METHOD AND APPARATUS FOR ELECTROMAGNETIC ENHANCEMENT OF BIOCHEMICAL SIGNALING PATHWAYS FOR THERAPEUTICS AND PROPHYLAXIS IN PLANTS, ANIMALS AND HUMANS

• US 20120089201A1
• Filed: 10/31/2011
• Published: 04/12/2012
• Est. Priority Date: 12/05/2003
• Status: Active Grant

• Current Assignee: Endonovo Therapeutics, Inc.
• Original Assignee: Rio Grande Neurosciences, Inc.
• Inventors: Pilla, Arthur A.
• Granted Patent: US 9,656,096 B2
• Time in Patent Office: Days
• US Class Current: 607/50
• CPC Class Codes: A01G 7/04 Electric or magnetic or acoustic treatment of plants for promoting growth
• CPC Class Codes: A61N 1/40 Applying electric fields by inductive or capacitive coupling microwave apparatus A61N5/00; Applying radio-frequency signals
• CPC Class Codes: A61N 2/008 for pain treatment or analgesia
• CPC Class Codes: A61N 2/02 using magnetic fields produced by coils, including single turn loops or electromagnets A61N2/12 takes precedence

Abstract

Apparatus and methods for delivering electromagnetic signals configured specifically to accelerate the asymmetrical kinetics of the binding of intracellular ions to their respective intracellular buffers, to enhance the biochemical signaling pathways plant animal and human molecules, cells, tissues, organs, portions of entire organisms and entire organisms employ for growth, repair and maintenance. Described herein are devices and methods that utilize repetitive bursts of waveforms configured to maximize the bound concentration of intracellular ions at their associated molecular buffers to enhance the biochemical signaling pathways living systems employ for growth, repair and maintenance. For example the systems and methods described herein may drive the binding of calcium to calmodulin (CaM), thereby enhancing the CaM-dependent nitric oxide (NO)/cyclic guanosine monophosphate (cGMP) signaling pathway.

Claims

1. An electromagnetic treatment device for accelerating cytosolic ion binding to a corresponding cytosolic buffer to modulate a biochemical signaling pathway employed for tissue growth, repair and maintenance, the device configured to increase the voltage across a target ion binding pathway according to the asymmetrical binding kinetics of the target pathway, wherein the target ion binding pathway has an ion bound time, the device comprising:

an applicator; and

a signal generator configured to apply an electromagnetic signal to the applicator to induce, in the target pathway, a peak electric field less than about 100 V/m, wherein the signal generated by the signal generator has a pulse duration, random signal duration or carrier period which is less than twice the ion bound time, applied in a burst of waveforms having a burst duration of greater than 10 μ

sec and a signal repetition rate greater than 0.01 waveforms or bursts per second.

2. The device of claim 1, wherein the applicator comprises a coil applicator.

3. The device of claim 1, wherein the applicator comprises an electrode applicator.

4. The device of claim 1, wherein the target ion binding pathway comprises calcium binding to calmodulin, and the on bound time is between about 10⁻

2-10 sec.

5. The device of claim 1, wherein the electromagnetic treatment device is lightweight.

6. The device of claim 1, wherein the electromagnetic treatment device is disposable.

7. The device of claim 1, wherein the electromagnetic treatment device is portable.

8. The device of claim 1, wherein the lightweight electromagnetic treatment device is configured to be worn.

9. The device of claim 1, wherein the electromagnetic treatment device is configured to be compatible with a diagnostic or surgical device or method.

10. The device of claim 1, wherein the electromagnetic treatment device is configured to be compatible with a pharmacological intervention or treatment.

11. The device of claim 1, wherein the waveforms generated by the control circuit have a carrier frequency within the ISM band.

12. The device of claim 1, wherein the waveforms generated by the control circuit have a carrier frequency of approximately 27.12 MHz.

13. The device of claim 1, further comprising an anatomical support configured to hold the treatment device adjacent to the target tissue.

