Method of preparation of products that modify the influence of external physical effects on the body

Abstract

This invention relates to the field of pharmaceuticals and cosmetology, namely, to a method for preparation of products capable of exerting a modifying influence on an organism subjected to external physical factors, namely enhancing or weakening the effects of the physical factor. A method for obtaining a cosmetic product, which is an artificial material object – iteration, produced by sequential vibration treatment of a neutral carrier in the presence of a biological substance selected from biological molecule, cell, group of cells or structures composed of cells, fluid media having a regulatory effect on functional and metabolic processes in skin, hair, nails and oral mucosa.

Description

[0001] Method of preparation of products that modify the influence of external physical effects on the body

[0002] This invention relates to the field of pharmaceuticals and cosmetology, namely, to a method for preparation of products capable of exerting a modifying influence on an organism subjected to external physical factors, namely enhancing or weakening the effects of the physical factor.

[0003] It is known from the prior art that certain long-lasting structural changes can appear in water after exposure to any vibration treatment - both mechanical (Gudkov S.V. et al., 2019; Astashev M.E. et al., 2023; Demangeat JL., 2022; Duval E. et al., 2012) and electromagnetic (D'Emilia E. et al., 2017; Sronsri C. et al., 2021; Wu T. et al., 2020).

[0004] It is also known from the prior art that when solutions of an initial substance are prepared by multiple dilutions using an external mechanical effect in the form of vertical shaking (vibration) at each dilution cycle up to the level of ultra-high dilutions, the latter acquire a number of new physical properties that determine their activity even at speculatively small amounts in dilutions of the initial substance.

[0005] Such properties include the ability of high dilutions obtained by applying multiply repeated vibration treatment to exert a non-contact (distant) effect on other substances or solvents [Jerman, I.; Ruzic, R.; Krasovec, R.; Skarja, M.; Mogilnicki, L. «Electrical Transfer of Molecule Information into Water, Its Storage, and Bioeffects on Plants and Bacteria», Electromagnetic Biology and Medicine 2005, 24 (3), 341—

[0006] 353. https: / / doi.org / 10.1080 / 1536837050038162Q; Ruzic, R., Jerman, I., Skarja, M., Leskovar, R., Mogilnicki, L. «Electromagnetic Transference of Molecular Information in Garden Cress Germination», Int J High Dilution Res 2008; 7(24): 122-131 2008, 7, 122-131; Igor Jerman, Linda Ogrizek, Vesna Pericek Krapez and Luka Jan, Physicochemical study of the molecular signal transfer of ul-tra-high diluted antibodies to interferon gamma. Int. J. Mol. Sci. 2023, 24; N.Penkov, N.Penkova. Analysis of Emission Infrared Spectra of Protein Solutions in Low Concentrations. Front. Phys., 18 December 2020 Sec. Interdisciplinary Physics, Volume 8 - 2020 | https: / / doi.org / 10.3389 / fphy.202Q.624779; Penkov N., 2021; Novikov V.V. and Yablokova E.V., 2022)], as well as the ability of dilutions to exert a modifying effect on the initial substance [WO2012017324, US7,229,648, US4,311,897, RU2192888, 2577137, 2577136, 2536230, 2519695, 2778521, 2509572, 2531048, 2517085, 2505312, 2577299] Modifying effects are manifested in changes in the structure of the molecules of the initial substance, their hydrate shell, which leads to modulation of biological activity of the initial substance [Tarasov SA, Gorbunov EA, Don ES, Emelyanova AG, Kovalchuk AL, Yanamala N, Schleker ASS, Klein- Seetharaman J, Groenestein R, Tafani JP, van der Meide P, Epstein 01. Insights into the Mechanism of Action of Highly Diluted Biologies. J Immunol. 2020;205(5): 1345-1354. doi: 10.4049 / jimmunol.2000098; Woods KN. Modeling of protein hydration dynamics is supported by THz spectroscopy of highly diluted solutions. Front Chem. 2023; 11 : 1131935. doi: 10.3389 / fchem.2023.1131935] and determines the presence of biological (pharmacological) activity in high dilutions.

[0007] The modifying effect underlying the specific pharmacological activity of multiply diluted drugs is quite pronounced, which allowed its evaluation and standardization using generally accepted analytical methods (see State Pharmacopoeia of the Russian Federation XV, General Pharmacopoeia Monography (GPM) 1.7.0001). The technology of preparing high dilutions in the form of serial dilution of a biological substance and vibration treatment of dilutions after the release of GPM received the official name ‘gradual’ technology. Currently, products based on gradual technology, gradualized drugs, are produced mainly from antibodies [Mkrtumyan A, Ametov A, Demidova T, Volkova A, Dudinskaya E, Vertkin A, Vorobiev S. A New Approach to Overcome Insulin Resistance in Patients with Impaired Glucose Tolerance: The Results of a Multicenter, Double-Blind, Placebo-Controlled, Randomized Clinical Trial of Efficacy and Safety of Subetta. J Clin Med. 2022; 11(5): 1390. doi: 10.3390 / jcml 1051390; Geppe NA, Blokhin BM, Shamsheva OV, Abdrakhmanova ST, Alikhanova KA, Myrzabekova GT. Efficacy and Safety of Ergoferon in Children from 6 Months to 6 Years Old with Acute Respiratory Viral Infections in Contemporary Outpatient Practice: A Multicenter, Double-Blind, Placebo-Controlled Randomized Trial. Can Respir J. 2021; 2021 :5570178. doi: 10.1155 / 2021 / 5570178; Lashch NU, Kamchatnov PR, Fedorova TN, Muzychuk OA, Khacheva KK, Pizova NV, Malygin AU, Shavlovskaya OA, Fateeva VV, Nikulina KV, Abrosimov AV, Gerasimova YA, Glushkov KS, Lebedeva AV. Efficacy and Safety of Divaza for the Correction of Oxidative Disturbances in Patients with Cerebral Atherosclerosis: A Randomized Controlled Trial. Cerebrovasc Dis. 2021; 50(4):472-482. doi: 10.1159 / 000515233; Avdeev SN, Vizel AA, Abrosimov VN, Zaicev AA, Ignatova GL, Khamitov RF, Mikhaylusova MP, Shapovalova JS, Pavlysh EF, Trofimov BI, Emelyanov AV, Martynenko TI, Martynenko VA, Kostina NE, Chizhov DA, Chizhova OY, Kuzubova NA, Makova EV, Makarova EV. Management of Cough in Patients with Chronic Obstructive Pulmonary Disease: Results of the Multicenter Randomized Placebo-Controlled Clinical Trial. Int J Chron Obstruct Pulmon Dis. 2021; 16: 1243-1253. doi: 10.2147 / COPD.S292109; Parfenov VA, Zhivolupov SA, Poverennova IE, Nesterova MV, Ushakova SE, Zhukova NG, Glazunov AB, Nikulina KV, Alexandrov MV, Lapatukhin VG, Zhestikova MG. Treatment of Cognitive Impairment and the Role of Demographic Factors in Disease Progression: The Final Results of the Russian Observational Program "DIAMANT". Eur Neurol. 2020; 83(6):591-601. doi: 10.1159 / 000508184; Ivashkin VT, Poluektova EA, Glazunov AB, Putilovskiy MA, Epstein OI. Pathogenetic approach to the treatment of functional disorders of the gastrointestinal tract and their intersection: results of the Russian observation retrospective program COMFORT. BMC Gastroenterol. 2019; 20(l):2. doi: 10.1186 / sl2876-019-l 143-5; Parfenov VA, Ostroumova OD, Ostroumova TM, Kochetkov Al, Fateeva VV, Khacheva KK, Khakimova GR, Epstein OI. Vascular cognitive impairment: pathophysiological mechanisms, insights into structural basis, and perspectives in specific treatments. Neuropsychiatr Dis Treat. 2019; 15: 1381-1402. doi: 10.2147 / NDT.S197032; Pushkar D, Vinarov A, Spivak L, Kolontarev K, Putilovskiy M, Andrianova E, Epstein O. Efficacy and safety of Afalaza in men with symptomatic benign prostatic hyperplasia at risk of progression: a multicenter, double-blind, placebo-controlled, randomized clinical trial. Cent European J Urol. 2018; 71(4):427-435. doi: 10.5173 / ceju.2018.1803; Mkrtumyan A, Romantsova T, Vorobiev S, Volkova A, Vorokhobina N, Tarasov S, Putilovskiy M, Andrianova E, Epstein O. Efficacy and safety of Subetta add-on therapy in type 1 diabetes mellitus: The results of a multicenter, double-blind, placebo- controlled, randomized clinical trial. Diabetes Res Clin Pract. 2018; 142: 1-9. doi: 10.1016 / j.diabres.2018.04.044; Rafalsky V, Averyanov A, Bart B, Minina E, Putilovskiy M, Andrianova E, Epstein O. Efficacy and safety of Ergoferon versus oseltamivir in adult outpatients with seasonal influenza virus infection: a multicenter, open-label, randomized trial. Int J Infect Dis. 2016; 51 :47-55. doi: 10.1016 / j .ijid.2016.09.002; Don E, van der Meide N, Egorov V, Putilovskiy M, Tarasov S. The level of natural autoantibodies to IFN-gamma in varicella infection treated with antiviral drug Anaferon for children: A pilot study. Immunol Lett. 2020; 222:90-94. doi: 10.1016 / j.imlet.2019.10.015; Tarasov SA, Gorbunov EA, Don ES, Emelyanova AG, Kovalchuk AL, Yanamala N, Schleker ASS, Klein-Seetharaman J, Groenestein R, Tafani JP, van der Meide P, Epstein OI. Insights into the Mechanism of Action of Highly Diluted Biologies. J Immunol. 2020; 205(5): 1345-1354. doi: 10.4049 / jimmunol.2000098; Woods KN. Modeling of protein hydration dynamics is supported by THz spectroscopy of highly diluted solutions. Front Chem. 2023; 11 : 1131935. doi: 10.3389 / fchem.2023.1131935; Alinkina E, Don E, Gizitdinova O, Samsonova L, Petrova A, Stepanov G, Tarasov S. A novel technique for studying the effects of technologically processed antibodies by evaluating the rate of oxidation of ascorbic acid during the reduction of the green-blue ABTS + radical. Spectrochim Acta A Mol Biomol Spectrosc. 2024; 304: 123323. doi: 10.1016 / j. saa.2023.123323; Emelianova AG, Petrova NV, Fremez C, Fontanie M, Tarasov SA, Epstein 01. Therapeutic potential of highly diluted antibodies in antibiotic-resistant infection. Eur J Pharm Sci. 2022; 173: 106161. doi: 10.1016 / j.ejps.2022.106161; Petrova NV, Tarasov SA, Epstein OI, Dubroca C, Sulpice T. Highly Diluted Antibodies to eNOS Restore Endothelium Function in Aortic Rings From Hypertensive Rats. Dose Response. 2022; 20(2): 15593258221099281. doi: 10.1177 / 15593258221099281; Don ES, Bobrovnik SA, Sherriff G, Myslivets AA, Tarasov SA, Epstein OI. Advanced approach to activity evaluation for released-active forms of antibodies to interferon-gamma by enzyme-linked immunoassay. J Immunoassay Immunochem. 2019;40(3):250-268. doi: 10.1080 / 15321819.2019.1567536; Kardash EV, Ertuzun IA, Khakimova GR, Kolyadin AN, Tarasov SA, Wagner S, Andriambeloson E, Ivashkin VT, Epstein OI. Dose-Response Effect of Antibodies to SI 00 Protein and Cannabinoid Receptor Type 1 in Released-Active Form in the Light-Dark Test in Mice. Dose Response. 2018; 16(2):1559325818779752. doi: 10.1177 / 1559325818779752; Don ES, Emelyanova AG, Yakovleva NN, Petrova NV, Nikiforova MV, Gorbunov EA, Tarasov SA, Morozov SG, Epstein OI. Dose-dependent antiviral activity of released-active form of antibodies to interferon-gamma against influenza A / California / 07 / 09(H1N1) in murine model. J Med Virol. 2017; 89(5):759- 766. doi: 10.1002 / jmv.24717; Don E, Farafonova O, Pokhil S, Barykina D, Nikiforova M, Shulga D, Borshcheva A, Tarasov S, Ermolaeva T, Epstein O. Use of Piezoelectric Immunosensors for Detection of Interferon-Gamma Interaction with Specific Antibodies in the Presence of Released-Active Forms of Antibodies to Interferon-Gamma. Sensors (Basel). 2016;16(l):96. doi: 10.3390 / sl6010096; Gorbunov EA, Nicoll J, Kachaeva EV, Tarasov SA, Epstein OI. Subetta increases phosphorylation of insulin receptor P-subunit alone and in the presence of insulin. Nutr Diabetes. 2015; 5(7):el69. doi: 10.1038 / nutd.2015.20; Gorbunov EA, Ertuzun IA, Kachaeva EV, Tarasov SA, Epstein OI. In vitro screening of major neurotransmitter systems possibly involved in the mechanism of action of antibodies to SI 00 protein in released- active form. Neuropsychiatr Dis Treat. 2015; 11 :2837-46. doi: 10.2147 / NDT.S92456; Bailbe D, Philippe E, Gorbunov E, Tarasov S, Epstein O, Portha B. The novel oral drug Subetta exerts an antidiabetic effect in the diabetic Goto-Kakizaki rat: comparison with rosiglitazone. J Diabetes Res. 2013; 2013:763125. doi: 10.1155 / 2013 / 763125; Nicoll J, Gorbunov EA, Tarasov SA, Epstein OI. Subetta treatment increases adiponectin secretion by mature human adipocytes in vitro. Int J Endocrinol. 2013; 2013:925874. doi: 10.1155 / 2013 / 925874; Andrianov VV, Epstein OI, Gainutdinova TKh, Shtark MB, Timoshenko AKh, Gainutdinov KL. Antibodies to calcium- binding SIOOB protein block the conditioning of long-term sensitization in the terrestrial snail. Pharmacol Biochem Behav. 2009; 94(l):37-42. doi: 10.1016 / j.pbb.2009.07.003; Castagne V, Lemaire M, Kheyfets I, Dugina JL, Sergeeva SA, Epstein 01. Antibodies to SI 00 proteins have anxiolytic-like activity at ultra-low doses in the adult rat. J Pharm Pharmacol. 2008; 60(3):309- 16. doi: 10.121 l / jpp.60.3.0005; Chu X, Zhavbert ES, Dugina JL, Kheyfets IA, Sergeeva SA, Epstein OI, Agmo A. Sildenafil and a compound stimulating endothelial NO synthase modify sexual incentive motivation and copulatory behavior in male Wistar and Fisher 344 rats. J Sex Med. 2008; 5(9):2085-99. doi: 10.1111 / j.1743-6109.2008.00937.x; Chu X, Agmo A.

