Peripheral opioid receptor antagonists and uses thereof
The present invention provides a compound of formula I: wherein X − , R 1 , and R 2 are as defined herein, and compositions thereof.
1. A composition comprising a compound of formula III
wherein A − is an anion of a Brønsted acid;
wherein at least 99.6% of the compound of formula III is in the R configuration;
wherein the compound of formula III is contained within a package that is substantially free of tungsten;
wherein the composition is substantially free of tungsten; and
wherein the composition comprises less than 190 ppm of a compound of formula II
wherein X − is an anion of a Brønsted acid.
2. The composition of claim 1 , wherein the Brønsted acid is selected from the group consisting of a hydrogen halide, a carboxylic acid, a sulfonic acid, a sulfuric acid, and a phosphoric acid.
3. The composition of claim 1 , wherein A − is selected from the group consisting of chloride, bromide, iodide, fluoride, sulfate, bisulfate, tartrate, nitrate, citrate, bitartrate, carbonate, phosphate, malate, maleate, fumarate, sulfonate, methylsulfonate, formate, carboxylate, methylsulfate, trifluoroacetate, and succinate.
4. The composition of claim 3 , wherein A − is bromide.
5. The composition of claim 1 , wherein X − is selected from the group consisting of chloride, bromide, iodide, fluoride, sulfate, bisulfate, tartrate, nitrate, citrate, bitartrate, carbonate, phosphate, malate, maleate, fumarate, sulfonate, methylsulfonate, formate, carboxylate, methylsulfate, trifluoroacetate, and succinate.
6. The composition of claim 5 , wherein X − is bromide.
7. The composition of claim 1 , wherein the composition contains tungsten in an amount of less than about 60 parts per billion.
8. The composition of claim 1 , wherein the compound of formula III is provided in a solution.
9. The composition of claim 8 , wherein the solution comprises about 8 mg of the compound of formula III in about 0.4 mL water.
10. The composition of claim 8 , wherein the solution comprises about 12 mg of the compound of formula III in about 0.6 mL water.
11. The composition of claim 1 , wherein the compound of formula III is a compound of formula III-1:
and the compound of formula II is a compound of formula II-1:
12. The composition of claim 1 , wherein the package is selected from the group consisting of: a syringe, a vial and an ampoule.
13. The composition of claim 11 , wherein the package is a syringe.
14. A method for treating a gastrointestinal disorder in a subject comprising administering the composition of claim 1 .
15. The method of claim 14 , wherein the gastrointestinal disorder is constipation.
16. The method of claim 15 , wherein the constipation is opioid-induced.
17. The method of claim 16 , wherein the subject receives an opioid chronically.
18. The method of claim 16 , wherein the subject is a cancer patient.
19. The method of claim 14 , wherein the method comprises administering the composition via subcutaneous injection to the subject.