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-10654863-B2
Application number	US-201815901828-A
Country	US
Kind code	B2
Filing date	Feb 21, 2018
Priority date	Jul 2, 2009
Publication date	May 19, 2020
Grant date	May 19, 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 of treating a patient having acute pain, comprising orally administering to the patient a pharmaceutically effective amount of a composition comprising benzhydrocodone and acetaminophen in an amount of 6.12 mg benzhydrocodone and 325 mg acetaminophen.

2. The method of claim 1 , wherein the composition is in the form of a tablet.

3. The method of claim 2 , wherein the tablet is an immediate release tablet.

4. The method of claim 3 , wherein the tablet is administered as a dosage of 1 to 2 tablets every 4 to 6 hours.

5. The method of claim 4 , wherein the dosage is up to 12 tablets in a 24 hour period.

6. The method of claim 4 , wherein the dosage is up to 10 tablets in a 24 hour period.

7. The method of claim 4 , wherein the dosage is up to 8 tablets in a 24 hour period.

8. The method of claim 4 , wherein the dosage is up to 6 tablets in a 24 hour period.

9. The method of claim 4 , wherein the dosage is up to 4 tablets in a 24 hour period.

10. The method of claim 4 , wherein administration of the composition is for a period of time not exceeding 14 days.

11. The method of claim 3 , wherein the tablet is contained in a blister pack.

12. The method of claim 3 , wherein the benzhydrocodone is in the form of benzhydrocodone hydrochloride, and wherein the 6.12 mg benzhydrocodone is equivalent to 6.67 mg benzhydrocodone hydrochloride.

13. The method of claim 3 , wherein the 6.12 mg benzhydrocodone is equivalent to 4.54 mg hydrocodone.

14. A method of treating a patient having pain, comprising orally administering to the patient from 1 to 2 immediate release tablets every 4 to 6 hours, wherein each tablet comprises a composition comprising 6.12 mg benzhydrocodone and 325 mg acetaminophen.

15. The method of claim 14 , wherein up to 12 tablets are administered in a 24 hour period.

16. The method of claim 14 , wherein up to 10 tablets are administered in a 24 hour period.

17. The method of claim 14 , wherein up to 8 tablets are administered in a 24 hour period.

18. The method of claim 14 , wherein up to 6 tablets are administered in a 24 hour period.

19. The method of claim 14 , wherein up to 4 tablets are administered in a 24 hour period.

20. The method of claim 14 , wherein administration of the composition is for a period of time not exceeding 14 days.

21. A method of treating a patient having pain, comprising orally administering to the patient from 1 to 2 immediate release tablets every 4 to 6 hours, wherein each tablet comprises the composition of claim 1 .

22. The method of claim 21 , wherein up to 12 tablets are administered in a 24 hour period.

23. The method of claim 21 , wherein up to 10 tablets are administered in a 24 hour period.

24. The method of claim 21 , wherein up to 8 tablets are administered in a 24 hour period.

25. The method of claim 21 , wherein up to 6 tablets are administered in a 24 hour period.

26. The method of claim 21 , wherein up to 4 tablets are administered in a 24 hour period.

27. The method of claim 21 , wherein administration of the composition is for a period of time not exceeding 14 days.

28. The method of claim 21 , wherein the pain is acute pain.

29. A method of treating a patient having pain, comprising orally administering to the patient a pharmaceutically effective amount of a composition that comprises from about 3 mg to about 54 mg benzhydrocodone hydrochloride and optionally from about 150 mg to about 350 mg acetaminophen.

30. The method of claim 29 , wherein the composition comprises about 3.33 mg, about 4.45 mg, about 8.90 mg, about 13.34 mg, about 26.68 mg, or about 53.36 mg benzydrocodone hydrochloride.

31. The method of claim 30 , wherein the composition comprises about 150 mg, about 162 mg, about 216.67 mg, about 200 mg, about 225 mg, about 250 mg, about 275 mg, about 300 mg, about 325 mg or about 350 mg acetaminophen.

32. The method of claim 29 , wherein the composition comprises about 4.45 mg benzydrocodone hydrochloride, and about 325 mg acetaminophen.

33. The method of claim 32 , wherein the composition is in the form of a tablet.

34. The method of claim 33 , wherein the tablet is an immediate release tablet.

35. The method of claim 34 , wherein the tablet is administered as a dosage of 1 to 2 tablets every 3 to 4 hours.

36. The method of claim 35 , wherein the dosage is up to 12 tablets in a 24 hour period.

37. The method of claim 29 , wherein the composition comprises 8.9 mg benzydrocodone hydrochloride, and 325 mg acetaminophen.

38. The method of claim 37 , wherein the composition is in the form of a tablet.

39. The method of claim 38 , wherein the tablet is administered as a dosage of 1 to 2 or 1 to 1.5 tablets or 1 tablet every 4 to 6 hours.

40. The method of claim 39 , wherein the dosage is up to 12 tablets in a 24 hour period.

41. The method of claim 29 , wherein the composition comprises 13.34 mg benzydrocodone hydrochloride.

42. The method of claim 41 , wherein the 13.34 mg benzhydrocodone hydrochloride is equivalent to 12.24 mg benzhydrocodone.

43. The method of claim 29 , wherein the composition comprises 13.34 mg benzydrocodone hydrochloride, and 325 mg acetaminophen.

44. The method of claim 43 , wherein the composition is in the form of a tablet.

45. The method of claim 44 , wherein the tablet is administered as a dosage of 1 to 2 or 1 to 1.5 tablets or 1 tablet every 4 to 6 hours.

46. The method of claim 45 , wherein the dosage is up to 6 tablets in a 24 hour period.

Assignees

• Kempharm Inc

Inventors

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

Classifications

• C07D491/08

  Bridged systems · CPC title

• A61K47/545

  Heterocyclic compounds (A61K47/558 takes precedence) · CPC title

• A61K45/06

  Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca · CPC title

• A61P25/30

  for treating abuse or dependence · CPC title

• A61K31/167 Primary

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