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 composition comprising a conjugate, wherein the conjugate is nicotinate-hydrocodone (nicotinate-HC) having the following structure:
2. The composition of claim 1 , wherein the conjugate is used to treat narcotic or opioid abuse; to reduce narcotic or opioid withdrawal; to treat moderate to severe pain; to reduce oral, intranasal or intravenous drug abuse; or to provide oral, intranasal or parenteral drug abuse resistance.
3. The composition 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.
4. The composition of claim 1 , wherein the conjugate 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.
5. The composition of claim 1 , wherein the conjugate is provided in an amount sufficient to provide a therapeutically bioequivalent AUC when compared to unconjugated hydrocodone.
6. The composition 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.
7. The composition 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.
8. A composition comprising a conjugate, wherein the conjugate is 2-aminobenzoate-hydrocodone (2-ABz-HC) having the following structure:
9. The composition of claim 8 , wherein the conjugate is used to treat narcotic or opioid abuse; to reduce narcotic or opioid withdrawal; to treat moderate to severe pain; to reduce oral, intranasal or intravenous drug abuse; or to provide oral, intranasal or parenteral drug abuse resistance.
10. The composition of claim 8 , 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.
11. The composition of claim 8 , wherein the conjugate 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.
12. The composition of claim 8 , wherein the conjugate is provided in an amount sufficient to provide a therapeutically bioequivalent AUC when compared to unconjugated hydrocodone.
13. The composition of claim 8 , 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.
14. The composition of claim 8 , 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.
15. A composition comprising a conjugate, wherein the conjugate is 3-hydroxybenzoate-hydrocodone (3-OH-Bz-HC) having the following structure:
16. The composition of claim 15 , wherein the conjugate is used to treat narcotic or opioid abuse; to reduce narcotic or opioid withdrawal; to treat moderate to severe pain; to reduce oral, intranasal or intravenous drug abuse; or to provide oral, intranasal or parenteral drug abuse resistance.
17. The composition of claim 15 , 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.
18. The composition of claim 15 , wherein the conjugate 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.
19. The composition of claim 15 , wherein the conjugate is provided in an amount sufficient to provide a therapeutically bioequivalent AUC when compared to unconjugated hydrocodone.
20. The composition of claim 15 , 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.
21. The composition of claim 15 , 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.
22. A composition comprising a conjugate, wherein the conjugate is 4-methoxybenzoate-hydrocodone (4-MeO-Bz-HC) having the following structure:
23. The composition of claim 22 , wherein the conjugate is used to treat narcotic or opioid abuse; to reduce narcotic or opioid withdrawal; to treat moderate to severe pain; to reduce oral, intranasal or intravenous drug abuse; or to provide oral, intranasal or parenteral drug abuse resistance.
24. The composition of claim 22 , 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.
25. The composition of claim 22 , wherein the conjugate 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.
26. The composition of claim 22 , wherein the conjugate is provided in an amount sufficient to provide a therapeutically bioequivalent AUC when compared to unconjugated hydrocodone.
27. The composition of claim 22 , 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.
28. The composition of claim 22 , 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.