14. A method for electromagnetic treatment of plants, animals, and humans by accelerating cytosolic ion binding to a corresponding cytosolic buffer in a target pathway to modulate a biochemical signaling pathways plants, animals and humans employ for tissue growth, repair and maintenance, the method comprising:

activating an electromagnetic treatment device to treat the target pathway by inducing an electric field waveform having a pulse duration, random signal duration or carrier period which is less than twice the cytosolic ion bound time to increase the voltage in the target pathway so as to accelerate ion binding of the cytosolic ion to the buffer, thereby modulating the target pathway.

15. The method of claim 14, wherein the step of activating comprises applying an electromagnetic signal to an applicator to induce, in the target pathway, a peak electric field less than about 100 V/m.

16. The method of claim 14, wherein the step of activating comprises applying an electromagnetic signal to an applicator to apply a burst of waveforms having a burst duration of greater than 10 μ

sec and a signal repetition rate greater than 0.01 waveforms or bursts per second.

17. The method of claim 14, wherein the step of activating comprises applying an electromagnetic signal to a coil applicator.

18. The method of claim 14, wherein the step of activating comprises applying an electromagnetic signal to an applicator comprising an electrode applicator.

19. The method of claim 14, wherein the target ion binding pathway comprises calcium binding to calmodulin, and the on bound time is between about 10⁻

2-10 sec.

20. The method of claim 14, further comprising applying the electromagnetic treatment device to a patient, wherein the electromagnetic treatment device is lightweight,

21. The method of claim 14, further comprising applying the electromagnetic treatment device to a patient, wherein the electromagnetic treatment device is disposable.

22. The method of claim 14, wherein the step of activating comprises applying waveforms having a frequency of approximately 27.12 MHz.

23. The method of claim 14, wherein the step of activating comprises applying waveforms consisting of about 1 to about 10 msec burst of between about 5 MHz to about 50 MHz in the ISM band, repeating between about 1 and about 5 bursts/sec and inducing a peak electric field between about 1 and about 100 V/m.

24. The method of claim 14, wherein the step of activating comprises applying EMF waveforms configured to modulate the production of cytokines and growth factors that any living organism employs in response to any physical or chemical insult.

25. The method of claim 14, wherein the step of activating comprises applying EMF waveforms configured to up regulate or down regulate the mRNA or gene associated with each growth factor or cytokine any living organism employs in response to any physical or chemical insult.

26. The method of claim 14, wherein the step of activating comprises applying EMF waveforms configured to enhance the biochemical signaling pathways of molecules, cells, tissues, organs, portions of entire organisms and entire organisms employ for growth, repair and maintenance.

27. The method of claim 14, wherein the step of activating comprises applying EMF waveforms configured to modulate biochemical signaling in anti-inflammatory pathways, biochemical signaling in cytokine release pathways, biochemical signaling in growth factor release pathways.

28. The method of claim 14, wherein the step of activating comprises applying EMF waveforms configured for chronic and acute musculoskeletal pain relief;

edema and lymph reduction, anti-inflammatory, post-surgical and post-operative pain and edema relief, nerve, bone and organ pain relief, angina pain relief, increased local blood flow, microvascular blood perfusion, treatment of tissue and organ ischemia, cardiac tissue ischemia, brain tissue ischemia from stroke or traumatic brain injury, treatment of neurological injury and neurodegenerative diseases such as Alzheimer'"'"'s and Parkinson'"'"'s;

wound repair, bone repair, tissue repair;

osteoporosis treatment and prevention;

degenerative bone disease treatment and prevention;

angiogenesis, neovascularization;

enhanced immune response;

treatment of diabetes Types I and II;

enhanced effectiveness of pharmacological agents;

nerve regeneration, skeletal muscle regeneration, cardiac muscle regeneration;

cancer treatment;

prevention of apoptosis;

modulation of heat shock proteins for prophylaxis and response to injury or pathology.

