RU2723488C2 - Method for initiation of tumor cell death with 3-aminophthalic acid hydrobromide and hf and uhf wave radiation energy - Google Patents

Abstract

FIELD: medicine; pharmaceuticals.SUBSTANCE: invention relates to a method for initiation of tumor cell death, intended for treating cancer patients having tumor tissues with metastases in all organs of the human body, by hyperthermia HF and UHF energy, characterized by that person for 3 days is transferred to a non-carbohydrate diet, to create glucose starvation and subsequent maximum saturation of oncological cells with electron-ion solution of hydrazide 3-aminophthalic acid preparation "Galavit" intravenously in megadose 36 mg/kg of human body weight for maximum accumulation in tumor tissues in 3–6 times more, than in healthy, and in 8 hours after introduction of 3-aminophthalic acid hydrazide solution preparation "Galavit" selective hyperthermia of tumor tissues HF energy in accordance with depth of their location and penetration depth of electromagnetic waves in a human body of 1100 centimeters, at the resolved frequency f=13.56 MHz, with a total heating rate of the tumor tissues of 0.07 °C/s for 204 s to the tumor tissue temperature of 51 °C, while heating the healthy tissues not higher than 40 °C.EFFECT: what is presented is a method for initiation of tumor cell death with 3-aminophthalic acid hydrochloride and HF and UHF wave energy.1 cl, 1 ex, 2 tbl

Description

The invention relates to medicine and is intended to induce the death of tumor cells in living biological objects with 3-aminophthalic acid hydroside and the energy of the wave RF and microwave radiation, known as RF and microwave hyperthermia.

Hyperthermia is called, in medicine, as a significant increase in human body temperature over 40 ° C. Hyperthermia for cancer treatment was used half a century ago. German doctor von Ardenne opened a "thermal" clinic in a water bath for hopelessly oncologically ill patients, whom he heated to 42 ° C. After this procedure, no more than 17% of people survived, but they were completely cured. The rest were dying, not withstanding such a high temperature. This technology is now used in the United States, where the human body is heated to 42.5 ° C, followed by its return to life. This treatment technology can be effectively used for the selective heating of oncological tissues with RF and microwave energy without a significant increase in the temperature of healthy tissues surrounding the tumor.

The method for initiating the death of tumor cells by electromagnetic energy of wave radiation consists in the complex simultaneous exposure of hydrazide with 3-aminophthalic acid, and HF and microwave energy of wave radiation. The drug "Galavit" is intended for the preparation of a solution for intravenous administration or oral administration in the form of tablets inside a person. After taking the Galavit solution, it takes 6-8 hours to maximize its accumulation and preservation in a significant amount in the tumor tissues of the human body. The maximum content of 3-aminophthalic acid hydrazide in the tumor tissues occurs precisely at this time period and it is 3-6 times higher than in healthy ones due to the selective absorption of this acid by the tumor tissues, while at the same time, during this period, the selective RF and microwave hyperthermia of the tumor cells for 192 sec with a wave radiation of MHz, with a heating rate of 0.06 ° C / sec to a final temperature for heating tumor cells of 50 ° C at a permitted frequency of electromagnetic field oscillations f = 13.56 MHz, f = 40.68 MHz, f = 433 92 MHz, f = 915 MHz and f = 2400. At this time, from 3 to 6 hours in normal cells of living biological objects, the Galavit drug is excreted naturally by the human kidneys, and is retained as much as possible in the tumor tissues, stimulating macrophages of the immune system, recognizes antigens "self", "alien" and T-lymphocytes, based on the oxidative decomposition of luminol in the presence of magnesium ions and copper ions. The result of this is a high fluorescence contrast of the tumor and an increase in its conductivity (dielectric properties) relative to the surrounding healthy biological tissues, reaching a difference of 3-6 times for different tumors. This allows one to specify the boundaries of tumors and simultaneous hyperthermia of tumor cells by the energy of wave radiation during fluorescence diagnostics, and to identify and thus destroy even undetectable tumor formations located in the deep layers of a biological object by wave radiation energy, causing a strong blue glow in the blood vessels of the tumor tissues , with the release of singlet oxygen, which destroys blood vessels, and causes necrosis of the total volume of tumor tissue.

When placed in an alternating electromagnetic field of high tension and frequency of various biological bodies, they also begin to emit a characteristic radiance of various intensities and colors, from which one can judge the properties of the object under study. The method of “high-frequency photography” (Kirlian effect, kirlianography in honor of the inventor V.K. Kirlian) is now widely known in Russia and abroad as a method of experimental studies of electromagnetic fields and bioenergetic interactions. But the greatest scientific and practical interest is the study of the glow of biological objects in an alternating electromagnetic field of high frequency. explained by the photoelectromagnetic effect of photo-wave radiation and the luminescence of biological objects.

