Apparatus and method for pre-conditioning/fixation and treatment of disease with heat activation/release with thermoactivated drugs and gene products

• US 20060216275A1
• Filed: 11/17/2005
• Published: 09/28/2006
• Est. Priority Date: 03/24/2005
• Status: Active Grant

• Current Assignee: Medifocus, Inc.
• Original Assignee: Celsion Corporation
• Inventors: Mon, John
• Granted Patent: US 8,765,116 B2
• Time in Patent Office: Days
• US Class Current: 424/93.200
• CPC Class Codes: A61B 18/1477 Needle-like probes
• CPC Class Codes: A61B 18/18 by applying electromagnetic radiation, e.g. microwaves radiation therapy A61N5/00
• CPC Class Codes: A61B 2018/143 multiple needles
• CPC Class Codes: A61B 2218/002 Irrigation
• CPC Class Codes: A61K 41/0052 Thermotherapy; Hyperthermia; Magnetic induction; Induction heating therapy
• CPC Class Codes: A61N 7/02 Localised ultrasound hyperthermia hyperthermia in general A61F7/00

Abstract

An apparatus and method for administering focused energy to a body using either a single energy applicator or multiple energy applicators to supply heat prior to, concurrently with and/or after delivery of a drug, gene and/or viral vector. A multi-modality treatment using a localized, focused and/or regional heating apparatus, which supplies heat to a defined area of a patient'"'"'s body. The apparatus is used heat is used to pretreat a specific body site, to activate thermoactivated drugs, genes, or viral vectors, and/or to deliver drugs, genes, or viral vectors to the specific body site. The heating apparatus is provided with one or more variable and adjustable probes and one or more delivery ports heat the specific treatment site and to deliver the thermoactivated drugs and genes to the specific treatment site. Each probe may optionally be provided with one or more temperature sensors to allow for the temperature in the specific treatment site and the surrounding tissue to be properly regulated. The use of the apparatus and method allow for the heat conditioning of a specific treatment site and for the delivery or activation of a drug, gene, or viral vector limited to only the specific treatment site, allowing for a more accurate treatment of diseased tissue without damaging healthy tissue. In addition, this method is uniquely used with non invasive technologies to help determine on a real time basis the completion of the treatment.

Claims

1. A method of administering a focused treatment to a defined area of a patient'"'"'s body, said method comprising the steps of:

introducing heat to the defined area of the patient'"'"'s body; and

delivering a drug, gene, or viral vector to targeted tissue to be treated within the defined area of the patient'"'"'s body.

2. The method of administering a focused treatment to a defined area of a patient'"'"'s body according to claim 1, wherein the step of introducing heat delivers heat to the defined area site prior to the delivery of thermoactivated drugs, genes and/or viral vector to pre-condition or condition the targeted tissue to be treated and/or fixate the drugs, genes and/or viral vector to the targeted tissue to be treated.

3. The method of administering a focused treatment to a defined area of a patient'"'"'s body according to claim 1, wherein the step of introducing heat delivers heat to the defined area site simultaneously with the delivery of thermoactivated drugs, genes and/or viral vector to the targeted tissue to be treated to pre-condition or condition the targeted tissue to be treated and/or fixate the drugs, genes and/or viral vector to the targeted tissue to be treated.

4. The method of administering a focused treatment to a defined area of a patient'"'"'s body according to claim 1, wherein the step of introducing the heat delivers heat to the defined area site post delivery of thermoactivated drugs, genes and/or viral vector to the targeted tissue to be treated to pre-condition, condition the targeted tissue to be treated and/or fixate the drugs, genes and/or viral vector to the targeted tissue to be treated.

5. The method of administering a focused treatment to a defined area of a patient'"'"'s body according to claim 1, wherein the step of introducing heat includes dynamic control of heat to optimize spatial delivery of rigid temperature release thermoactivated drugs and/or genes and/or viral vector to the targeted tissue to be treated.

6. The method of administering a focused treatment to a defined area of a patient'"'"'s body according to claim 5, wherein the thermoactivated drugs and/or genes and/or viral vector are encapsulates and the rigid temperature release formulation releases, activates and/or expresses the majority of the encapsulates within a temperature range having 0-2 degrees C. tolerance.

7. The method of administering a focused treatment to a defined area of a patient'"'"'s body according to claim 1, wherein the step of introducing heat includes dynamic control of heat to optimize spatial delivery of a broad range temperature release thermoactivated drugs and/or genes and/or viral vector to the targeted tissue to be treated.