[0008] Sexual incentive motivation in old male rats: the effects of sildenafil and a compound (Impaza) stimulating endothelial NO synthase. Pharmacol Biochem Behav. 2008; 89(2):209-17. doi: 10.1016 / j.pbb.2007.12.012; Epstein OI, Zapara TA, Simonova OG, Ratushnyak AS, Shtark MB. Plasticity of neuronal responses induced by low concentrations of exogenous ligands affecting cellular calcium stores. Front Biosci. 2004; 9:809-15. doi: 10.2741 / 1244; Epstein OI, Beregovoy A, Sorokina NS, Starostina MV, Shtark MB, Gainutdinov KhL, Gainutdinova TKh, Muhamedshina DI. Membrane and synaptic effects of anti-S-100 are prevented by the same antibodies in low concentrations. Front Biosci. 2003; 8:a79-84. doi: 10.2741 / 1025],

[0009] The applicant found that even without dilution of the initial substance, successive vibration treatment of a test tube containing various molecules, including biological ones, i.e., antibodies, together with a closely located test tube containing a solvent, results in the solvent changing its physical-chemical properties and turning into an artificial material object called ‘iteration’. It was found that iterations were distributed by physical -chemi cal properties into fractions, each of which reproduced some pharmacological properties of the initial molecule.

[0010] The technical objective of the present invention was to obtain products that modify the effect of external physical factor on the body in order to protect the body from adverse external physical factor or, if necessary, to enhance the effect of the physical factor on the body, as well as on the biological object from which the preparation is made using the physical factor.

[0011] The applicant has discovered a way to produce products able to exert a protective effect against external physical factors by obtaining artificial material objects based on physical factors, iterations, prepared using external rhythmic effect (Fig. 1).

[0012] There are articles in the prior art relating to high dilutions. For example, 'Interaction between highly diluted samples, protein solutions and water in a controlled magnetic field' by V. V. Novikov was published in Applied Sciences in 2022.

[0013] This article describes a stock solution of a substance that has been diluted multiple times (HD) and an experiment investigating the remote action of HD IFNy on IFNy in the presence of electromagnetic radiation. However, this is not relevant to the present invention, as the application discloses iterations prepared from a neutral carrier in the presence of a biological product.

[0014] Page 15 of the article (Novikov, 2022) states that the ability to influence ROS production changes under the influence of a magnetic field in solutions, while the claims indicate a method of obtaining an iteration by successively shaking a carrier treated with magnetic radiation and a neutral carrier. In other words, the neutral (not irradiated) carrier eventually acquires properties to modify the action of external physical factors on the body, which is not disclosed herein.

[0015] Another example is the article 'The Role of Water in the Effect of Weak Combined Magnetic Fields on the Production of Reactive Oxygen Species (ROS) by Neutrophils' by V. Novikov, published in Applied Sciences in 2020. The article examines how physical factors influence the modification of water properties to enhance ROS release by neutrophils. It also indicates that using irradiated water dilutions leads to an increase in ROS release by neutrophils. However, the article does not mention the method of obtaining iteration by successively shaking a carrier treated with magnetic radiation, which acquires the ability to modify the effect of external physical factors on the body.

[0016] Iteration preparation technology is fundamentally different from the technology used to prepare high dilutions. High dilutions involve a sequential reduction in the concentration of the starting substance by physical action on the solution. In contrast, iteration technology involves sequential vibratory action on a neutral carrier in the presence of a solution of the substance. These are two distinct technologies.

[0017] Therefore, the articles cited above are not relevant to the present application. Some articles provide information on the distance effects of products obtained using the high dilution preparation technique. However, this information relates to the properties of such preparations, whereas the presence of the substance in close proximity to a neutral carrier within the iterative preparation technology is a condition for its realization, which is in no way disclosed in the articles. Thus, the average person skilled in the art, having knowledge of the high dilution technology or the properties thereof, would not be able to implement the iteration technology.

[0018] At the initial stage, the claimed method includes vibration treatment of a test tube with an intact solvent and with an artificial substance obtained by exposing the solvent to a physical factor, which leads to the transformation of the solvent into a material object - a ‘iteration zero’ with new physical-chemical properties that differ from both the properties of an intact solvent and an artificial substance, and whose distinctive feature is the ability to exert a modifying effect on a body exposed to the physical factor from which the artificial substance was prepared. Next, the first iteration is obtained as a result of exposing an intact carrier to vibration treatment in the presence of a ‘iteration zero’, then subsequent iterations (the second, third, etc.) are obtained from each previous iteration by vibration treatment of an intact solvent.

