Devices and methods for pain management

• US 6,541,021 B1
• Filed: 03/10/2000
• Issued: 04/01/2003
• Est. Priority Date: 03/18/1999
• Status: Expired due to Fees

• Current Assignee: DURECT Corporation
• Original Assignee: DURECT Corporation
• Inventors: Theeuwes, Felix, Johnson, Randolph Mellus
• Primary Examiner(s): Page, Thurman K.
• Assistant Examiner(s): GHALI, ISIS A D
• Application Number:
  US09/522,535
• Time in Patent Office: 1,117 Days
• Field of Search: 424/449, 424/443, 424/423, 514/12
• US Class Current: 424/422
• 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:

completely implanting in a subject, at an implantation site, a controlled release drug delivery device comprising a pump and a formulation, the formulation comprising a drug selected from the group consisting of fentanyl and a fentanyl congener, wherein the formulation comprises an amount of the drug sufficient for treatment of pain in the subject for a period of at least about 3 days, and wherein the implantation site is selected from the group consisting of a subcutaneous site, a subdermal site, an intramuscular site, an intra-adipose tissue site, and an intra-lymphatic site; and

parenterally delivering the formulation from the drug delivery device to the subject whereby the drug enters the systemic circulation and is thereby transported to a site of action, whereby the drug is present at the site of action in an amount sufficient to treat pain.

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 microliters per day to about 2 milliliters per day.

4. The method of claim 1, wherein the drug in the formulation is delivered at a rate of from about 0.01 micrograms per hour to 200 micrograms 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 pump is selected from the group consisting of an electromechanical pump, an electroosmotic pump, a hydrolytic pump, a piezoelectric pump, an elastomeric pump, a vapor pressure pump, and an electrolytic pump.

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

9. The method of claim 1, wherein the formulation comprises an amount of the drug sufficient to provide for treatment of pain in the subject for a period of more than 30 days.

10. The method of claim 1, wherein the formulation comprises an amount of the drug sufficient to provide for treatment of pain in the subject for a period of more than 100 days.

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

12. The method of claim 11, wherein sufentanil is delivered at a rate of from about 0.01 μ

g/hr to about 200 μ

g/hr.

47. The method of claim 1, wherein the pump comprises an osmotic pump.

50. The method of claim 1, wherein the drug is delivered at a rate of from about 3 micrograms per hour to 85 micrograms per hour.

51. The method of claim 1, wherein the drug is delivered at a rate of from about 5 micrograms per hour to 200 micrograms per hour.

78. The method of claim 1, wherein the drug is fentanyl.

82. The method of claim 1, wherein the formulation is delivered at a volume rate of less than 100 μ

l per day.

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

completely implanting in a subject, at an implantation site, a controlled release drug delivery device comprising a pump and a formulation comprising sufentanil, wherein the formulation comprises an amount of sufentanil sufficient for treatment of pain in the subject for a period of at least about 3 days, and wherein the implantation site is selected from the group consisting of a subcutaneous site, a subdermal site, an intramuscular site, an intra-adipose tissue site, and an intra-lymphatic site; and

parenterally delivering the formulation to the subject whereby sufentanil enters the systemic circulation and is thereby transported to a site of action, and whereby sufentanil is present at the site of action in an amount sufficient to treat pain.

14. The method of claim 13, wherein the formulation comprises an amount of sufentanil sufficient for treatment of pain in the subject for a period of more than 20 days.

41. The method of claim 13, wherein the drug delivery device is implanted at a subcutaneous site.

42. The method of claim 13, wherein the formulation is delivered at a volume rate of from about 0.01 microliters per day to about 2 milliliters per day.

43. The method of claim 13, wherein said delivering of the formulation is substantially continuous.

44. The method of claim 13, wherein said delivering is for a period of from about 4 weeks to 12 months.

45. The method of claim 13, wherein the drug delivery device comprises an amount of sufentanil sufficient to provide for treatment of pain in the subject for a period of more than 30 days.

46. The method of claim 13, wherein the drug delivery device comprises an amount of sufentanil sufficient to provide for treatment of pain in the subject for a period of more than 100 days.

52. The method of claim 13, wherein sufentanil is delivered at a rate of from about 3 micrograms per hour to 85 micrograms per hour.

53. The method of claim 13, wherein sufentanil is delivered at a rate of from about 5 micrograms per hour to 200 micrograms per hour.

60. The method of claim 13, wherein the drug delivery device comprises an amount of sufentanil sufficient for treatment of pain in the subject for a period of more than 30 days.

83. The method of claim 13, wherein the formulation is delivered at a volume rate of less than 100 μ

l per day.

