.

Pharmaceutical Business Intelligence

  • Anticipate P&T budget requirements
  • Evaluate market entry opportunities
  • Find generic sources and suppliers
  • Predict branded drug patent expiration

► Plans and Pricing

Upgrade to enjoy subscriber-only features like email alerts and data export. See the Plans and Pricing

DrugPatentWatch Database Preview

Claims for Patent: 6,277,384

« Back to Dashboard

Claims for Patent: 6,277,384

Title: Opioid agonist/antagonist combinations
Abstract:The invention is directed in part to oral dosage forms comprising a combination of an orally analgesically effective amount of an opioid agonist and an orally active opioid antagonist, the opioid antagonist being included in a ratio to the opioid agonist to provide a combination product which is analgesically effective when the combination is administered orally, but which is aversive in a physically dependent subject. Preferably, the amount of opioid antagonist included in the combination product provides at least a mildly negative, "aversive" experience in physically dependent addicts (e.g., precipitated abstinence syndrome).
Inventor(s): Kaiko; Robert F. (Weston, CT), Colucci; Robert D. (Newtown, CT)
Assignee: Euro-Celtique S.A. (Luxembourg)
Application Number:09/218,662
Patent Claims: 1. An oral dosage form, comprising an orally therapeutically effective dose of an opioid agonist, and an opioid antagonist, the dosage form having a ratio of opioid antagonist to opioid agonist that provides a combination product which is analgesically effective when the combination is administered orally, but which (i) is aversive in physically dependent human subjects when administered at the same dose or at a higher dose than said therapeutically effective dose; and (ii) maintains an analgesic effect but does not increase analgesic efficacy of the opioid agonist relative to the same therapeutic dose of opioid analgesic when administered to human patients without said opioid antagonist.

2. The oral dosage form of claim 1, wherein the amount of antagonist included in the oral dosage form causes an aversive experience in a physically dependent addict taking about 2-3 times said therapeutically effective dose.

3. The oral dosage form of claim 1, wherein the opioid agonist is hydrocodone and the antagonist is naltrexone.

4. The oral dosage form of claim 3, wherein the ratio of naltrexone to hydrocodone is from about 0.03:1 to about 0.27:1.

5. The oral dosage form of claim 3, wherein the ratio of naltrexone to hydrocodone is from about 0.05:1 to about 0.20:1.

6. The oral dosage form of claim 1, wherein the opioid agonist is selected from the group consisting of morphine, hydromorphone, hydrocodone, oxycodone, codeine, levorphanol, meperidine, methadone, and mixtures thereof.

7. The oral dosage form of claim 1, further comprising an additional non-opioid drug selected from the group consisting of an NSAID, a COX-2 inhibitor, acetaminophen, aspirin, an NMDA receptor antagonist, a drug that blocks a major intracellular consequence of NMDA-receptor activation, an antitussive, an expectorant, a decongestant, an antihistamine and mixtures thereof.

8. The oral dosage form of claim 1, further comprising one or more pharmaceutically acceptable inert excipients.

9. The oral dosage form of claim 6, wherein said opioid antagonist is selected from the group consisting of naltrexone, naloxone, nalmephene, cyclazocine, levallorphan, and mixtures thereof.

10. The oral dosage form of claim 6, wherein said opioid antagonist is naltrexone.

11. The oral dosage form of claim 1, further comprising a sustained release carrier which imparts sustained release properties to said opioid agonist.

12. The oral dosage form of claim 1, wherein said opioid antagonist is naltrexone and said opioid agonist is oxycodone, wherein the ratio of naltrexone to oxycodone is from about 0.037:1 to about 0.296:1.

13. The oral dosage form of claim 1, wherein said opioid antagonist is naltrexone and said opioid agonist is codeine, wherein the ratio of naltrexone to codeine is from about 0.005:1 to about 0.044:1.

14. The oral dosage form of claim 1, wherein said opioid antagonist is naltrexone and said opioid agonist is hydromorphone, wherein the ratio of naltrexone to hydromorphone is from about 0.148:1 to about 1.185:1.

15. The oral dosage form of claim 1, wherein said opioid antagonist is naltrexone and said opioid agonist is levorphanol, wherein the ratio of naltrexone to levorphanol is from about 0.278:1 to about 2.222:1.