[0019] Furthermore, an obligatory part of the solution is the division of the obtained iterations into fractions by evaluating their physical-chemical properties using generally accepted analytical methods and further determination of their biological (pharmacological) properties using generally accepted methods for experimental pharmacology.

[0020] Products based on iterations of physical factors can be used both along with the exposure to these factors and after its termination, or used for preventive purposes before adverse effects.

[0021] For each specific case, it is necessary to select the most appropriate iteration fractions, since they can have a multidirectional effect. In this regard, in one case, iterations can weaken the impact of a physical factor, and in another one, if necessary, enhance it.

[0022] The modifying effect of the preparation obtained by the claimed method lies in its protective effect or in enhancing the influence of the physical factor on the body.

[0023] The modifying effect of the product, obtained by the claimed method lies in its protective effect or in enhancing the influence of the physical factor on the body. Within the scope of this invention, a protective effect is considered to weaken the harmful effect of a physical factor on the body (part of the body); in some cases, for example, in the treatment of oncological diseases, the effect of a physical factor on the body may be enhanced.

[0024] In some cases, for example, in the treatment of oncological diseases, there may be an amplification of the influence of the physical factor on the body or biological object.

[0025] A physical factor means any physical effect that has features peculiar only to it, for example, radiation, low temperature, dustiness and gas content of the air environment, exposure to noise, infra- and ultrasound, vibration, the presence of electromagnetic fields, laser and ionizing radiation, humidity, air velocity; thermal radiation; non-ionizing electromagnetic fields (EMF) and radiation - electrostatic field, permanent magnetic field, electric and magnetic fields of industrial frequency (50 Hz), broadband EMF generated by a PC, electromagnetic radiation of the radio frequency range, broadband electromagnetic pulses, electromagnetic radiation of the optical range (including laser and ultraviolet); ionizing radiation; industrial noise; ultrasound, infrasound, vibration (local, general); aerosols (dust) of predominant fibrogenic effect; lighting - natural (absent or insufficient), artificial (insufficient illumination, pulsation of illumination, excessive brightness, high unevenness of brightness distribution, direct and reflected disability glare); electrically charged air particles - aeroions and so on. The physical factor is selected depending on what physical effect it is necessary to protect the body from.

[0026] Physical impact refers to a distant influence characterized by qualitative and quantitative criteria specific to the particular physical factor, accompanied by changes in morpho-physiological, metabolic, immunological, and other processes in the body.

[0027] Products that are iterations of physical factors have great potential for implementation, since unlike drugs commonly used in adverse physical effects that exert a general, non-specific adaptive effect on the body by activating metabolism or the immune system, iterations of physical factors exert a directed, specific effect.

[0028] The protective effect of the product prepared using the claimed method by employing successive vibration treatment of a neutral carrier in the presence of an artificial substance is directed at the same targets in the body: molecules, functional or metabolic processes affected by the physical factor itself, which is accompanied by the sensitization of targets and modification of external physical effects.

[0029] Various fractions of iterations of the physical factor can have a multidirectional, i.e., activating or suppressing, effect on the same functional and metabolic processes. In this regard, an adequate fraction of iterations should be selected for each case experimentally.

[0030] The claimed invention provides a method for producing a biological drug product including the following steps:

[0031] 1) preparation of ‘iteration zero’ - an artificial material object obtained by exposure of the solvent to external vibration treatment in the presence of artificial substance prepared by contact of a neutral carrier / solvent with a physical factor (with their further incubation);

[0032] 2) obtaining the first iteration by exposure of the intact solvent to vibration treatment in the presence of ‘iteration zero’;

[0033] 3) obtaining a series of iterations, where each successive iteration is obtained by exposure of the solvent to vibration treatment in the presence of the previous iteration.

[0034] In the first step, a ‘iteration zero’ is obtained, into which the solvent is transformed by joint vibration treatment of the solvent and the initial artificial substance (with their further exposure - incubation). Then, by vibration treatment of the preceding iteration and the solvent from the solvent, subsequent iterations, the first, second, third, etc., are obtained.

[0035] To obtain an artificial substance, contact of a neutral carrier or solvent with an external physical factor is necessary, which is provided by exposing a test tube with a carrier or solvent to an external physical factor (irradiation, heating, ultrasound treatment, etc., depending on the selected physical factor) for a certain period of time, which is selected experimentally individually for each carrier / solvent or a physical factor (usually more than 1 sec.).

[0036] The process of obtaining iterations may differ in terms of the time during which the external vibration treatment is applied, or incubation - post-vibration contact of the artificial substance (or iterations) with the solvent; the type of external rhythmic physical effect - horizontal or vertical mechanical treatment (shaking, rotation on a vortex), ultrasound, electromagnetic field, etc., as well as variants of external rhythmic effect in frequency and amplitude. Various solvents, such as water or a water-alcohol mixture, may also be used. The series of iterations may be derived from a single artificial substance, or a combination thereof, for example, for protection against several adverse physical factors acting simultaneously.

[0037] The time of external vibration treatment and incubation (co-incubation of test tubes with intact solvent and iteration or artificial substance at room temperature) is selected experimentally for each specific case depending on the nature of external physical effect.

[0038] Test tubes and vials are placed side by side - close to each other or at a distance, mostly 1-3 cm. Separate vibration treatment of artificial substance (or iterations in the case of the preparing subsequent iterations) and solvent with their further incubation is also possible, when tubes with artificial substance (or iterations in the case of the preparing subsequent iterations) and solvent are placed next to each other for a period of 1 sec or more.

[0039] Iterations resulting from successive external vibration treatment on test tubes with solvent and preceding iterations or initial substance (to obtain the ‘iteration zero’) are a product with a specific activity, since they protect only or predominantly from the physical factor used to produce the initial artificial substance.

[0040] It has been experimentally established that fractions of iterations with common physical, first of all, spectral properties have common features; therefore, the separation of iterations into fractions is a necessary technological step in the creation of drug products of this type, with further experimental determination of their specific pharmacological (protective) activity.

[0041] The method of separation into fractions, according to this invention, comprises the following steps:

[0042] 1. Using known analytical methods, each iteration obtained is evaluated in terms of physical -chemi cal properties, such as specific electrical conductivity (SEC), radiometry, pH, the amount of dissolved oxygen, dynamic light scattering, high-resolution thermography, immunosorbent assay etc. 2. After evaluation of the physical-chemical properties, iterations are separated into fractions exhibiting their own physical-chemical properties different from those of the initial neutral solvent.

[0043] 3. The specific pharmacological activity, which is similar to the activity of the physical agent used to obtain an initial artificial substance, is determined experimentally for each fraction.

[0044] The external vibration treatment used to obtain iterations means horizontal, vertical mechanical shaking or a combination thereof, as well as external effect exerted by acoustic and microfluidics methods [RU2724254], electromagnetic, ultrasonic influence or other external rhythmic influence. The test tubes with solvent and artificial substance (or the preceding iteration) may be subjected to joint (simultaneous) vibration treatment or each of the test tubes is independently of the other exposed to vibration treatment. In this case, different types of external rhythmic effect may also be used.

[0045] Intrinsic physical-chemical properties mean the appearance of long-lasting physicalchemical properties in iterations that are quantitatively or qualitatively different from the physical -chemi cal properties of the initial artificial substance or neutral solvent.

[0046] The neutral carrier can be either a solvent, whose transformation results in iterations: water, aqueous-alcoholic solution, or solids - lactose or any pharmaceutically acceptable solvent or excipient.

[0047] An intact carrier / solvent is understood to be a neutral carrier / solvent, until the moment of vibration treatment.

[0048] The product obtained using the claimed method can be used in liquid or solid dosage form. Thus, for example, a product obtained using the claimed method can be used in solid dosage form and contains a technologically necessary (effective) amount of a neutral carrier saturated with iterations and pharmaceutically acceptable additives, which include, for example, lactose, microcrystalline cellulose, magnesium stearate and others. To obtain the solid oral form of the claimed drug in a fluidized bed unit (for example, the ‘Huttlin Pilotlab’ type manufactured by Huttlin GmbH), irrigation is performed until the granules of a neutral substance, lactose (milk sugar), introduced into the fluidized bed are saturated with a previously obtained aqueous or aqueous alcohol solution of iterations with simultaneous drying in the flow of heated air supplied under the grate at a temperature not exceeding 40 °C. The resulting tablet mass is evenly mixed and tableted by direct dry pressing (e.g., in tablet press Korsch XL 400) [W02007105981(A1), 09 / 20 / 2007], After tableting, tablets weighing 300 mg and impregnated with aqueous or aqueous-alcoholic solution of iterations are obtained. The figures below, together with the drawings attached, are offered to illustrate the present invention:

[0049] Fig. l. The scheme of the technology for obtaining iterations.

[0050] Fig. 2. Effect of vibrational iterations on physico-chemical properties of intact water. The values obtained for the studied samples were normalized to the values of intact water (control). The data are presented in relative units (mean ± SD). Brackets indicate statistically significant differences between the corresponding groups (p < 0.05).

[0051] The production of an artificial product is hereinafter described in more detail with reference to the enclosed Figure 1, which shows the scheme of the technology for obtaining iterations: The production of an artificial product (iterations) consists of several stages:

[0052] 1. A test tube with the initial artificial substance and a test tube with a neutral carrier (water) are placed close together and subjected to joint vibrational treatment using a vortex.

[0053] 2. The test tubes are then incubated at room temperature. Empirically, a minimum incubation time of 1 minute has been established as sufficient for obtaining iterations. In some cases, the incubation time can be reduced or skipped if the transformation of the neutral solvent into a material object (iteration) has been experimentally confirmed.

[0054] After stages 1 and 2, a change occurs in the physical properties of the solvent in the first test tube compared to the intact solvent.