In accordance with modern concepts, aqueous solutions of alkalis and acids in the human body are considered as an associated liquid consisting of separate associated elements - neutral clusters and cluster ions of the general formula (H ₂ O) _n , [(H ₂ O) _n ] ⁺ , [( H ₂ O) _n ] ^- , [(NO ₂ ) _n ], [(H ₂ O ₂ ) _n ], [(NaO ₂ ) _n ] [(ClO ₂ ) _n ], [(CO ₂ ) _n ] etc. .d, where the number of water molecules bound into hydrogen bonds can reach n times, according to some authors, under the influence of HF and microwave energy, hundreds or even thousands of units. These effects respectively change the electrical conductivity and biophotoluminescence of biological tissues. Changing the position of one structural element (water molecule) under the influence of any external factor or changing the orientation of surrounding neighboring water molecules in the cells provides high sensitivity of the entire water information system to various external influences (electromagnetic, thermal, sound fields, bio-exposure, etc.). In addition, in water clusters, due to the interaction between covalent and hydrogen bonds between oxygen atoms and hydrogen atoms, the proton (H ⁺ ) can migrate by the relay mechanism, leading to proton delocalization within the cluster providing singlet oxygen with a characteristic bright glow that kills cancer cells. This property explains the extremely labile, mobile nature of the interaction of clusters with each other.

The structured state of aqueous solutions is a sensitive sensor of various fields - electromagnetic, acoustic, energy-information, etc. In addition, aqueous solutions, various chemical elements, is a source of super-weak and weak alternating electromagnetic radiation. In this case, the induction of an external electromagnetic field can occur, causing resonance effects of combining (superposition) of external electromagnetic fields with its own fields in biological objects under photo-wave radiation, which can change the structural and informational characteristics of biological objects, 80-90% of which are solutions of water with various chemical impurities and cause their photoluminescence.

Under the influence of a high frequency electromagnetic field in biological objects and aqueous solutions of various chemicals, the molecules N ₂ , H ₂ , O ₂ and CO ₂ are excited, polarized and ionized. As a result, an ionized gas is formed with separated electrons having negative charges, which create an electrically conductive medium for the formation of a corona discharge in biological objects of various colors, which, depending on the electrically conductive properties of an object saturated with various chemical solutions, can color the luminous corona in various color schemes. The shape of the glow corona, its density, brightness and surface distribution are determined mainly by the electromagnetic parameters of the object.

Some cells of the body granulocytes and monocytes in the blood, and tissue macrophages, in the fight against foreign cells secrete active forms of singlet oxygen contained in superoxide radicals, hydrogen peroxide H ₂ O ₂ , and hydroxyl radical JOH in this case, weak chemiluminescence is observed, which is amplified many times in the presence of hematoporpherin drug "Photogem". These effects are also amplified many times by the action of short-term electrical impulses on blood vessels and cells, causing an increase in the permeability of cell membranes - riticulomas and stimulation of the release of reactive oxygen species by the cell metachondria. This effect of the influence of electrical impulses at the beginning of the 19th century was successfully demonstrated to the public by Nicolo Tesla, when exposed to pulsed high-frequency energy of vessels with liquids with the ability to emit light and fluorescent lamps that glowed without connecting to electric wires, with bright light in the hands of Nikola Tesla, with whom he also juggled, which caused genuine delight among the audience, while at the same time a phenomenon inexplicable by nature, which only Nicolo Tesla knew.

These factors in biology are called collective luminescence stimuli that alter the state of blood and tissue phagocytes and their ability to increase the release of reactive oxygen species, and accordingly the apoptosis of tumor cells and the protective functions of healthy cells.

In cancer cells, aerobic respiration is absent in the mitochondria and is replaced by glycolysis. Hydrazide 3-aminophthalic acid, upon entry into the cancer cell, inhibits glycolysis, but is not able to transfer it to the path of normal aerobicity. Perhaps this is due to the competitive presence of glucose. In order to completely disable glycolis in tumor cells, it is necessary to completely exclude the access of glucose or for 3-aminophthalic acid hydrazide to prevail over glucose in the substrate. In healthy cells in small amounts in cytazole, it exhibits protective antioxidant properties. In cancer cells, when there is an overabundance of it, it stimulates oxidation processes, which, when they are overabundant, have a toxic effect on cancer cells.

It can be argued that the effect would have been higher if treatment had been based on powerful doses of 3-aminophthalic acid hydrazide against the background of complete blocking of the intake of carbohydrates - glucose, as competitors of 3-aminophthalic acid hydrazide in cancer cells. For this, in our opinion, it is necessary to transfer a person to a carbohydrate-free diet for 3 days, for a complete absence at this time in the human diet of carbohydrates, which in the gastrointestinal tract turn into glucose, which is essential for the nutrition of cancer cells. With this introduction of cancer cells into artificial glucose "starvation", then a person must enter high single megadoses of 35 mg / kg 3-aminophthalic acid hydrazide of a person’s live weight. The required amount of the drug based on the maximum permissible single dose of 3-aminophthalic acid hydrazide not exceeding 35 mg / kg. Under the action of enzymes in the human body, 3-aminophthalic acid hydrazide binds to blood hemin with magnesium and copper ions under the action of the enzyme ferrochelatase, thus increasing the fluorescence contrast of the tumor and increasing its conductivity relative to surrounding healthy biological tissues. When 3-aminophthalic acid hydrazide enters the blood vessels of the tumor, having a large branched network with thin peripheral vessels and a low speed of blood movement in them, the blood flow in these vessels of the tumor tissue decreases even more when they are heated, which leads to blood clotting in the tumor vessels tissues, not allowing them to cool, due to the lack of a closed circulatory system. In the main organs of man, rich in blood vessels closed into the main circulatory system, cooling of healthy border tissues subject to HF and microwave hyperthermia occurs. A “hungry” tumor is maximally saturated with 3-minophthalic acid hydrazide, 3-6 times higher than in normal healthy tissues, it stimulates the formation of macrophages and T-lymphocytes under the action of the ferrachelase enzyme, in a sufficiently large amount on membranes and interstitial fluid. It is this chemical compound that is formed during the interaction of 3-aminophthalic acid hydrazide and the internal environment of the body. Under the action of the oxidizing agent of the hydroxyl radical, the formation of the luminal radical occurs, which then reacts with the super oxide radical to form an internal peroxide (dioxide), and when it decomposes, an excited 3-aminophthalate molecule is formed. The transition of this molecule to the ground state is accompanied by the emission of light quanta, which, as a result of chemical reactions associated with reactive oxygen species and organic free radicals, kill tumor cells.

