Method for adjusting an apparatus for treatment using nuclear magnetic resonance

Abstract

The present invention provides a method for adjusting a device for treatment using nuclear magnetic resonance, which allows the device parameters to be set more accurately in a simpler and more effective way depending on the indication, particularly with regard to targeted control, value acquisition, readjustment and calibration. [Solution] A method for adjusting, particularly calibrating, an apparatus for treatment using nuclear magnetic resonance is provided, which includes determining the effect of the treatment using nuclear magnetic resonance on the cellular clock of a cell culture or of a user and / or the user's chronotype, and setting the apparatus for treatment using nuclear magnetic resonance based on the determination.

Description

[Technical Field]

[0001] The present invention relates to a method for adjusting, selectively controlling, value collection, readjustment and especially calibration of an apparatus for treatment using nuclear magnetic resonance. The present invention also relates to an apparatus for treatment using nuclear magnetic resonance, a treatment system and the use of nuclear magnetic resonance for therapeutic and cosmetic purposes in particular. [Background technology]

[0002] The use of nuclear magnetic resonance imaging to achieve therapeutic and cosmetic effects is known.

[0003] The therapeutic effect of treating human or animal tissue using nuclear magnetic resonance has already been described in US Pat. No. 5,623,999 (patentee Axel Muntermann).

[0004] The treatment device, operating under the trademark name MBST™, is a device in which a magnetic field having a uniform field strength is superimposed with a perpendicularly irradiated alternating magnetic field in the treatment zone to achieve nuclear magnetic resonance in the treatment zone. Nuclear magnetic resonance can be generated in the treatment zone by appropriately adjusting the frequency of the alternating magnetic field to the field strength of the perpendicular uniform magnetic field. The field strength of the uniform magnetic field is modulated at a modulation frequency f m and is therefore composed of a base quantity and a variable modulation quantity. The modulation achieves a Larmor state once per period, resulting in periodic generation of nuclear magnetic resonance in the treatment volume.

[0005] Inhomogeneities in the basic static magnetic field B0 are compensated via an adiabatic fast passage (AFP) pathway, which results in a reversal of the nuclear spin orientation.

[0006] A receiving coil with electronic monitoring electronics installed in the treatment unit is used to optically and acoustically monitor the proper functioning of the nuclear magnetic resonance treatment field, the treatment parameters, compensation of influencing interfering factors such as metals in the treatment area, changes in the magnetic field strength and the intensity of the energy dose introduced into the body, the required resonance state and certain other important test parameters that can be used in the readjustment process for quality, effectiveness and safety.

[0007] It has been found that treatments using nuclear magnetic resonance can achieve both cosmetic effects, for example in the treatment of connective tissue fragility and cellulite in the skin, as well as therapeutic effects in all areas of disturbed or degenerated cell function within bone joints, organs, ligaments, muscles, tendons, as well as post-operative wound healing, skin burns, bone-related metabolic or circulatory disorders, fracture healing, etc., and other regenerative areas.

[0008] The body's own signals and electrical processes are becoming more and more important in science. The first signals are, for example, the ECG or EEG.

[0009] Studies have shown that piezoelectric processes in the cell regeneration area (ATP) are absolutely necessary to compensate for or maintain disturbed cell function (Non-Patent Document 1).

[0010] When these piezoelectric processes are absent or insufficiently generated (lack of kinetic energy due to the pushing and pulling processes), degenerative effects occur that can be very effectively and efficiently compensated for by the injected nuclear magnetic resonance field.

[0011] The basis for this is to follow the conduction pathways that resonate with the regeneration site of selected cell populations (cartilage, bone, skin, organ cells, etc.).

[0012] Research has provided evidence that, using monitoring and control electronics of nuclear magnetic resonance techniques, it is possible to very significantly increase cellular oxygen concentration (hypoxia) and ATP after nuclear magnetic resonance treatment (see non-patent document 1), and to accelerate or slow down the rate of cell division depending on the control pattern (non-patent document 2).

[0013] A crucial factor for the success of targeted treatment using nuclear magnetic resonance is the accurate determination of the cellular resonance window of the individual cell populations to be regenerated.