29. The method of claim 14, wherein the step of activating comprises applying EMF waveforms configured to employ a carrier frequency within those employed by mobile communication and wireless devices.

30. The method of claim 14, wherein the step of activating comprises applying EMF waveforms configured to modulate plasticity and cognition in humans and animals.

31. The method of claim 14, wherein the step of activating comprises applying EMF waveforms configured to modulate neurotransmitter release to modulate cognition and neuromuscular junction activity.

32. The method of claim 14, wherein the step of activating comprises applying EMF waveforms according to a regime defined to maximize the desired physiological outcome of tissue growth, repair and maintenance, or cognition.

33. A method of treating a region of a patient'"'"'s body to enhance calmodulin-dependent signaling pathways, the method comprising:

placing an electromagnetic treatment device on or over a region of the patient'"'"'s body to be treated;

activating an electromagnetic treatment device to generate an electric field having a pulse duration, random signal duration or carrier period which is less than twice the bound time of cytosolic calcium to calmodulin to accelerate calcium ion binding to calmodulin in the region of the patient'"'"'s body.

34. The method of claim 33, wherein activating comprises generating an electric field comprising an about 1 to about 10 msec burst of between about 5 MHz to about 50 MHz waves in the ISM band, repeating between about 1 and about 10 bursts/sec and inducing a peak electric field between about 1 and about 100 V/m.

35. The method of claim 33, wherein the burst of waves has a carrier frequency of about 27.12 MHz.

36. The method of claim 33, wherein the burst of waves comprises one of:

sinusoidal, rectangular, chaotic, or random wave shapes.

37. The method of claim 33, wherein placing comprises placing a coil applicator of the electromagnetic treatment device on or over the region of the patient'"'"'s body to be treated.

38. The method of claim 33, further comprising enhancing CaM-dependent signaling, including NO/cGMP signaling to accelerate blood and lymph vessel dilation for relief of post-operative, post traumatic and musculoskeletal pain and edema.

39. The method of claim 33, further comprising enhancing CaM-dependent signaling, including NO/cGMP signaling to enhance angiogenesis and microvascularization for hard and/or soft tissue repair.

40. The method of claim 33, further comprising enhancing CaM-dependent signaling, including NO/cGMP signaling to enhance bone repair.

41. The method of claim 33, further comprising enhancing CaM-dependent signaling, including NO/cGMP signaling to enhance cartilage repair.

42. The method of claim 33, further comprising enhancing CaM-dependent signaling, including NO/cGMP signaling to reverse or prevent osteoporosis.

43. The method of claim 33, further comprising enhancing CaM-dependent signaling, including NO/cGMP signaling to accelerate deoxyribonucleic acid synthesis,

44. The method of claim 33, further comprising enhancing CaM-dependent signaling, including NO/cGMP signaling to modulate growth factor release.

45. The method of claim 33, further comprising enhancing CaM-dependent signaling, including NO/cGMP signaling to modulate cytokine production.

46. The method of claim 33, further comprising enhancing CaM-dependent signaling, including NO/cGMP signaling to accelerate the production of matrix proteins for tissue repair and maintenance.

47. The method of claim 33, further comprising enhancing CaM-dependent signaling, including NO/cAMP signaling to modulate cell and tissue differentiation,

48. The method of claim 33, further comprising enhancing CaM-dependent signaling pathways to prevent or reverse neurodegeneration.

49. The method of claim 33, further comprising enhancing CaM-dependent signaling to modulate heat shock protein release.

50. The method of claim 33, further comprising enhancing CaM-dependent signaling to modulate neurotransmitter release to modulate cognition and neuromuscular junction activity.

51. The method of claim 33, further comprising enhancing CaM-dependent signaling to up regulate or down regulate the mRNA or gene expression associated with an enzyme, cytokine or growth factor employed for repair, growth and maintenance of tissue.