8. The method of administering a focused treatment to a defined area of a patient'"'"'s body according to claim 7, wherein the thermoactivated drugs and/or genes and/or viral vector are encapsulated, the broad range temperature release formulation releases, activates and/or expresses the majority of the encapsulates within a temperature range having 0-15 degrees C. tolerance, and the targeted tissue is heated to a temperature range of approximately 40 degrees C. through 55 degrees C.

9. The method of administering a focused treatment to a defined area of a patient'"'"'s body according to claim 1, wherein the step of introducing heat includes control of a static and/or steady state heating profile to optimize the spatial delivery of rigid temperature release thermoactivated drugs and/or genes and/or viral vector to the targeted tissue to be treated where thermoactivated drugs and/or genes and/or viral vector are encapsulates and the rigid temperature release formulation releases activates and/or expresses the majority of the encapsulates within a range of 0-2 degrees C. tolerance.

10. The method of administering a focused treatment to a defined area of a patient'"'"'s body according to claim 1, wherein the step of introducing heat includes control of a static and/or steady state heating profile to optimize the spatial delivery of a broad range temperature release thermoactivated drugs and/or genes and/or viral vector to the targeted tissue to be treated where thermoactivated drugs and/or genes and/or viral vector are encapsulates and the broad range temperature release formulation releases, activates and/or expresses the majority of the encapsulates within a temperature range having 0-15 degrees C. tolerance and the targeted tissue is heated to a temperature range of approximately 40 degrees C. through 55 degrees C.

11. The method of administering a focused treatment to a defined area of a patient'"'"'s body according to claim 1, the step of introducing the heat delivers heat to the defined area site pre-delivery, simultaneously and/or post delivery of the drug and/or gene and/or viral vector to pre-condition, condition, and/or fixate to the targeted tissue to be treated.

12. The method of administering a focused treatment to a defined area of a patient'"'"'s body according to claim 11, wherein said drug and/or gene and/or viral vector is a thermoactivated drug, gene, or viral vector.

13. The method of administering a focused treatment to a defined area of a patient'"'"'s body according to claim 12, wherein said thermoactivated drug, gene, or viral vector is activated only in said defined area of said patient'"'"'s body by the use of said delivered heat.

14. The method of administering a focused treatment to a defined area of a patient'"'"'s body according to claim 1, wherein the step of introducing heat to said defined area of said patient'"'"'s body is performed concurrently with the step of delivering said drug, gene, or viral vector to said defined area of said patient'"'"'s body.

15. The method of administering a focused treatment to a defined area of a patient'"'"'s body according to claim 14, wherein said drug, gene, or viral vector is a thermoactivated drug, gene, or viral vector.

16. The method of administering a focused treatment to a defined area of a patient'"'"'s body according to claim 15, wherein said thermoactivated drug, gene, or viral vector is activated only in said defined area of said patient'"'"'s body by the use of the introduced heat.

17. The method of administering a focused treatment to a defined area of a patient'"'"'s body according to claim 1, wherein the step of introducing heat to said defined area of said patient'"'"'s body is performed after the step of delivering said drug, gene, or viral vector to said defined area of said patient'"'"'s body.

18. The method of administering a focused treatment to a defined area of a patient'"'"'s body according to claim 17, wherein said drug, gene, or viral vector is a thermoactivated drug, gene, or viral vector.

19. The method of administering a focused treatment to a defined area of a patient'"'"'s body according to claim 18, wherein said thermoactivated drug, gene, or viral vector is activated only in said defined area of said patient'"'"'s body by the use of said introduced heat.

20. The method of administering a focused treatment to a defined area of a patient'"'"'s body according to claim 1, whereby the step of introducing heat to said defined area of said patient'"'"'s body defines said defined area to be treated by said drug, gene, or viral vector.

21. The method of administering a focused treatment to a defined area of a patient'"'"'s body according to claim 1, wherein said heat is introduced to the targeted tissue by the use of a method selected from the group consisting of Radio Frequency Ablation (RFA), Microwave Ablation (MA), Laser Ablation (LA), Ultrasound Ablation (UA), Hi Energy Focused Ultrasound (HIFU), focused microwaves (FM), and combinations thereof.

22. The method of administering a focused treatment to a defined area of a patient'"'"'s body according to claim 1, wherein said heat is introduced to the targeted tissue by the use two or more of the methods selected from the group consisting of Radio Frequency Ablation (RFA), Microwave Ablation (MA), Laser Ablation (LA), Ultrasound Ablation (UA), Hi Energy Focused Ultrasound (HIFU), and focused microwaves (FM).

23. The method of administering a focused treatment to a defined area of a patient'"'"'s body according to claim 1, said method further comprising the step of:

controlling the size, shape, and volume of said defined area by the extent of heat energy delivered and temperature achieved over time to the desired boundaries.