3-aminophthalic acid hydrazide is actively imported into endoplasmic reticules (EPR) (endoplasmic reticulum, consisting of membranes and defining directivity, and active transport of substrates against gradients) of cells. It should be noted that the energy processes in cancer cells are transferred from metachondria to the endoplasmic reticulum. It is here that 3-aminophthalic acid hydrazide is accumulated in metachondria and the cancer cell environment in this place is significantly different from ordinary cells, it is simply rearranged here. A “hungry” cancer cell at this time can repeatedly accumulate 3-aminophthalic acid hydrazide, as perceives it on its membrane transporters for glucose. Since there are many times more glucose-consuming receptors in the oncollet than in healthy ones, although the transport systems for the supply of glucose and 3-aminophthalic acid hydrazide to the cell are common, this is the Trojan horse for oncocytes. Thus, it is very simple to deceive oncocytes and pump 3-aminophthalic acid hydrazide into them, with the solution of the problem of feeding megadoses of 3-aminophthalic acid hydrazide, and then the phenomenon of the death of cancer cells, under the influence of HF and microwave electromagnetic hyperthermia, will be strengthened many times.

A “hungry” tumor is maximally saturated with 3-aminophthalic acid hydrazide, 8-10 times higher than in normal healthy tissues, in a fairly large amount on membranes and interstitial fluid. A “hungry” tumor in the absence of glycolysis saturates for a maximum of 3-5 hours, and many times higher than in normal healthy tissues, it stimulates the formation of macrophages and T-lymphocytes under the action of the enzyme ferrachelase, in a sufficiently large amount on membranes and interstitial fluid. It is this chemical compound that is formed during the interaction of 3-aminophthalic acid hydrazide and hydrogen peroxide in the internal environment of the body. Under the action of the lipid peroxide radical oxidizer and the formation of hydrogen, significantly enhanced temperature and the action and additional photodynamic action of the electromagnetic fields of the HF and microwave, active hydrogen and oxygen radicals are formed, which then reacts with superoxide radicals that accelerate and form internal peroxide (dioxide), H ₂ O ₂ during their hyperthermic decomposition, RF and microwave energy of 3-aminophthalic acid hydrazide. In this case, there is a multiple amplification in the formation of excited oxygen molecules. The transition of the 3-aminophthalic acid hydrazide molecules of the sodium salts of the hematoporpherin drug Photogem and internal hydrogen peroxide from the excited to the ground state is accompanied by the emission of light quanta and strong luminescence. As a result of these chemical reactions associated with a high release of active forms of hydrogen and oxygen and organic free radicals, cancer cells are burned.

The method of "selective starvation" of cancer cells superficial and deeply located in the human body, by subsequent administration or administration of various sensitizers, to selectively saturate tumor cells with highly electroconductive electron-ion solutions of electrophotosensitizers with the maximum separation of electrophysical properties, tumor and healthy tissues, followed by selective exposure to them high-frequency electromagnetic fields in combination with other methods - this is the most relevant scientific and practical direction in the fight against cancer.

A number of researchers argue that the minimum molar concentration of 3-aminophthalic acid hydrazide, which is a prooxidant (lipid-oxidizing compounds that neutralize free radicals), kill cancer cells in the blood and tissues without affecting healthy ones, due to the localized oxidative stress-damage process resulting from oxidation, cell DNA and depletion of adenosine triphosphate (ATP) -source of cell energy due to the additional effects of RF and microwave energy. 3-aminophthalic acid hydrazide and intracellular hydrogen peroxides, among other molecules accompanying it, aggressive action, causes the functioning of a certain enzyme responsible for the "nutrition" of cancer cells to malfunction, can accumulate in the cytosol of cells. It is assumed that with further exposure to HF and microwave energy, the blood vessels of the tumors are disrupted and cytokine reactions, TNF-a, activating microphages, leukocytes and lymphocytes are actively damaged and cause a stable 100% therapeutic effect.

