Method for enhancing delivery of chemotherapy employing high-frequency force fields

• US 5,386,837 A
• Filed: 02/01/1993
• Issued: 02/07/1995
• Est. Priority Date: 02/01/1993
• Status: Expired due to Term

• Current Assignee: MMTC Limited (Government of India)
• Original Assignee: MMTC Limited (Government of India)
• Inventors: Sterzer, Fred
• Primary Examiner(s): Kamm, William E.
• Assistant Examiner(s): Parker, Marianne
• Application Number:
  US08/011,817
• Time in Patent Office: 736 Days
• Field of Search: 600/2, 607/2, 607/3, 607/154, 607/901, 607/58, 607/72-74, 607/148, 128/898, 128/24.1, 128/24 AA, 128/630, 606/32
• US Class Current: 128/898
• CPC Class Codes: A61B 18/00 Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body eye surgery A61F9/007; ear surgery A61F11/00
• CPC Class Codes: A61M 37/0092 using ultrasonic, sonic or infrasonic vibrations, e.g. phonophoresis

Abstract

Pulse shocks of high-frequency wave energy (e.g. RF, microwave, high-energy infra-red or laser electromagnetic wave energy or ultrasonic acoustic wave energy), rather than DC electric pulses, are employed to non-invasively produce force fields of an intensity sufficient to create transient pores in the plasma membranes of targeted cells, such as tumor cells or other diseased cells, through which either locally or systemically applied drug or chemotherapeutic agents can easily enter and be taken up by the targeted cells, even for (1) the cells of a deep-seated tumor, (2) non-localized metastasized tumor cells within a patient'"'"'s body, or (3) cells (e.g., blood cells) temporarily removed to outside of a patient'"'"'s body.

Claims

1. In an electrochemotherapeutic treatment method comprising the steps of (1) systemically administering an agent which includes at least one of a drug agent and a chemotherapeutic agent to a patient, and (2), a short time after the systemic administration of said agent, applying force-field shock pulses to at least one site of said patient of sufficiently high-intensities to open large transient pores in plasma membranes of cells of each site to which said force-field shock pulses are applied, thereby permitting said agent to enter said cells of that site through said pores and result in locally enhanced therapeutic effect;

the improvement wherein said step (2) comprises the step of;

a) applying at least one of said force-field shock pulses that comprises a burst of high-frequency wave energy to a given site of said patient of sufficiently high-intensity to open large transient pores in plasma membranes of cells of said given site.

2. The method defined in claim 1, wherein:

said burst of high-frequency wave energy comprises high-frequency electromagnetic wave energy.

3. The method defined in claim 2, wherein:

said burst of high-frequency electromagnetic wave energy comprises radio-frequency wave energy.

4. The method defined in claim 2, wherein:

said burst of high-frequency electromagnetic wave energy comprises microwave wave energy.

5. The method defined in claim 1, wherein:

said burst of high-frequency wave energy comprises ultrasonic acoustic wave energy.

6. The method defined in claim 1, wherein said step (a) comprises the step of:

applying to said one site a train of said high-frequency wave-energy force-field shock pulses in which energy in each pulse of said train and duty cycle of said pulse train are sufficiently low to effect only a minimal rise in temperature of said cells at said given site.

7. The method defined in claim 1, wherein step (a) comprises the step of:

b) applying to a tumor lesion at said one site at least one directed beam of said force-field shock pulses of high-frequency wave-energy bursts.

8. The method defined in claim 7, wherein step (b) comprises the step of:

c) applying to a relatively superficially-seated tumor lesion at said one site a single directed beam of said force-field shock pulses of high-frequency wave-energy bursts.

9. The method defined in claim 7, wherein step (b) comprises the step of:

c) simultaneously applying to a relatively deep-seated tumor lesion at said one site from different directions a plurality of separate directed beams of said force-field shock pulses of high-frequency wave-energy bursts that effectively intersect at said one site;

wherein said plurality of separate directed beams at their intersection have a combined intensity which is sufficient to open large transient pores in the plasma membranes of cells at said one site, although the intensity of said force-field shock pulses of any single one of said separate directed beams is insufficient in itself to do so.

10. The method defined in claim 7, wherein said agent is preferentially absorbed by cells of a given type of metastasized tumors within said patient'"'"'s body relative to its absorption by normal cells of said patient'"'"'s body, and wherein step (b) comprises the step of:

c) applying said force-field shock pulses of high-frequency wave-energy bursts to at least a substantial portion of said patient'"'"'s whole body;

whereby said patient'"'"'s metastasized tumors of said given type are treated.

11. In an electrochemotherapeutic method for treating prostate disease of a patient comprising the steps of (1) systemically administering an agent which includes at least one of a drug agent and a chemotherapeutic agent to the patient, and (2), a short time after the systemic administration of said agent, applying sufficient squeezing pressure to non-prostate tissue which surrounds an orifice of the patient in a vicinity of the patient'"'"'s prostate both to compress the prostate and non-prostate tissue and to increase a distance from a given location within said orifice to said non-prostate tissue;

the improvement wherein said method comprises the further step of;

while said pressure is being applied, irradiating said prostate through said non-prostate tissue from said given location within said orifice with a force-field shock of pulsed microwave energy of sufficiently high-intensity to open large transient pores in plasma membranes of cells of said prostate and thereby permit said agent to enter into and be taken up by said cells of said prostate through said pores, to thereby enhance a therapeutic effect of said agent on said prostate.

12. The method defined in claim 11, wherein said step comprises:

irradiating said prostate with a force-field shock of pulsed microwave energy in which the energy in each pule of said pulsed microwave energy and the duty cycle of said pulsed microwave energy are insufficient to raise said prostate'"'"'s temperature to a temperature which in itself is therapeutic.

13. The method defined in claim 11, wherein said step comprises:

irradiating said prostate with a force-field shock of pulsed microwave energy in which the energy in each pulse of said pulsed microwave energy and the duty cycle of said pulsed microwave energy are only sufficient to effect a minimal rise in said prostate'"'"'s and non-prostate'"'"'s tissue temperature.

14. The method defined in claim 11, wherein:

the step of applying squeezing pressure comprises applying squeezing pressure to that non-prostate tissue which surrounds a patient'"'"'s urethra thereby to increase the diameter of said urethra; and

the step of irradiating said prostate includes the step of irradiating said prostate from said urethra.