52. A method of applying a wearable electromagnetic treatment device to drive the binding of calcium to calmodulin in a target tissue by applying electromagnetic waveforms to a tissue that match the asymmetrical kinetics of binding of calcium to calmodulin, thereby enhancing calmodulin-dependent signaling, the method comprising:

positioning a wearable applicator of an electromagnetic treatment device adjacent to the target tissue; and

providing an electromagnetic signal to the applicator from the electromagnetic treatment device to induce an electric field of amplitude of less than about 100 V/m at the target tissue and wherein the signal comprises an about 1 to about 10 msec burst of between about 5 MHz to about 50 MHz carrier waves in the ISM band, repeating between about 1 and about 10 bursts/sec;

whereby calmodulin-dependent signaling is enhanced in the target tissue.

53. The method of claim 52, wherein the burst of carrier waves have a frequency of approximately 27.12 MHz.

54. The method of claim 52, wherein the carrier waves have a wave shape selected from the group of wave shapes comprises one of:

sinusoidal, rectangular, chaotic, or random wave shapes.

55. The method of claim 52, wherein positioning comprises placing a coil applicator of the electromagnetic treatment device on or over the region of the patient'"'"'s body to be treated.

56. The method of claim 52, wherein positioning comprises placing a coil applicator of the electromagnetic treatment device on or over the region of the patient'"'"'s body to be treated, which device is programmed to deliver an EMF waveform configured to enhance CaM-dependent signaling to do one or more of:

accelerate blood and lymph vessel dilatation for relief of post-operative, post traumatic and musculoskeletal pain and edema;

enhance angiogenesis and microvascularization for hard and/or soft tissue repair;

enhance bone repair;

enhance cartilage repair;

reverse or prevent osteoporosis;

accelerate deoxyribonucleic acid synthesis;

modulate growth factor release;

modulate cytokine production;

modulate the production of matrix proteins for tissue repair and maintenance;

modulate cell and tissue differentiation;

prevent or reverse neurodegeneration;

modulate heat shock protein release;

up regulate or down regulate the mRNA or gene expression associated with an enzyme, cytokine or growth factor employed for repair, growth and maintenance of tissue.

57. The method of claim 52, wherein positioning comprises placing a coil applicator of the electromagnetic treatment device on or over the region of the patient'"'"'s body to be treated, which device is programmed to deliver an EMF waveform configured to enhance CaM-dependent signaling for chronic and acute musculoskeletal pain relief;

edema and lymph reduction, anti-inflammatory, post-surgical and post-operative pain and edema relief, nerve, bone and organ pain relief, angina pain relief, increased local blood flow, microvascular blood perfusion, treatment of tissue and organ ischemia, cardiac tissue ischemia, brain tissue ischemia from stroke or traumatic brain injury, treatment of neurological injury and neurodegenerative diseases such as Alzheimer'"'"'s and Parkinson'"'"'s;

wound repair, bone repair, tissue repair;

osteoporosis treatment and prevention;

degenerative bone disease treatment and prevention;

angiogenesis, neovascularization;

enhanced immune response;

treatment of diabetes Types I and II;

enhanced effectiveness of pharmacological agents;

nerve regeneration, skeletal muscle regeneration, cardiac muscle regeneration;

cancer treatment;

prevention of apoptosis;

modulation of heat shock proteins for prophylaxis and response to injury or pathology.

58. The method of claim 52, wherein positioning comprises placing a coil applicator of the electromagnetic treatment device on or over the region of the patient'"'"'s body to be treated, which device is programmed to deliver an EMF waveform configured to enhance CaM-dependent signaling to modulate plasticity and cognition in humans and animals.

59. The method of claim 52, wherein positioning comprises placing a coil applicator of the electromagnetic treatment device on or over the region of the patient'"'"'s body to be treated, which device is programmed to deliver an EMF waveform configured to enhance CaM-dependent signaling to modulate neurotransmitter release to modulate cognition and neuromuscular junction activity.