Benzoic acid, benzoic acid derivatives and heteroaryl carboxylic acid conjugates of hydrocodone, prodrugs, methods of making and use thereof

Patent metadata

Field	Value
Publication number	US-2018104352-A1
Application number	US-201715843875-A
Country	US
Kind code	A1
Filing date	Dec 15, 2017
Priority date	Jul 2, 2009
Publication date	Apr 19, 2018
Grant date	—

Abstract

The presently described technology provides methods of treating a patient having moderate to severe pain, narcotic or opioid abuse or narcotic or opioid withdrawal. The presently described methods are carried out by comprising administering to the patient a pharmaceutically effective amount of a composition comprising acetaminophen and benzoate-hydrocodone hydrochloride. The composition has reduced side effects when compared with unconjugated hydrocodone.

First claim

1 - 14 . (canceled)

15 . A method for treating a patient having moderate to severe pain, narcotic or opioid abuse; or narcotic or opioid withdrawal comprising administering to the patient a pharmaceutically effective amount of a composition of a conjugate of hydrocodone wherein the conjugate exhibits lower mean exposure to hydrocodone about more than 53 mg when compared to unconjugated hydrocodone; or has reduced side effects when compared with an equivalent molar amount of unconjugated hydrocodone.

16 . The method of claim 15 , wherein the composition is a prodrug.

17 . The method of claim 15 , wherein the composition is used to reduce or prevent oral, intranasal or intravenous drug abuse; or to provide oral, intranasal or parenteral drug abuse resistance.

18 . The method of claim 15 , wherein the composition exhibits an improved AUC and rate of release of hydrocodone over time when compared to an equivalent molar amount of unconjugated hydrocodone over the same time period.

19 . The method of claim 15 , wherein the composition is provided in a dosage form selected from the group consisting of: a tablet, a capsule, a caplet, a suppository, a troche, a lozenge, an oral powder, a solution, an oral film, a thin strip, a slurry, and a suspension.

20 . The method of claim 15 , wherein the composition is provided in an amount sufficient to provide a therapeutically bioequivalent AUC for hydrocodone at about lower than 53 mg when compared to an equivalent molar amount of unconjugated hydrocodone.

21 . The method of claim 15 , wherein at least one composition is provided in an amount sufficient to provide a therapeutically bioequivalent AUC and C max for hydrocodone at about lower than 53 mg when compared to an equivalent molar amount of unconjugated hydrocodone.

22 . The method of claim 15 , wherein one of the reduced side effects comprises a lower than normal concentration of oxygen in arterial blood of the patient.

23 . The method of claim 15 , wherein one of the reduced side effects comprises reduced respiratory depression in the patient.

Assignees

• Kempharm Inc

Inventors

• Mickle Travis
• Guenther Sven
• Mickle Christal
• Chi Guochen
• Kanski Jaroslaw
• Martin Andrea K
• Bera Bindu

Classifications

• A61K2300/00

  Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00 · CPC title

• A61K31/167 Primary

  having the nitrogen of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol · CPC title

• A61K31/485

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

• A61K47/542

  Carboxylic acids, e.g. a fatty acid or an amino acid · CPC title

• A61K47/55

  the modifying agent being also a pharmacologically or therapeutically active agent, i.e. the entire conjugate being a codrug · CPC title