg of zoledronic acid administered intravenously.
20. The method of claim 3 , wherein the zoledronic acid is administered in a manner that results in a 48 hour sustained plasma factor that is at least twice that of 1 mg of zoledronic acid administered intravenously.
21. The method of claim 3 , wherein the zoledronic acid is administered in a manner that results in a 24 hour sustained plasma factor that is at least 1.2 times that of 4 mg of zoledronic acid administered intravenously.
22. The method of claim 3 , wherein the zoledronic acid is administered in a manner that results in a 48 hour sustained plasma factor that is at least twice that of 4 mg of zoledronic acid administered intravenously.
23. A pharmaceutical dosage form for oral administration comprising:
a) zoledronic acid in a salt form; or
b) one of the following:
1) zoledronic acid in a salt or an acid form and
(Ion 1) in a salt form, in an amount that is less than 0.1% w/w and greater than 0% w/w;
2) zoledronic acid in a salt or an acid form and
(Ion 2) in a salt form, in an amount that is less than 0.1% w/w and greater than 0% w/w; or
3) zoledronic acid in a salt or an acid form and a combination of Ion 1 in a salt form, in an amount that is less than 0.1% w/w and greater than 0% w/w, and Ion 2 in a salt form, in an amount that is less than 0.1% w/w and greater than 0% w/w;
wherein the dosage form is free of therapeutically active agents that are not zoledronic acid in a salt or an acid form, Ion 1 in a salt form, or Ion 2 in a salt form;
wherein any amount in % w/w is based upon the total weight of zoledronic acid in a salt or an acid form, Ion 1, Ion 2, and any corresponding counter ions; and
wherein the bioavailability of zoledronic acid in the dosage form is about 1.2% to about 4% in a human being.
24. The method of claim 23 , wherein the dosage form contains at least 20% zoledronic acid in a disodium salt form by weight.
25. The method of claim 23 , wherein the zoledronic acid is administered in a dosage form containing at least 30% zoledronic acid in a disodium salt form by weight.
26. The method of claim 23 , wherein the dosage form contains about 50 mg to about 100 mg of zoledronic acid in a disodium salt form.
27. The method of claim 23 , wherein the dosage form contains at least 40% zoledronic acid in a disodium salt form by weight.
28. The method of claim 23 , wherein the dosage form contains at least 50% zoledronic acid in a disodium salt form by weight.
29. The method of claim 23 , wherein the dosage form contains at least 60% zoledronic acid in a disodium salt form by weight.
30. The method of claim 23 , wherein the zoledronic acid is orally administered once weekly.