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

administering parenterally to the subject, from a completely implanted drug delivery device comprising a pump, a formulation comprising a drug selected from the group consisting of fentanyl and a fentanyl congener, wherein the device is implanted at an implantation site selected from the group consisting of a subcutaneous site, a subdermal site, an intramuscular site, all intra-adipose tissue site, and an intra-lymphatic site, said administering being at a volume rate of less than about 2 ml/day, wherein the drug enters the systemic circulation and is thereby transported to a site of action, and wherein said administering is for a period of at least about 3 days, and whereby the drug is present at the site of action in an amount sufficient to treat pain in the subject.

16. The method of claim 15, wherein the formulation comprises a drug present in a concentration of from about 1 mg/ml to about 450 mg/ml.

17. The method of claim 15, wherein the pump is selected from the group consisting of an electromechanical pump, an electroosmotic pump, a hydrolytic pump, a piezoelectric pump, an elastomeric pump, a vapor pressure pump, and an electrolytic pump.

18. The method of claim 15, wherein systemic delivery is substantially continuous.

19. The method of claim 15, wherein said administering is for a period of from about 4 weeks to 12 months.

20. The method of claim 15, wherein the formulation comprises sufentanil.

21. The method of claim 20, wherein sufentanil is delivered at a rate of from about 0.01 μ

g/hr to about 200 μ

g/hr.

22. The method of claim 20, wherein the formulation comprises an amount of sufentanil sufficient for treatment of pain in the subject for a period of more than 7 days.

23. The method of claim 20, wherein the formulation comprises an amount of sufentanil sufficient for treatment of pain in the subject for a period of more than 20 days.

25. The device of claim 21, wherein the formulation comprises an amount of the drug sufficient for treatment of pain in the subject for a period of at least about 3 days to about 10 days.

27. The device of claim 25, wherein the formulation comprises an amount of drug sufficient for treatment of pain in the subject for a period of at least about 100 days.

48. The method of claim 15, wherein the pump comprises an osmotic pump.

54. The method of claim 15, wherein the drug is delivered at a rate of from about 3 micrograms per hour to 85 micrograms per hour.

55. The method of claim 15, wherein the drug is delivered at a rate of from about 5 micrograms per hour to 200 micrograms per hour.

56. The device of claim 25, wherein the device is adapted for delivery of drug at a rate of from about 3 micrograms per hour to 85 micrograms per hour.

61. The method of claim 15, wherein the drug delivery device comprises an amount of drug sufficient for treatment of pain in the subject for a period of more than 30 days.

79. The method of claim 15, wherein the drug is fentanyl.

84. The method of claim 15, wherein the formulation is delivered at a volume rate of less than 100 μ

l per day.

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

a controlled drug delivery device adapted for complete implantation at an implantation site in a subject, the device comprising a pump and a formulation comprising a drug selected from the group consisting of fentanyl and a fentanyl congener, wherein the implantation site is selected from the group consisting of a subcutaneous site, a subdermal site, an intramuscular site, an intra-adipose tissue site, and an intra-lymphatic site, and wherein the formulation comprises an amount of the drug sufficient for treatment of pain in the subject for a period of at least about 3 days;

wherein the implantable device is adapted for parenteral delivery of the formulation to the subject for transport of the drug by the systemic circulation to a site of action in the subject, whereby the drug is present at the site of action in an amount effective for treatment of pain.

26. The device of claim 24, wherein the formulation comprises an amount of the drug sufficient for treatment of pain in the subject for a period of at least about 4 weeks.

28. The device of claim 24, wherein the device delivers the formulation at a rate of from about 0.01 micrograms of the drug per hour to 200 micrograms of the drug per hour.

29. The device of claim 24, wherein the formulation comprises sufentanil.

30. The device of claim 24, wherein the device is adapted for delivery of the formulation at a volume rate of from about 0.01 microliters per day to 2 milliliters per day.

31. The device of claim 24, wherein the formulation comprises an amount of the drug sufficient for treatment of pain in the subject for a period of more than 7 days.

32. The device of claim 24, wherein the formulation comprises an amount of the drug sufficient for treatment of pain in the subject for a period of more than 20 days.

33. The device of claim 24, wherein the formulation comprises an amount of the drug sufficient for treatment of pain in the subject for a period of more than 30 days.

49. The device of claim 24, wherein the pump is an osmotic pump.

57. The device of claim 24, wherein the device is adapted for delivery of drug at a rate of from about 5 micrograms per hour to 200 micrograms per hour.

62. The device of claim 24, wherein the drug delivery device comprises an amount of drug sufficient for treatment of pain in the subject for a period of more than 30 days.

80. The device of claim 24, wherein the drug is fentanyl.

85. The device of claim 24, wherein the device is adapted for delivery of the formulation at a volume rate of less than 100 μ

l per day.

34. A method for treating pain in a subject, the method comprising:

implanting in a subject a controlled release drug delivery device, wherein said drug delivery device comprises a pump operatively connected to a housing, wherein said housing defines a reservoir and said reservoir contains a formulation, wherein said formulation comprises a drug selected from the group consisting of fentanyl and a fentanyl congener, and wherein said implanting is at a implantation site selected from the group consisting of a subcutaneous site, a subdermal site, an intramuscular site, an intra-adipose tissue site, and an intra-lymphatic site; and

delivering parenterally and systemically from said drug delivery device said formulation in an amount sufficient to treat pain in said subject for a period of at least about 3 days, and wherein said drug delivery device is completely implanted in said subject.

