Implantable devices and methods for treatment of pain by delivery of fentanyl and fentanyl congeners

• US 6,835,194 B2
• Filed: 06/27/2002
• Issued: 12/28/2004
• Est. Priority Date: 03/18/1999
• Status: Expired due to Fees

• Current Assignee: DURECT Corporation
• Original Assignee: DURECT Corporation
• Inventors: Brown, James, Poutiatine, Andrew, Wickman, Peter, Culwell, John, Filice, James A., Laidlaw, Barbara, Litmanovitz, Dana, Yum, Su-Il, Dinka, John, Gillis, Edward M., Theeuwes, Felix, Johnson, Randolph Mellus
• Primary Examiner(s): Page, Thurman K.
• Assistant Examiner(s): GHALI, ISIS A D
• Application Number:
  US10/188,325
• Publication Number:
  US 20030088236A1
• Time in Patent Office: 915 Days
• Field of Search: 604/890.1, 604/891.1, 604/93.01, 604/131-133, 424/422, 424/449
• US Class Current: 604/890.1
• CPC Class Codes: A61F 2/02 Prostheses implantable into the body closure means for urethra or rectum or for artificial body openings therefor A61F2/0004
• CPC Class Codes: A61F 2250/0067 Means for introducing or releasing pharmaceutical products into the body
• 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 9/0024 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 2005/14264 with means for compensating influence from the environment
• CPC Class Codes: A61M 31/002 Devices for releasing a drug at a continuous and controlled rate for a prolonged period of time artificial gland structures or devices A61F2/022; intra-uterine contraceptive devices A61F6/14; tampons for introducing into the vagina A61F13/20, A61L15/00; suppositories or bougies for intra-vaginal or intra-uterine application A61K9/02; physical forms of medicinal preparations for sustained or differential drug release A61K9/20, A61K9/50
• CPC Class Codes: A61M 5/141 with capillaries for restricting fluid flow
• CPC Class Codes: A61M 5/14276 specially adapted for implantation
• CPC Class Codes: A61M 5/1452 pressurised by means of pistons
• CPC Class Codes: A61M 5/168 Means for controlling media flow to the body or for metering media to the body, e.g. drip meters, counters ; Monitoring media flow to the body flow control in general G05D7/00
• CPC Class Codes: A61M 5/16804 Flow controllers
• CPC Class Codes: A61M 5/16881 Regulating valves on-off valves, e.g. clamps A61M39/28
• CPC Class Codes: A61P 25/04 Centrally acting analgesics, e.g. opioids
• CPC Class Codes: Y02A 50/30 Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

The invention features devices and methods for treatment of pain. The drug delivery device is a drug delivery system adapted for whole implantation in a subject and to provide pain relief by delivery of fentanyl or a fentanyl congener (e.g., sufentanil) over a protracted period of time (e.g., at least 3 days or more than 3 days). The device comprises a housing defining a reservoir that contains a drug formulation, a pump operatively connected to the housing so as to facilitate movement of drug out of the reservoir and out of the device, and a thermal expansion element which defines a flow pathway comprising a thermal expansion channel to accommodate thermal expansion of formulation in the reservoir. The device can further comprise a valve positioned within the flow pathway so as to prevent movement of drug out of the reservoir prior to use.

Claims

1. A controlled drug delivery device, adapted for whole implantation in a subject, the device comprising:

a housing defining a reservoir, the reservoir containing a formulation comprising a drug selected from the group consisting of fentanyl or a fentanyl congener, wherein the drug is present in an amount sufficient for treatment of pain in a subject for a period of at least about 3 days;

a pump operatively connected to the housing; and

a thermal expansion element comprising an inlet, a thermal expansion channel adapted to contain a volume of formulation associated with thermal expansion, and an outlet;

wherein in use, the inlet, thermal expansion channel, and outlet define a flow pathway from the reservoir and out of the device such that actuation of the pump effects movement of formulation through the flow pathway.