[0014] Different cell populations have different low frequency resonance response patterns, which are exploited in treatments using nuclear magnetic resonance.

[0015] One focus of current treatment using nuclear magnetic resonance is pain patients experiencing degenerative changes in the musculoskeletal system, such as arthritis, osteoporosis, and sports and accident injuries.

[0016] For example, the document: Non-Patent Document 3 describes the significant improvement of pain symptoms in rheumatoid arthritis patients by treatment with MBST™ nuclear magnetic resonance therapy.

[0017] MBST™ therapy systems operate at lower magnetic field strengths than diagnostic imaging magnetic resonance tomography systems. However, it has been surprisingly found that good treatment success can be achieved accurately with such systems operating at low magnetic field strengths.

[0018] It has further been found that the efficacy of the treatment depends, inter alia, on the modulation frequency of the homogeneous magnetic field, the number of treatments, the duration of the treatments, and the interval between multiple treatments.

[0019] Depending on the indication, these parameters were first empirically determined, and optimal treatment parameters were determined and validated to further improve the efficacy of MBST™ therapy and expand the range of applicable indications. [Prior art documents] [Patent documents]

[0020] [Patent Document 1] European Patent No. 1089792 [Non-patent literature]

[0021] [Non-Patent Document 1] Steinecker-Frohnwieser B, Weigl L, Weberhofer G, Kullich W, Kress HG, “The Influence of Nuclear Magnetic Resonance Therapy (NMRT) and Interleukin IL1-b Stimulation on Cal 78 Chondrosarcoma Cells and C28 / I2 Chondrocytes” J Orthopedics Rheumatol. 2014; 1(3):9 [Non-patent document 2] N. Budny; Com. Director Prof. Dr. med. D. Palmes, Prof. Dr. med. Dipl.-Ing.HU Spiegel; Inaugural dissertation to obtain the doctor rerum medicinalium from the Medical Faculty of the Westphalian Wilhelms-University in Munster, clinic for General and Visceral Surgery, Department of Surgical Research, University Hospital Munster, Germany; October 2015 [Non-patent document 3] Kullich W., J. Overbeck, HU Spiegel, (2013) “One-year-survey with multicenter data of more than 4,500 patients with degenerative rheumatic diseases treated with therapeutic nuclear magnetic resonance” J Back Musculoskelet Rehabil 26, 93-104 Summary of the Invention [Problem to be solved by the invention]

[0022] Taking this background into consideration, the present invention is based on the object of providing a method for adjusting a device for treatment using nuclear magnetic resonance, which method allows the device parameters to be set more accurately in a simpler and more effective way depending on the indication, in particular with regard to targeted control, value acquisition, readjustment and calibration. [Means for solving the problem]

[0023] The object of the present invention has already been achieved by a method for adjusting, in particular a method for calibrating, an apparatus for treatment using nuclear magnetic resonance, by a treatment system and by the use of nuclear magnetic resonance as set forth in one of the independent claims. [Brief explanation of the drawings]

[0024] [Figure 1]Figure 1 shows the number of mRNA copies of representative genes from the central feedback loop of the internal clock plotted over time, representing the oscillation of the internal clock. The oscillations of cryptochrome 1, period 1, period 2, and clock 1 are shown. A comparison of the oscillations of sham-treated cells and cells treated with nuclear magnetic resonance for 1 h on four consecutive days at the same time in each case is shown. A phase shift can be clearly seen, which is significant in the case of the period 1 and cryptochrome 1 genes (cosinor fit analysis, GraphPad Prism 6.0). [Figure 2] Figures showing changes in hif-1α and hif-3α mRNA concentrations from the hypoxia signaling pathway in sham-treated cells and cells treated for 1 hour at the same time on four consecutive days using nuclear magnetic resonance (NMR) (A and E), and selective synchronization of hif-1α and hif-3α mRNA oscillation in whole zebrafish larvae with the same treatment regime (B and F), while hif-2α remains unaffected in both cells and whole zebrafish larvae (Figure 2, C and D). [Figure 3] Synchronization of circadian hif-1 protein oscillations in zebrafish cells achieved by nuclear magnetic resonance after four repeated 1-h treatments on the one hand (A) and one 4-h treatment on the other hand (B). [Figure 4] Figure 1 shows the dose-dependent reduction in oxidized peroxiredoxin (A), free oxygen radicals (B), and hif-1α protein (C). Treatment for 4 hours reduces the amount of protein and free oxygen radicals, respectively, compared to treatment for only 1 hour. [Figure 5] 1 is a schematic flow chart of a method for adjusting an apparatus for treatment using nuclear magnetic resonance. [Figure 6] 1 is a schematic diagram of an apparatus for treatment using nuclear magnetic resonance; DETAILED DESCRIPTION OF THE INVENTION