Tumor cells, in contrast to normal cells, accumulate a significant amount of theolactone homocysteine (HTL). Prior to insertion of homocysteine into the protein, it becomes a biological defect in the form of (HTL). In ordinary cells, there is little homocysteine, therefore, theolactone practically does not form from it, but conversion to a cancer cell requires significant activation of methylation, which in turn starts a special biochemical cycle in which homocysteine is involved. In this case, the protein synthesizing the cancer cell machine works at full capacity, therefore it is more often mistaken for taking 3-aminophthalic acid hydrazide for glucose.

3-aminophthalic acid hydrazide is actively imported into endoplasmic reticules (EPR) (an endoplasmic reticulum consisting of membranes and setting the direction and active transport of substrates against gradients) of cells. It should be noted that the energy processes in cancer cells are transferred from metachondria to the endoplasmic reticulum. It is here that 3-aminophthalic acid hydrazide accumulates in the EPR and the cancer cell environment in this place is significantly different from ordinary cells, it is simply rearranged here. From this point on, it is possible to start using HF and microwave electromagnetic hyperthermia the destructive effect of 3-aminophthalic acid hydrazide and HF and microwave energy on the cancer cell. A “hungry” cancer cell at this time can repeatedly accumulate 3-aminophthalic acid hydrazide, as perceives it on its membrane transporters for glucose.

The study of biophysical and biochemical mechanisms determine two concepts of the death of cancer cells, one suggests the significance of the other significance of RF and microwave hyperthermia. The general combination of these methods will lead to the apparent death of cancer cells. The main task for researchers is to strengthen the effect of maximum selective absorption of 3-aminophthalic acid hydrazide by cancer cells as much as possible with the subsequent subsequent high-frequency irradiation of cancer cells in order to increase the treatment efficiency to 100%.

It has already been proven that such an effect is possible by the example of disinfection of biological objects from viral, fungal and bacterial infections with HF and microwave energy. Numerous studies conducted by us in the Krasnoyarsk State Agrarian University and VIZR in St. Petersburg have confirmed the 100% effectiveness of disinfecting vegetable seeds and living bioobjects saturated highly conductive electron-ionic solutions of micronutrients of high frequency and microwave energy against viral infections having a similar origin with cancer cells. The results are shown in the following works: A.S. No. 563938 of the USSR. A method of processing seeds of agricultural crops / Tsuglenok N.V., Tsuplenok G.I. - Publ. 03/16/1977, Bull. No. 25. USSR Certificate No. 950214. The method of presowing treatment of seeds / Tsuglenok N.V. - Registered in the register 04/14/1982. 45. Intensification of thermal processes of seed preparation for sowing with energy of high-frequency and microwave: methodical recommendations / N.V. Loam. - M .: Agropromizdat, 1989. Guidelines for the use of HF and microwave energy in the processes of preparing seeds for sowing / N.V. Loam. - M.: RZh Gosagroprom of the USSR, 1989 .-- 19 p. Ways of disinfecting tomato seeds against a viral infection / Yu.I. Vlasov [et al.] // All-Russian Research Institute for Plant Protection (VIZR). - 1989.- T. 71. - S. 49-54. The method of disinfection of egg powder. Patent Number: 1734632. Published: May 23, 1992 Authors: Tsuglenok N.V., Kolmakov Yu.V. IPC: A23v 5/02. Method for preparing medium for diluting sperm of a manufacturer Patent number: 1769422. Published: June 27, 1995. Authors: Tsuglenok, Ostashko, Chess, Silantyev, Kontsedal.

It is proved that oncoviruses under the influence of carcinogens integrate into a healthy cell and dissolve in it over time, turning it into a cancer cell. Any viruses are killed by temperature or acid. Other methods against oncoviruses and cancer cells are basically powerless; they simply do not exist. A new photodynamic method of using laser photosensitizers deserves special attention in this direction. But the small penetration depth of the electromagnetic wave of laser emitters does not allow to burn deep malignant tumors.

The biophysical meaning of this method is to selectively saturate and accumulate highly electroconductive electron-ion solutions of electrophotosensitizers in tumor cells and to maximize the separation of electrophysical properties of tumor and healthy tissues by 3-aminophthalic acid hydrazide and significantly increase the difference in electrical potentials of tumor and healthy cells and intercellular cells on the walls of the reticulum. It is worth noting another very important biophysical process - an increase in the electrical conductivity of viruses consisting of a protein shell filled with a mixture of nucleic acids and analogous tumor cells filled with solutions of intercellular fluid determined by a significant concentration of ions and electrons and their mobility in comparison with healthy tissues .. When the temperature rises HF and microwave heating in tumor tissues, the mobility of ions and electrons increases significantly, increasing their electrical conductivity and dielectric loss, which further enhances their selective heating and apoptosis of tumor tissues.

Most importantly, this method is harmless, does not have special side effects for biological objects.

