Devices and methods for pain management

• US 20030171401A1
• Filed: 11/26/2002
• Published: 09/11/2003
• Est. Priority Date: 03/18/1999
• Status: Active Grant

• Current Assignee: DURECT Corporation
• Original Assignee: DURECT Corporation
• Inventors: Theeuwes, Felix, Johnson, Randolph Mellus
• Granted Patent: US 6,689,373 B2
• Time in Patent Office: Days
• US Class Current: 514/317
• CPC Class Codes: A61K 31/4468 having a nitrogen directly attached in position 4, e.g. clebopride, fentanyl
• CPC Class Codes: A61K 31/4535 containing a heterocyclic ring having sulfur as a ring hetero atom, e.g. pizotifen
• CPC Class Codes: A61K 47/10 Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
• CPC Class Codes: A61K 47/14 Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
• CPC Class Codes: A61K 47/26 Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
• CPC Class Codes: A61K 9/0004 Osmotic delivery systems; Sustained release driven by osmosis, thermal energy or gas
• CPC Class Codes: A61K 9/0014 Skin, i.e. galenical aspects of topical compositions non-active ingredients are additionally classified in A61K47/00; A61K9/0009, A61K9/0021, A61K9/7015, A61K9/7023 take precedence; cosmetic preparations A61K8/00, A61Q; preparations for wound dressings or bandages A61L26/00
• CPC Class Codes: A61K 9/0019 Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner non-active ingredients are additionally classified in A61K47/00
• CPC Class Codes: A61K 9/0024 Solid, semi-solid or solidifying implants, which are implanted or injected in body tissue compositions for intravenous administration, normal injectable solutions or dispersions for, e.g. subcutaneous administration A61K9/0019; brain implants A61K9/0085; (coated) prostheses, catheters or stents A61L
• CPC Class Codes: A61M 37/0069 Devices for implanting pellets, e.g. markers or solid medicaments for introducing of radioactive sources for interstitial radiation therapy, i.e. brachytherapy A61N5/1027
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/04 Centrally acting analgesics, e.g. opioids

Abstract

The invention features devices and methods for the systemic delivery of fentanyl or a fentanyl congener (e.g., sufentanil) to treat pain. In the present invention, a drug formulation comprising fentanyl or a fentanyl congener is stored within a drug delivery device (e.g., contained in a reservoir or impregnated within a matrix within the controlled drug delivery device). The drug formulation comprises an amount of drug sufficient for treatment and is stable at body temperatures (i.e., no unacceptable degradation) for the entire pre-selected treatment period. The drug delivery devices store the drug formulation safely (e.g., without dose dumping), provide sufficient protection from bodily processes to prevent unacceptable degradation of the formulation, and release the drug formulation in a controlled fashion at a therapeutically effective rate to treat pain. In use, the drug delivery device is implanted in the subject'"'"'s body at an implantation site, and the drug formulation is released from the drug delivery device to a delivery site. The delivery site may be the same as, near, or distant from the implantation site. Once released at the delivery site, the drug formulation enters the systemic circulation and is transported to the site of action in the body to modulate the pain response (e.g., the brain or other pain sensory location).

Claims

1. A method of treating pain in a subject, the method comprising the steps of:

implanting a controlled release drug delivery device in an implantation site in the body of the subject; and

delivering systemically from said drug delivery device a formulation comprising fentanyl or a fentanyl congener in an amount effective to alleviate pain in the subject.

2. The method of claim 1, wherein the drug delivery device is implanted at a subcutaneous site.

3. The method of claim 1, wherein the formulation is delivered at a volume rate of from about 0.01 μ

l/day to 2 ml/day.

4. The method of claim 1, wherein the fentanyl or a fentanyl congener in the formulation is delivered at a rate of from about 0.01 μ

g per hour to 200 μ

g per hour.

5. The method of claim 1, wherein said delivering of the formulation is substantially continuous.

6. The method of claim 1, wherein the drug delivery device is coupled to a proximal end of a catheter for delivery of the formulation to a delivery site at a distance from the implantation site.

7. The method of claim 1, wherein the drug delivery device is a convective drug delivery device.

8. The method of claim 7, wherein the convective device is selected from the group consisting of an electromechanical pump, an electroosmotic pump, a hydrolytic system, a piezoelectric pump, an elastomeric system, a vapor pressure pump, an electrolytic pump and an osmotic bursting matrix.

9. The method of claim 7, wherein the convective device is an osmotic pump.

10. The method of claim 1, wherein the drug delivery device is a diffusion system.

11. The method of claim 1, wherein the drug delivery device is an erodible drug-comprising matrix.

12. The method of claim 1, wherein said delivering is for a period of from about 4 weeks to 12 months.

13. The method of claim 1, wherein the drug delivery device comprises an amount of fentanyl or fentanyl congener sufficient for alleviation of pain in the subject for a period of more than 3 days.

