KR20070015908A - Electromagnetic therapy apparatus and method - Google Patents

Abstract

Apparatus and methods for electromagnetic treatment of plants, animals, and people are disclosed. The method comprises the steps of constructing, using waveform constructing means, at least one waveform to be coupled to the target path structure 101 in accordance with a mathematical model having at least one waveform parameter; Selecting a value of the at least one waveform parameter such that the at least one waveform is detectably configured in the target path structure above the background activity of the target path structure (102); Generating an electromagnetic signal from said constructed at least one waveform (103) using a coupling device; And coupling the electromagnetic signal to the path structure using the coupling device 104.

Electromagnetic therapy, waveform parameters, target path structure

Description

Electromagnetic treatment apparatus and method

The present invention relates generally to apparatus and methods for the therapeutic and prophylactic treatment of plant, animal and human tissues, organs, cells and molecules in vitro and in vivo conditions. will be. In particular, embodiments in accordance with the present invention employ molecules and cells, tissues, and, using power and amplitude comparison assays to evaluate signals for thermal noise ratio (“SNR”) in target path structures. It relates to the use of non-thermal, time-varying magnetic fields constructed for proper binding to target pathway structures such as organs. Another embodiment according to the present invention is a lightweight, portable coupling devices such as inductors, electrodes, and garments, socks and fashion accessories as well as knees, elbows, lower back, shoulders, Of arbitrary waveform electromagnetic signals to target path structures such as molecules, cells, tissues, and organs using a driver circuit that can be coupled into positioning devices such as the foot and other anatomical glands. Relates to the application of bursts.

Another embodiment according to the invention relates to the application of steady state periodic signals of arbitrary waveform electromagnetic signals to target path structures such as molecules, cells, tissues, and organs. Examples of therapeutic and prophylactic applications of the present invention include relief of pain in the musculoskeletal system, reduction of edema, increased local blood flow, microvascular blood perfusion, wound recovery, bone recovery, osteoporosis treatment and angiogenesis, neovascularization, enhanced Exudate, and enhanced pharmacological agents. One embodiment according to the present invention also provides therapeutic and prophylactic procedures and physical therapy such as heat, cooling, ultrasound, vacuum assisted wound closure, wound dressings, orthopedic correction devices, and surgical procedures. Can be used in conjunction.

It is now well established that the application of weak non-magnetic fields ("EMF") can produce physiologically meaningful results in biological effects in vivo and in vitro conditions. Time-varying electromagnetic fields, including rectangular waveforms such as pulsing electromagnetic fields ("PEMF"), and pulsed frequency fields ranging from a few hertz to about 15 to about 40 MHz. Sinusoidal waveforms such as radio frequency fields ("PRE") are clinically beneficial when used as an adjuvant therapy for various musculoskeletal injuries and pathological conditions.

Beginning in the 1960s, the development of modern therapeutic and prophylactic devices has been stimulated by clinical problems associated with non-combining fractures and delayed fractures. Early work has shown that electrical pathways can be the means by which bones respond to mechanical inputs. Early treatment devices used implanted and non-invasive electrodes that delivered direct current ("DC") to the fracture location. Anti-invasive techniques have since been developed using electric and electromagnetic fields. These physical therapies were originally invented to provide a noninvasive "contactless" means of inducing electrical / mechanical waveforms at the cellular / tissue level. Clinical applications of these techniques in orthopedic surgery have led to applications approved by worldwide supervisory groups for the treatment of fractures such as non-bonded fractures and new fractures as well as spine fusion. Several EMF devices are currently establishing standard medical facilities for orthopedic clinical procedures for treatments that are difficult to treat. The probability of success for these devices was very high. The database of these findings is large enough to enable use that has been recommended as a safe, non-invasive, alternative method for initial bone grafts. Additional clinical findings on these techniques have been reported in double-blind studies for the treatment of pain from arthritis as well as avascular necrosis, tendonitis, osteoarthritis, wound suppuration, blood circulation and other musculoskeletal injuries.

Cell studies have highlighted the effects of weak and low frequency electromagnetic fields on both signal transduction pathways and growth factor synthesis. It can be seen that EMF promotes the secretion of growth factors after a short, trigger-like duration. Ion / ligand binding processes in cell membranes are generally considered early EMF target pathway structures. The clinical relationship to the treatments for the example of bone regeneration is an upregulation, such as modulation of growth factor production, as part of the normal molecular coordination of bone regeneration. Cell-level studies have shown effects on calcium ion transport, cell proliferation, insulin growth factor ("IGF-II") release, and IGF-II receptor expression in osteoblasts. Effects on insulin growth factor-I ("IGF-I") and IGF-II have also been shown in the fracture callus of rats. Stimulation of transforming growth factor beta ("TGF-β") messenger RNA ("mRNA") into PEMF has been shown in a rat bone induction model. Studies also suggest upregulation of TGF-β mRNA by PEMF in MG-63 of human osteoblast-like cell line designation, where there are increases in TGF-β1, collagen, and osteocalcin synthesis. PEMF promoted an increase in TGF-β1 in both hypertrophic and atrophic cells from human non- connective tissue. Other studies have shown an increase in both TGF-β1 mRNA and protein in osteoblast cultures resulting from the direct effects of the calcium / calmodulin dependent pathway. Cartilage cell studies have been described in therapeutic applications for joint regeneration, for example, in US Pat. No. 4, 315, 503 (1982), Ryaby and US Pat. No. 5,723, 001 (1998), Pilla. Presenting a therapeutic application for, the TGF-β1 mRNA from EMF and protein synthesis showed a similar increase.