The accumulation of aminophthalhydroside in the tumor occurs within 6-8 hours after taking Galavit orally. Then, the level of aminophthalhydroside in the tumor gradually and significantly decreases, 8 hours after taking the Galavit preparation inside 10-30 mg / kg of a person’s weight in the form of a solution in 50-200 ml of drinking water 8 hours before the diagnosis and hyperthermia of the tumor tissues of the HF and Microwave energy of wave radiation, after which the tumors denature and within 2-4 weeks the decay products of the tumor cells are excreted by the body on its own. This healing effect is explained by the fact that in 6-8 hours in normal cells of living biological objects, 3-aminophthalic acid hydrazide is rapidly excreted by the kidneys, while maintaining a high contrast of the content of 3-aminophthalic acid hydrazide in the tumor, which significantly increases its concentration and respectively, electrical conductivity with a significant change and enhancement of the dielectric properties of tumors relative to surrounding healthy biological tissues.

The main task for researchers remains to maximize the effect of maximum selective absorption of 3-aminophthalic acid hydrazide by cancer cells and increase the effectiveness of treatment by increasing the electrical conductivity of metachondria and reticulums of cancer cells. It has already been proven that such an effect is possible, and most importantly, that it is harmless, without any special side effects. The electrical conductivity of cancer cells is due to the presence of mobile charged electrons in them on the reticulums and in the nucleus of the cell and ions in the mitochondria of the cell. The value of electrical conductivity depends on the number of electric charges and their mobility. The electrical conductivity of living tissues is determined by the concentration of ions and their mobility, which is different in different tissues, and therefore biological objects have the properties of conductors, semiconductors and dielectrics. In the intercellular fluid, the maximum content of ions and the electrical conductivity of the tumor tissue is high and is more than 1 S⋅m-1. Large protein molecules have a lower electrical conductivity, up to 0.003 S⋅m-1. Intracellular membranes have a conductivity below (1-3⋅10 ^-5 ) cm⋅m-1. The highest values of electrical conductivity in the human body are in liquid media (blood, lymph, bile, urine, cerebrospinal fluid and tumor tissue 0.6–2.0 S⋅m-1) and muscle tissue (0.2 S⋅m-1 ) Bone, adipose, and nerve tissues have the lowest electrical conductivity, especially coarse-fiber connective tissue and tooth enamel tissue (10 ^-3 -10 ^-6 S cm-1).

A much more complex character is the electrical conductivity of cells and tissues at high and microwave currents. In this case, biological objects have both conductivity and capacitance, which characterize their dielectric constant. The frequency dependence of electrical parameters and the absorption of electromagnetic field energy are determined by the size and shape of the cells, their permeability, the ratio between the volume of cells and intercellular spaces, the concentration of free ions in the cells and the content of free water in them. All these factors lead to a change in the electrical conductivity of biological objects. A particularly significant factor for the metabolism of cancer cells is the content of glucose or its substitutes, in this case 3-aminophthalic acid hydrazide. If there are malignant tumors and metastases in the human body that actively and intensively absorb glucose or its substitute, aminolevoleic acid, they are converted to ATP in cancer cells significantly, lower than in healthy cells, as a result of which, cancer cells become very warm and increase the temperature of the human body 1-2 ° C. This physiological mechanism induces an increase in the temperature of the tumor and surrounding normal tissues. The total temperature rise, at present, is recorded by a microwave radiometer, which allows one to determine the temperature in the deep layers of the human body.

This process was partially studied by us when exposed to a biological object with tumor tissues, which were subjected to complex daily exposure to a constant magnetic field with an intensity of 25 μT and an alternating magnetic field with a frequency of 3.1 Hz and an intensity of 5 μT, exposure time of 60 minutes per day at a time 5 days. The proposed method for the impact of constant and variable effects on ion exchange in the mitochondria of cells and on negatively charged electrons on the reticulums and cell nuclei allowed the induction of death of tumor cells using magnetotherapy, which 40%, compared with the control, freed biological objects from tumor cells ( patent No. 2307681, authors: Tsuglenok N.V., Sergeeva E.Yu., Klimatskaya L.G. RU). Therefore, this direction of using magnetic and electromagnetic fields and their impact on the energy of tumor cells deserve special attention, confirmed by researchers from South Korea, who proposed using a powerful magnetic field to destroy tumor cells. In a powerful magnetic field, the tumor begins to kill itself.

A known method of destruction of cancer cells during microwave irradiation (RF Patent No. 2174021, IPC A61N 5/02) before exposure to hyperthermia, the tumor is exposed to microwave radiation with a wavelength of 1.3-2 cm and the resonance frequency of the absorption of the tumors is detected. Then they carry out a similar effect on healthy tissues bordering on the tumor and reveal the value of the resonance frequency of absorption of these healthy tissues. Simultaneously with hyperthermia, the values of the resonant frequencies are monitored by the absorption of energy by tumors and healthy tissues, and when the values of the resonant frequencies come closer together, the absorption of energy by tumors and healthy tissues is judged on the effectiveness of the treatment. This method allows to increase the effectiveness of the treatment of tumors by microwave hypothermia when they are heated to 43 ° C.

The main disadvantage of this method is a small difference in the heating of tumor and healthy tissues.