[0055] The test tube with the neutral carrier (solvent), altered by the first vibrational treatment is called the ‘iteration zero’ of the substance (10).

[0056] 3. Then, 10 is placed close to a test tube with water (a new portion), and both test tubes are subjected to vibrational treatment and incubation at room temperature. As a result, the water in the second test tube also changes its properties and transforms into the first iteration of the substance (II).

[0057] 4. The described vibrational treatment procedure is repeated to obtain subsequent iterations from the previous ones — 12, 13,..., In iterations of the substance.

[0058] 5. Afterward, the stage of selecting the obtained iterations, which have separated into fractions after vibrational treatment.

[0059] Fractions that are potential candidates for the claimed product after vibrational treatment should differ in physical properties from the solvent. For practical purposes, it is sufficient to select candidates after obtaining a series of six iterations and choose two main groups that differ the most in physical properties, especially in their influence on the spectral characteristics of the initial artificial substance. It has been empirically established that these fractions also differ the most in biological and chemical properties, allowing for the selection of the most suitable iteration for a specific task. It is sufficient to use only one iteration from the entire series of obtained iterations or to mix several iterations of one fraction together.

[0060] Given the methods we use, the first six iterations (11-16) can only be divided into four fractions based on their physical characteristics, the ratio of which may vary for each initial substance, or one of the fractions may be absent. Technical terms proposed for the fractions are native, seminative, semi-active, and active.

[0061] 1. Native - Iterations that, according to conductometry (C) and radiometry (GHz) results, do not have significant changes in physicochemical properties compared to the intact neutral carrier (water) and, according to terahertz (Thz) spectroscopy (effect on initial artificial substance) and immunoassay (ELISA), do not possess modifying activity towards the initial artificial substance, i.e., C-, GHz-, THz-, ELISA.

[0062] 2. Semi-native - Iterations in which statistically significant changes in physicochemical properties were found compared to the intact neutral carrier (water), but like natives, do not possess modifying activity towards the initial artificial substance, i.e., C+ and / or GHz+, THz-, ELISA-.

[0063] 3. Semi-active - Iterations that do not have significant changes in physicochemical properties compared to the intact neutral carrier (water), but unlike natives, possess modifying activity towards the initial artificial substance, i.e., C-, GHz-, THz+ and / or ELISA+.

[0064] 4. Active - Iterations in which statistically significant differences in physicochemical properties were found compared to the intact neutral carrier (water) and which possess modifying activity towards the initial artificial substance, i.e., C+ and / or GHz+, THz+ and / or ELISA+.

[0065] Usually, the choice is made between the semi-native and active fractions, which are tested on the same biological or pharmacological experimental models to determine their activity, which in varying degrees of different fractions of iterations to exert a modifying effect on a body exposed to the physical factor.

[0066] Example 1. Iterations obtained using electric current and water as a neutral carrier.

[0067] To prepare the initial substance, 18 ml of purified water (water with resistivity of 18.2 m cm obtained using a Milli-Q Integral 5 water purification system (Merck, Darmstadt, Germany)) was added into a glass cuvette (Hellma Analytics, Mullheim, Germany, Cat. No. 704- 001-30-10). Flat electrodes made of AISI 304 stainless steel were placed along two opposite walls of the cuvette. The electrode area completely covered the wall of the cuvette. Next, a potential difference (sinusoidal waveform, 0.8V amplitude, and a frequency of 12.6Hz) was applied to these electrodes for 60 minutes. The specified eclectic signal was supplied using an analog output module (NI 9263, National instruments, USA) installed in a chassis (Chassis cDAQ™-9185, National instruments, USA). The installation was controlled by LabView software (National instruments, USA). After 60 minutes of electrical exposure, the initial substance was ready for the preparation of iterations.

[0068] The process of obtaining iterations included several stages. A vial with a capacity of 60 ml with the initial substance (electrically-treated water) in a volume of 50 ml and a vial with a capacity of 250 ml with purified water (neutral carrier) in a volume of 180 ml were rotated on a vortex for 10 seconds at 3000 rpm in close contact. After this, both vials were incubated for 1 minute at room temperature in close contact. Using the above-described procedure, 35 ml of Io (iteration 0) was obtained.

[0069] Next, a 40 ml vial with Io (35 ml) was placed adjacent to a new 40 ml vial with 35 ml of neutral carrier and vortexed for 10 seconds at 3000 rpm in close contact. Then both vials were incubated for 1 minute at room temperature in close contact. As a result, the vial with the neutral carrier was named Ii. Then the procedure for obtaining the next iteration (No. 2, No. 3, etc.) was repeated several times by joint vortexing of a vial with a new portion of neutral carrier and the previous iteration.

[0070] Type 1 (ultrapure) water with a resistivity of 18.2 mQ- cm (Milli-Q Integral 5, Millipore) was used as the neutral carrier for the preparation of iterations, as well as for all other reagents used in this work. The quality of purified water was monitored daily by measuring resistivity using a SevenCompact S230 conductivity meter (Mettler Toledo) and pH using a SevenCompact S220 pH meter (Mettler Toledo). For liquids, automatic pipettes of various volumes were used (Eppendorf, Germany; Socorex, Switzerland), as well as measuring glassware of accuracy class A (Borosil, India; Steklopribor, Ukraine). Dry reagents were weighed using an analytical balance of accuracy class I (Pioneer PA214C, Ohaus, USA). A calibrated laboratory timer (Traceable, VWR) was used to measure all incubation times. The vibration effect was carried out using an MS 3 basic shaker (vortex) (IKA-Werke, Germany) with a standard insert.

[0071] Temperature and humidity in the laboratory during sample preparation and subsequent measurements were monitored using a verified IVA-6N thermohygrometer; the temperature was 22±3°C, and the humidity was 20-70%. To prepare iterations, transparent borosilicate glass vials (40 and 60 ml, Glastechnik Grafenroda, Infochroma AG, Switzerland) or vials (100, 250, and 500 ml, Simax, Czech Republic) were used.

[0072] Each of the obtained iterations also has its own physical and chemical properties, determined in the following ways:

[0073] 1. Conductometry. To evaluate the physicochemical properties of a series of iterations, the conductometry method was used. To measure specific electrical conductivity (SEC), 10 ml of sample was taken into 15 ml vials and an electrode (Mettler Toledo, USA) was positioned so that the electrode membrane was completely immersed in the solution, after which the SEC was measured. In total, 12 iterations were obtained. Using the conductometry method, it was revealed that iterations No. 1, 3, 4, 6, 7, 12 have significant differences from the neutral carrier.

[0074] 2. Radiometry. The assessment of the iterations' intrinsic electromagnetic radiation was carried out using the radiometry method on a special installation, which consisted of a Faraday cage - an aluminum frame covered with a copper mesh. Inside the cage there was placed a tripod with a claw for attaching a detector, a thermal shaker (BIOSAN PST- 60HL-4) for heating the samples, and a TES-92 electromagnetic radiation (EMR) detector (TES Electrical Electronic Corp., Taiwan), which makes it possible to detect EMR flux density in the range from 1 pW / m2to 30.93 W / m2and frequency range from 50 MHz to 3.5 GHz. The measurement mode used was maximum average value (MAX AVG). The test sample (10 ml) was placed in a Petri dish, then the Petri dish with the sample was placed on a thermal shaker and the sample was heated to a temperature of 37±1°C. After this, the detector was placed above the sample at a distance of 0.5 cm, and the lid of the Petri dish was removed. The measurements were carried out with a closed Faraday cage. The measurement time was 10 minutes. After the time had elapsed, the maximum average value of the EMR flux density from the device display was recorded. Using the radiometric method, it was revealed that iterations No. 1, 3, 4, 6, 7, 12 have significant differences from neutral carrier.

[0075] 3. Terahertz spectroscopy. Analysis of changes in spectral characteristics in the terahertz region of the target molecule after adding iterations was carried out using a TeraView TeraPulse Lx terahertz spectrometer (England). To do this, 1 part (5 pL) of the iterations or neutral carrier was added to 99 parts (495 pl) of a solution of the substance, which is a specific target for the iterations under study, and the refractive and transmission spectra were recorded. To analyze the data, the coefficients of the equation of the well-known Debye function that describes the resulting spectra (Penkov N., Fesenko E. Development of terahertz time-domain spectroscopy for properties analysis of highly diluted antibodies. Appl. Sci. 2020; 10:7736. doi: 10.3390 / appl0217736.) and characterizes the dielectric constant in relaxation regions was used. Using terahertz spectroscopy, it was revealed that iterations No. 1, 2, 4, 7, 8, 10, 12 have significant differences from the neutral carrier in the value of the coefficients Asl (amplitude of the relaxation process Rl) or As2 (amplitude of the relaxation process R2).

[0076] Thus, using the above methods, the obtained I1-I12 (iterations No. 1 - 12) were divided into the following fractions: having altered physicochemical properties and exhibiting a modifying effect (II, 14, 17, 112); having altered physical-chemical chemical properties and not exhibiting a modifying effect (13, 16); not having altered physicochemical properties, but exhibiting a modifying effect (12, 18, 110); not having altered physicochemical properties and not exhibiting a modifying effect (15, 19, Il 1).

[0077] Since it is known that the basis of the functional activity of nervous and muscle tissue is electrical excitability, iterations prepared on the basis of eclectic treatment should exhibit specific activity in relation to electrically excitable tissues. The assessment of the specific activity manifested at the moment is carried out on the model of studying the electrical activity of nervous tissue.

[0078] Example 2. Iterations obtained using signal of electrical activity of the brain and water as a neutral carrier.

