Implantable osmotic pump

• US 6,632,217 B2
• Filed: 04/19/2001
• Issued: 10/14/2003
• Est. Priority Date: 04/19/2001
• 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): Lam, Ann Y.
• Application Number:
  US09/838,662
• Publication Number:
  US 20020183722A1
• Time in Patent Office: 908 Days
• Field of Search: 604/891.1, 604/892.1, 604/65-67, 604/118, 604/122, 604/126, 604/131-133, 604/246, 604/256, 604/288.01, 604/288.04
• US Class Current: 604/892.1
• CPC Class Codes: A61M 2005/14513 with secondary fluid driving or regulating the infusion
• CPC Class Codes: A61M 2205/75 with filters
• CPC Class Codes: A61M 2205/7527 liquophilic, hydrophilic
• CPC Class Codes: A61M 5/14276 specially adapted for implantation
• CPC Class Codes: A61M 5/14526 the piston being actuated by fluid pressure

Abstract

An implantable osmotic pump for delivering a pharmaceutical agent to a patient includes an osmotic engine, a substantially toroidal compartment disposed at least partially around the osmotic engine and a piston disposed within the compartment. The osmotic engine is configured to cause the piston to travel within the compartment and deliver a dose pharmaceutical agent contained within the compartment when the pump is implanted in an aqueous environment. A dose escalation assembly may be fitted to the pump, the dose escalation assembly being adapted to selectively increase the rate at which the pharmaceutical agent is delivered from the pump.

Claims

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

an osmotic engine;

a substantially toroidal compartment adapted to store a pharmaceutical agent, and a piston disposed within the compartment, the osmotic engine being configured to cause the piston to travel within the compartment and deliver the pharmaceutical agent when the pump is implanted in the patient.

2. The pump of claim 1, further including a tube coiled at least partially around the osmotic engine, an inner lumen of the tube defining the pharmaceutical agent compartment.

3. The pump of claim 2, wherein the tube includes at least one material selected from a group including metals, polymers and polyimid.

4. The pump of claim 1, wherein the compartment is disposed at least partially around the osmotic engine.

5. The pump of claim 2, wherein tube is rigid and wherein the osmotic engine is disposed within the tube.

6. The pump of claim 1, wherein the osmotic engine includes a base, a cylindrical wall attached to the base and a free end opposite the base.

7. The pump of claim 2, further including a housing configured to enclose at least the osmotic engine and the tube.

8. The pump of claim 7, wherein the housing includes a first housing half and a second housing half that mates with the first housing half.

9. The pump of claim 8, wherein each of the first and second housing halves define a saucer shape.

10. The pump of claim 8, wherein each of the first and the second housing halves are substantially circular in shape.

11. The pump of claim 8, wherein the first housing half defines a substantially circular opening.

12. The pump of claim 1, further including a membrane enclosure, the membrane enclosure being partially surrounded by the osmotic engine and including an initial dose semipermeable membrane that is configured to allow water from the patient to reach the osmotic engine when the pump is implanted.

13. The pump of claim 12, wherein the pump is configured to deliver an initial dose of the pharmaceutical agent to the patient at a selected initial infusion rate, the selected initial infusion rate being related to at least one of a thickness, a composition and a surface area of the initial dose semipermeable membrane.

14. The pump of claim 12, wherein the initial dose semipermeable membrane is fitted with an initial dose impermeable membrane that initially seals the initial dose semipermeable membrane.

15. The pump of claim 14, further including a volume of a saturated saline solution between the initial dose semipermeable membrane and the initial dose semipermeable membrane.

16. The pump of claim 12, further including a dose escalation assembly fitted in the membrane enclosure, the dose escalation assembly being adapted to selectively increase an amount of water from the patient that reaches the osmotic engine when the pump is implanted.

17. The pump of claim 16, wherein the dose escalation assembly includes a first impermeable membrane configured to enable water from the patient to reach the osmotic engine through a first fluid path only after being breached.