However, prior art in this field applies unnecessarily high amplitudes and powers to the target path structure, requires unnecessarily long treatment times, and is not portable.

Therefore, it is possible to minimize the size of circuits and lightweight devices, such as coupling devices that more effectively control the biochemical processes that control tissue growth and regeneration, shorten treatment times, and allow the device to be portable and, if desired, disposed of. There is a need for an apparatus and method of coupling applicators. Devices that combine lightweight applicators with miniaturized circuits, such as coupling devices that can be more effectively controlled, shorten treatment time, and can be implanted to control tissue growth and regeneration There is another need for a method.

Apparatus and methods are provided for delivering electromagnetic signals to target pathway structures such as molecules, cells, tissues, and organs of humans, animals, and plants for therapeutic and prophylactic purposes. One preferred embodiment in accordance with the present invention employs a power-to-noise ("Power SNR") approach to noise and combines lightweight stretch coils with a miniaturized size to construct waveforms with biological effects. This advantageously allows a device using a power SNR approach, miniaturized circuitry, and lightweight, flexible coils to be fully portable and, if desired, portable and, if desired, implantable.

In particular, broad spectral density bursts of electromagnetic waveforms, configured to achieve maximum signal power within the bandpass of a biological target, are selective for target path structures such as living organs, tissues, cells and molecules. Is applied. The waveforms are selected using a unique amplitude / power comparison with the amplitude / power of the thermal noise in the target path structure. The signals include at least one sinusoidal, rectangular, disordered and random wave forms of bursts, having a frequency content in the range of about 0.01 Hz to about 100 MHz at about 1 to about 100,000 bursts per second, Has a burst repetition rate in the range of about 0.01 to about 1000 bursts / second. The peak signal amplitude in the target pathway structure, such as tissue, will be in the range of about 1 AV / cm to about 100 mV / cm. Each signal burst envelope waveform will be a random function that provides a means for accommodating different electromagnetic field properties to treat tissue. One preferred embodiment according to the present invention is a 20 millisecond pulse burst comprising about 5 to about 20 microsecond symmetrical or asymmetrical pulses repeating from about 1 to about 100 kilohertz within a burst. It includes. The burst envelope is a regulated 1 / f function and is applied at random repetition rates. The resulting waveform can be delivered via inductive or capacitive coupling.

The object of the present invention is to use a power-to-noise ratio (“Power SNR”) analysis of noise to construct optimized, biologically effective waveforms, and then by a waveform construction device such as a miniaturized electrical circuit. The purpose is to construct the power spectrum of the waveform by mathematical stimuli by combining the configured waveform to a target path structure using a coupling device such as powered ultralight wire coils.

Yet another object of the present invention is to use plants, animals and people's molecules with some input waveforms, although the electrical equivalents are non-linear, as in the Hodgkin-Huxley membrane model. To assess power SNR for target pathway structures such as cells, tissues, and organs.

Another object of the present invention is to provide plant, animal, and plant applications using selected electromagnetic fields by optimizing the power spectrum of the waveform for application to selected biochemical target pathway structures such as molecules, cells, tissues, and organs of plants, animals, and humans. To provide a method and apparatus for treating fields and people.

Another object of the present invention is to adopt significantly lower peak amplitudes and shorter pulse durations. This can be done via power SNR by adapting the frequency range in the signal to the frequency responsiveness and sensitivity of target pathway structures such as molecules, cells, tissues and organs of plants, animals and people.

The above and other objects and advantages of the present invention will become apparent from the following detailed description of the drawings, the detailed description of the invention, and the claims appended hereto.

Preferred embodiments of the present invention will be described in more detail below with reference to the accompanying drawings:

1 is a flow chart of a method for electromagnetic treatment of target pathway structures such as tissues, organs, cells, and molecules of plants, animals and humans in accordance with the present invention;

2 is a diagram of a control circuit and electrical coils applied to a knee joint in accordance with a preferred embodiment of the present invention;

3 is a block diagram of a minimized circuit in accordance with a preferred embodiment of the present invention;

4A is a line drawing of a wire coil, such as an inductor, in accordance with a preferred embodiment of the present invention;

4B is a line drawing of a stretchable magnetic wire in accordance with a preferred embodiment of the present invention;

5 depicts waveforms delivered to target pathway structures such as molecules, cells, tissues and organs in accordance with a preferred embodiment of the present invention;

6 is a view of a position fixing device such as a wrist support in accordance with a preferred embodiment of the present invention;

FIG. 7 is a graph showing the maximum increased myosin phosphorylation for PMRF constructed in accordance with an embodiment of the present invention; FIG. And

8 is a graph showing a power consumption comparison between a PMHz and a 60 Hz signal constructed according to an embodiment of the invention.