[0025] Preferred embodiments and refinements of the invention are specified by the subject matter of the dependent claims, the description and the drawings.

[0026] The present invention relates to a method for adjusting devices for procedures using nuclear magnetic resonance, in particular for the selective control, value acquisition and readjustment, and in particular for calibrating such devices.

[0027] The present invention is particularly directed to magnetic field strengths of less than 50 Gauss, most preferably less than 30 Gauss, and modulation frequencies f less than 100 Hz. m This invention relates to a device for generating nuclear magnetic resonance that generates a magnetic field using a magnetic field.

[0028] The frequency of the perpendicularly applied alternating magnetic field is preferably less than 100 kHz, and most preferably less than 50 kHz.

[0029] Modulation frequency f m is preferably 1 Hz to 100 Hz.

[0030] In accordance with the present invention, the effect of a treatment using nuclear magnetic resonance on a user's cellular clock and / or the user's chronotype is determined, and an apparatus for treatment using nuclear magnetic resonance is adjusted based on this determination.

[0031] According to the present invention, human cell cultures or cell cultures of animal origin can also be subjected to a nuclear magnetic resonance treatment, and the effect of the nuclear magnetic resonance treatment on the cellular clocks of the cells in the cell culture can be determined.

[0032] In particular, cell cultures of human origin such as liver cells or chondrocytes can be used.

[0033] Research in the field of liver regeneration has shown that the rate of cell division can be both slowed down and accelerated by modifying treatment parameters (see Non-Patent Document 2). During cell division, messenger substances have been observed that can substantially accelerate cell division and therefore regeneration.

[0034] To calibrate the device, the effect of the treatment using nuclear magnetic resonance on the circadian clock of each cell type is determined. To this end, the parameters used to perform the treatment are varied and the parameters for the treatment are set according to their effect on the circadian clock.

[0035] Furthermore, it is known that all living organisms, including humans, possess an internal circadian clock, which allows them to maintain time perception at the cellular level for several days without external stimuli such as light through transcriptional and metabolic processes. This circadian clock is interrelated with the hypoxia signaling pathway. Hypoxia-inducible factor 1 (Hif-1α) is known to be responsible for erythropoietin expression and major metabolic changes in response to low oxygen concentrations, particularly glucose metabolism.

[0036] Furthermore, there are many genes that are regulated by Hif-1 and play a role in many cellular circuits, for example in cell proliferation, apoptosis or angiogenesis.

[0037] In this regard, reference is made in particular to the following publications:

[0038] Egg, M.; Paulitsch, M.; Ennemoser, Y.; Wustenhagen, A.; Schwerte, T.; Sandbichler, AM; Fiechtner, B.; Koblitz, L.; 31 / 5, pp. 680 - 689. (DOI)

[0039] Egg, M.; Koblitz, L.; Hirayama, J.; Schwerte, T.; Folterbauer, C.; Kurz, A.; Fiechtner, B.; Most, M.; Salvenmoser, W.; Sassone-Corsi, P.; Pelster, B. (2013) "Linking oxygen to time: The bidirectional interaction between the hypoxic signaling pathway and the circadian clock", CHRONOBIOLOGY INTERNATIONAL 30 / 4, pp. 510 - 529

[0040] Pelster, B.; Egg, M. (2015) "Multiplicity of Hypoxia-Inducible Transcription Factors and Their Connection to the Circadian Clock in the Zebrafish", PHYSIOLOGICAL AND BIOCHEMICAL ZOOLOGY 88 / 2, pp. 146 - 157. (DOI)

