Methods and implantable devices and systems for long term delivery of a pharmaceutical agent

• US 6,436,091 B1
• Filed: 11/16/1999
• Issued: 08/20/2002
• Est. Priority Date: 11/16/1999
• Status: Expired due to Fees

• Current Assignee: Microsolutions Incorporated
• Original Assignee: Microsolutions Incorporated
• Inventors: Harper, Derek J., Milo, Charles F.
• Primary Examiner(s): Casler, Brian L.
• Assistant Examiner(s): Serke, Catherine
• Application Number:
  US09/442,128
• Time in Patent Office: 1,008 Days
• Field of Search: 604/890.1, 604/891.1, 604/892.1, 604/93.01, 604/118, 604/181-182, 604/244, 604/288-1-2, 424/422-424
• US Class Current: 604/892.1
• CPC Class Codes: A61M 2005/14513 with secondary fluid driving or regulating the infusion
• 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

Abstract

Implantable devices and osmotic pump and catheter systems for delivering a pharmaceutical agent to a patient at selectable rates include an impermeable pump housing and a moveable partition disposed within the housing, the partition dividing the housing into an osmotic driving compartment having an open end and a pharmaceutical agent compartment having a delivery orifice. A plurality of semi permeable membranes may be disposed in the open end of the osmotic driving compartment and a number of impermeable barriers may seal selected ones of the plurality of semi permeable membranes from the patient until breached. Breaching one or more of the impermeable barriers increases the surface area of semi permeable membrane exposed to the patient and controllably increases the delivery rate of the pharmaceutical agent through the delivery orifice and catheter. Each of the plurality of semi permeable membranes may have a selected surface area, composition and/or thickness, to allow a fine-grained control over the infusion rate while the pump is implanted in the patient.

Claims

1. An implantable osmotic pump system for delivering a pharmaceutical agent to a patient, comprising:

an implantable pump, including;

a pump housing;

a moveable partition disposed within the housing, the partition dividing the housing into an osmotic driving compartment having an open end and a pharmaceutical agent compartment having a delivery orifice;

a first semi permeable membrane disposed in the open end of the osmotic driving compartment, the first semi permeable membrane being exposed to the patient;

a second semi permeable membrane disposed in the open end of the osmotic driving compartment, and

a first impermeable barrier disposed over the second semi permeable membrane, the second semi permeable membrane being sealed from the patient until the first barrier is breached, wherein breaching the first barrier increases the surface area of semi permeable membrane exposed to the patient and increases a delivery rate of a pharmaceutical agent through the delivery orifice.

2. The pump system of claim 1, wherein the first impermeable barrier includes at least one of titanium and stainless steel.

3. The pump system of claim 1, further comprising a saturated solution including NaCl between the first impermeable barrier and the second semi permeable membrane.

4. The pump system of claim 1, wherein the first and second semi permeable membranes have a same composition.

5. The pump system of claim 1, wherein the first and second semi permeable membranes have a same thickness.

6. The pump system of claim 1, wherein the first and second semi permeable membranes have mutually different compositions.

7. The pump system of claim 1, wherein the first and second semi permeable membranes have mutually different thickness.

8. The pump system of claim 1, further including:

a third semi permeable member, and

a second impermeable barrier, the second impermeable barrier being disposed over the third semi permeable membrane, the third semi permeable membrane being sealed from the patient until the second impermeable barrier is breached, wherein breaching the second barrier increases the surface area of semi permeable membrane exposed to the patient and increases a delivery rate of the pharmaceutical agent through the delivery orifice.

9. The pump system of claim 8, further comprising a saturated solution including NaCl between the second barrier and the third semi permeable membrane.

10. The pump system of claim 1, wherein the pharmaceutical agent compartment contains sufentanil.

11. The pump system of claim 10, wherein the sufentanil is at a concentration selected between about 200 μ

g/mL and about 15,000 μ

g/mL.

12. The pump system of claim 1, wherein the delivery rate of the pharmaceutical agent through the delivery orifice is selected from about:

0.5 micrograms per day to about 25 micrograms per day when the pump is configured to deliver the pharmaceutical agent intraventricularly;

0.5 micrograms per day to about 50 micrograms per day when the pump is configured to deliver the pharmaceutical agent intrathecally;

5 micrograms per day to about 300 micrograms per day when the pump is configured to deliver the pharmaceutical agent epidurally, and

10 micrograms per day to about 300 micrograms per day when the pump is configured to deliver the pharmaceutical agent subcutaneously.