2. The device of claim 1, wherein the flow pathway of the thermal expansion element is at least partially defined by a plug seated within the housing.

3. The device of claim 1, wherein the flow pathway of the thermal expansion element is at least partially defined by a plug seated within the housing, and an inner wall of the housing.

4. The device of claim 1, wherein the thermal expansion element comprises a valve positioned and adapted for maintaining a sealed reservoir until opened.

5. The device of claim 4, wherein the thermal expansion element comprises a plunger, wherein at least a portion of the plunger is slidably positioned within the flow pathway and seated within the valve such that when in a closed position the plunger and valve occlude the flow pathway to prevent movement of formulation out of the outlet.

6. The device of claim 1, wherein the flow pathway narrows from a wider inlet and thermal expansion channel to a narrower outlet.

7. The device of claim 1, wherein the device is adapted for delivery of drug at a rate of from about 0.01 micrograms per hour to 2000 micrograms per hour.

8. The device of claim 1, wherein said drug is present in a concentration of about 5 mg/mL to about 400 mg/mL.

9. The device of claim 1, wherein the drug is sufentanil.

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

wholly implanting at an implantation site in a subject the drug delivery device of claim 1; and

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

11. The method of claim 10, wherein the thermal expansion element of the device comprises a valve and a plunger, at least a portion of the plunger being slidably positioned within the flow pathway and seated within the valve such that when in a closed position the plunger and valve occlude the flow pathway to prevent movement of formulation past the thermal expansion channel in a direction toward the outlet, and wherein the method further comprises the step of actuating the plunger so as to open the valve prior to said implanting.

12. The method of claim 10, wherein the drug delivery device is implanted at a subcutaneous site.

13. The method of claim 10, wherein the formulation is delivered at a volume rate of from about 0.01 μ

l/day to 2 ml/day.

14. The method of claim 10, wherein drug is delivered at a rate of from about 0.01 μ

g per hour to 2,000 μ

g per hour.

15. The method of claim 10, wherein the drug is sufentanil.

16. The method of claim 10, wherein said delivering is for a period of from about 4 weeks to 12 months.

17. The method of claim 10, wherein the device comprises an amount of drug sufficient to provide for alleviation of pain in the subject for a period of more than 30 days.

18. A controlled drug delivery device, adapted for whole implantation in a subject, the device comprising:

a housing defining a reservoir, the reservoir containing a formulation comprising sufentanil in an amount sufficient for treatment of pain in a subject for a period of at least about 3 days;

a pump operatively connected to the housing; and

a thermal expansion element comprising an inlet, a thermal expansion channel adapted to contain a volume of formulation associated with thermal expansion, and a delivery outlet;

wherein in use, the inlet, thermal expansion channel, and outlet define a flow pathway from the reservoir and out of the device such that actuation of the pump effects movement of formulation through the flow pathway.

19. The device of claim 18, wherein the flow pathway of the thermal expansion element is at least partially defined by a plug seated within the housing.

20. The device of claim 18, wherein the flow pathway of the thermal expansion element is at least partially defined by a plug seated within the housing, and an inner wall of the housing.

21. The device of claim 18, wherein the thermal expansion element comprises a valve.

22. The device of claim 18, wherein the thermal expansion element comprises a plunger, wherein at least a portion of the plunger is slidably positioned within the flow pathway and seated within the valve such that when in a closed position the plunger and valve occlude the flow pathway to prevent movement of formulation through the outlet.

23. The device of claim 18, wherein said drug is present in a concentration of about 50 mg/mL to about 400 mg/mL.

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

wholly implanting at an implantation site in a subject the drug delivery device of claim 18; and

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

25. The method of claim 23, wherein the drug delivery device is implanted at a subcutaneous site.

26. The method of claim 23, wherein the formulation is delivered at a volume rate of from about 0.01 μ

l/day to 2 ml/day.

27. The method of claim 23, wherein the device comprises an amount of drug sufficient to provide for alleviation of pain in the subject for a period of more than 30 days.