Time-varying currents derived from PEMF or PRF devices flow in target pathway structures such as molecules, cells, tissues and organs, which are stimulated where cells and tissues can respond by physiologically meaningful means. Things. The electrical properties of the target path structure affect the levels and distributions of induced currents. Molecules, cells, tissues and organs are all in the induced current path as cells in gap junction contact. Ion or ligand interactions at the binding sites on the macromolecules that may reside on the surface of the membrane are voltage dependent processes, which are electrochemical and can respond to induced electromagnetic fields (“E). The current arrives at these sites via the surrounding ionic medium The presence of cells in the path of the current causes the induced current ("J") to decay more rapidly over time ("J (t)"). This is due to the added electrical impedance of the cells from the membrane capacitance and time constants of other voltage sensitive membrane processes such as bonding and membrane transport.

Equivalent electrical circuit models representing various interfaced and charged interface configurations have been obtained. For example, calcium ( "Ca ^{+ 2")} in combination, because the inducing E concentration of the Ca ^{2 +} binding in the binding site can be described in the frequency domain by an impedance expression such as the following:

The expression above takes the form of a series resistance-capacitance coupled electrical equivalent circuit. ω is an angular frequency (angular frequency) is defined as 2πf, f is the frequency, in the case where ^{i = -1 1/2, Z} b (ω) are combined impedance and _ion R And C _ion are equivalent bond resistance and capacitive bond in the ionic bond path. The value of the equivalent bond time constant, τion = R _ion C _ion , is related to the ionic bond rate constant, k _b , via τion = R _ion C _ion = 1 / k _b . Thus, the characteristic time constant of this pathway is determined by the ion bonding kinetics.

Derived from a PEMF or PRF signal E will affect the number of Ca ^{2 +} ions per unit time to allow current to flow into an ion binding path. This electrical equivalent is equivalent coupling capacity coupled C _ion It is the change in voltage beyond, which is a direct measure of the change in electrical charge stored by C _ions . In the electric charge binding site, and directly proportional to the surface concentration of Ca ^{2 +} ion, an equivalent to a storage or other ion on the other charging the concatenated part with the cell surface type of charge that the charge. In addition to direct kinetic analyzes of coupling rate constants, electrical impedance measurements provide values for the time constants needed for the construction of a PMF waveform to fit the bandpass of target path structures. This allows for a range of frequencies that are essentially required for any given E waveform given for proper coupling to target impedances such as band pass.

Is a Ca ^{2 +} binding to: Ion binding molecules for the control is the frequency EMF target, for example calmodulin ( "CaM" calmodulin). The use of this pathway is based on the acceleration of wound regeneration, eg bone regeneration, which involves the regulation of growth factors released at various stages of regeneration. Growth factors such as platelet-derived growth factor ("PDGF"), fibroblast growth factor ("FGF"), and epidermal growth factor ("EGF") are all included in the appropriate stages of treatment. Angiogenesis is also essential for wound regeneration and is regulated by PMF. All of these factors are Ca / CaM-dependent.

Using Ca / CaM paths, the waveform-derived power can be configured to sufficiently surpass background thermal noise power. Under exact physiological conditions, this waveform has a physiologically significant biological effect.

Application of the Power SNR model to Ca / CaM is essentially required in the known CaM binding kinetics of the electrical equivalent of Ca ^{+ 2.} First in the command binding kinetics, combined changes in the concentration of Ca ^{2 +} in the CaM binding site a delayed time is equivalent binding time constant, _ion R And C _ions can be characterized in the frequency domain with ion = R _ion C _ion , in the case of equivalent coupling resistance and capacitive coupling in the ion bonding path. τ _ion is related to the ionic bond rate constant, k _b , via τ _ion = R _ion C _ion = 1 / k _b . The published values for k _b are then cell array models to evaluate SNR by comparing the voltage induced by the PRF signal for thermal wave fluctuations in voltage at CaM binding sites. Can be adopted from. V _max = 6.5 x l0 ^{~ 7} sec ^{~ 1} , [Ca ²⁺ ] = 2.5 μM, KD = 30 μM, [Ca ^{2 +} CaM] = K _D ([Ca ^{2 +} l + [CaM]) adopting the numeric value, it was calculated a ^{_{k b = 665 sec ~ 1 (}} τ ion = 1.5 msec). While values for such τ _ions can be adopted in an electrical equivalent circuit for ion bonding, power SNR analysis can be performed for the waveform structure.

According to one embodiment of the present invention, a mathematical model can be constructed to assimilate thermal noise so that it can be present in all voltage dependent processes and exhibits a minimum threshold requirement to establish an appropriate SNR. The power spectral density, S _n (ω), of thermal noise can be expressed as:

Where Z _M (x, ω) is the electrical impedance of the target path structure, x is the dimension of the target path structure and R _e specifies the actual part of the impedance of the target path structure. Z _M (x, ω) can be expressed as:

This equation is based on the electrical impedance of the target pathway structure and the extracellular fluid resistance ("R _e "), intracellular fluid resistance ("R _i ") and intermembrane resistance ("R _g ") that are electrically connected to the target path structure. The contributions from) clearly show that all contribute to noise filtering.

