Peripheral opioid receptor antagonists and uses thereof

Patent metadata

Field	Value
Publication number	US-9724343-B2
Application number	US-201615276347-A
Country	US
Kind code	B2
Filing date	Sep 26, 2016
Priority date	Sep 30, 2008
Publication date	Aug 8, 2017
Grant date	Aug 8, 2017

Abstract

The present invention provides a compound of formua I:

wherein X − , R 1 , and R 2 are as defined herein, and compositions thereof.

First claim

The invention claimed is:

1. A composition comprising a unit dosage form of a compound of formula III

wherein the compound of formula III is present at 7% to 75% based on the total weight of the composition;
wherein A − is an anion of a Brønsted acid;
wherein the composition comprises a chelating agent comprising calcium EDTA disodium;
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 a compound of formula III-1:

and the compound of formula II is a compound of formula II-1:

9. The composition of claim 1 , wherein the composition is contained within a package that is substantially free of tungsten.

10. The composition of claim 9 , wherein the package is selected from the group consisting of: a syringe, a vial and an ampoule.

11. The composition of claim 10 , wherein the package is a syringe.

12. The composition of claim 1 , wherein the composition is a solid composition.

13. The composition of claim 12 , wherein the solid composition is provided in tablet form.

14. The composition of claim 13 , wherein the composition comprises 75 mg to 450 mg of the compound of formula III.

15. The composition of claim 13 , wherein the composition comprises 150 mg of the compound of formula III.

16. A method for treating a gastrointestinal disorder in a subject comprising administering the composition of claim 1 .

17. The method of claim 16 , wherein the gastrointestinal disorder is constipation.

18. The method of claim 17 , wherein the constipation is opioid-induced.

19. The method of claim 16 , wherein the method comprises intravenously administering the composition to the subject.

20. The method of claim 16 , wherein the method comprises orally administering the composition to the subject.

Assignees

• Wyeth Llc

Inventors

• Bazhina Nataliya
• Donato Iii George Joseph
• Fabian Steven R
• Lokhnauth John
• Megati Sreenivasulu
• Melucci Charles
• Ofslager Christian
• Patel Niketa
• Radebaugh Galen
• Shah Syed M
• Szeliga Jan
• Zhang Huyi
• Zhu Tianmin

Classifications

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• G01N2030/027

  Liquid chromatography · CPC title

• C07D471/08

  Bridged systems · CPC title

• Y10T436/145555

  Hetero-N · CPC title

• G01N30/02

  Column chromatography · CPC title