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-9872915-B2
Application number	US-201514816915-A
Country	US
Kind code	B2
Filing date	Aug 3, 2015
Priority date	Jul 2, 2009
Publication date	Jan 23, 2018
Grant date	Jan 23, 2018

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

The invention claimed is:

1. 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 comprising acetaminophen and benzoate-hydrocodone hydrochloride wherein the composition has reduced side effects when compared with unconjugated hydrocodone.

2. The method of claim 1 , wherein the composition comprises benzoate-hydrocodone hydrochloride and acetaminophen having a molar ratio from 0.001:1 to 1000:1.

3. The method of claim 1 , wherein the composition is a conjugate.

4. The method of claim 1 , wherein the composition is a prodrug.

5. The method of claim 1 , 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.

6. The method of claim 1 , wherein the composition exhibits an improved AUC and rate of release of hydrocodone over time when compared to unconjugated hydrocodone over the same time period; exhibits lower exposure to hydrocodone at about more than 53 mg when compared to an equivalent molar amount of unconjugated hydrocodone.

7. The method of claim 1 , wherein the composition exhibits an improved AUC and rate of release of hydromorphone over time when compared to unconjugated hydrocodone over the same time period; exhibits lower exposure to hydromorphone at about more than 53 mg when compared to an equivalent molar amount of unconjugated hydrocodone.

8. The method of claim 1 , wherein the composition exhibits lower maximum peak exposure (C max ) to hydrocodone at about more than 53 mg when compared to an equivalent molar amount of unconjugated hydrocodone.

9. The method of claim 1 , wherein the composition exhibits lower maximum peak exposure (C max ) to hydromorphone at about more than 53 mg when compared to an equivalent molar amount of unconjugated hydrocodone.

10. The method of claim 1 , 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.

11. The method of claim 1 , 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.

12. The method of claim 1 , 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.

13. The method of claim 1 , wherein one of the reduced side effects comprises a lower than normal concentration of oxygen in arterial blood of the patient.

14. The method of claim 1 , wherein one of the reduced side effects comprises 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

• C07D489/02 Primary

  with oxygen atoms attached in positions 3 and 6, e.g. morphine, morphinone · CPC title

• C07D491/08

  Bridged systems · CPC title

• A61K47/556

  enzyme catalyzed therapeutic agent [ECTA] · CPC title

• A61K31/167 Primary

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