의 적분의 제곱 루트를 취함에 의해서 계산되었다. SNR이 다음의 비율에 의해 표현될 수 있다: A typical approach to the evaluation of SNR uses the value of the root mean square (RMS) noise voltage alone. This spans all frequencies related to both complete membrane reactivity, or bandwidth of the target path structure.

Calculated by taking the square root of the integral of. SNR can be expressed by the following ratio:

Where V _M (ω) is the maximum amplitude of the voltage at each frequency delivered by the waveform selected for the target path structure.

Referring to FIG. 1, FIG. 1 illustrates target pathway structures such as molecules, cells, tissues and organs of plants, animals, and humans for therapeutic and prophylactic purposes in accordance with one embodiment of the present invention. Is a flow chart of a method for delivering electromagnetic signals to a. A mathematical model with at least one waveform parameter was applied to construct at least one waveform, such as molecules, cells, tissues, and organs, for binding to the target pathway structure (step 101). The constructed waveform depends on the state of the cell and tissue, whether the state is at least one stable, growing, replacing, and reactive to injury, wherein the waveform is the thermal of the baseline at voltage and electrical impedance in the target path structure. The SNR or power SNR model may be selected so that it is possible to select at least one waveform parameter for a known target path structure that is provided to be detected in the target path structure beyond its background activity, such as wave fluctuations (step 102). Satisfy. One preferred embodiment of the generated electromagnetic signal is at least one, where the components of the plurality of frequencies comprise components of the plurality of frequencies in the range of about 0.01 Hz to about 100 MHz when the power SNR model is satisfied. It consists of a burst of arbitrary waveforms having a waveform parameter of (step 102). The repetitive electromagnetic signal may be generated, for example inductively or capacitively, from the at least one configured waveform (step 103). By the output of a coupling device, such as an electrode or inductor, placed close to the target path structure, the electromagnetic signal is coupled to the target path structure such as molecules, cells, tissues and organs (step 104). This binding promotes the stimulation of cells and tissues in a physiologically meaningful way.

2 depicts one preferred embodiment of the device according to the invention. The miniature control circuit 201 is coupled to one end of at least one connector 202, such as a wire. The opposite end of the at least one connector is coupled to a coupling device, such as a pair of electrical coils 203. Minimal control circuit 201 is constructed in such a way as to apply the mathematical model used to construct the waveforms. For a given and known target path structure, it is possible to select waveform parameters that meet the NR or power SNR model so that the waveform can be detected in the target path structure beyond the background activity so that the configured waveforms are the SNR or power SNR model. Must meet. One preferred embodiment in accordance with the present invention is a molecule, cell, tissue, and organ such as comprising about 10 to about 100 msec bursts of about 1 to about 100 microsecond rectangular pulses repeated at about 0.1 to about 10 pulses per second. Apply a mathematical model to induce the magnetic field of time variation in the target path structure. The peak amplitude of the induced electric field is between about 1 μV / cm and about 100 mV / cm and changes according to the modified 1 / f function when f = frequency. Waveforms constructed using one preferred embodiment according to the present invention can be applied to target pathway structures such as molecules, cells, tissues and organs for desirable total exposure times of 1 minute to 240 minutes per day. However, other exposure times can be used. The waveforms configured by the minimal control circuit 201 are directly connected to a coupling device 203 such as electrical coils via the connector 202. Coupling device 203 delivers a pulsed magnetic field constructed by a mathematical model that can be used to provide treatment to a target path structure, such as knee joint 204. The minimum control circuit 201 applies the pulsed magnetic field for a defined time and can automatically repeat the application of the pulsed magnetic field at a given time period, for example 10 times a day, as many applications are required. One preferred embodiment according to the present invention may be fixed in position for treating the knee joint 204 by a position fixing device. The position fixing device may be portable as an anatomical support and is also described below with reference to FIG. 6. When electrical coils are used as coupling device 203, they can be powered by Faraday's law with a magnetic field of time variation that induces an electrical field of time variation in the target path structure. The electromagnetic signal generated by the coupling device 203 can also be applied using electrochemical coupling where the electrodes are in direct contact with the skin or other external electrically conductive boundaries of the target path structure. In another embodiment according to the present invention, the electromagnetic signal generated by the binding device 203 is also a void present between the binding device 203, such as an electrode, and a target pathway structure, such as molecules, cells, tissues, and organs. If an air gap is present, it can be applied using an electrostatic bond. Incorporating a pulsed magnetic field into target pathway structures such as molecules, cells, tissues, and organs reduces inflammation and thereby relieves pain and promotes recovery therapeutically and prophylactically. An advantage of the preferred embodiment according to the invention is that the ultralight coils and the minimized circuit make it possible to use in any position of the human body where pain relief and recovery is necessary with universal physiotherapy modalities. The beneficial result of the preferred embodiment according to the invention is that the health of living organisms can be maintained and promoted.