[0079] To prepare the initial substance, 18 ml of purified water (water with resistivity of 18.2 M0hm*cm obtained using a Milli-Q Integral 5 water purification system (Merck, Darmstadt, Germany)) was added into a glass cuvette (Hellma Analytics, Mullheim, Germany, Cat. No. 704- 001-30-10). Flat electrodes made of AISI 304 stainless steel were placed along two opposite walls of the cuvette. The electrode area completely covered the wall of the cuvette. Next, a potential difference was applied to these electrodes, which represented a signal of electrical activity of the brain (the signal was averaged over all channels of five EEG recordings, healthy volunteers), lasting 5 minutes, in the frequency range from 0 to 50 Hz. The specified eclectic signal was supplied using an analog output module (NI 9263, National instruments, USA) installed in a chassis (Chassis cDAQ™-9185, National instruments, USA). The installation was controlled by Lab View software (National instruments, USA). After 5 minutes of electrical exposure, the initial substance was ready for the preparation of iterations. The process of obtaining iterations included several stages. A vial with a capacity of 60 ml with the initial substance (water treated by signal of electrical activity of the brain) in a volume of 50 ml and a vial with a capacity of 250 ml with purified water (neutral carrier) in a volume of 180 ml were rotated on a vortex for 10 seconds at 3000 rpm in close contact. After this, both vials were incubated for 1 minute at room temperature in close contact. Using the above-described procedure, 35 ml of Io (iteration 0) was obtained.

[0080] Next, a 40 ml vial with Io (35 ml) was placed adjacent to a new 40 ml vial with 35 ml of neutral carrier and vortexed for 10 seconds at 3000 rpm in close contact. Then both vials were incubated for 1 minute at room temperature in close contact. As a result, the vial with the neutral carrier was named Ii. Then the procedure for obtaining the next iteration (No. 2, etc.) was repeated several times by joint vortexing of a vial with a new portion of neutral carrier and the previous iteration.

[0081] Type 1 (ultrapure) water with a resistivity of 18.2 mQ- cm (Milli-Q Integral 5, Millipore) was used as the neutral carrier for the preparation of iterations, as well as for all other reagents used in this work. The quality of purified water was monitored daily by measuring resistivity using a SevenCompact S230 conductivity meter (Mettler Toledo) and pH using a SevenCompact S220 pH meter (Mettler Toledo). For liquids, automatic pipettes of various volumes were used (Eppendorf, Germany; Socorex, Switzerland), as well as measuring glassware of accuracy class A (Borosil, India; Steklopribor, Ukraine). Dry reagents were weighed using an analytical balance of accuracy class I (Pioneer PA214C, Ohaus, USA). A calibrated laboratory timer (Traceable, VWR) was used to measure all incubation times. The vibration effect was carried out using an MS 3 basic shaker (vortex) (IKA-Werke, Germany) with a standard insert.

[0082] Temperature and humidity in the laboratory during sample preparation and subsequent measurements were monitored using a verified IVA-6N thermohygrometer; the temperature was 22±3°C, and the humidity was 20-70%. To prepare iterations, transparent borosilicate glass vials (40 and 60 ml, Glastechnik Grafenroda, Infochroma AG, Switzerland) or vials (100, 250, and 500 ml, Simax, Czech Republic) were used.

[0083] In this study Ii (iteration No. 1) was used (hereinafter referred to as Sample 1). The distribution of the obtained iterations into fractions was made as described in the Example 1.

[0084] The study was conducted on a model of haloperidol catalepsy, which is used to assess the antiparkinsonian potential of the Sample 1.

[0085] Sexually mature BALB / C male mice were divided into two groups (n=13 for Sample 1 and n=14 for Sample 2). Sample 1 (iteration No. 1) or Sample 2 (placebo) was administered orally daily for 5 days. The test was performed the day after the last administration of the drugs. Haloperidol was administered intraperitoneally at a dose of 0.1 mg / kg. 30, 60, 90 minutes after haloperidol administration, the severity of catalepsy was assessed using the “lecturer” pose: the mouse was placed against a horizontal rod fixed at a height of 4 cm with a diameter of 0.5 cm so that it rested on both front paws. The time the animal remained motionless was recorded (maximum 2 minutes). The total duration of catalepsy in each attempt was assessed. When working with animals, all generally accepted standards of experimental ethics were observed (Directive 2010 / 63 / EU of the European Parliament and of the council on the protection of animals used for scientific purposes, September 22, 2010).

[0086] The effectiveness of the experimental sample was assessed by its ability to change the duration of the effect of haloperidol, that is, by reducing the duration of maintaining the “lecturer” pose.

[0087] For statistical processing of the results, the normality of distribution was assessed using the Shapiro-Wilk test, and the homogeneity of variance was assessed using the Bartlett test. Groups were compared using the Kruskal-Wallis test, Dunn's test, and permutation test. Differences between groups were considered statistically significant at p<0.05.

[0088] The experiment showed that in the group with the introduction of the claimed drug, the duration of catalepsy increased more slowly and was lower than in control group (90 minutes after the start of the experiment - statistically significant) (see Table 1).

[0089] Table 1. Maximum duration of maintaining the “lecturer” pose (seconds) depending on the time after haloperidol injection (M±m).

[0090] Note: * - statistically significant differences from the placebo group.

[0091] Thus, the Sample 1 (iteration of water treated by signal of electrical activity of the brain) demonstrated the ability to suppress the cataleptic effect of haloperidol in mice, which may indicate an antiparkinsonian effect. Example 3. Iterations obtained using UV-treated water and water as a neutral carrier.

[0092] Type 1 purified water with a resistivity of 18.2 mOhmxcm (Purelab Option Q, Elga Labwater) was collected into a 2 -liter jar. Using a measuring cylinder, water from a 2-liter jar was transferred in a volume of 35 ml into a vial (or 100 ml into a jar), tightly closed with a lid and placed in a bactericidal chamber (Tecnal Scientific Equipments, USA). The chamber door was covered on the inside with thick fabric, which prevents the reflection of UV rays from the glass of the door. After placing the vial (or jar) centered inside the chamber, the UV lamp (wavelength 253.7 nm; located on the “ceiling” of the chamber) was turned on. Incubation of the vial (or jar) under UV radiation continued for 10 minutes. At the end of incubation, the vial (or jar) was removed from the chamber. Water irradiated in this way was used as an initial substance.

[0093] The process of obtaining iterations included several stages. A vial with a capacity of 40 ml with a freshly prepared stock solution of the initial substance in a volume of 35 ml and a vial with a capacity of 40 ml with purified water (neutral carrier) in a volume of 35 ml were rotated on a vortex for 10 seconds at 3000 rpm in close contact. After this, both vials were incubated for 1 minute at room temperature in close contact. Using the above-described procedure, 35 ml of iteration 0 (Io) was obtained.

[0094] Next, a 40 ml vial Io (35 ml) was placed adjacent to a new 40 ml vial with 35 ml of neutral carrier and vortexed for 10 seconds at 3000 rpm in close contact. Then both vials were incubated for 1 minute at room temperature in close contact. As a result, the vial with the neutral carrier was named Ii. Then the procedure for obtaining the next iteration (No. 2, No. 3, etc.) was repeated several times by joint vortexing of a vial with a new portion of neutral carrier and the previous iteration.

[0095] Temperature and humidity in the laboratory during sample preparation and subsequent measurements were monitored using a verified IVA-6N thermohygrometer; the temperature was 22±3°C, and the humidity was 20-70%. To prepare iterations, transparent borosilicate glass vials (40 and 60 ml, Glastechnik Grafenroda, Infochroma AG, Switzerland) or vials (100, 250, and 500 ml, Simax, Czech Republic) were used.

[0096] Type 1 (ultrapure) water with a resistivity of 18.2 mO- cm (Milli-Q Integral 5, Millipore) was used as the neutral carrier for the preparation of iterations, as well as for all other reagents used in this work. The quality of purified water was monitored daily by measuring resistivity using a SevenCompact S230 conductivity meter (Mettler Toledo) and pH using a SevenCompact S220 pH meter (Mettler Toledo). For liquids, automatic pipettes of various volumes were used (Eppendorf, Germany; Socorex, Switzerland), as well as measuring glassware of accuracy class A (Borosil, India; Steklopribor, Ukraine). Dry reagents were weighed using an analytical balance of accuracy class I (Pioneer PA214C, Ohaus, USA). A calibrated laboratory timer (Traceable, VWR) was used to measure all incubation times. The vibration effect was carried out using an MS 3 basic shaker (vortex) (IKA-Werke, Germany) with a standard insert.

[0097] In this study Ii-Ie (iterations No. 1-6) were used. The distribution of the obtained iterations into fractions was made as described in the Example 1.

[0098] The activity of the samples was tested on the A549 cell line. To evaluate the effect of aqueous iteration samples, they were added directly to the cell culture. A549 cells were cultured in 96-well plates (Coming-Costar, USA) in DMEM medium (Sigma- Aldrich, USA) for 24 hours (37°C, 5% CO2). The proportion of purified water samples (control) and aqueous iteration solutions (I1-L5) were 1 / 5 of the volume of the well (total volume in the well was 100 pl). On a separate plate, 1 column with A549 cells was incubated under the same conditions with the addition of purified water (intact water), the proportion of which was also 1 / 5 of the total volume of the well. After 24 hours, the plate with purified water samples (control) and aqueous iteration solutions (I1-L5) were placed in a chamber where it was exposed to UV radiation (253.7 nm) for 30 seconds. A plate with one column filled with A549 cells in the presence of purified water (intact water) at the same time was placed in a microbiological safety box for 30 seconds without any treatment. After 30 sec, both plates were incubated for 24 hours (37°C, 5% CO2). At the end of incubation, an MTT test was performed.