[0041] Sandbichler, A.M.: Jansen, B.; Peer, B.A.; Paulitsch, M.; Pelster, B.; Egg, M. (2018) "Metabolic Plasticity Enables Circadian Adaptation to Acute Hypoxia in Zebrafish Cells", CELLULAR PHYSIOLOGY AND BIOCHEMISTRY 46 / 3, pp. 1159 - 1174. (DOI)

[0042] In mammals, and thus in humans, the circadian clock is hierarchically organized and includes a region located in the hypothalamus known as the suprachiasmatic nucleus (SCN), organ- and / or tissue-specific peripheral clocks, and cellular clocks present in all cells of the organism, which are synchronized with the peripheral clocks by the SCN. Synchronization of the internal clock with the external day-night rhythm occurs primarily through information from light photons. Light photons are transmitted through the retina of the eye to the SCN, where they induce both neuronal and humoral changes. In all organisms that live under light, including humans, many physiological processes are circadianly regulated. These physiological processes include, in particular, body temperature, blood pressure, skin resistance, and cardiac activity, as well as hormone secretion or organ-specific activity (e.g., the liver, kidneys, and heart, each of which undergoes its own specific day-night rhythm). Circadian rhythms, synchronized with the external day-night rhythm, are beneficial for the organism, and long-term disruption of this synchronization (caused by shift work, jet lag or sleep disorders) contributes to the development of a wide range of diseases, including cardiovascular diseases, hormone-induced tumors, diabetes, obesity, as well as pain and inflammatory diseases such as arthropathy.

[0043] The simplified molecular mechanism of the cellular circadian clock consists of several feedback loops, of which the central feedback loop is described below.

[0044] In a central negative feedback loop, the brain and muscle ARNT-like protein (Bmal1) and the "circadian locomotor output cycles kaput 1" (Clock1) protein dimerize and bind to E-box promoter elements in the DNA of their antagonists, the period genes (Per1-3) and cryptochromes (Cry1 / 2). As a result, expression of these genes' mRNAs, and therefore their protein products, increases in the cytoplasm, where both proteins attach to each other and dimerize. From there, they again translocate into the nucleus, where the protein complex blocks Clock / Bmal1 gene expression. The negative feedback loop is completed by phosphorylation of the PER / CRY complex by casein kinase Iε (CKIε) and its subsequent degradation in the proteasome.

[0045] Well-known representatives of this central feedback loop include the "clock genes" clock1, bmal1, per1, per2, cry1, and cry2.

[0046] At the molecular level, the hypoxia signaling pathway is closely intertwined with the internal clock, for example, in zebrafish and mammals. Therefore, the two signaling pathways are clearly highly conserved processes, allowing for inferences regarding the existing interactions between the two signaling pathways in humans. And, like the circadian clock, the hypoxia signaling pathway also plays a central role in many human diseases. In particular, this specification refers to diseases associated with decreased oxygen saturation in tissues, such as heart attack or stroke, or other diseases in which decreased oxygen saturation is required under normal physiological conditions, such as in joints. In particular, this specification refers to osteoarthritis, and indeed, the importance of the hypoxia signaling pathway for the onset and progression of osteoarthritis has been studied and described several times.

[0047] Biologically essential proteins that regulate and modulate cellular metabolism under hypoxia are transcription factors from the hypoxia-inducible factor (Hif) family, the most important representative of which is Hif-1α.

[0048] Both signaling pathways, the circadian clock and the hypoxia signaling pathway, are further interdependent on the available amount of free oxygen radicals (ROS), which are further very tightly compartmentalized and regulated under physiological conditions by various oxygen-based oxygen radical scavengers (antioxidants), such as catalase, superoxide dismutase, and glutathione peroxidase, or by low-molecular-weight proteins known as peroxiredoxins (PRXs), which themselves undergo circadian redox cycling. The role of free oxygen radicals (ROS) in inflammatory processes and in natural cellular aging processes has already been thoroughly reviewed and described and remains the focus of current research.

