Microstimulator-based electrochemotherapy methods and systems

• US 6,733,485 B1
• Filed: 04/26/2002
• Issued: 05/11/2004
• Est. Priority Date: 05/25/2001
• Status: Expired due to Fees

• Current Assignee: Boston Scientific Neuromodulation Corporation (Boston Scientific Corporation)
• Original Assignee: Advanced Bionics Corporation (Sonova Holding AG)
• Inventors: Whitehurst, Todd K., Haller, Matthew I., McGivern, James P., Kuzma, Janusz A.
• Primary Examiner(s): Thanh, LoAn H.
• Assistant Examiner(s): Thissell, Jeremy
• Application Number:
  US10/133,770
• Time in Patent Office: 746 Days
• Field of Search: 604/20, 604/890.1, 604/891.1, 604/500, 607/120, 607/901
• US Class Current: 604/500
• CPC Class Codes: A61M 2205/3523 using telemetric means
• 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 5/14276 specially adapted for implantation
• CPC Class Codes: A61N 1/205 for promoting a biological process
• CPC Class Codes: A61N 1/326 for promoting growth of cells, e.g. bone cells

Abstract

A small implantable stimulator(s) includes at least two electrodes for delivering electrical stimulation to surrounding tissue and/or a pump and at least one outlet for delivering a drug or drugs to surrounding tissue. One electrochemotherapy method disclosed includes delivery of electrical stimulation in the form of a direct electric current and/or a periodic waveform that locally potentiates the cytotoxic effects of a systemically and/or locally administered chemotherapy agent(s). Open- and closed-loop systems are disclosed.

Claims

1. A method for treating a patient with neoplastic disease, comprising:

providing at least one stimulator having at least two electrodes and at least one reservoir and at least one infusion outlet in fluid communication with the reservoir;

implanting the at least one stimulator in a neoplasm;

containing at least one drug in the at least one reservoir;

providing operating power to the at least one stimulator;

providing stimulation parameters to the at least one stimulator;

delivering the at least one drug via the at least one infusion outlet in accordance with the stimulation parameters to neoplastic tissue near the at least one stimulator; and

delivering electrical stimulation in accordance with the stimulation parameters to the neoplastic tissue near the at least one stimulator;

wherein the at least one stimulator has a size and shape suitable for placement entirely within the neoplasm; and

wherein the at least one drug is delivered systemically.

2. The method of claim 1 wherein the electrical stimulation delivered to the neoplastic tissue is direct electric current delivered at between about 1 mA and about 1 Amp.

3. The method of claim 1 wherein the electrical stimulation delivered to the neoplastic tissue is electrical current pulses delivered at between about 1 mA and about 5 Amps.

4. The method of claim 1 wherein the at least one drug delivered to the neoplastic tissue is at least one of bleomycin, cisplatin, doxorubicin, and cyclophosphamide.

5. The method of claim 1 further comprising

providing at least one sensor;

using the at least one sensor to sense at least one physical condition; and

providing the stimulation parameters based at least in part upon the at least one sensed condition.

6. The method of claim 5 wherein the sensed physical condition includes at least one of tissue necrosis, tissue volume, pressure, oxygen level, impedance, neurotransmitter level, change in neurotransmitter level, pH level, pH level change, hormone level, hormone level change, hormone therapy agent level, change in hormone therapy agent level, anesthetic agent level, change in anesthetic agent level, enzyme level, change in enzyme level, ketone level, change in ketone level, electrolyte level, change in electrolyte level, interleukin level, change in interleukin level, cytokine level, change in cytokine level, lymphokine level, change in lymphokine level, chemokine level, change in chemokine level, growth factor level, change in growth factor level, medication level, medication level change, chemotherapy agent level, change in chemotherapy agent level, immunotherapy agent level, change in immunotherapy agent level, level of PSA, change in PSA level, level of AFP, change in AFP level, level of AFu, change in AFu level, level of GGT, change in GGT level, level of SA, change in SA level, level of CEA, change in CEA level, EMG, level of a blood-borne substance, change in the level of a blood-borne substance, level of a local interstitial fluid, and change in the level of a local interstitial fluid.