18. The pump of claim 16, wherein the dose escalation assembly includes:

a first impermeable membrane configured to enable water from the patient to reach the osmotic engine through a first fluid path only after being breached, and

a second impermeable membrane configured to enable water from the patient to reach the osmotic engine through a second fluid path only after being breached, the first path being distinct from the second path.

19. The pump of claim 18, wherein the first and second impermeable membranes are disposed in the membrane enclosure in a stacked configuration wherein the first impermeable membrane must be breached before the second impermeable membrane can be breached.

20. The pump of claim 18, wherein the first fluid path includes a first semipermeable membrane and wherein the second fluid path includes a second semipermeable membrane that is distinct from the first semipermeable membrane.

21. The pump of claim 20, wherein the pump is configured to deliver a first dose of the pharmaceutical agent to the patient at a selected first infusion rate and a second dose of the pharmaceutical agent to the patient at a selected second infusion rate that is greater than the first infusion rate, the selected first and second infusion rates being related to at least one of a thickness, a composition and a surface area of the first and second semipermeable membranes, respectively.

22. The pump of claim 1, wherein the osmotic engine includes a hygroscopic salt.

23. The pump of claim 1, wherein the osmotic engine includes an absorbent polymer.

24. The pump system of claim 23, wherein the absorbent polymer includes a material selected from a group including poly(acrylic acid), potassium salt;

poly(acrylic acid), sodium salt;

poly(acrylic acid-co-acrylamide), potassium salt;

poly(acrylic acid), sodium salt-graft-poly(ethylene oxide);

poly (2-hydroxethyl methacrylate);

poly(2-hydroxypropyl methacrylate) and poly(isobutylene-co-maleic acid) or derivatives thereof.

25. The pump of claim 1, wherein the compartment has a substantially constant inner diameter over a length thereof.

26. The pump of claim 1, wherein the compartment has a non-constant inner diameter over a length thereof.

27. The pump of claim 2, wherein the tube is coiled at least twice around the osmotic engine.

28. The pump of claim 2, further comprising an epoxy layer encasing at least the tube.

29. The pump of claim 2, wherein the tube includes polyimid.

30. The pump of claim 2, wherein the tube defines a proximal end adjacent the osmotic engine and a distal end at an end opposite the proximal end, and wherein the pump further includes a catheter coupled to the distal end.

31. The pump of claim 30, wherein the catheter and the pump are dimensioned to infuse a volume of up to about 20 μ

L/day over a treatment period.

32. The pump of claim 30, wherein the catheter and the pump are dimensioned to infuse a dose of Sufentanil of up to 1500 μ

g/day over a treatment period.

33. The pump of claim 30, wherein the catheter includes a radiopaque tip.

34. The pump of claim 1, wherein the piston includes one of a sphere, an elastomeric cylinder and an elastomeric conical section.

35. The pump of claim 34, wherein the piston includes at least one of stainless steel, a refractory metal, plastic, nylon and rubber.

36. The pump of claim 1, wherein the compartment is pre-loaded with a volume of the pharmaceutical agent.

37. The pump of claim 36, wherein the pharmaceutical agent is therapeutically effective for at least one therapy selected from pain therapy, hormone therapy, gene therapy, angiogenic therapy, anti-tumor therapy, chemotherapy, allergy therapy, hypertension therapy, antibiotic therapy, bronchodilation therapy, asthmatic therapy, arrhythmia therapy, nootropic therapy, cytostatic and metastasis inhibition therapy, migraine therapy, gastrointestinal therapy, schizophrenia therapy, depression therapy, stress therapy and/or other pharmaceutical therapies.

38. The pump of claim 36, wherein the pharmaceutical agent includes an opioid.

39. The pump of claim 36, wherein the pharmaceutical agent includes at least one of a morphine-like agonist, a partial agonist, an agonist-antagonist and an alpha 2-adrenoreceptor agonist.