[0049] Here, we found that treatment with NMR significantly shifted the phase of oscillation of the circadian period 1 and cryptochrome 1 genes in the zebrafish fibroblast cell line Z3. This phase shift occurred under complete light deprivation (see Figure 1). Furthermore, the expression of oxygen-regulated genes, such as hif-1α and hif-3α, at the mRNA level was significantly altered in cells and whole zebrafish larvae (Figure 2, A, B, E, and F), whereas the isoform hif-2α was completely unaffected (Figure 2, C and D), again indicating a specific and selective effect of NMR on HIF isoforms. At the hif-1α protein level, we found a clear synchronization effect of NMR on the circadian rhythm of the protein in cell cultures (Figure 3, A and B), occurring after both a single 4-hour treatment and four repeated 1-hour treatments. Furthermore, the amounts of oxidized peroxiredoxin (PRX), free oxygen radicals, and HIF-1 protein (FIGS. 4A, B, and C) are modulated in the same direction, in this case decreased, depending on time and dose.

[0050] With this new knowledge, the equipment for obtaining nuclear magnetic resonance can be adjusted and adapted so that improved treatment success can be achieved.

[0051] For example, a microcomputer chip card can be used to input stored treatment sequences into the control unit via a chip card reader to ensure precise and accurate execution of the nuclear magnetic resonance treatment.

[0052] For example, a number of optional consecutive treatment time intervals which can be stored on a chip card ensure optimal control specifications for the treatment device.

[0053] The sequence, treatment procedure and treatment time in the microcomputer chip card can be selectively altered to initiate the resonance effect during the treatment time, which is crucial for triggering the resynchronization of the cellular circadian clock.

[0054] A receiving coil installed in the treatment unit and including electronic monitoring electronics can be used to optically and acoustically monitor the proper operation of the nuclear magnetic resonance treatment field, treatment parameters, changes in magnetic field strength and intensity, energy dose introduced into the body, required resonance conditions, and other predetermined critical verification parameters, and can be used in the readjustment process for quality, effectiveness, and safety.

[0055] This readjustment to optimize treatment parameters can be performed through a feedback loop.

[0056] Further monitoring electronics measure and monitor temperature changes in the area of ​​the skin in order to identify metabolic changes and take such changes into account as optimization parameters in the control and monitoring process of the treatment procedure control electronics.

[0057] The device can be particularly parameterized and used in such a way as to achieve synchronization of cellular circadian clocks, thereby improving the effectiveness of treatment, particularly for osteoarthritis patients.

[0058] In particular, the time of treatment, the duration of treatment, the treatment interval, i.e., the period between treatments, the modulation frequency of the magnetic field relative to the adiabatic cycle, and / or the magnetic field strength of the magnetic field generated by the device for treatment using a magnetic field are adjusted according to the respective phases of the cellular clock.

[0059] Regarding treatment intervals, treatment is administered in a 12-hour or 24-hour rhythm ±2 hours according to one embodiment of the present invention. Other treatment intervals are possible.

[0060] The device used for this purpose preferably has a treatment duration, a modulation frequency f m and / or a memory for storing patient data along with parameterization data such as treatment intervals.

[0061] Based on this, a treatment plan can be stored in the device, so that the device will perform a treatment only if the treatment is performed according to the stored treatment plan.

[0062] According to the present invention, the user's individual circadian clock, or chronotype, is taken into account in calibrating the device.

[0063] Essentially, there are two physiologically characterized human chronotypes (with intermediate types between them): one known as morning types ("larks") and the other known as evening types ("owls").

[0064] Particularly suitable for this purpose are measurements of body temperature, heart rate, skin resistance and / or blood pressure, preferably over a period of at least 24 hours, more preferably at least 48 hours, to represent the user's individual circadian clock.

[0065] In particular, on this basis, treatment intervals and / or optimal times for treatment can be determined.

[0066] The invention further relates to a device for treatment using nuclear magnetic resonance, which is prepared by the method described above.

[0067] The invention further relates to a treatment system comprising a device for treatment using nuclear magnetic resonance, the treatment system comprising means, in particular a sensor, for determining the clonotype of a user.

[0068] According to one embodiment of the invention, the sensor is configured to measure the user's body temperature, blood pressure, skin resistance and / or heart rate.