3 shows a block diagram of one preferred embodiment according to the present invention of a minimal control circuit 300. Minimal control circuit 300 produces waveforms that drive coupling devices such as the wire coils described above in FIG. 2. The minimum control circuit 300 can be activated by activation means such as an on / off switch. The minimum control circuit 300 has a power supply such as lithium battery 301. One preferred embodiment of the power supply has an output voltage of 3.3 V but other voltages may be used. In another preferred embodiment according to the invention the power supply can be coupled to the invention by means of a plug and a wire, for example, to be an external power supply such as an electric current outlet such as an AC / DC outlet. have. The switching power supply 302 controls the voltage for the micro-controller 303. One preferred embodiment of the micro-controller 303 uses an 8-bit 4 MHz micro-controller 303 but any other bit MHz combination micro-controllers may be used. The switching power supply 302 also transmits the current of the storage capacitor 304. One preferred embodiment according to the invention uses a storage capacitor having a 220 μF output but other outputs may be used. The storage capacitors 304 allow high frequency pulses to be sent to a coupling device such as inductors (not shown). Micro-controller 303 also controls pulse shaper 305 and pulse phase timing control 306. Pulse shaper 305 and pulse phase timing control 306 determine the shape of the pulse, the width of the burst, the burst envelope shape, and the burst repetition rate. Essential waveform generators, such as sinusoidal or arbitrary number generators, may also be combined to provide specific waveforms. The voltage level translation sub-circuit 308 controls the induced field transmitted to the target path structure. Switching hexfet 308 allows pulses of irregular amplitude to be sent to output 309 which routes the waveform to at least one coupling device, such as an inductor. The micro-controller 303 can also control the total exposure time of monotherapy of target pathway structures such as molecules, cells, tissues, and organs. The minimum control circuit 300 may be built to automatically repeat the application of a pulsed magnetic field for as many times as necessary in a given time period, for example 10 times a day, by applying a pulsed magnetic field for a defined time. Can be. One preferred embodiment according to the present invention uses treatment times of about 10 minutes to about 30 minutes.

4A and 4B, one preferred embodiment in accordance with the present invention of a coupling device 400, such as an inductor, is shown. Coupling device 400 may be an electrical coil 401 wound around several strands of stretchable magnetic wire 402. The multiple strands of stretchable magnetic wire 402 allow the electrical coil 401 to conform to specific anatomical configurations, such as the limbs or joints of a human or animal. One preferred embodiment of the electrical coil 401 has several strands having an outer diameter between about 2.5 cm and about 50 cm and about 0.01 mm to about 0.1 mm in diameter of about 10 to about 50 wheels that are initially wound round. Including magnetic wires but other numbers of wheels and wire diameters may be used. One preferred embodiment of the electrical coil 401 may be wrapped in a non-toxic PVC mold 403 but other non-toxic molds may also be used.

5, one embodiment of the waveform 500 in accordance with the present invention is depicted. Pulse 501 is repeated in burst 502 with a finite duration 503. Duration 503 is when the duty cycle, which can be defined as the ratio of burst duration to signal period, is between about 1 and about 10 ⁻⁵ . One preferred embodiment according to the present invention has a burst for about 10 to about 50 msec, with a modified 1 / f amplitude envelope 504 and having a finite duration corresponding to a burst period between about 0.1 and about 10 seconds. Microsecond pulses of pseudo rectangle 10 are used for pulse 501 applied at 502.

6 depicts one preferred embodiment according to the present invention of a position fixing device such as a wrist support. Position fixation device 601, such as a wrist support, is worn on human hand neck 602. The position fixing device may be configured to be portable, may be configured for easy disposal, and may be configured to be implantable. The position fixing device is in situ by a number of methods, for example by stitching and fixing the present invention onto the position fixing device by Velcro ^® , and configuring the position fixing device to be elastic. It can be used in combination with the present invention by a method of holding on.

In another preferred embodiment according to the invention, the invention is a standalone of any size to be used anywhere, for example at home, in a clinic, in a treatment center, and outdoors, with or without a positioning device. It can be configured as a device of. Wrist support 601 may be made of anatomical and supportive materials, such as neoprene. Coils 603 are wrist supports 601 such that the signal configured by the present invention can be applied from, for example, the waveform depicted in FIG. 5, the position of the upper side of the wrist to the palm position of the lower side of the wrist. It is integrated into the inside. The micro-circuit 604 is attached to the outside of the wrist support 601 using a fastening device such as Velcro (not shown). The micro-circuit is coupled to one end of at least one connecting device, such as the flexible wire 605. The other end of the connection device is coupled to the coils 603. Other embodiments according to the present invention of the positioning device include other anatomical collars such as knees, elbows, lower back, shoulders, clothing, fashion accessories, and hosiery.

Example 1

A power SNR approach to PMF signal construction was experimentally tested for phosphorylation of calcium dependent myosin in standard enzyme assays. Cells such that the reaction mixture is not linear in time, while the phosphorylation rate of minutes that example, and the sub-selection were also saturated in Ca ^{2 +} concentrations. This opens the biological window for Ca ^{2 +} / CaM to have EMF- response. If Ca ^{2 +} is at the saturation level with respect to CaM, unless the reaction is shown as a time span of a minute level, the system is not reactive with respect to PMF at the levels used in this study. Experiments were performed using myosin light chain ("MLC") and myosin light chain kinase ("MLCK") isolated from the sandbags of turkeys. The reaction mixture was 40 mM Hepes buffer, pH 7.0; 0.5 mM magnesium acetate; 1 mg / ml bovine serum albumin, 0.1% (w / v) Tween 80; And a base solution containing 1 mM EGTA12. Glass Ca ^{2 +} was changed in the range of 1-7 μM. Ca ^{2 +} if the buffering action once established, is 70 nM CaM, 160 nM MLC and 2 nM MLCK were added to a freshly prepared basic solution to form a final reaction mixture. The low MLC / MLCK ratio allowed to have a linear time profile in the minute level time range. This provided enzymatic activities that could be produced again and minimized the time errors of pipetting.