[0099] For MTT test, MTT reagents (Sigma-Aldrich, USA), DMEM medium (Sigma-Aldrich, USA), demethyl sulfoxide (DMSO, NeoFroxx, Germany), phosphate-buffered saline (PBS, Sigma-Aldrich, USA) were used. MTT stock solution was prepared by dissolving 0.05 g of dry reagent in 10 ml of sterile PBS with filtration through 0.2 pm syringe filters (Chromafil, Germany). The working solution was prepared immediately before use by adding 1 ml of MTT stock solution to 9 ml of DMEM medium. The medium from the wells was completely removed and replaced with MTT solution in a volume of 100 pl in each well, after which the plate was incubated for 2 hours, 37°C, 5% CO2. Then the plate was examined under a microscope, visually monitoring the formed formazan crystals. To dissolve the formed crystals, MTT solution was taken from the wells and DMSO was added in a volume of 100 pl to each well, after which the plate was incubated at room temperature for 10 minutes. Absorbance was measured using a Multiskan GO microplate reader (Thermo Fisher Scientific, USA) at wavelengths of 554 nm and 700 nm. The optical density values in each well were obtained according to the formula: OD = OD554-OD700.

[0100] The survival rate was calculated by finding the ratios of optical densities using the formula: A — ODsample / ODintact water (without exposure)-

[0101] The effect of samples on cell survival was assessed by the ratio of the optical densities of samples and control (intact water) after exposure to UV radiation: Dif = (ODsampie - Odcontroi (purified water (after UV)) / Odcontroi (purified water (after UV)-

[0102] For replicates within a group of one sample, the mean value, standard deviation, coefficient of variation, and assessment for outliers were calculated using Excel software (Microsoft, USA). Differences between groups were considered statistically significant at p<0.05.

[0103] The results of assessing the effect of Ii-Ie (iterations No. 1-6) on the survival of A549 cell line after UV irradiation are presented in Table 2.

[0104] Table 2. Survival of A549 cell line after UV irradiation.

[0105] *- p<0.05 compared to control.

[0106] Thus, we can conclude that the use of the iterations of UV-treated water affects the survival of A549 cell line after UV irradiation.

[0107] Example 4. Iterations obtained using water exposed to electromagnetic field and water as a neutral carrier.

[0108] To prepare the initial substance, 18 ml of purified water (water with resistivity of 18.2 mfi cm obtained using a Milli-Q Integral 5 water purification system (Merck, Darmstadt, Germany)) was exposure to electromagnetic field. The electromagnetic field was created by supplying direct (~41mA) and alternating current (~0.07mA, with frequencies of 6 and 12.6Hz) to a copper coil (675 mm long, 152 mm internal diameter, resistance ~ 13.2 Ohm, conversion factor ~ 1 .44 mT / A) inside which a cuvette with water (18 ml) was placed. The duration of preincubation was 60 minutes. Cubic optical glass cuvette (Hellma Analytics, Mullheim, Germany, Cat. No. 704-001-30-10) was used. When applying an electromagnetic field to water, the coil was placed in a three-layer permalloy container (ZG-209, Magnetic Shield, USA). After the electromagnetic field exposure, the initial substance was ready for the preparation of iterations.

[0109] The process of obtaining iterations included several stages. A vial with a capacity of 5 ml with a freshly prepared stock solution of the initial substance (water exposed to electromagnetic field) in a volume of 5 ml and a vial with a capacity of 40 ml with purified water (neutral carrier) in a volume of 35 ml were rotated on a vortex for 10 seconds at 3000 rpm in close contact. After this, both vials were incubated for 2 minute at room temperature in close contact. Using the above-described procedure, 35 ml of iteration 0 (Io) was obtained.

[0110] Next, a 40 ml vial with Io (35 ml) was placed adjacent to a new 40 ml vial with 35 ml of neutral carrier and vortexed for 10 seconds at 3000 rpm in close contact. Then both vials were incubated for 1 minute at room temperature in close contact. As a result, the vial with the neutral carrier was named Ii. Then the procedure for obtaining the next iteration (No. 2, No. 3, etc.) was repeated several times by joint vortexing of a vial with a new portion of neutral carrier and the previous iteration.

[0111] Type 1 (ultrapure) water with a resistivity of 18.2 mQ- cm (Milli-Q Integral 5, Millipore) was used as the neutral carrier for the preparation of iterations, as well as for all other reagents used in this work. The quality of purified water was monitored daily by measuring resistivity using a SevenCompact S230 conductivity meter (Mettler Toledo) and pH using a SevenCompact S220 pH meter (Mettler Toledo). For liquids, automatic pipettes of various volumes were used (Eppendorf, Germany; Socorex, Switzerland), as well as measuring glassware of accuracy class A (Borosil, India; Steklopribor, Ukraine). Dry reagents were weighed using an analytical balance of accuracy class I (Pioneer PA214C, Ohaus, USA). A calibrated laboratory timer (Traceable, VWR) was used to measure all incubation times. The vibration effect was carried out using an MS 3 basic shaker (vortex) (IKA-Werke, Germany) with a standard insert.

[0112] Temperature and humidity in the laboratory during sample preparation and subsequent measurements were monitored using a verified IVA-6N thermohygrometer; the temperature was 22±3°C, and the humidity was 20-70%. To prepare iterations, transparent borosilicate glass vials (40 and 60 ml, Glastechnik Grafenroda, Infochroma AG, Switzerland) or vials (100, 250, and 500 ml, Simax, Czech Republic) were used.

[0113] In this study U (iteration No. 6) was used (hereinafter referred to as Sample 1). The distribution of the obtained iterations into fractions was made as described in the Example 1. Sample 1, as well as the control (purified water) were tested for their ability to preactivate (prime) neutrophils. To test the priming effect, samples were preincubated with a neutrophil suspension for 20 minutes.

[0114] The study was performed on mouse peritoneal neutrophils. Peritoneal neutrophils, were isolated from male Balb / c mice weighing 24-26 g. To obtain cells, 150 pl of a zymosan suspension with a concentration of 5 mg / ml (Zymozan A from Saccharomyces carevisiae, Sigma, USA) was injected into the peritoneal cavity of the mice. After 12 hours, the animals were sacrificed by cervical dislocation and their peritoneal cavity was washed with 6 ml of chilled Hank's solution without calcium. The exudate was collected with a pipette and centrifuged for 5 min at 600 g. The supernatant was discarded, and the pellet was resuspended in 5 ml of calcium-free Hanks solution and left for 60 min at 4°C. The number of isolated cells was counted in a hemocytometer. Cell viability was determined using trypan blue.

[0115] The Sample 1 or control (200 pl) was initially prepared in water, and the addition of concentrated (5x) Hanks solution (50 pl) was required to create normotonic conditions. Next, a suspension of neutrophils (50 pl), which was previously prepared in Hanks’ normotonic medium, was added to the prepared normotonic mixture. Thus, the final concentration of neutrophils per sample for testing was ~1 million cells / sample in a total volume of 300 pl. The test sample was placed directly into a chemiluminescence measurement cuvette (plastic roundbottom tubes 55 by 12 mm, catalog number 55.484, Sarstedt, Germany). Then, samples were incubated at 37°C for 20 minutes, and chemiluminescence measurements were performed.

[0116] For the resulting cell suspensions, the maximum intensity of chemiluminescence was measured after adding a solution of luminol (Enzo Life Sciences, USA) to a final concentration of 0.35 mM, as well as the chemotactic formylated peptide N-formyl-Met-Leu-Phe (fMLF) (Sigma, USA) to a final concentration of 2 pM. Recording of chemiluminescence kinetics was carried out over a period of 5-10 minutes, although the maximum was reached less than a minute after the addition of fMLF. An LKB 1251 chemiluminometer (LKB, Sweden) was used to record chemiluminescence. To analyze the results (estimate the maximum intensity of chemiluminescence), MS Office Excel (15.0.5415.1000) was used.

[0117] It was shown that the ability of neutrophils to produce ROS increases after their incubation with Sample 1 by ~ 13% (p<0.02) compared to the effect of control (see Table 3). Table 3. Maximum chemiluminescence intensity (normalized).

[0118] Thus, it was established that iteration of water exposed to electromagnetic field is capable of influencing the production of ROS by neutrophils.

[0119] Example 5. Iterations obtained using water exposed to electromagnetic field and water as a neutral carrier.

[0120] To prepare the initial substance, 18 ml of purified water (water with resistivity of 18.2 m cm obtained using a Milli-Q Integral 5 water purification system (Merck, Darmstadt, Germany)) was exposure to electromagnetic field. The electromagnetic field was created by supplying direct (~41mA) and alternating current (~0.07mA, with frequencies of 6 and 12.6Hz) to a copper coil (675 mm long, 152 mm internal diameter, resistance ~ 13.2 Ohm, conversion factor ~ 1 .44 mT / A) inside which a cuvette with water (18 ml) was placed. The duration of preincubation was 60 minutes. Cubic optical glass cuvette (Hellma Analytics, Mullheim, Germany, Cat. No. 704-001-30-10) was used. When applying an electromagnetic field to water, the coil was placed in a three-layer permalloy container (ZG-209, Magnetic Shield, USA). After the electromagnetic field exposure, the initial substance was ready for the preparation of iterations.

[0121] The process of obtaining iterations included several stages. A vial with a capacity of 5 ml with a freshly prepared stock solution of the initial substance (water exposed to electromagnetic field) in a volume of 5 ml and a vial with a capacity of 40 ml with purified water (neutral carrier) in a volume of 35 ml were rotated on a vortex for 10 seconds at 3000 rpm in close contact. After this, both vials were incubated for 1 minute at room temperature in close contact. Using the above-described procedure, 35 ml of iteration 0 (Io) was obtained.