16. The oral dosage form of claim 1, wherein said opioid antagonist is naltrexone and said opioid agonist is meperidine, wherein the ratio of naltrexone to meperidine is from about 0.0037:1 to about 0.0296:1.

17. The oral dosage form of claim 1, wherein said opioid antagonist is naltrexone and said opioid agonist is methadone, wherein the ratio of naltrexone to methadone is from about 0.056:1 to about 0.444:1.

18. The oral dosage form of claim 1, wherein said opioid antagonist is naltrexone and said opioid agonist is morphine, wherein the ratio of naltrexone to morphine is from about 0.018:1 to about 0.148:1.

19. The oral dosage form of claim 1, wherein said opioid antagonist is naltrexone and said opioid agonist is oxycodone, wherein the ratio of naltrexone to oxycodone is from about 0.056:1 to about 0.222:1.

20. The oral dosage form of claim 1, wherein said opioid antagonist is naltrexone and said opioid agonist is codeine, wherein the ratio of naltrexone to codeine is from about 0.0083:1 to about 0.033:1.

21. The oral dosage form of claim 1, wherein said opioid antagonist is naltrexone and said opioid agonist is hydromorphone, wherein the ratio of naltrexone to hydromorphone is from about 0.222:1 to about 0.889:1.

22. The oral dosage form of claim 1, wherein said opioid antagonist is naltrexone and said opioid agonist is levorphanol, wherein the ratio of naltrexone to levorphanol is from about 0.417:1 to about 1.667:1.

23. The oral dosage form of claim 1, wherein said opioid antagonist is naltrexone and said opioid agonist is meperidine, wherein the ratio of naltrexone to meperidine is from about 0.0056:1 to about 0.022:1.

24. The oral dosage form of claim 1, wherein said opioid antagonist is naltrexone and said opioid agonist is methadone, wherein the ratio of naltrexone to methadone is from about 0.083:1 to about 0.333:1.

25. The oral dosage form of claim 1, wherein said opioid antagonist is naltrexone and said opioid agonist is morphine, wherein the ratio of naltrexone to morphine is from about 0.028:1 to about 0.111:1.

26. A method of preventing oral abuse of an oral opioid formulation, comprising preparing an oral dosage form which comprises a therapeutically effective dose of an opioid agonist and incorporating therein an opioid antagonist in a ratio to said opioid agonist such that the oral dosage form is analgesically effective when administered orally, but (i) is aversive in physically dependent human subjects when administered at the same dose or at a higher dose than said therapeutically effective dose; and (ii) maintains an analgesic effect but does not increase analgesic efficacy of the opioid agonist relative to the same therapeutic dose of opioid analgesic when administered to human patients without said opioid antagonist.

27. The method of claim 26, wherein the amount of antagonist included in the oral dosage form causes an aversive experience in physically dependent addicts taking about 2-3 times said therapeutically effective dose of the opioid.

28. The method of claim 26, wherein the opioid agonist is hydrocodone and the antagonist is naltrexone.

29. The method of claim 28, wherein the ration of naltrexone to hydrocodone is from about 0.03:1 to about 0.27:1.

30. The method of claim 28, wherein the ratio of naltrexone to hydrocodone is from about 0.05:1 to about 0.20:1.

31. The method of claim 26, wherein the opioid agonist or analgesic is selected from the group consisting of morphine, hydromorphone, hydrocodone, oxycodone, codeine, levorphanol, meperidine, methadone, and mixtures thereof and the opioid antagonist is selected from the group consisting of naltrexone, naloxone, nalmephene, cyclazocine, levallorphan, and mixtures thereof.

32. The method of claim 26, wherein the opioid antagonist is naltrexone and the opioid agonist is oxycodone in a naltrexone/oxycodone ratio from about 0.037:1 to about 0.296:1.

33. The method of claim 26, wherein the opioid antagonist is naltrexone and the opioid agonist is oxycodone in a naltrexone/oxycodone ratio from about 0.056:1 to about 0.222:1.

34. The method of claim 26, further comprising incorporating into said oral dosage form an additional non-opioid drug selected from the group consisting of an NSAID, a COX-2 inhibitor, acetaminophen, aspirin, an NMDA receptor antagonist, a drug that blocks a major intracellular consequence of NMDA-receptor activation, an antitussive, an expectorant, a decongestant, an antihistamine and mixtures thereof.