40. The pump of claim 36, wherein the pharmaceutical agent includes at least one agent selected from a group including morphine, hydromorphone, levorphanol, methadone, fentanyl, sufentanil, buprenorphine, pentazocine and butorphanol.

41. The pump of claim 40, wherein the sufentanil is at a concentration up to about 500,000 μ

g/mL.

42. The pump of claim 36, wherein the pharmaceutical agent includes an agent selected from a group including Dihydrocodeine, Hydromorphone, Morphine, Diamorphine, Levorphanol, Butorphanol, Alfentanil, Pentazocine, Buprenorphine, Nefopam, Dextropropoxyphene, Flupirtine, Tramadol, Oxycodone, Metamizol, Propyphenazone, Phenazone, Nifenazone, Paracetamol, Phenylbutazone, Oxyphenbutazone, Mofebutazone, Acetyl Salicylic Acid, Diflunisal, Flurbiprofen, Ibuprofen, Diclofenac, Ketoprofen, Indomethacin, Naproxen, Meptazinol, Methadone, Pethidine, Hydrocodone, Meloxicam, Fenbufen, Mefenamic Acid, Piroxicam, Tenoxicam, Azapropazone, Codein, Bupivacaine, Ketamine, Meperidine and DADL.

43. The pump of claim 36, wherein the pharmaceutical agent includes an agent that is an alpha-2 adrenergetic agonist selected from a group including Clonidine, Tizadine, ST-91, Medetomidine, Dexmedetomidine and related alpha-2 adrenergetic agonists.

44. The pump of claim 36, wherein the pharmaceutical agent includes an agent that is an NMDA receptor agonist selected from a group including Dexmethorphan, Ifenprodil, MK-801, and related NMDA agonists.

45. The pump of claim 36, wherein the pharmaceutical agent includes an agent that is a somatostatin analog selected from a group including Octreotide, Sandostatin, Vapreotide, Lanreotide, and related Somatostatin analogs.

46. The pump of claim 36, wherein the pharmaceutical agent includes an agent that is a non-opioid analgesic selected from a group including Ketorolac, super oxide dismutase, baclofen, calcitonin, serotonin, vasoactive intestinal polypeptide, bombesin, omega-conopeptides, and related non-opioid analgesics.

47. The pump of claim 36, wherein the pharmaceutical agent includes an anti-allergic agent selected from a group including Pheniramine, Dimethindene, Terfenadine, Astemizole, Tritoqualine, Loratadine, Doxylamine, Mequitazine, Dexchlorpheniramine, Triprolidine and Oxatomide.

48. The pump of claim 36, wherein the pharmaceutical agent includes an anti-hypertensive agent selected from a group including Clonidine, Moxonidine, Methyldopa, Doxazosin, Prazosin, Urapidil, Terazosin, Minoxidil, Dihydralalzin, Deserpidine, Acebutalol, Alprenolol, Atenolol, Metoprolol, Bupranolol, Penbutolol, Propranolol, Esmolol, Bisoprolol, Ciliprolol, Sotalol, Metipranolol, Nadolol, Oxprenolol, Nifedipine, Nicardipine, Verapamil, Diltiazim, Felodipine, Nimodipine, Flunarizine, Quinapril, Lisinopril, Captopril, Ramipril, Fosinoprol and Enalapril.

49. The pump of claim 36, wherein the pharmaceutical agent includes an antibiotic agent selected from a group including Democlocycline, Doxycycline, Lymecycline, Minocycline, Oxytetracycline, Tetracycline, Sulfametopyrazine, Ofloaxcin, Ciproflaxacin, Aerosoxacin, Amoxycillin, Ampicillin, Becampicillin, Piperacillin, Pivampicillin, Cloxacillin, Penicillin V, Flucloxacillin, Erythromycin, Metronidazole, Clindamycin, Trimethoprim, Neomycin, Cefaclor, Cefadroxil, Cefixime, Cefpodoxime, Cefuroxine, Cephalexin and Cefradine.