24. The method of administering a focused treatment to a defined area of a patient'"'"'s body according to claim 23, wherein said step of controlling the size, shape, and volume of said defined area further includes the use of one or more temperature sensor.

25. The method of administering a focused treatment to a defined area of a patient'"'"'s body according to claim 24, wherein said use of one or more temperature sensor(s) is positioned within said defined area or along the margins of said defined area.

26. The method of administering a focused treatment to a defined area of a patient'"'"'s body according to claim 1, wherein the use of one or more of said steps of introducing heat and delivering a drug, gene, or viral vector to said defined area of said patient'"'"'s body is performed by the use of a variable and adjustable probe device.

27. The method of administering a focused treatment to a defined area of a patient'"'"'s body according to claim 26, wherein said probe device includes the use of one or more one temperature sensor(s).

28. The method of administering a focused treatment to a defined area of a patient'"'"'s body according to claim 26, wherein said probe device includes the use of one or more fluid port(s) for delivering a drug, gene, or viral vector to said defined area of said patient'"'"'s body.

29. The method of administering a focused treatment to a defined area of a patient'"'"'s body according to claim 26, wherein said probe tool includes the use of one or more energy delivery port for delivering heat energy to said defined area of said patient'"'"'s body.

30. The method of administering a focused treatment to a defined area of a patient'"'"'s body according to claim 29, wherein said probe device includes the use of one or more energy delivering probe(s) which is provided with at least one or more energy delivery port(s) and a metallic rod positioned within said at least one or more energy delivery port(s);

wherein said step of introducing energy to said defined area of said patient'"'"'s body comprises the sub-steps of;

positioning at least one or more probe(s) of said at least one energy delivering probe within said defined area of said patient'"'"'s body;

removing said metallic rod from said at least one or more energy delivery ports;

inserting one or more heating prong(s) within said one or more energy delivering probe(s) and extending said heating prong out of said energy delivery port; and

delivering energy to said defined area of said patient'"'"'s body via said heating delivering probe.

31. The method of administering a focused treatment to a defined area of a patient'"'"'s body according to claim 26, the method further comprising the step of monitoring the volumetric heating of said defined area by the use of a plurality of said temperature sensors along said variable and adjustable probe device, wherein said probe device includes at least one or more variable and adjustable probes where each variable and adjustable probe includes a plurality of said temperature sensors.

32. The method of administering a focused treatment to a defined area of a patient'"'"'s body according to claim 1, wherein said defined area of said patient'"'"'s body is heated to a temperature no greater than approximately 55 degrees C.

33. The method of administering a focused treatment to a defined area of a patient'"'"'s body according to claim 1, wherein said defined area of said patient'"'"'s body is heated to a temperature of about 41 degrees C.

47. The method of administering a focused treatment to a defined area of a patient'"'"'s body according to claim 1, further comprising the step of determining the completion of the focused treatment when combined with non-invasive approaches including one of realtime MRI, ultrasound, CT, laser, infrared, PET, and/or other imaging technologies.

48. The method of administering a focused treatment to a defined area of a patient'"'"'s body according to claim 1, further comprising the step of determining the completion of the focused treatment when combined with non-invasive approaches selected from the group of microwave or RF radiometer technologies.

49. The method of administering a focused treatment to a defined area of a patient'"'"'s body according to claim 1, wherein the step of introducing the heat initially releases, activates, enhances, and/or expresses delivery of thermoactivated drugs, genes and/or viral vector to the targeted tissue to be treated, and then the drugs, genes and/or viral vector will effect the targeted tissue to be more susceptible to heat damage at the targeted tissue to be treated.

50. The method of administering a focused treatment to a defined area of a patient'"'"'s body according to claim 1, wherein the step of introducing heat to said defined area of said patient'"'"'s body is performed before the step of delivering said drug, gene, or viral vector to said defined area of said patient'"'"'s body.

51. The method of administering a focused treatment to a defined area of a patient'"'"'s body according to claim 50, wherein said drug, gene, or viral vector is a thermoactivated drug, gene, or viral vector.

52. The method of administering a focused treatment to a defined area of a patient'"'"'s body according to claim 51, wherein said thermoactivated drug, gene, or viral vector is activated only in said defined area of said patient'"'"'s body by the use of the introduced heat.

53. The method of administering a focused treatment to a defined area of a patient'"'"'s body according to claim 1, wherein the step of introducing heat delivers heat to the defined area site;

before, simultaneously, and/or post the delivery of thermoactivated drugs, genes and/or viral vector to the targeted tissue to be treated to pre-condition or condition the targeted tissue to be treated and/or fixate the drugs, genes and/or viral vector to the targeted tissue to be treated.

