Devices and methods for pain management

• US 6,689,373 B2
• Filed: 11/26/2002
• Issued: 02/10/2004
• 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:
  US10/306,727
• Publication Number:
  US 20030171401A1
• Time in Patent Office: 441 Days
• Field of Search: 424/422, 424/423, 424/424, 424/425, 424/449, 424/473, 424/484, 424/450, 604/890.1, 604/891.1, 604/892.1, 514/282
• 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 a drug delivery device in a subject at an 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, wherein the drug delivery device is adapted for controlled release of drug, the device comprising;

a formulation comprising a drug selected from the group consisting of fentanyl and a fentanyl congener, wherein the drug is in the formulation in an amount for treatment of pain in the subject for a period of at least about 3 days; and

a housing defining a drug delivery outlet and a reservoir, wherein the formulation is within the reservoir, and the reservoir comprises a biocompatible material impermeable to the formulation; and

parenterally delivering the formulation to the subject from the reservoir and through the drug delivery outlet 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 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.

6. 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.

7. 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.

8. The method of claim 1, wherein the formulation is delivered at a volume rate of less than about 2 ml/day.

9. The method of claim 1, wherein said delivering is for a period of at least about 3 days.

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

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 mcg/hr to about 200 mcg/hr.

13. The method of claim 11, wherein sufentanil is delivered at a rate of from about 3 micrograms per hour to 85 micrograms per hour.

14. The method of claim 11, wherein sufentanil is delivered at a rate of from about 5 micrograms per hour to 200 micrograms per hour.

15. The method of claim 1, 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.

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

drug delivery device adapted for controlled release of drug and for complete implantation at an implantation site in a subject 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, the device comprising

a formulation comprising a drug selected from the group consisting of fentanyl and a fentanyl congener, wherein the drug is in the formulation in an amount for treatment of pain in the subject for a period of at least about 3 days; and

a housing defining a drug delivery outlet and a reservoir, wherein the formulation is within the reservoir, and the reservoir comprises a biocompatible material impermeable to the formulation;

wherein the implantable device is adapted for parenteral delivery of the formulation through the drug delivery outlet and 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.

17. The device of claim 16, wherein the formulation comprises an amount of the drug sufficient for treatment of pain in the subject for a period of at least about 7 days.

18. The device of claim 16, wherein the device is adapted for delivery of the formulation at a rate of from about 0.01 micrograms of the drug per hour to 200 micrograms of the drug per hour.

19. The device of claim 16, wherein the device is adapted for delivery of drug at a rate of from about 5 micrograms per hour to 200 micrograms per hour.

20. The device of claim 16, wherein the formulation comprises sufentanil.

21. The device of claim 16, 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.