The reaction mixture was prepared fresh daily for a series of experiments and aliquoted at 100 μL into 1.5 ml Eppendorf tubes. All Eppendorf test tubes containing the reaction mixture were stored at 0 ° C. and then transferred to a specially designed bath maintained at 37 ± 0.1 ° C. by uniform perfusion of preheated water by passing through a Fisher Scientific model 900 heat exchanger. Temperature was immersed in one Eppendorf test tube during all runs and monitored using a thermistor temperature probe such as Cole-Parmer model 8110-20. The reaction was started with 2.5 μM 32P ATP and stopped with Laemmli Sample Buffer solution containing 30 μM EDTA. The minimum amount of five blank samples was counted in each experiment. The blank (Blanks) were included on the total black mixture are one of the active ingredients Ca ^{2 +,} CaM, MLC or MLCK missing. Experiments with blank counts greater than 300 cpm were rejected. The phosphorylation was allowed to proceed for 5 minutes and evaluated by counting bound 32P in MLC using the TM Analytic model 5303 Mark V liquid scintillation counter.

The signal contained repetitive bursts of high frequency waveforms. The amplitude remained constant at 0.2 G and the repetition rate was 1 burst / second for all exposures. The burst duration varied in the range of 65 μsec to 1000 μsec based on projections of the power SNR analysis that showed that the appropriate power SNR would be performed so that the burst duration would reach 500 μsec. The results are shown in FIG. 7 when the burst width 701 is plotted on the x-axis in μsec and myosin phosphorylation 702 as treated / sham is plotted on the y-axis. PMF effect on Ca ^{2 +} binding to CaM, as those described by Power SNR model, it can be seen that reached its maximum at about 500 μsec.

These results confirm that the PMF signal constructed by one embodiment of the present invention can maximize myosin phosphorylation for sufficient burst duration to achieve adequate power SNR for a given magnetic field amplitude.

Example 2

The use of the power SNR model according to one embodiment of the present invention has also been demonstrated in an in vivo wound regeneration model. The rat wound model was well characterized both biomechanically and biochemically and was used in this study. Healthy, young mature SpragueDawley rats weighing more than 300 grams were used.

The animals were anesthetized with intraperitoneal administration of Ketamine 75 mg / kg and Medetomidine 0.5 mg / kg. After proper anesthesia, the back was shaved, pretreated with diluted betadine / alcohol solution and wrapped in surgical fabric using sterile techniques. Using a # 10 surgical knife, an 8-cm linear incision was made through the skin descending toward the fascia on the dorsal part of each rat. The wound edge was bluntly cut to break the remaining epithelial fibers, leaving an open wound approximately 4 cm in diameter. Hemostasis was applied to the applied pressure to avoid any injury to the edges of the skin. The skin edges were then closed with 4-0 Ethilon serial sutures. After surgery, the animals received intraperitoneal administration of Buprenorphine 0.1-0.5 mg / kg. They were placed in individual cages and randomly provided with food and water.

The PMF exposure includes two pulsed radio frequency waveforms. The first was a standard clinical PRF signal containing 65 μsec bursts of 27.12 MHz sinusoidal waves at 1 Gauss amplitude and repeating at 600 bursts / second. The second was a PRF signal constructed by one embodiment of the present invention. For this signal the burst duration increased to 2000 μsec and its amplitude and repetition rate decreased to 0.2 G and 5 bursts / second, respectively. PRF was applied twice a day for 30 minutes.

Tensile strength was performed immediately after wound incision. Two 1 cm wide strips of skin were traversed vertically from each sample into the wound and used to measure tensile strength as kg / mm ² . The long pieces were cut from the same area in each mouse to ensure consistency of the measurements. The strips were then mounted on a tensiometer. The strips were loaded at 10 mm / min and the maximum force generated before the wound was pulled apart was recorded. The final tensile strength for comparison was determined by taking the average of the maximum loadings in kilograms per mm ² of two strips from the same wound.

The results show that 19.3 ± 4.3 kg / mm ² vs. The control group (p <.01) showed a 48% increase to 13.0 ± 3.5 kg / mm ² . In contrast, the mean tensile strength for a 2000 μsec 0.2 Gaussian PRF signal, constructed by one embodiment of the present invention using the Power SNR model, was 21.2 ± 5.6 kg / mm ^{2 for the} treated group. vs. The control group (p <.01) showed a 54% increase to 13.7 ± 4.1 kg / mm ² . The results for the two signals were not significantly different from each other.