14. The method of claim 1, wherein the drug delivery device comprises an amount of fentanyl or fentanyl congener sufficient to provide for alleviation of pain in the subject for a period of more than 100 days.

15. The method of claim 1, wherein the drug delivery device comprises an amount of fentanyl, or fentanyl congener sufficient to provide for alleviation of pain in the subject for a period of more than 100 days.

16. The method of claim 1, wherein the formulation comprises sufentanil.

17. The method of claim 16, wherein sufentanil is delivered at a rate of from about 0.01 μ

g/hr to about 200 μ

g/hr.

18. The method of claim 16, wherein the drug delivery device comprises an amount of sufentanil sufficient for alleviation of pain in the subject for a period of more than 2 days.

19. The method of claim 16, wherein the drug delivery device comprises an amount of sufentanil sufficient for alleviation of pain in the subject for a period of more than 20 days.

20. A method of treating pain in a subject suffering from pain, the method comprising:

administering a formulation comprising fentanyl or a fentanyl congener to a subject,

said administering being by systemic delivery at a volume rate of less than about 2 μ

l/day;

wherein pain is alleviated in the subject.

21. The method of claim 20, wherein said administering is by implanting a drug delivery device at an implantation site in the subject.

22. The method of claim 20, wherein the implantation site is a subcutaneous site.

23. The method of claim 20, wherein the drug delivery device is a convective device.

24. The method of claim 23, wherein the convective device is selected from the group consisting of an electromechanical pump, an electroosmotic pump, a hydrolytic system, a piezoelectric pump, an elastomeric system, a vapor pressure pump, an electrolytic pump and an osmotic bursting matrix.

25. The method of claim 20, wherein the convective device is an osmotic pump.

26. The method of claim 20, wherein the drug delivery device is a diffusion system.

27. The method of claim 20, wherein the drug delivery device is an erodible drug-comprising matrix.

28. The method of claim 20, wherein systemic delivery is substantially continuous.

29. The method of claim 20, wherein the formulation is administered for a preselected administration period.

30. The method of claim 29, wherein the preselected administration period is from about 4 weeks to 12 months.

31. The method of claim 20, wherein the formulation comprises sufentanil.

32. The method of claim 31, wherein sufentanil is delivered at a rate of from about 0.01 μ

g/hr to about 200 μ

g/hr.

33. The method of claim 31, wherein the formulation is within a drug delivery device implanted in the subject.

34. The method of claim 33, wherein the drug delivery device comprises an amount of sufentanil sufficient for alleviation of pain in the subject for a period of more than 2 days.

35. The method of claim 33, wherein the drug delivery device comprises an amount of sufentanil sufficient for alleviation of pain in the subject for a period of more than 20 days.

36. The method of claim 20, wherein the drug delivery device is substantially completely implanted.

37. A device for the treatment of pain, comprising:

an implantable controlled drug delivery device for implanting at an implantable site in a patient in need of pain treatment, the device comprising a formulation comprising fentanyl or a fentanyl congener;

wherein the implantable device is suitable for delivery of fentanyl or fentanyl congener into the systemic circulation in an amount effective for treatment of pain in the subject.

38. The device of claim 37, wherein the device comprises an amount of formulation sufficient for delivery of an amount of fentanyl or fentanyl congener effective for treatment of pain in the subject for a period of at least about 3 days to about 10 days.

39. The device of claim 37, wherein the device comprises an amount of formulation sufficient for delivery of an amount of fentanyl or fentanyl congener effective for treatment of pain in the subject for a period of at least about 4 weeks.

40. The device of claim 37, wherein the device comprises an amount of formulation sufficient for delivery of an amount of fentanyl or fentanyl congener effective for treatment of pain in the subject for a period of at least about 100 days.

41. The device of claim 37, wherein the device administers formulation at a rate of from about 0.01 μ

g/hour to 200 μ

g/hr.

42. The device of claim 37, wherein the formulation comprises sufentanil.

43. The device of claim 37, wherein the device is suitable for delivery of fentanyl or fentanyl congener at a rate of from about 0.01 μ

g/hr to about 200 μ

g/hr.

44. The device of claim 37, wherein the device is suitable for delivery of fentanyl or fentanyl congener at a volume rate of from about 0.01 μ

l/day to 2 ml/day.

45. The device of claim 37, wherein the drug delivery device comprises an amount of fentanyl or fentanyl congener sufficient for delivery for alleviation of pain in the subject for a period of more than 2 days.

46. The method of claim 37, wherein the drug delivery device comprises an amount of fentanyl or fentanyl congener sufficient for delivery for alleviation of pain in the subject for a period of more than 20 days.

47. The method of claim 37, wherein the drug delivery device comprises an amount of fentanyl or fentanyl congener sufficient for alleviation of pain in the subject for a period of more than 100 days.