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-10577376-B2
Application number	US-201715843875-A
Country	US
Kind code	B2
Filing date	Dec 15, 2017
Priority date	Jul 2, 2009
Publication date	Mar 3, 2020
Grant date	Mar 3, 2020

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, acute or chronic 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:
a) the benzoate-hydrocodone hydrochloride has reduced side effects when compared with an equivalent molar amount of unconjugated hydrocodone, and/or
b) the benzoate-hydrocodone hydrochloride exhibits lower mean exposure to hydrocodone when administered at about more than 53 mg when compared to an equivalent molar amount of unconjugated hydrocodone.

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

3. 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.

4. The method of claim 1 , 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.

5. 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.

6. 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.

7. The method of claim 1 , wherein one of the reduced side effects comprises reduced respiratory depression in the patient.

8. The method of claim 1 , wherein the method is for acute pain.

9. The method of claim 1 , wherein the method is for chronic pain.

10. The method of claim 5 , wherein the composition is provided in a tablet dosage.

11. The method of claim 10 , wherein the tablet comprises 6.67 mg of benzoate-hydrocodone hydrochloride.

12. The method of claim 11 , wherein the tablet comprises 6.12 mg of benzoate-hydrocodone.

13. The method of claim 1 , wherein the pharmaceutically effective amount of the composition is provided in a pharmaceutical kit comprising one or more individual doses.

14. The method of claim 13 , wherein the pharmaceutical kit comprises about 1 individual dose to about 100 individual dosages.

15. The method of claim 14 , wherein the individual dosages comprises from about 1 to about 60 individual dosages.

16. The method of claim 15 , wherein the individual dosages comprises from about 10 to about 30 individual dosages.

17. The method of claim 1 , wherein the composition further comprises one or more of microcrystalline cellulose, crospovidone, starch 1500 G, povidone K30, or stearic acid.

Assignees

• Kempharm Inc

Inventors

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

Classifications

• A61K47/556

  enzyme catalyzed therapeutic agent [ECTA] · CPC title

• A61K47/542

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

• C07D491/08

  Bridged systems · CPC title

• 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

• A61K47/55

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