These results show that one embodiment of the present invention allows a new PRF signal to be configured to be produced with significantly lower power. According to one embodiment of the present invention, a PRF signal composed of low power means, for a clinical PRF signal that accelerated wound regeneration but required more than two orders of magnitude to produce greater power, a rat model. Accelerated wound regeneration.

Example 3

In this example, Jurkat cells respond to PMF stimulation of T-cell receptors where cell cycle arrest has occurred and thus behave like T-lymphocytes stimulated by antigens at T-cell receptors, such as normal anti-CD3. For example, in bone repair, the results are 60 Hz and PEMF intestines both Jurkat cells DNA, as expected by PMF interacting with T-cell receptors in the absence of costimulatory signals. It has been shown to reduce synthesis. This is consistent with an anti-inflammatory response, as observed in clinical applications of PMF stimuli. The PEMF signal according to one embodiment of the present invention is more effective. Dosimetry analysis performed in accordance with one embodiment of the present invention provides reasons why both signals are effective and PEMF signals have a greater effect than 60 Hz signals in Jurkat cells in most EMF-sensitive growth stages. Indicates.

Comparison of the radiation dose measurements from the two signals adopted involves evaluating the ratio of the power spectrum of the thermal noise voltage, which is the power SNR, to the power spectrum of the induced voltage in the EMF-sensitive target path structure. The target pathway structure used is ionic binding at receptor sites on Jurkat cells suspended in 2 mm of culture medium. The average peak electric field was 1 mV / cm at the binding site from the PEMF signal containing 5 msec bursts of 200 μsec pulses and repeating at 15 / sec, while the average peak electric field was 50 μV / cm for the 60 Hz signal.

8 is a graph of the results when the induced field frequency 801 as Hz is plotted on the x-axis and the power SNR 802 is plotted on the y-axis. FIG. 8 depicts having sufficient power spectrum with power SNR -1 so that both signals can be detected within the frequency range of coupling kinetics. However, the maximum power SNR for the PEMF signal is significantly higher than the maximum power SNR for the 60 Hz signal. This is because the PEMF signal has many frequency components that fall within the bandpath of the coupling path. The single frequency component of the 60 Hz signal lies at the midpoint of the bandpath of the target path. The power SNR calculation used in this example is dependent on τ _ion obtained from the rate constant for ionic bonding. Had this calculation been a priori, it would have been concluded that both signals would satisfy the essential requirements of basic detectability and could regulate EMF-sensitive ion binding at the starting point of the control cascade for DNA synthesis in these cells. The previous examples showed that using rate constants for Ca / CaM binding could lead to successful projections of biologically effective EMF signals in various systems.

Having described embodiments of devices and methods for delivering electromagnetic therapy to humans, animals and plant molecules, cells, tissues and organs, the adjustments and changes have been made in the light of the teachings described above. It has been specified that it can be accomplished by those of ordinary skill. It will therefore be understood that variations of the specific embodiments of the disclosed invention may be achieved which are within the scope and spirit of the invention as defined by the appended claims.

Claims (45)

