Benzoic acid, benzoic acid derivatives and heteroaryl carboxylic acid conjugates of hydrocodone, prodrugs, methods of making and use thereof
View Patent ↗The presently described technology provides compositions comprising aryl carboxylic acids chemically conjugated to hydrocodone (morphinan-6-one, 4,5-alpha-epoxy-3-methoxy-17-methyl) to form novel prodrugs/compositions of hydrocodone, including benzoates and heteroaryl carboxylic acids, which have a decreased potential for abuse of hydrocodone. The present technology also provides methods of treating patients, pharmaceutical kits and methods of synthesizing conjugates of the present technology.
1. A method for treating pain in an individual comprising the step of orally administering a pharmaceutically effective amount of a composition comprising a conjugate, wherein the conjugate is benzoate-hydrocodone (Bz-HC) having the following structure:
2. The method of claim 1 wherein the conjugate exhibits an improved AUC and rate of release over time when compared to unconjugated hydrocodone over the same time period; exhibits less variability in the oral PK profile when compared to unconjugated hydrocodone; or has reduced side effects when compared with unconjugated hydrocodone.
3. 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.
4. The method of claim 1 wherein the conjugate is provided in an amount sufficient to provide a therapeutically bioequivalent AUC when compared to unconjugated hydrocodone.
5. The method of claim 1 wherein the conjugate is provided in an amount sufficient to provide a therapeutically bioequivalent AUC and C max when compared to an equivalent molar amount of unconjugated hydrocodone.
6. The method of claim 1 wherein the conjugate is provided in an amount sufficient to provide a therapeutically bioequivalent AUC and a lower C max when compared to an equivalent molar amount of unconjugated hydrocodone.
7. The method of claim 1 wherein the composition is used for treating pain mediated by binding of an opioid primarily to μ opioid receptors of the patient.
8. The method of claim 7 , wherein the conjugate binds reversibly to the μ opioid receptors of the patient.
9. The method of claim 7 , wherein the conjugate binds reversibly to the μ opioid receptors of the patient without a CNS depressive effect.
10. The method of claim 1 wherein the composition also reduces narcotic or opioid abuse.
11. The method of claim 1 wherein the composition also reduces narcotic or opioid withdrawal.
12. The method of claim 1 wherein the composition also reduces oral, intranasal or intravenous narcotic or opioid abuse.
13. The method of claim 1 wherein the composition also provides oral, intranasal or parenteral narcotic or opioid abuse resistance.