50. The pump of claim 36, wherein the pharmaceutical agent includes a bronchodialotors and anti-asthmatic agents selected from a group including:

Pirbuterol, Orciprenaline, Terbutaline, Fenoterol, Clenbuterol, Salbutamol, Procaterol, Theophylline, Cholintheophyllinate, Theophylline-ethylenediamine and Ketofen.

51. The pump of claim 36, wherein the pharmaceutical agent includes an anti-arrhythmic agent selected from a group including Viquidil, Procainamide, Mexiletine, Tocainide, Propafenone and Ipratropium.

52. The pump of claim 36, wherein the pharmaceutical agent includes a centrally acting substance selected from a group including Amantadine, Levodopa, Biperiden, Benzotropine, Bromocriptine, Procyclidine, Moclobemide, Tranylcypromine, Tranylpromide, Clomipramine, Maprotiline, Doxepin, Opipramol, Amitriptyline, Desipramine, Imipramine, Fluroxamin, Fluoxetin, Paroxetine, Trazodone, Viloxazine, Fluphenazine, Perphenazine, Promethazine, Thioridazine, Triflupromazine, Prothipendyl, thiothixene, Chlorprothixene, Haloperidol, Pipamperone, Pimozide, Sulpiride, Fenethylline, Methylphenildate, Trifluoperazine, Oxazepam, Lorazepam, Bromoazepam, Alprazolam, Diazepam, Clobazam, Buspirone and Piracetam.

53. The pump of claim 36, wherein the pharmaceutical agent includes a cytostatics and metastasis inhibitor selected from a group including Melfalan, Cyclophosphamide, Trofosfamide, Chlorambucil, Busulfan, Prednimustine, Fluororacil, Methotrexate, Mercaptopurine, Thioguanin, Hydroxycarbamide, Altretamine and Procarbazine.

54. The pump of claim 36, wherein the pharmaceutical agent includes an anti-migrane agent selected from a group including Lisuride, Methysergide, Dihydroergotamine, Ergotamine and Pizotifen.

55. The pump of claim 36, wherein the pharmaceutical agent includes a gastrointestinal agents selected from a group including Cimetidine, Famotidine, Ranitidine, Roxatidine, Pirenzipine, Omeprazole, Misoprostol, Proglumide, Cisapride, Bromopride and Metoclopramide.

56. The pump of claim 16, wherein the dose escalation assembly includes:

a first saturated saline solution between the first impermeable membrane and the first semipermeable membrane, and

a second saturated saline solution between the second impermeable membrane and the second semipermeable membrane.

57. The pump of claim 1, wherein the pharmaceutical agent includes Sufentanil and wherein the pump is configured for:

a daily delivery rate of Sufentanil of up to about 25 micrograms per day when the pump is configured to be implanted intraventricularly;

a daily delivery rate of Sufentanil of up to about 50 micrograms per day when the pump is configured to be implanted intrathecally;

a daily delivery rate of Sufentanil of up to about 500 micrograms per day when the pump is configured to be implanted epidurally;

a daily delivery rate of Sufentanil of up to about 1500 micrograms per day when the pump is configured to be implanted subcutaneously, and

a daily delivery rate of Sufentanil of up to about 1500 micrograms per day when the pump is configured to be implanted intravascularly.

58. A kit, comprising:

an implantable osmotic pump for delivering a pharmaceutical agent to a patient, including an osmotic engine, a tube coiled around the osmotic engine, the tube defining an inner tube-shaped compartment adapted to store a pharmaceutical agent, and a piston disposed within the tube-shaped compartment, the osmotic engine being configured to exert a force on the piston to cause the piston to travel within the tube-shaped compartment and deliver the pharmaceutical agent when the pump is implanted in the patient, and

a catheter configured to attach to the pump.