[0069] In one embodiment of the present invention, a combined sensor is provided that measures body temperature, skin resistance and heart rate over a period of at least 24 hours, preferably at least 48 hours.

[0070] In another embodiment, skin resistance is preferably measured exclusively over this period. See, in this regard, Vidacek et al., "Personality differences in the phase of the circadian rhythms: a comparison of morningness and extraversion," ERGONOMICS 1988, Vol. 31, No. 6, 873-888. This document shows that skin resistance alone can be used to determine chronotype.

[0071] Based on the measurements, the clonotype can be determined in an external unit in which the sensor is located, or in the control unit of the device generating the nuclear magnetic resonance, or in a separate external computer unit.

[0072] Of great importance is that the control unit of the device generating the nuclear magnetic resonance is provided with information regarding the user's clonotype.

[0073] According to one embodiment, the sensor transmits data wirelessly to a control unit of the device.

[0074] According to another embodiment, the measured data are stored in an external unit comprising the sensor and are transferred in particular to the control unit of the device by connecting the external unit to the device.

[0075] The information about the user's clonotype can be stored in an external memory, but also in the memory of the control unit of the device for treatment using nuclear magnetic resonance.

[0076] The device generating the nuclear magnetic resonance is preferably controlled through a removable memory, in particular a complex microprocessor chip card with memory, which is used to initiate the biological process of re-triggering the circadian clock through multiple programmable program steps with configurable timing.

[0077] The treatment procedure is preferably automated, running through multiple programmed steps with predefined timing.

[0078] The treatment data and treatment time are preferably buffered in the control unit to allow treatment to continue without interruption or corruption in the event of a power failure.

[0079] In another embodiment, biological and electrical patient data is measured using sensors and stored prior to treatment on the patient and then used directly for the treatment process as a reference or treatment basis, or input into the control unit prior to initiating treatment.

[0080] To adjust the device, the user's individual circadian clock can be taken into account via data from sensors, in particular the treatment time, treatment duration, treatment interval and / or modulation frequency f m can be predetermined depending on the data transferred from the sensors.

[0081] The present invention relates to the use of nuclear magnetic resonance to synchronize and / or reclock the circadian clock of a user's cells. In particular, it has been found that the phase of period 1 and cryptochrome 1 mRNA oscillation can be shifted by selective nuclear magnetic resonance treatment, thereby synchronizing the circadian clock. Furthermore, the circadian oscillation of HIF-1α protein at the cellular level can also be synchronized by nuclear magnetic resonance. Furthermore, time- and dose-dependent changes can be produced in HIF-1, PRX, and the amount of free oxygen radicals, the significance of which for human pathophysiology has already been mentioned (see above).

[0082] The use of nuclear magnetic resonance according to the invention relates exclusively to cosmetic treatments, in particular to the treatment of cellulite, as well as to therapeutic treatments, in particular post-operative treatments.

[0083] Nuclear magnetic resonance methods can be applied very efficiently and highly effectively in situations where cell function is disturbed or degenerated, such as in post-operative wound healing, skin burns, metabolic or circulatory disorders in the bone area, fracture healing, in the area of ​​bone joints, organs, ligaments, muscles, tendons, as well as in other regenerative areas.

[0084] Depending on the desired objective, the parameters of the treatment using nuclear magnetic resonance, in particular the time of treatment, the treatment interval, the treatment duration and / or the modulation frequency f m is set or input to result in the maximum or minimum phase shift or optimal possible synchronization of the circadian clock.

[0085] The subject matter of the present invention will now be explained in more detail with reference to the drawings in FIGS.