A known method of destruction of cancer cells of tumor tissues (RF Patent No. 2106159 IPC A61N 5/02, A61N 5/6) the essence of the invention includes the introduction of ferromagnetic particles into the region of tumor localization, followed by local induction heating, in the temperature range from 42 ° C to 45 ° C, over time, determined by the type of tumor, its size, location and type of ferromagnetic particles selected for induction heating, while heating is carried out only at times when the blood supply to the tissue decreases, i.e. during exhalation and diastole of the patient’s heart. The heating range is controlled by a microwave depth thermometer, and heating is carried out automatically, using a computer, in biocontrol mode, according to the algorithms of a mathematical model of fluctuations in the thermal conductivity and heat capacity of the fabric, hysteresis of heating and heat removal.

The main disadvantages of this method is the small localization of magnetic particles in the tumor and the difficulty of maintaining a fixed temperature in various spatial regions of the tumor, which does not lead to a complete cure of patients.

A known method for the destruction of cancer tumors using magnetic nanoparticles (Presentation of a new magnetic field therapy system for the treatment of human solid tumors with magnetic fluid hyperthermia. Andreas Jordan, Regina Scholz, Klaus Maier-Hau, Manfred Johannsen, Peter Wust, Jacek Nadobny, Hermann Schirra, Helmut Schmidt, Serdar Deger, Stefan Loening, Wolfgang Lanksch, Roland Felix Journal of Magnetism and Magnetic Materials 225 (2001) 118-126).

The destruction of cancer cells is based on the thermolysis of magnetic nanoparticles introduced into the tumor and their induction heating in an alternating magnetic field at frequencies of 50-100 kHz.

However, this method does not allow local destruction of cancer cells and requires powerful electromagnets with currents of tens of kA at relatively high frequencies. In addition, powerful alternating magnetic fields can affect the processes of movement and diffusion of ions across cell membranes, as well as induce inducing alternating electric fields that affect the functioning of neural networks in the human body, associated with heating not only magnetic particles, but also all cells, located in the area of introduction of magnetic particles, and a strong spatial heterogeneity of the heating temperature both inside the tumor and healthy tissues.

There is a method of short-focus x-ray therapy with a total focal zone of 100-120 Gy and remote gamma therapy for radiation destruction of malignant cells with a total focal zone of 30-40 Gy (see Sh. H. Gantsev. Oncology, M .: Medical Information Agency. 2004, pp. 190-204; Stephen J., Withrow E., MacEwen G. Smal animal clinical oncology - 2001, p. 305-308).

However, this method, despite the prevalence, has the following disadvantages. In the treatment of certain types of malignant neoplasms, for example melanoma, with the help of remote gamma therapy, even in combination with immunotherapy, as experience shows, leads to a 75-90% tumor recurrence, and after 2-6 months metastases occur.

Known neuron-capture method for the selective destruction of melanoma (see VN Mitin, NG Kozlovskaya, AM Arnopolskaya Neuron-capture therapy of oral tumors in dogs. All-Russian Veterinary Journal. 2006. No. 1, pp. 9-10) .

The method involves intravenous administration of L-borphenylalanine, which selectively accumulates in a specific melanoma tumor, since L-phenylalanine is an essential amino acid from which melanin is produced, which forms melanocytes contained in melanoma cells. Thus, selective accumulation of L-borphenylalanine in melanoma cells occurs. Upon irradiation of a spatial zone commensurate with a tumor containing L-borphenylalanine by a beam of slow neurons obtained from a nuclear reactor through a neuron waveguide, melanoma cells are destroyed due to the induced secondary local radiation of boron.

However, this method has the following disadvantages:

1. Radiation exposure of patients, which is only partially reduced when using a lithium protective apron.

2. A complex and very expensive installation, including a compact nuclear reactor, requiring qualified non-medical specialists, in particular nuclear physicists, to serve.

3. Long-term patient exposure for an hour when monitoring the cardiovascular system.

4. The use of general anesthesia.

A known method of photodynamic destruction of tumors, including intravenous administration of a photosensitizer and irradiation of the tumor with continuous laser radiation with a wavelength that matches the absorption band of the photosensitizer (see Photodynamic therapy / Ed.TJ Dougherty / J. Clin. Laser Med Surg. 1996, Vol. 14, P 219-348; RF Patent No. 2184578, IPC A61N 5/06). The selective photodynamic mechanism of destruction of cancer cells is based on a higher density (contrast) of photosensitizer accumulation in tumor cells compared to healthy cells, which is associated with a higher density of blood vessels in the tumor compared to healthy biological tissue.

However, this contrast for various tumors does not exceed two to three times. When laser radiation is absorbed by a photosensitizer, the dye molecules transform into an excited electronic state and, when they collide with oxygen molecules dissolved in biological tissues, transfer it from an unexcited to an excited electronic singlet state with a typical lifetime of several microseconds. During this time, the molecules of singlet oxygen, having passed a characteristic path commensurate with the size of the cells when interacting with the plasma membrane of the cell, damage it, and the cell dies due to necrosis. Thus, cell destruction occurs only during exposure to laser radiation in the spatial region of laser beam irradiation.

The photodynamic method for the destruction of cancer cells has several disadvantages. The photosensitizers phthalacinins porphyrins and chlorins used in practice have absorption bands in the ultraviolet or visible spectral range of the photosensitizers, and the lasers used cannot effectively penetrate to a depth of not more than a few millimeters. In addition, the photodynamic method has a low contrast accumulation of photosensitizers in cancer cells.

