Peripheral opioid receptor antagonists and uses thereof

Patent metadata

Field	Value
Publication number	US-2017007597-A1
Application number	US-201615276347-A
Country	US
Kind code	A1
Filing date	Sep 26, 2016
Priority date	Sep 30, 2008
Publication date	Jan 12, 2017
Grant date	—

Abstract

The present invention provides a compound of formula I:

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

First claim

1 . A composition comprising 7% to 75% of a compound of formula III

based on the total weight of the composition;
wherein A − is an anion of a Brønsted acid;
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 compound of formula III 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

• A61K9/0053

  Mouth and digestive tract, i.e. intraoral and peroral administration · CPC title

• A61M5/178

  Syringes · CPC title

• A61K9/0019

  Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner (non-active ingredients are additionally classified in A61K47/00) · CPC title

• A61K31/485 Primary

  Morphinan derivatives, e.g. morphine, codeine · CPC title