[0086] Figure 1 shows the number of mRNA copies of representative genes from the central feedback loop of the internal clock plotted over time, representing the oscillation of the internal clock. The oscillations of cryptochrome 1, period 1, period 2, and clock 1 are shown. A comparison of the oscillations of sham-treated cells and cells treated with nuclear magnetic resonance (NMR) for 1 h on four consecutive days at the same time in each case is shown. A phase shift is clearly visible, which is significant in the case of the period 1 and cryptochrome 1 genes (cosinor fit analysis, GraphPad Prism 6.0). Figure 2 shows changes in hif-1α and hif-3α mRNA concentrations from the hypoxia signaling pathway in sham-treated cells and cells treated for 1 hour at the same time on four consecutive days using nuclear magnetic resonance (NMR) (A and E), and selective synchronization of hif-1α and hif-3α mRNA oscillation in whole zebrafish larvae with the same treatment regime (B and F), while hif-2α remains unaffected in both cells and whole zebrafish larvae (Figure 2, C and D). Figure 3 shows the synchronization of circadian hif-1 protein oscillations in zebrafish cells achieved by nuclear magnetic resonance after four repeated 1-h treatments (A) and after a single 4-h treatment (B) on the other hand. Figure 4 shows the dose-dependent reduction in oxidized peroxiredoxin (A), free oxygen radicals (B), and HIF-1α protein (C). Treatment for 4 hours reduces the amount of protein and free oxygen radicals compared to treatment for only 1 hour. FIG. 5 is a schematic flow chart of a method for adjusting an apparatus for treatment using nuclear magnetic resonance. FIG. 6 is a schematic diagram of an apparatus for treatment using nuclear magnetic resonance.

[0087] The effects of treatment using nuclear magnetic resonance on various biological parameters will now be described with reference to the graphs of Figures 1-6.

[0088] In each of Figures 1 and 2, the x-axis represents time and the y-axis represents the specific number of mRNA copies based on 16 ng of total RNA. In each case, a sham-treated control group is compared to cell cultures treated with the MBST™ Therapy Device for 1 hour on 4 consecutive days in each case. Treatments were administered at the same time of day.

[0089] For this purpose, cell cultures of zebrafish fibroblasts were used.

[0090] FIG. 1 shows the mRNA oscillations of the cryptochrome 1, period 1, period 2, and clock 1 genes.

[0091] It can be seen that the circadian mRNA oscillations of the period1 and cry1 genes were shifted by approximately 2 hours compared to sham-treated control cells. Thus, the phase of these gene oscillations was shifted normally without the influence of external light. Significant differences between the treatment groups were evident, which was statistically verified by cosine curve fitting (Graphpad Prism 6).

[0092] FIG. 2 shows the mRNA levels of the hif-1α, hif-2α and hif-3α genes over the course of a day.

[0093] It can be seen by nuclear magnetic resonance that the isoforms hif-1α and hif-3α are selectively regulated at the cellular level (A and E) and in the whole organism (B and F), while hif-2α remains unaffected in both cells and whole zebrafish larvae.

[0094] Figure 3 shows the amount of cellular HIF-1α protein over the course of a day. Nuclear magnetic resonance imaging (NMR) shows the synchronization of the circadian rhythm of HIF-1α protein expression in both treatment variants (four 1-hour treatments [A] compared to one treatment over 4 hours [B]).

[0095] Figure 4 shows the dependence of the nuclear magnetic resonance effect on dose, with only a single treatment for 4 hours showing a significant reduction in the amount of oxidized Prx (A), free oxygen radicals (B), and hif-1α (C), in contrast to a single treatment for only 1 hour.

[0096] FIG. 5 is a flowchart of a method for adjusting an apparatus for a procedure using nuclear magnetic resonance, according to an exemplary embodiment of the present invention.

[0097] First, the phase of the patient's internal clock is determined through skin resistance, blood pressure, body temperature and / or heart rate, i.e., the individual chronotype is determined. Based on this, the treatment duration, the time interval between successive treatments, the daytime window for treatment, and / or the modulation frequency f of the device for treatment using nuclear magnetic resonance are determined as a function of the chronotype. m is set.

[0098] Based on this setting, multiple treatments are performed, which can be therapeutic or cosmetic treatments.

[0099] 6 is a schematic diagram of a system 6 according to the invention for administering treatment to a user using nuclear magnetic resonance. The system 6 comprises an apparatus 1 for generating nuclear magnetic resonance in the tissue to be treated.

[0100] The device 1 shown here is shown schematically to comprise coil 2 and coil 3, which face each other in a Helmholtz configuration and are used to generate a uniform magnetic field extending along the indicated x-axis.