Closest to the claimed method is the destruction of biological tissue, which consists in introducing ethanol into it using hollow play, characterized in that 95% ethanol is introduced in an amount equal to half the volume of biological tissue to be destroyed, then 5 ml of 20-30% ethanol are introduced, after which is carried out by heating with a high-frequency current with the simultaneous introduction of 20-30% ethanol in an amount equal to the volume of biological tissue to be destroyed. The device contains a high-frequency current generator with two cylindrical electrodes located coaxially relative to each other, internal in the form of a hollow needle through which ethanol is introduced into the tumor (Abstract No. 2006113533 of the patent of the Russian Federation). The disadvantage of this method can be attributed to: the unreasonableness of the selective absorption of ethanol by cancerous and healthy cells, the difficulty of introducing a coaxial electrode into heterogeneous tumors, for organizing uniform heating of tumor tissues that are not equally located from the bare end of the needle.

The objective of the present invention is the local destruction of deep-seated malignant neoplasms in biological tissues, pre-selectively, maximally saturated for 6-8 hours with 3-aminophthalic acid hydrazide, while at the same time after 8 hours of RF and microwave heating of tumors and with secondary heating of the boundary layers of healthy tissues of surrounding tumors , due to heat transfer of heat from tumor tissues with minimal destruction of surrounding healthy biological tissue cells.

The proposed method for initiating the death of tumor cells, including saturation of tumor cells with a solution of 3-aminophthalic acid hydrazide in a megadose of 36 mg per kg of human weight of the Galavit preparation, administered intravenously to humans or in a megadose of 300 mg orally for its accumulation in tumor tissues, after 6-8 hours after administration of the drug, with a difference of 3-6 times higher than in healthy ones, characterized in that before the administration of the drug, a person is preliminarily switched to a carbohydrate-free diet for 3 days to create glucose “starvation” of tumor cells and tumor selective hyperthermia is performed tissues saturated with 3-aminophthalic acid hydrazide, due to a proportional increase in dielectric properties and electrical conductivity, HF and microwave energy of photo-wave radiation is performed after 8 hours from the start of administration of the Galavit preparation, at a tumor tissue heating rate of 0.07 ° C / s, for 204 sec to a temperature of 51 ° C, and heating healthy tissues to 40 ° C.

A single-dose megadose of Galavit 3-aminophthalic acid hydrazide for intravenous administration of 36 mg per kg of human weight and oral administration is 300 mg of Galavit 3-aminophthalic acid hydrazide and heating and hyperthermia of tumor tissues saturated with 3-aminophthalic acid hydrazide solution "Galavit" is produced by the HF and microwave energy of the wave radiation, in accordance with the depth of penetration of the electromagnetic wave and the depth of the location of the tumor tissue, at the allowed frequencies: f-13.56 MHz - 1100 cm; f = 27 MHz - 545 cm; f = 40.68 MHz - 370 cm; f = 433.92 MHz - 34.5 cm; f = 915 MHz - 16.5 cm and f = 2450 MHz - 6.1 cm.

According to studies on RF and microwave hyperthermia of tumor tissues, at a temperature of 51 ° C, the border between the necrosis zone and healthy tissue is several cells. The destruction zone of tumor tissue includes a small periphery of normal healthy tissues, which excludes the regenerating cells from metastasis by their secondary necrosis from tumor tissues.

The physical nature of microwave radiation is the physical field of moving electric charges in electric and magnetic fields, which are a single electromagnetic field (EMF), characterized by an oscillation frequency f. The difference is only in the frequency with which electromagnetic oscillations of the corresponding wavelength occur. The biological effect of EMF on a living organism consists in the absorption of energy by biological tissues, characterized by biophysical parameters - dielectric constant and conductivity. The tissues of the human body, due to the high content of water in them, should be considered as lossy dielectrics. With general body irradiation, EMF energy penetrates to a depth of 0.5 wavelength. The intensity of exposure, exposure and dielectric loss and conductivity characterize the selective absorption of EMF by various tissues at the same EMF radiation density.

where, λ is the wavelength,

C is the propagation velocity of the electromagnetic wave,

f is the frequency of the electromagnetic field.

The frequency with which oscillations of the electromagnetic field occur significantly affects the depth of penetration of an electromagnetic wave into a biological object.

The reason is commensurability with various physical objects. At f = 13.56 MHz, the wavelength of the EMF λ = 22 m, at λ = 40.68 MHz, the wavelength of the EMF λ = 7.4 m, at f = 433.92 MHz, the wavelength of the EMF λ = 69 cm, at f = 915 MHz, the wavelength of the EMF λ = 33 cm, and at f = 2450 MHz, the wavelength of the EMF λ = 12.2 cm (Table 1)

This determines the choice of equipment for local hyperthermia of tumors located at different depths in biological objects.

Tumor tissues saturated with 3-aminophthalic acid hydrazide are 6-8 times higher than its content in healthy tissues, and accordingly, its electrical conductivity is so many times different, i.e. the ability of tumor tissues to conduct an electric current is due to the presence in the tumors of an acid electrolyte, free charge carriers, electrically charged particles, which, under the influence of an external electric field in the thickness of the tumor, create a conduction current.