[0122] Next, a 40 ml vial with Io (35 ml) was placed adjacent to a new 40 ml vial with 35 ml of neutral carrier and vortexed for 15 seconds at 3000 rpm in close contact. Then both vials were incubated for 2 minutes at room temperature in close contact. As a result, the vial with the neutral carrier was named Ii. Then the procedure for obtaining the next iteration (No. 2, No. 3, etc.) was repeated several times by joint vortexing of a vial with a new portion of neutral carrier and the previous iteration. Type 1 (ultrapure) water with a resistivity of 18.2 mQ- cm (Milli-Q Integral 5, Millipore) was used as the neutral carrier for the preparation of iterations, as well as for all other reagents used in this work. The quality of purified water was monitored daily by measuring resistivity using a SevenCompact S230 conductivity meter (Mettler Toledo) and pH using a SevenCompact S220 pH meter (Mettler Toledo). For liquids, automatic pipettes of various volumes were used (Eppendorf, Germany; Socorex, Switzerland), as well as measuring glassware of accuracy class A (Borosil, India; Steklopribor, Ukraine). Dry reagents were weighed using an analytical balance of accuracy class I (Pioneer PA214C, Ohaus, USA). A calibrated laboratory timer (Traceable, VWR) was used to measure all incubation times. The vibration effect was carried out using an MS 3 basic shaker (vortex) (IKA-Werke, Germany) with a standard insert.

[0123] Temperature and humidity in the laboratory during sample preparation and subsequent measurements were monitored using a verified IVA-6N thermohygrometer; the temperature was 22±3°C, and the humidity was 20-70%. To prepare iterations, transparent borosilicate glass vials (40 and 60 ml, Glastechnik Grafenroda, Infochroma AG, Switzerland) or vials (100, 250, and 500 ml, Simax, Czech Republic) were used.

[0124] In this study mixture of Ii (iteration No. 1) and E (iteration No. 3) was used (hereinafter referred to as Sample 1). The distribution of the obtained iterations into fractions was made as described in the Example 1.

[0125] Sample 1, as well as control (purified water), were administered to male Balb / c mice (24-26 g) through an intragastric tube in an amount of 10 ml / kg once a day for 5 days. There were 10 mice each group.

[0126] Blood was collected by decapitation into a centrifuge tube with heparin, then diluted with saline to a volume of 1 ml, mixed by pipetting and centrifuged at 600 g for 5 minutes. The resulting supernatant was used to determine the concentration of IFNg. Measurements were performed using an ELISA kit for determining the IFNg concentration (RAB0222, Sigma Aldrich, USA). The optical density was measured at 405 nm with a microplate photometer Multi scan EX, (Thermo).

[0127] It was shown that the concentration of IFNg in the blood serum of mice increased by approximately 75% after administration of iteration No. 1 compared to the effect of the control (p<0.001) (see Table 4). Table 4. Concentration of IFNg in mouse blood serum (M±SD).

[0128] Thus, it was established that mixture of iterations (water exposed to electromagnetic field) is capable of influencing the production of cytokines in the blood serum of mice.

[0129] Example 6. Effect of vibrational iterations of magnetized water on the physicochemical properties of intact water.

[0130] Materials and methods

[0131] Preparation of the initial substance

[0132] To obtain the initial substance for the preparation of vibrational iterations, a shielded magnetic installation was used comprising a chamber shielding an external magnetic field (MuMETAL® Zero Gauss Chamber ZG-209, Magnetic Shield Corporation, USA), a copper solenoid with a double-layer winding (PETV-2 wire, tZ=8mm, and the length of each winding was 675 mm), a waveform generator (3351 IB, Keysight Technologies, USA), and a DC power supply (E36312A, Keysight Technologies, USA). 250 mL of ultrapure water was added into a bottle made of transparent borosilicate glass (250 mL, Simax, Czech Republic) using a measuring cylinder. Then the bottle was placed inside the chamber of the magnetic installation and exposed for one hour to the following selected magnetic field types:

[0133] - Static magnetic field 60 pT (hereinafter referred to as SMF),

[0134] - Combined magnetic field with a static component of 60 pT and an alternating component of 50 nT at 12.6 Hz (hereinafter referred to as CMF),

[0135] - Hypomagnetic field of about 10-20 nT (hereinafter referred to as HMF).

[0136] Preparation of vibrational iterations

[0137] The vibrational iterations of magnetized water were prepared using technology described in Example 1, but Magnetized water (the initial substance: SMF-, CMF-, or HMF- exposed water) and intact water as a neutral carrier were used. A bottle made of transparent borosilicate glass (250 mL) with neutral carrier (ultrapure water) in a volume of 200 mL in close contact with the bottle with the initial substance (magnetized water) was vibrated on a vortex for 10 s at 3000 rpm (MS 3 basic with the MS 1.21 platform, IKA-Werke, Germany). Next, both bottles were incubated for 1 min at room temperature, keeping them in close contact. As a result of the above treatment, 200 mL of vibrational iteration zero was obtained (hereinafter referred to as 10). To obtain the first vibrational iteration (II), the bottle with vibrational iteration 10 was placed next to the bottle with the neutral carrier in a volume of 200 mL and subjected to joint (in close contact) vibration treatment on the vortex for 10 s at 3000 rpm. Then both bottles were incubated for 1 min at room temperature, keeping them in close contact. After this procedure, the resulting neutral carrier was considered to be the first vibrational iteration of the initial substance (II). Then the subsequent vibrational iterations (up to 17) were obtained from each previous one. Samples from 10 to 17 comprised a row of vibrational iterations. All vibrational iterations of water exposed to the magnetic field of a certain type were prepared on the same day. The temperature and humidity in the laboratory during sample preparation and subsequent measurements were monitored using a verified IVA-6N thermohygrometer (NPK MICROFOR LLC, Russia). During the experiment, the humidity in the room was 45-50%, and the temperature was 24.5 °C. Ultrapure water (type 1) with a resistivity of 18.2 MQ- cm (Milli-Q Integral 5, Millipore, France) was used as a neutral carrier for the preparation of the vibrational iterations and as a control. Automatic pipettes of various volumes (Eppendorf, Germany; Socorex, Switzerland) and measuring glassware of accuracy class A (Borosil, India; Steklopribor, Ukraine) were used for sampling liquids. A calibrated laboratory timer (Traceable, VWR, Germany) was used to measure the incubation time of water in a magnetic field.

[0138] In this study, three types of samples were examined (Table 5.):

[0139] Table 5.

[0140] Methods of analysis

[0141] The selected vibrational iterations, as well as water exposed to the corresponding magnetic field, were added to intact water in a volume ratio of 1:9, after which the resulting mixtures were analyzed with conductometry, radiometry, and THz spectroscopy. Intact water was used as a control. The results are shown in Fig. 2.

[0142] Statistical analysis

[0143] Statistical data processing was carried out in the R Studio software (2023.09.1 Build 494 © 2009-2023, R Foundation for Statistical Computing, Vienna, Austria) using the R package version 4.2.2. The data were tested for normality of the distribution using the Shapiro- Wilk test and for homogeneity of the variances by the Bartlett test. For Fig. , the groups were compared using the Student / Welch t-test with Holm’s correction for multiple comparisons. The differences between the groups were considered significant at p < 0.05.

[0144] Results

[0145] The introduction of water samples exposed to each field (i.e. the initial substances) into intact water caused a change in the physico-chemical properties of the resulting mixture compared with intact water (compare grey and white bars in Fig. 2).

[0146] The magnitude of changes (15-40%) depends on the magnetic field type used for water magnetization. The introduction of the vibrational iterations into intact water also caused changes in the physico-chemical properties of the resulting mixtures compared to intact water (compare blue and pink bars with white bars in Fig. ). Moreover, the magnitude of changes depends on the type of magnetic field used to prepare the vibrational iterations as well as on the fraction to which the vibrational iteration belongs. Thus: - The Semi-native fraction of vibrational iterations of SMF -water (10) increased the specific electrical conductivity by 22% and the radiation flux (EMR flux density) by 21%. The Active fraction of vibrational iterations of SMF -water (16) increased the dielectric permittivity (As2) by 24%.

[0147] - The Native fraction of the vibrational iterations of CMF -water (10) increased the dielectric permittivity (As2) by 12%.

[0148] - The Active fraction of the vibrational iterations of CMF-water (17) decreased the specific electrical conductivity by 21%.

[0149] - The Native fraction of the vibrational iterations of HMF -water (14) decreased the specific electrical conductivity by 5% and increased the radiation flux (EMR flux density) by 20%. The Active fraction of the vibrational iterations of HMF -water (13) decreased the electrical conductivity by 11% and increased the radiation flux (EMR flux density) by 27%.

[0150] Conclusions

[0151] The study of the vibrational iterations of magnetized water has shown that they differ from each other in physico-chemical properties. They also change physico-chemical properties and THz characteristics of intact water, i.e. have a modifying effect on intact water.

[0152] Example 7. Effect of vibrational iterations of electrically activated water on the physico-chemical properties of intact water

[0153] Materials and methods

[0154] Preparation of the initial substance

[0155] To obtain water that underwent the electrochemical activation procedure (ECA water), a device for processing solutions with an electric signal was used. The installation is a hardware and software complex that consists of an arbitrary waveform generator (NI 9263, National Instruments, USA) and a measuring module (NI 9215, National Instruments, USA) mounted in a chassis (cDAQ-9185, National instruments, USA). The installation is running LabVIEW software (National Instruments, USA). The water incubation period was monitored using a laboratory timer (VWR® Traceable®, Germany).