59. The kit of claim 58, wherein the catheter and the pump are dimensioned to infuse a volume of up to about 20 μ

L/day over a treatment period.

60. The kit of claim 58, wherein the catheter and the pump are dimensioned to infuse a dose of Sufentanil of up to about 1500 μ

g/day over a treatment period.

61. The kit of claim 58, wherein pump further includes a membrane enclosure, the membrane enclosure being partially surrounded by the osmotic engine and including an initial dose semipermeable membrane that is configured to allow water from the patient to reach the osmotic engine when the pump is implanted.

62. The kit of claim 61, further including a dose escalation assembly fitted in the membrane enclosure, the dose escalation assembly being adapted to selectively increase an amount of water from the patient that reaches the osmotic engine when the pump is implanted.

63. The kit of claim 62, wherein the dose escalation assembly includes:

a first impermeable membrane configured to enable water from the patient to reach the osmotic engine through a first fluid path only after being breached, and

a second impermeable membrane configured to enable water from the patient to reach the osmotic engine through a second fluid path only after being breached, the first path being distinct from the second path.

64. The kit of claim 63, further including a dose escalation pen configured to breach at least one of the first and second impermeable membranes.

65. The kit of claim 64, wherein the dose escalation pen includes a dose selection actuator that is adapted to re-configure the dose escalation pen to selectively breach one of the first and second impermeable membranes.

66. The kit of claim 58, wherein the tube-shaped compartment is pre-loaded with the pharmaceutical agent.

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

implanting a pump into the patient, the pump including a pump engine and a compartment adapted to store a pharmaceutical agent, the compartment defining at least a partial torus around the osmotic engine, and

causing a piston to travel a distance within the compartment and to deliver a dose of pharmaceutical agent out of the compartment, the dose corresponding to the distance traveled by the piston within the compartment.

68. The method of claim 67, wherein the implanting step implants the pump one of intravascularly, subcutaneously, epidurally, intrathecally and intraventricularly.

69. The method of claim 68, wherein the pharmaceutical agent includes Sufentanil and wherein the pump is configured for:

a daily delivery rate of Sufentanil of up to about 25 micrograms per day when the pump is configured to be implanted intraventricularly;

a daily delivery rate of Sufentanil of up to about 50 micrograms per day when the pump is configured to be implanted intrathecally;

a daily delivery rate of Sufentanil of up to about 500 micrograms per day when the pump is configured to be implanted epidurally;

a daily delivery rate of Sufentanil of up to about 1500 micrograms per day when the pump is configured to be implanted subcutaneously, and a daily delivery rate of Sufentanil of up to about 1500 micrograms per day when the pump is configured to be implanted intravascularly.

70. The method of claim 68, wherein travel of the piston within the compartment causes a delivery of a volume up to about 20 μ

L/day over a treatment period.

71. The method of claim 67, further comprising the step of selectively increasing the dose in a stepwise manner over a treatment period without removing the pump from the patient.

72. The method of claim 71, wherein the pump engine includes an osmotic engine and wherein the pump includes an initial dose semipermeable membrane initially exposed to the patient and at least one second semipermeable membrane initially not exposed to the patient and wherein the increasing step includes a step of selectively exposing the at least one second semipermeable membrane to the patient.

73. The method of claim 67, wherein the pump the engine includes an osmotic engine in fluid communication with the piston and wherein the causing step includes a step of increasing a volume of the osmotic engine.

74. A pump, comprising:

a pump engine;

a tube coiled around the engine, the tube defining an inner tube-shaped compartment adapted to store a fluid, and

a piston disposed within the tube-shaped compartment, the engine being adapted to cause the piston to travel within the tube-shaped compartment and to force a dose of the fluid out of the pump.