35. The method of claim 34, wherein the pump selected from the group consisting of:

an electromechanical pump, and electroosmotic pump, an effervescent pump, a hydraulic pump, a piezoelectric pump, an elastomeric pump, a vapor pressure pump, and an electrolytic pump.

36. The method of claim 34 where said drug delivery device is implanted at a subcutaneous site.

37. The method of claim 34 wherein said formulation is delivered at a volume rate from about 0.01 microliters per day to about 2 milliliters per day.

38. The method of claim 34 wherein said delivering of said formulation is substantially continuous.

39. The method of claim 34 wherein said drug delivery device is coupled to a proximal end of a catheter for delivery of said formulation to a distal end of said catheter at location set apart from said drug delivery device.

40. The method of claim 34 wherein the drug is delivered at a rate from about 0.01 micrograms per hour to about 200 micrograms per hour.

58. The method of claim 34, wherein the drug is delivered at a rate of from about 3 micrograms per hour to 85 micrograms per hour.

59. The method of claim 34, wherein the drug is delivered at a rate of from about 5 micrograms per hour to 200 micrograms per hour.

63. The method of claim 34, wherein the drug delivery device comprises an amount of drug sufficient for treatment of pain in the subject for a period of more than 30 days.

81. The method of claim 34, wherein the drug is fentanyl.

86. The method of claim 34, wherein the formulation is delivered at a volume rate of less than 100 μ

l per day.

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

a controlled release drug delivery device adapted for complete implantation at an implantation site in a subject, the device comprising a pump and a formulation comprising sufentanil, wherein the formulation comprises an amount of sufentanil sufficient for treatment of pain in the subject for a period of at least about 3 days, and wherein the implantation site is selected from the group consisting of a subcutaneous site, a subdermal site, an intramuscular site, an intra-adipose tissue site, and an intra-lymphatic site; and

wherein the drug delivery device is adapted for parenteral delivery of the formulation to the subject for transport of the drug by the systemic circulation to a site of action in the subject, whereby the drug is present at the site of action in an amount effective for treatment of pain.

65. The device of claim 64, wherein the drug delivery device comprises an amount of the drug sufficient for treatment of pain in the subject for a period of more than 30 days.

66. The device of claim 64, wherein the device is suitable for delivery of fentanyl or fentanyl congener at a volume rate of from about 0.01 microliters per day to 2 milliliters per day.

67. The device of claim 64, wherein the device is adapted for delivery of drug in the formulation at a rate of from about 3 micrograms per hour to 85 micrograms per hour.

68. The device of claim 64, wherein the device is adapted for delivery of drug in the formulation at a rate of from about 5 micrograms per hour to 200 micrograms per hour.

69. The device of claim 64, wherein the pump is an osmotic pump.

87. The device of claim 64, wherein the device is adapted for delivery of the formulation at a volume rate of less than 100 μ

l per day.

70. A device for treatment of pain, comprising:

a controlled release drug delivery device adapted for complete implantation at an implantation site in a subject, the device comprising a pump operably connected to housing, wherein said housing defines a reservoir and said reservoir comprises a formulation, wherein said formulation comprises a drug selected from the group consisting of fentanyl and a fentanyl congener, wherein the drug is in an amount sufficient for treatment of pain in the subject for a period of at least about 3 days, and wherein the implantation site is selected from the group consisting of a subcutaneous site, a subdermal site, an intramuscular site, an intra-adipose tissue site, and an intra-lymphatic site;

wherein the drug delivery device is adapted for parenteral delivery of the drug to the subject for transport of the drug by the systemic circulation to a site of action in the subject, whereby the drug is present at the site of action in an amount effective for treatment of pain.

71. The device of claim 70, wherein the drug delivery device comprises an amount of the drug sufficient for treatment of pain in the subject for a period of more than 30 days.

72. The device of claim 70, wherein the device is suitable for delivery of the drug at a volume rate of from about 0.01 microliters per day to 2 milliliters per day.

73. The device of claim 70, wherein the device is adapted for delivery of the drug in the formulation at a rate of from about 3 micrograms per hour to 85 micrograms per hour.

74. The device of claim 70, wherein the device is adapted for delivery of drug in the formulation at a rate of from about 5 micrograms per hour to 200 micrograms per hour.

75. The device of claim 70, wherein the pump is an osmotic pump.

76. The device of claim 70, wherein the drug is fentanyl.

77. The device of claim 70, wherein the drug is sufentanil.

88. The device of claim 70, wherein the device is adapted for delivery of the formulation at a volume rate of less than 100 μ

l per day.