Another important parameter of dielectric and semiconductor materials such as tumors are dielectric losses. They serve to determine the electric power spent on heating dielectrics and semiconductors in an electromagnetic field. In the reference literature, for the characteristics of the ability of a dielectric to absorb the energy of an alternating electric field, it uses tanδ of the dielectric loss angle and permittivity ε. The physical meaning of tanδ is the presence of dielectric losses leading to a phase shift between the current and voltage, where the angle between them becomes less than 90 ° by an amount, the quantitative wave energy loss is proportional to the dielectric loss ε tanδ.

Losses on electrical conductivity in dielectrics having a low specific volume resistance, for example, are absolutely chemically pure water. In nature, water is an excellent solvent and dissolves acids well, and therefore the electrical conductivity of such water has a large number of charged ions, which, under the influence of an alternating electric field, begin to move in time with a changing wave electromagnetic field, converting electrical energy into heat. Tumor tissues are maximally saturated with 3-aminophthalic acid hydroside, in this case they are semiconductors containing several times more charged ions in comparison with surrounding healthy tissues and, accordingly, their heating rate is many times higher than that of surrounding healthy tissues at the same time. In such tumor tissues, relaxation dielectric losses are additionally observed due to the rotation of the polar water molecules in the direction of the electric field lines. Intramolecular friction occurs, which once again enhances the heating of tumor tissues.

The specific power of the dielectric loss, referred to the unit volume of the dielectric is called the dielectric loss, which can be calculated by the formula:

Ore = E ² fεtgδ, 10 ^-12 W / cm ³

This ratio determines the degree of heating of various structures of tumor and healthy tissues of a biological substance in an electric field. For this, it is necessary to know ε and tanδ of tumor and healthy tissues, and thus very accurately calculate the heating rate to a given temperature of heating of tumor and surrounding healthy tissues in a uniform electromagnetic field (EMF).

Selective absorption of 3-aminophthalic acid hydrazide by the tumor tissues leads to their selective heating of the tumors and electromagnetic photoluminescence to a higher temperature of 51 ° C during heating of healthy tissues surrounding them to a temperature of 40 ° C during the same time, which leads to the inactivation of tumor tissues and their subsequent destruction, which then, within a few days, is painlessly excreted by the body. The rate of heating by the wave energy of an electromagnetic field depends on the power of dielectric generators and magnetrons.

Knowing the specific power of Ore released in a biological object taking into account ε and tanδ of tumor and healthy tissues, it is possible to very accurately calculate the heating rate to a given temperature of heating of tumor and surrounding healthy tissues in a uniform electromagnetic field (EMF). according to the formula:

Ore _op = E ² fε _op tg _op δ, 10 ^-12 W / cm ³

With an oscillatory power of electromagnetic field generators of 700-850 watts, 200-300 grams of tumor tissue can be heated to a temperature of 60 ° C in 2-3 minutes, the specific power released in the tumors, and their heating temperature is determined by the formula:

where, Co is the heat capacity of the tumor, feces;

m is the mass of the tumor in grams;

ΔТ is the temperature difference of the heating;

t is the heating time, sec.

This formula allows you to choose the necessary total specific power R _beats for RF and microwave heating of tumor tissues P _beats up to a given difference in heating temperatures and specific power P _beats allocated in healthy tissues determined by the general formula:

P _{beats rev} = P _{beats op} + P _beats

Then the specific power in the irradiation region, taking into account the dielectric properties:

R _{beats rev} = (E ² fε _op tgδ _op + E ² fε _zd tgδ _zd ) 10 ^-12

Knowing the dielectric properties of the tumor ε _op tgδ _op and healthy tissues δ _zd tgδ _zd , it is possible by calculation to determine the temperature of their heating ΔT to the required set temperatures and determine the heating time t and the total specific power Rud about the irradiated area. (Table 2)

Similarly, knowing the dielectric parameters εtgδ and the specific density of tumor tissues saturated with electrophotosensitizers in biological objects γ g / cm ³ , it is possible to calculate the specific power released in tumor tissues R _{beats op} , to determine the set temperature and calculate the time of their heating by HF and microwave energy according to the above formulas.

Claims (1)

A method for initiating the death of tumor cells, intended for the treatment of cancer patients with tumor tissues with metastases in all organs of the human body by hyperthermia of high-frequency and microwave energy, characterized in that a person is transferred to a carbohydrate-free diet for 3 days to create glucose starvation and subsequent maximum saturation of cancer cells with an electron-ionic solution of 3-aminophthalic acid hydrazide of the drug “Galavit” intravenously in a megadose of 36 mg / kg of human weight for maximum accumulation in tumor tissues is 3-6 times more than in healthy tissues and 8 hours after administration of the solution Galavit 3-aminophthalic acid hydrazide, selective hyperthermia of tumor tissues with high-frequency energy is carried out in accordance with the depth of their location and the depth of penetration of an electromagnetic wave into the human body 1100 centimeters, at an allowed frequency f = 13.56 MHz, with a total tumor heating rate of 0 , 07 ° C / s, for 204 seconds to a temperature tumor tissue 51 ° C, when heating healthy tissue is not higher than 40 ° C.