35. The method of claim 26, wherein said oral dosage form further comprises a sustained release carrier such that the dosage form is administrable on a twice-a-day or on a once-a-day basis.

36. The method of claim 26, wherein the opioid antagonist is naltrexone and the opioid agonist is codeine in a naltrexone/codeine ratio from about 0.005:1 to about 0.044:1.

37. The method of claim 26, wherein the opioid antagonist is naltrexone and the opioid agonist is hydromorphone in a naltrexone/hydromorphone ratio from about 0.148:1 to about 1.185:1.

38. The method of claim 26, wherein the opioid antagonist is naltrexone and the opioid agonist is levorphanol in a naltrexone/levorphanol ratio from about 0.278:1 to about 2.222:1.

39. The method of claim 26, wherein the opioid antagonist is naltrexone and the opioid agonist is meperidine in a naltrexone/meperidine ratio from about 0.0037:1 to about 0.0296:1.

40. The method of claim 26, wherein the opioid antagonist is naltrexone and the opioid agonist is methadone in a naltrexone/methadone ratio from about 0.056:1 to about 0.444:1.

41. The method of claim 26, wherein the opioid antagonist is naltrexone and the opioid agonist is morphine in a naltrexone/morphine ratio from about 0.018:1 to about 0.148:1.

42. The method of claim 26, wherein the opioid antagonist is naltrexone and the opioid agonist is codeine in a naltrexone/codeine ratio from about 0.0083:1 to about 0.033:1.

43. The method of claim 26, wherein the opioid antagonist is naltrexone and the opioid agonist is hydromorphone in a naltrexone/hydromorphone ratio from about 0.222:1 to about 0.889:1.

44. The method of claim 26, wherein the opioid antagonist is naltrexone and the opioid agonist is levorphanol in a naltrexone/levorphanol ratio from about 0.417:1 to about 1.667:1.

45. The method of claim 26, wherein the opioid antagonist is naltrexone and the opioid agonist is meperidine in a naltrexone/meperidine ratio from about 0.0056:1 to about 0.022:1.

46. The method of claim 26, wherein the opioid antagonist is naltrexone and the opioid agonist is methadone in a naltrexone/methadone ratio from about 0.083:1 to about 0.333:1.

47. The method of claim 26, wherein the opioid antagonist is naltrexone and the opioid agonist is and morphine in a naltrexonel/morphine ratio from about 0.028:1 to about 0.111:1.

48. The oral dosage form of claim 1, wherein said combination decreases analgesia as assessed by direct measurement in patients or by use of one or more surrogate measures of opioid effect in human subjects.

49. The method of claim 26, wherein said ratio of opioid antagonist to opioid agonist decreases analgesia as assessed by direct measurement in patients or by use of one or more surrogate measures of opioid effect in human subjects.

50. An oral dosage form, comprising an orally therapeutically effective dose of an opioid agonist, and an opioid antagonist, the dosage form having a ratio of opioid antagonist to opioid agonist that provides a combination product which is analgesically effective when the combination is administered orally, but which (i) is aversive in physically dependent human subjects when administered at the same dose or at a higher dose than said therapeutically effective dose; and (ii) maintains or decreases analgesic efficacy of the opioid agonist relative to the same therapeutic dose of opioid analgesic when administered to human patients without said opioid antagonist.
« Back to Dashboard

For more information try a trial or see the database preview and plans and pricing

How are People Using DrugPatentWatch?

Drugs may be covered by multiple patents or regulatory protections. All trademarks and applicant names are the property of their respective owners or licensors. Although great care is taken in the proper and correct provision of this service, thinkBiotech LLC does not accept any responsibility for possible consequences of errors or omissions in the provided data. The data presented herein is for information purposes only. There is no warranty that the data contained herein is error free. thinkBiotech performs no independent verifification of facts as provided by public sources nor are attempts made to provide legal or investing advice. Any reliance on data provided herein is done solely at the discretion of the user. Users of this service are advised to seek professional advice and independent confirmation before considering acting on any of the provided information. thinkBiotech LLC reserves the right to amend, extend or withdraw any part or all of the offered service without notice.

`abc