7. The method of claim 5 wherein the at least one sensor is a part of the stimulator.

8. The method of claim 1 further comprising providing and implanting more than one stimulator.

9. A method for treating a patient with neoplastic disease, comprising:

providing at least one stimulator having at least two electrodes and at least one reservoir and at least one infusion outlet in fluid communication with the reservoir;

implanting at least one electrode and at least one infusion outlet in a neoplasm;

containing at least one drug in the at least one reservoir;

providing operating power to the at least one stimulator;

providing stimulation parameters to the at least one stimulator;

delivering the at least one drug via the at least one infusion outlet in accordance with the stimulaton parameters to neoplastic tissue near the at least one infusion outlet; and

delivering electrical stimulation in accordance with the stimulation parameters to the neoplastic tissue near the at least two electrodes;

wherein the at least one stimulator has a size and shape suitable for placement entirely within or near the neoplasm.

10. The method of claim 9, further comprising:

providing at least one sensor;

using the sensor to sense a physical condition; and

determining the stimulation parameters based at least in part upon the sensed condition.

11. The method of claim 10 wherein the at least one sensor is a part of the stimulator.

12. The method of claim 10 wherein the sensed physical condition includes at least one of tissue necrosis, tissue volume, pressure, oxygen level, impedance, neurotransmitter level, change in neurotransmitter level, pH level, pH level change, hormone level, hormone level change, hormone therapy agent level, change in hormone therapy agent level, anesthetic agent level, change in anesthetic agent level, enzyme level, change in enzyme level, ketone level, change in ketone level, electrolyte level, change in electrolyte level, interleukin level, change in interleukin level, cytokine level, change in cytokine level, lymphokine level, change in lymphokine level, chemokine level, change in chemokine level, growth factor level, change in growth factor level, medication level, medication level change, chemotherapy agent level, change in chemotherapy agent level, immunotherapy agent level, change in immunotherapy agent level, level of PSA, change in PSA level, level of AFP, change in AFP level, level of AFu, change in AFu level, level of GGT, change in GGT level, level of SA, change in SA level, level of CEA, change in CEA level, EMG, level of a blood-borne substance, change in the level of a blood-borne substance, level of a local interstitial fluid, and change in the level of a local interstitial fluid.

13. The method of claim 9 further comprising providing and implanting more than one stimulator.

14. A method for treating a patient with neoplastic disease, comprising:

providing at least one stimulator having at least two electrodes;

implanting at least one electrode in a neoplasm;

providing operating power to the at least one stimulator;

providing stimulation parameters to the at least one stimulator;

providing at least one cytotoxic drug;

delivering the at least one drug to the neoplasm; and

delivering electrical stimulation in accordance with the stimulation parameters to the neoplastic tissue near the at least two electrodes;

wherein the at least one stimulator has a size and shape suitable for placement entirely within or near the neoplasm; and

wherein the at least one drug is delivered systemically.

15. The method of claim 14 wherein the at least one drug is also delivered locally.

16. The method of claim 14 wherein the electrical stimulation delivered to the neoplastic tissue is direct electric current delivered at between about 1 mA and about 1 Amp.

17. The method of claim 14 wherein the electrical stimulation delivered to the neoplastic tissue is electrical current pulses delivered at between about 1 mA and about 5 Amps.

18. The method of claim 14 wherein the at least one drug delivered to the neoplasm is at least one of bleomycin, cisplatin, doxorubicin, and cyclophosphamide.

19. The method of claim 14 further comprising

providing at least one sensor;

using the at least one sensor to sense at least one physical condition; and

providing the stimulation parameters based at least in part upon the at least one sensed condition.

20. The method of claim 14 wherein the stimulation parameters are fixed.