75. The pump of claim 74, wherein the pump engine includes an osmotic engine.

76. The pump of claim 74, wherein the fluid includes a pharmaceutical agent.

77. The pump of claim 74, further including a catheter coupled to the tube.

78. The pump of claim 74, wherein the pump is fully implantable in a body and wherein pump engine and the tube are enclosed in a biocompatible pump housing.

79. The pump of claim 74, further including a dose escalation assembly, the escalation assembly being configured to selectively increase the dose of fluid delivered.

80. The pump of claim 74, wherein the dose escalation assembly comprises means for increasing the dose delivered in a stepwise manner.

81. The pump of claim 74, wherein the piston includes one of a sphere, an elastomeric cylinder and an elastomeric conical section.

82. An osmotic pump, comprising:

an osmotic engine, and

a pump housing enclosing the osmotic engine and defining a substantially toroidal space adapted to contain a volume of pharmaceutical agent.

83. The osmotic pump of claim 82, wherein the pump housing defines a substantially circular outline.

84. The osmotic pump of claim 82, wherein the substantially toroidal space defines an inner and an outer radius, and wherein the osmotic engine is disposed within the inner radius.

85. The osmotic pump of claim 82, further comprising a tube disposed within the toroidal space, the tube defining an inner lumen adapted to contain the volume of pharmaceutical agent.

86. The osmotic pump of claim 82, wherein the pump housing includes a first housing half and a second housing half, the first and second housing halves defining, when mated together, the substantially toroidal space, the substantially toroidal space being fluid tight.

87. The osmotic pump of claim 82, further comprising a semipermeable membrane enclosure and a semipermeable membrane fitted within the semipermeable membrane enclosure.

88. The osmotic pump of claim 87, wherein a single semipermeable membrane is fitted within the semipermeable membrane enclosure and wherein the pump is a single stage pump.

89. The osmotic pump of claim 87, wherein the pump is an n-stage pump and wherein the semipermeable membrane enclosure is fitted with n semipermeable membranes, each of the n stages being configured to be selectively activated after implantation of the pump.

90. The osmotic pump of claim 82, further comprising an OFF switch mechanism configured to be selectively activated after implantation of the pump.

91. The osmotic pump of claim 82, further comprising a filter assembly to filter the pharmaceutical agent.

92. The osmotic pump of claim 91, wherein the filter assembly includes a plug of porous material, the porous material defining pores selected to have an average size of between about 2 microns and about 80 microns.

93. The osmotic pump of claim 91, wherein the filter assembly includes a plug of porous material, the porous material being hydrophilic.

94. The osmotic pump of claim 91, wherein the filter assembly includes a plug of porous material, the porous material being hydrophobic.

95. An implantable osmotic pump, comprising:

a semipermeable membrane;

a housing adapted to enclose a volume of pharmaceutical agent and a portion of the semipermeable membrane;

an osmotic engine adapted to cause the pharmaceutical agent to be delivered out of he pump as an osmotic pressure differential develops across the semipermeable membrane, and

at least one of;

an OFF switch, the OFF switch being effective to reduce the osmotic pressure differential across the semipermeable membrane substantially to zero, and

an ON switch, the ON switch being effective to enable the pump to begin to deliver the pharmaceutical agent out of the pump.

96. The pump of claim 95, wherein the OFF switch includes an OFF switch impermeable membrane and wherein the OFF switch is configured to reduce the osmotic pressure substantially to zero only when the OFF switch impermeable membrane is breached.

97. The pump of claim 96, wherein the OFF switch defines a lumen adapted to allow fluid to bypass the semipermeable membrane when the OFF switch impermeable membrane is breached.

98. The pump of claim 95, wherein the ON switch includes an impermeable membrane disposed over the semipermeable membrane, the pump being adapted to begin delivery of the pharmaceutical agent only after the impermeable membrane is breached.

99. The pump of claim 98, further including a volume of saturated saline solution disposed between the semipermeable membrane and the impermeable membrane.