54. The method of administering a focused treatment to a defined area of a patient'"'"'s body according to claim 1, wherein said defined area of said patient'"'"'s body is heated to a range of temperature of about 41-55 degrees C.

34. An apparatus for administering a focused treatment to a defined area of a patient'"'"'s body comprising:

a catheter;

one or more variable and adjustable probe(s) movably at least partially disposed within the catheter; and

a controller for adjusting a length of said at least one or more variable and adjustable probe(s) so that it extends outside the catheter.

35. The apparatus for administering a focused treatment to a defined area of a patient'"'"'s body according to claim 34 further comprising:

one or more temperature sensor(s) positioned at the tip or along the side of at least one or more of said variable and adjustable probe(s).

36. The apparatus for administering a focused treatment to a defined area of a patient'"'"'s body according to claim 34 further comprising:

one or more fluid delivery port(s) positioned at the tip or along the side of said one or more variable and adjustable probe(s).

37. The apparatus for administering a focused treatment to a defined area of a patient'"'"'s body according to claim 34 further comprising:

one or more energy delivery port(s) positioned at the tip or along the side of at least one or more of said variable and adjustable probe(s).

38. The apparatus for administering a focused treatment to a defined area of a patient'"'"'s body according to claim 37,

wherein said one or more of said variable and adjustable probes is an energy delivering probe having at least one or more of said energy delivery ports,

wherein said energy delivering probe is either metallic or non-metallic;

wherein said energy delivering probe includes an internal metallic rod that is removable from said energy delivering probe;

said apparatus further includes one or more heating prong(s) which is (are) capable of being inserted into said energy delivering probe once said metallic rod is removed from said energy delivering probe, wherein said one or more heating prong(s) is (are) capable of being extended out of said at least one or more energy delivery port.

39. The apparatus for administering a focused treatment to a defined area of a patient'"'"'s body according to claim 37 further comprising:

an energy emitter for emitting energy through said energy delivery port;

wherein said energy emitter emits energy using one or more of the methods selected from the group consisting of Radio Frequency Ablation (RFA), Microwave Ablation (MA), Laser Ablation (LA), Ultrasound Ablation (UA), Hi Energy Focused Ultrasound (HIFU), focused microwaves (FM), and combinations thereof.

40. The apparatus for administering a focused treatment to a defined area of a patient'"'"'s body according to claim 37 further comprising:

at least one or more energy emitter(s) is positioned at the tip or along the side of at least one of said at least one or more variable and adjustable probes.

41. The apparatus for administering a focused treatment to a defined area of a patient'"'"'s body according to claim 37 further comprising:

at least one or more temperature sensor positioned at the tip or along the side of at least one or more of said variable and adjustable probes;

at least one or more fluid delivery port positioned at the tip or along the side of at least one or more of said variable and adjustable probes; and

at least one or more energy delivery port or energy emitter positioned at the tip or along the side of at least one or more of said variable and adjustable probes.

42. The apparatus for administering a focused treatment to a defined area of a patient'"'"'s body according to claim 37, wherein said apparatus includes a plurality of said variable and adjustable probes.

43. The apparatus for administering a focused treatment to a defined area of a patient'"'"'s body according to claim 42, wherein said catheter has at least one catheter port through which said plurality of variable and adjustable probes extend out of when said variable and adjustable probes are in an extended position.

44. The apparatus of administering a focused treatment to a defined area of a patient'"'"'s body according to claim 37, wherein at least one or more of said at least one or more variable and adjustable probes includes an energy emitter for emitting energy through said energy delivery port.

45. The apparatus of administering a focused treatment to a defined area of a patient'"'"'s body according to claim 44, wherein a plurality of said variable and adjustable probes are encased at least partially within said catheter, wherein each of said plurality of variable and adjustable probes includes at least one or more of the elements selected from the group consisting of a temperature sensor, a port for delivering a drug, gene, or viral vector, or an energy emitter.

46. The apparatus of administering a focused treatment to a defined area of a patient'"'"'s body according to claim 44, wherein a plurality of said variable and adjustable probes are encased at least partially within said catheter, wherein each of said plurality of probes includes a plurality of the elements selected from the group consisting of a temperature sensor, a port for delivering a drug, gene, or viral vector, or an energy emitter, wherein said plurality of elements are positioned at the tip of said probes or along the length of said probes.

55. The apparatus for administering a focused treatment to a defined area of a patient'"'"'s body according to claim 43, wherein said plurality of variable and adjustable probes extend out of said catheter in one of J-shaped array, oval-shaped array or linear array to fix and control the size and shape of a treatment zone so that the treatment is focused on diseased tissue of the defined area and avoids damaging surrounding healthy tissue.