[0101] To generate nuclear magnetic resonance, an alternating magnetic field is applied by coil 4 perpendicular to the uniform magnetic field generated by coils 2 and 3 .

[0102] The frequency is adjusted so that the Larmor state is achieved.

[0103] Furthermore, the uniform magnetic field generated by coils 2 and 3 has a basic quantity and a modulation frequency f m and a modulation amount modulated in a rectangular shape by the modulation signal.

[0104] The modulation causes a resonant condition to occur within the treatment volume at least once during each period.

[0105] The device 1 may store user data, duration of treatment, treatment interval and / or modulation frequency f m The device includes a memory for storing data relating to the

[0106] The treatment time window, treatment duration, treatment interval and / or modulation frequency are implemented as a function of the chronotype of the person to whom the treatment is administered.

[0107] According to the invention, the system 6 comprises means for determining the chronotype of the user.

[0108] In the present case, this is a sensor 5 which forms part of an external unit that can be attached to the user and which transfers data, preferably wirelessly, to the control unit of the device 1. This can also be achieved, for example, via the internet.

[0109] For example, the sensor 5 may measure heart rate, body temperature or skin resistance over a period of at least 24 hours. Based on the measurements, the chronotype of each user is determined.

[0110] A treatment profile comprising optimized treatment parameters can then be established, preferably automatically by the control unit of the device, depending on the phase of the user's circadian clock.

[0111] This applies in particular to the time at which the procedure is performed.

[0112] The device 1 preferably comprises a device control unit which also comprises a memory containing the above-mentioned data, and the device control unit preferably automatically calculates the optimized treatment parameters, for example based on a calculation program or based on a database, and stores them in the memory in association with the respective user data.

[0113] By setting the parameters of the treatment device based on such data, the effectiveness of treatment using nuclear magnetic resonance can be improved in a simple manner.

[0114] The microcomputer chip card is used to input the stored treatment sequence into the control unit via a chip card reader, thereby ensuring targeted and proper execution of the MBST™ magnetic resonance procedure.

[0115] The sequences, treatment procedures and treatment times in the microcomputer chip card can be selectively changed, verified and readjusted to initiate resonance effects during the treatment duration.

[0116] This is crucial for a very significant increase in cellular ATP and hypoxia levels and for triggering the resynchronization of the cellular circadian clock.

[0117] Studies have shown that it can boost the immune system's defenses, thereby eliminating degeneration of cell function.

Claims

1. 1. A treatment system comprising an apparatus for treatment using nuclear magnetic resonance, a sensor for determining a user's chronotype and a control unit for controlling said device; The device includes two coils facing each other, which are used to generate a uniform magnetic field; the apparatus includes a further coil configured to irradiate an alternating magnetic field within the uniform magnetic field to generate nuclear magnetic resonance; the control unit is configured to control generation of nuclear magnetic resonance in the device based on the determination by the sensor; Treatment system.

2. The treatment system of claim 1 , wherein the sensor is configured to measure a user's body temperature, blood pressure, skin resistance, and / or heart rate.

3. The treatment system of claim 1 or 2, wherein the sensor is configured to transmit data to the control unit.

4. The treatment system of any one of claims 1 to 3, wherein the sensor is part of an external unit.

5. 1. The use of nuclear magnetic resonance to alter the circadian clock of cells in a non-human mammal and / or cell culture, comprising: Two coils facing each other are used to generate a uniform magnetic field, Use of nuclear magnetic resonance, wherein a further coil is used to irradiate an alternating magnetic field within said uniform magnetic field to generate nuclear magnetic resonance.

6. Use of nuclear magnetic resonance for purposes other than human surgery, therapy and diagnosis, Two coils facing each other are used to generate a uniform magnetic field, a further coil is used to irradiate an alternating magnetic field within the uniform magnetic field to generate nuclear magnetic resonance; Use of nuclear magnetic resonance, said nuclear magnetic resonance being controlled according to measurement data of a user provided by a sensor.

7. 7. The use according to claim 5 or 6, comprising altering the hypoxia signalling pathway of a cell.

8. The use according to any one of claims 5 to 7, which comprises modifying the amount of free oxygen radicals in a cell.

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