Constructing (101), using waveform constructing means, at least one waveform to be coupled to the target path structure in accordance with a mathematical model having at least one waveform parameter; Selecting (102) a value of the at least one waveform parameter such that the at least one waveform is detectably configured in the target path structure beyond the background activity of the target path structure; Generating (103) an electromagnetic signal from said constructed at least one waveform using a coupling device; And Coupling (104) the electromagnetic signal to the path structure using the coupling device. According to claim 1, And said target pathway structure comprises at least one of a molecule, a cell, a tissue, and an organ. According to claim 1, The at least one waveform parameter is at least one frequency component parameter constituting the at least one waveform such that it is between about 0.01 Hz and about 100 MHz, a burst amplitude envelope parameter along an arbitrary amplitude function, a burst amplitude along a defined amplitude function An envelope parameter, a burst width parameter that varies in each iteration according to an arbitrary width function, a burst width parameter that varies in each iteration according to a defined width function, about 1 μV / cm and about 100 mV / cm in the target path structure A peak induced electric field parameter varying between and a peak induced electric field parameter varying between about 1 μT and about 0.1 T in the target pathway structure for electromagnetic treatment of plants, animals and people. Way. The method of claim 3, wherein The defined amplitude function comprises at least one 1 / frequency function, logarithmic function, disordered function, and exponential function. According to claim 1, Selecting 102 the value of the at least one waveform parameter further comprises selecting at least one value of the waveform parameter that satisfies the signal ratio model for noise. Method for electromagnetic treatment of people. According to claim 1, Selecting 102 the value of the at least one waveform parameter further comprises selecting at least one value of the waveform parameter that satisfies the power signal ratio model for noise. And methods for electromagnetic treatment of people. According to claim 1, The generating (103) of the electromagnetic signal further comprises inductively generating the electromagnetic signal. According to claim 1, The generating (103) of the electromagnetic signal further comprises the step of capacitive generation of the electromagnetic signal. According to claim 1, Combining (104) the electromagnetic signal further comprises electrochemically coupling the electromagnetic signal to the target path structure. According to claim 1, Coupling (104) the electromagnetic signal further comprises electrostatically coupling the electromagnetic signal to the target path structure. According to claim 1, The coupling device comprises an inductor. The method for electromagnetic treatment of plants, animals and people. According to claim 1, The coupling device comprises an electrode for the electromagnetic treatment of plants, animals and people. According to claim 1, And further assisting the use of at least one standard medical treatment and non-standard medical treatments with the electromagnetic treatment. According to claim 1, And using the at least one standard physical therapy and non-standard physical therapies in conjunction with the electromagnetic therapy further assisting the electromagnetic treatment of plants, animals, and people. According to claim 1, Further comprising using said electromagnetic therapy to regulate the production and use of growth factors, cytokines, and control substances by living cells. Method for a miracle cure. According to claim 1, Further comprising using the electromagnetic therapy to regulate tissue growth and regeneration. According to claim 1, And using said electromagnetic therapy to alleviate chronic and venus pain of musculoskeletal and nervous system sources. According to claim 1, Further comprising using said electromagnetic treatment to reduce edema. According to claim 1, And using said electromagnetic therapy for the treatment of pressure ulcers in cases of diabetes and said ulcers being chronic. According to claim 1, And using said electromagnetic therapy for at least one of increasing blood flow and microvascular blood perfusion. According to claim 1, And using said electromagnetic therapy for at least one of neovascularization and angiogenesis. According to claim 1, Using the electromagnetic therapy to enhance an immune response to malignant and benign pathological conditions. According to claim 1, Further comprising using said electromagnetic therapy to enhance exudate secretion. 10. A method for electromagnetic treatment of plants, animals, and people. According to claim 1, And using a positioning device to deliver said electromagnetic therapy to said plants, animals, and people. The method of claim 24, And wherein said positioning device comprises at least one of an anatomical support, an anatomical garment, and a garment. The method of claim 24, And wherein said garment comprises at least one of garments, fashion accessories, and hosiery. The method of claim 24, And said wave form construction means and said coupling device are portable. The method of claim 24, And said corrugating means and said coupling device are easy to dispose. The method of claim 24, And said wave form construction means and said coupling device are implantable. According to a mathematical model having at least one waveform parameter that can be selected, the at least one waveform to be coupled to the target path structure such that at least one waveform is detectably configured in the target path structure beyond the background activity of the target path structure. Waveform construction means 201 for constructing a waveform; A coupling device 203 coupled to the waveform construction means 201 by at least one connection means 202 for generating an electromagnetic signal from the constructed at least one waveform and for coupling the electromagnetic signal to the target path structure. Electromagnetic therapeutic apparatus for plants, animals and people comprising a. The method of claim 30, And wherein said target pathway structure comprises at least one of molecules, cells, tissues and organs. The method of claim 30, The at least one waveform parameter according to at least one frequency component parameter constituting the at least one waveform, a burst amplitude envelope parameter following an arbitrary amplitude function, a defined amplitude function such that the at least one waveform parameter is between about 0.01 Hz and about 100 MHz Burst Amplitude Envelope Parameters, Burst Width Parameters Changing at Each Repetition According to Arbitrary Width Function, Burst Width Parameters Changing at Each Repetition According to Defined Width Function, about 1 μV / cm and about 100 mV in the Target Path Structure electromagnetic field for plants, animals and people characterized by a peak induced electric field parameter varying between / cm and a peak induced electric field parameter varying between about 1 μT and about 0.1 T in the target pathway structure. Treatment device. The method of claim 30, Electromagnetic therapy device for plants, animals and people, characterized in that the defined amplitude function comprises at least one 1 / frequency function, logarithm function, disorder function, and exponential function. The method of claim 30, And said value of said at least one waveform parameter is selected to meet a ratio model of signal to noise. The method of claim 30, And wherein the value of the at least one waveform parameter is selected to meet a ratio model of power signal to noise model. The method of claim 30, The coupling device (203) comprises an inductively generated coupling device for electromagnetic treatment device for plants, animals and people. The method of claim 30, The coupling device (203) includes a capacitively generated coupling device. The electromagnetic therapeutic device for plants, animals and people. The method of claim 30, Electromagnetic therapy device for plants, animals and people, characterized in that the coupling device (203) comprises an inductor. The method of claim 30, Electromagnetic therapeutic device for plants, animals and people, characterized in that the coupling device (203) comprises an electrode. The method of claim 30, Electronics for plants, animals and people further comprising a positioning device 600 for positioning the electromagnetic therapy device 200 for delivering treatment to the plants, animals and people. Miracle Healing Device. 41. The method of claim 40 wherein Electromagnetic therapy device for plants, animals and people, characterized in that the position fixing device (600) is at least one of an anatomical support (601), an anatomical garment, and clothing. 42. The method of claim 41 wherein Said clothing is at least one of garments, fashion accessories, and hosiery. The method of claim 30, At least one of the corrugating means (201), the connecting means (202) and the coupling device (203) is portable. The method of claim 30, At least one of the corrugating means (201), the connecting means (202) and the coupling device (203) is easy to dispose of. The electromagnetic treatment device for plants, animals and people. 31. The method of claim 30 At least one of the constituent means (201), the connecting means (202) and the coupling device (203) is implantable, characterized in that the electromagnetic treatment device for plants, animals and people.

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