13. The pump system of claim 1, wherein the first and second semi permeable membranes include cellulose acetate.

14. The pump system of claim 1, wherein the first semi permeable membrane is shaped as a torus and is disposed adjacent an outer periphery of the first impermeable barrier and wherein the second semi permeable membrane is disposed in a center opening of the torus.

15. The pump system of claim 1, further comprising a catheter coupled to the delivery orifice.

16. The pump system of claim 15, wherein the catheter has an inner diameter of between about 0.001 inches and about 0.010 inches.

17. The pump system of claim 15, wherein the catheter includes a guidewire lumen and a pharmaceutical agent infusion lumen.

18. The pump system of claim 17, wherein the pharmaceutical agent infusion lumen has an inner diameter selected between about 0.001 inches to about 0.010 inches.

19. The pump system of claim 17, wherein the guidewire lumen includes a valve to prevent back flow of fluid into the guidewire lumen.

20. The pump system of claim 15, wherein the catheter and the pump are dimensioned to infuse a volume of pharmaceutical agent of between about 1 μ

L/day and about 10 μ

L/day over a treatment period.

21. The pump system of claim 15, wherein the catheter and the pump are dimensioned to infuse a dose of pharmaceutical agent of between about 0.5 μ

g/day and about 300 μ

g/day over a treatment period.

22. The pump system of claim 15, wherein at least a portion of the catheter is radiopaque.

23. An integrated implantable pump and catheter system for delivering a dose of pharmaceutical agent to a patient over a treatment period, comprising:

a pump housing;

a moveable partition disposed within the housing, the partition dividing the housing into an driving engine compartment and a pharmaceutical having an open end agent compartment having a delivery orifice;

a catheter coupled to the delivery orifice;

a preloaded amount of pharmaceutical agent in the pharmaceutical agent compartment, and

a mechanical an infusion rate selection structure disposed within the open end configured to allow the infusion rate of the pump to be increased while the system is implanted in the patient, the infusion rate selection structure including a plurality of semi permeable membranes, wherein selectively exposing a surface area of the plurality of semipermeable membranes to the patient increases the infusion rate of the pharmaceutical agent.

24. The system of claim 23, wherein the pump and catheter are dimensioned to deliver sufentanil at an infusion rate of about 0.5 μ

g/day to about 300 μ

g/day over a treatment period.

25. The system of claim 23, wherein each of the plurality of semi permeable membranes has a selected thickness, composition and surface area, the selected thickness, composition and surface area contributing to a rate at which the pharmaceutical agent is infused into the patient.

28. The system of claim 23, wherein the pharmaceutical agent includes Sufentanil.

29. The pump of claim 28, wherein each of the plurality of semi permeable membranes has a selected thickness, composition and surface area, the selected thickness, composition and surface area contributing to a rate at which the pharmaceutical agent is infused into the patient.

26. A method of delivering a pharmaceutical agent to a patient, comprising the steps of:

implanting an osmotic pump within the patient, the osmotic pump including a pump housing, a moveable partition disposed within the housing, the partition dividing the housing into a driving engine compartment having an open end and a pharmaceutical agent compartment, a preloaded amount of the pharmaceutical agent in the pharmaceutical agent compartment, and a mechanical infusion rate selection structure disposed within the open end configured to allow an infusion rate of the pump to be increased while the pump is implanted in the patient, the infusion rate selection structure including a plurality of semi-permeable membranes, and

controlling a surface area of the plurality of the semi permeable membranes exposed to the patient to control and infusion rate of the pharmaceutical agent to the patient.

27. The method of claim 26, further comprising the step of controlling at least one of a thickness and a composition of each of the plurality of semi permeable membranes.

30. An implantable pump for delivering a dose of pharmaceutical agent to a patient over a treatment period, comprising:

a pump housing;

a moveable partition disposed within the housing, the partition dividing the housing into an driving engine compartment and a pharmaceutical agent compartment having a delivery orifice;

a preloaded amount of pharmaceutical agent in the pharmaceutical agent compartment, and a mechanical infusion rate selection structure configured to allow the infusion rate of the pump to be increased while the system is implanted in the patient, the infusion rate selection structure including a plurality of semi permeable membranes, wherein selectively exposing a surface area of the plurality of semipermeable membranes to the patient increases the infusion rate of the pharmaceutical agent.

31. The pump of claim 30, wherein the pump is dimensioned to deliver the pharmaceutical agent at an infusion rate of about 0.5 μ

g/day to about 300 μ

g/day over the treatment period.

32. The pump of claim 30, wherein the pharmaceutical agent includes Sufentanil.