[0156] 18 ml of purified water was added to the optical glass cuvette (cat. no. 704-001-30-10, Hellma Analytics, Germany). Two plate electrodes made of AISI 304 stainless steel were placed along the two opposite walls of the cuvette (from the inside). The electrode area completely covered the corresponding cuvette wall. Then, for 60 minutes, a potential difference with the following parameters was applied to the plate electrodes: • Constant electrical signal with a voltage of 0.8 V;

[0157] • Sinusoidal electrical signal with a voltage of 0.8 V and a frequency of 12.6 Hz;

[0158] • A constant electrical signal with a voltage of 8 V;

[0159] • Sinusoidal electrical signal with a voltage of 8 V and a frequency of 12.6 Hz;

[0160] • An electrical signal with a voltage of 0 V (i.e., where the electrical signal generator is turned off).

[0161] Thus, 5 types of EC A- water samples were obtained.

[0162] Preparation of vibrational iterations

[0163] Vibrational iterations were prepared from each type of ECA-water obtained in accordance with the parameters of the electrical signals applied to the electrodes (i.e., 5 different series of vibrational iterations were obtained from 5 types of ECA-water samples). Transparent borosilicate glass vials (250 ml, Simax, Czech Republic) were used to prepare the rows of vibrational iterations. The method of preparation of vibrational iterations is presented below.

[0164] • ECA-water in a volume of 18 ml was placed in a borosilicate glass vial. Then 180 ml of intact water (neutral carrier) was added to another similar vial. The filled vials were placed close to each other and subjected to joint vibration on a vortex (MS 3 basic with MS 1.21 platform, IKA-Werke, Germany) for 10 seconds at 3000 rpm, after which they were left to incubate for 1 min at room temperature (24.5 °C). As a result, 180 ml of vibrational iteration zero was obtained in a vial with intact water (hereinafter 10).

[0165] • To obtain vibrational iteration No. 1 (II), a vial with 180 ml of vibrational iteration 10 was placed adjacent to another borosilicate glass vial with intact water (neutral carrier) in a volume of 180 ml and subjected to joint (with close contact) vibration action on a vortex for 10 seconds at 3000 rpm, after which was left to incubate for 1 min at room temperature. As a result, 180 ml of vibrational iteration 11 was obtained in a vial with intact water.

[0166] • The above steps were repeated in the same way to obtain vibrational iterations up to 17. Samples from 10 to 17 made up a row of iterations.

[0167] Vibrational iterations of ECA-water were prepared on the same day at room temperature. If the properties of vibrational iterations or mixtures containing them were studied not on the day of preparation, then on the day of analysis of the vibrational iterations, they were processed once on a vortex for 10 seconds at 3000 rpm. Before preparing the mixtures with EC A- water, it was subjected to repeated exposure to an electric signal for 1 hour at the same parameters that were used initially.

[0168] Tested samples

[0169] In accordance with the purpose of the work, the vibrational iterations of ECA-water, their mixtures with intact water (to assess their post-vibrational activity in relation to intact water) were studied. To perform water EC A, voltages of less than 0.8 V and more than 8 V were selected, which exceeds the threshold of water electrolysis, which is about 1.5-2.0 V. The electrical effect was carried out by both constant and sinusoidal signals. The frequency of the sinusoidal signal was 12.6 Hz, which corresponds to the frequency of ion cyclotron resonance of water (12.6 Hz). Thus, 2 groups of samples were prepared.

[0170] Group 1. Vibrational iterations of ECA-water:

[0171] • Vibrational iterations of water to which a constant electrical signal with a voltage of 0.8 V was applied (hereinafter referred to as vibrational iterations of "ECA-water 0.8 V");

[0172] • Vibrational iterations of water to which a sinusoidal electrical signal with an amplitude of 0.8 V and a frequency of 12.6 Hz was applied (hereinafter referred to as vibrational iterations of "ECA-water 0.8 V, 12.6 Hz");

[0173] • Vibrational iterations of water to which a constant electrical signal with a voltage of 8 V was applied (hereinafter referred to as vibrational iterations of "ECA-water 8 V");

[0174] • Vibrational iterations of water, to which a sinusoidal electrical signal with an amplitude of 8 V and a frequency of 12.6 Hz was applied (hereinafter referred to as vibrational iterations of "ECA-water 8 V, 12.6 Hz");

[0175] • Vibrational iterations of water previously placed in a cuvette for electrical treatment, but in the absence of voltage applied to the cuvette electrodes (hereinafter referred to as vibrational iterations of "ECA-water 0 V").

[0176] Group 2. Mixtures of vibrational iterations ECA-water with intact water in a volume ratio of 1 : 9 and control:

[0177] • Vibrational iterations of ECA-water 0.8 V + intact water;

[0178] • Vibrational iterations of ECA-water 0.8 V, 12.6 Hz + intact water;

[0179] • Vibrational iterations of ECA-water 8 V + intact water;

[0180] • Vibrational iterations of ECA-water 8 V, 12.6 Hz + intact water;

[0181] • Vibrational iterations of ECA-water 0 V + intact water; Control (mixture of "intact water + intact water").

[0182] Conductometry, radiometry, and THz spectroscopy

[0183] The properties of the samples were studied by conductometry (determination of electrical conductivity) and radiometry (measurement of radiation power flux density). The study by THz spectroscopy (determination of the dielectric constant, i.e. the contribution of the main (Debye) relaxation process in the overall dielectric response) was carried out in two ways:

[0184] 1) Mixing 1 part of the test sample (control or vibrational iterations of EC A- water) with 99 parts of intact water;

[0185] 2) Mixing 1 part of the test sample (control or vibrational iterations ECA-water) with 9 parts of intact water.

[0186] 9 measurements of samples were carried out by conductometry, at least 6 by radiometry, and at least 10 measurements were made by THz spectroscopy.

[0187] In this work, vibrational iterations were analyzed using intact water as a control, classified into 4 groups (fractions) by their unique physico-chemical properties, as well as by their ability to influence physico-chemical properties of intact water (the so-called "modifying effect") (Table_6). These 4 types of fractions were named "Active", "Native", "Semi-active" and "Semi-active".

[0188] Table 6. Note: the test result was considered positive (“+”) if it met the acceptance criteria. Otherwise, the result was taken as negative The acceptance criteria: the values obtained for vibrational iterations should statistically significantly (p < 0.05) differ from those of intact water by ±5% or more (by conductometry and THz spectroscopy) and by +10% or more (by radiometry). The values obtained for intact water were taken as 100%.

[0189] To study the effects of vibrational iterations on intact water the following vibrational iterations were selected:

[0190] • From a row of vibrational iterations of "EC A- water 0V": 15 (Active), 13 (SemiNative);

[0191] • From a row of vibrational iterations of "ECA-water 0.8 V": 14 (Active), 10 (Native);

[0192] • From a row of vibrational iterations of "ECA-water 0.8 V, 12.6 Hz": 11 (Active), 16 (Semi -Native);

[0193] • From a row of vibrational iterations of "ECA-water 8 V": 17 (Active), 14 (SemiNative);

[0194] • From a row of vibrational iterations of "ECA-water 8 V, 12.6 Hz": 11 (Active), 17 (Semi -Native).

[0195] Dynamic light scattering

[0196] The light scattering intensity was determined in the studied solutions and the distribution of the hydrodynamic diameters of optical heterogeneities in the range of 50-200 nm was obtained using a Photocor Compact-Z analyzer (Fotokor LLC, Russia). The analyzer is equipped with a semiconductor thermostatbilized continuous laser with k = 638 nm (maximum power 80 MW) with a thermostatic cell (25 = 0.1 °C). The signals were recorded for 20 seconds, and the number of accumulated signals was 10 with at least 10 measurements of each sample. To establish the diameters of the particles according to the Stokes-Einstein equation, the water viscosity was taken as 0.89 MPa s. The size distributions were calculated using the DynaLS software, version 2.8.3 (Alango, Israel) supplied with the device.

[0197] Determination of the attenuation coefficient of the electrical signal transmitted through the studied sample (oscillography)

[0198] 18 ml of a mixture of "vibrational iterations of ECA-water (group 1) + intact water" (group 2) in a volume ratio of 1 :9 was poured into a clean cuvette of the electrical signal processing device and electrodes were immersed in it. Next, an electrical signal was provided, the parameters of which coincided with the parameters of the signal used to prepare the ECA- water; the duration of exposure to the electric signal was 3 min. The procedure was repeated 5 times. In all cases (for both constant and alternating (sinusoidal) signals to the plate electrodes ("-" electrode and "+" electrode), the cuvettes were connected to an arbitrary waveform generator NI 9263 (National Instruments, USA). The signal was recorded using the module NI 9215 (National Instruments, USA), from which two oscillograms were synchronously obtained: one between the plate electrodes, and the second between one plate electrode and an additional needle electrode, which is located at the center. At the same time, the voltage attenuation coefficient of the applied signal was estimated:

[0199] • the attenuation coefficient for constant signals was calculated as the ratio of the average potential difference between the central and plate negative electrodes of the cuvette to the average potential difference between the plate negative and positive electrodes of the cuvette;

[0200] • the attenuation coefficient for variable (sinusoidal) signals was calculated as the ratio of the average amplitude of the potential difference between the central and plate electrodes of the cuvette to the average amplitude of the potential difference between the plate electrodes of the cuvette.

[0201] Statistical analysis

[0202] Statistical data processing was performed in the RStudio 2023.09.1+494 software (© 2009-2023 R Foundation for Statistical Computing, Vienna, Austria) using the R package version 4.2.2. The normality of the distribution was evaluated using the Shapiro-Wilk test, and the homogeneity of the variances was evaluated using the Bartlett test. The groups were compared using the Student-Welch t-test and the Kruskal-Wallis test, followed by the Dann test. The differences between the groups were considered statistically significant at p < 0.05.

[0203] Results

[0204] It has been shown that different vibrational iterations have different effects on intact water (Table 7). Table 7. Changes in the physico-chemical properties of intact water after addition of vibrational iterations of ECA-water in 1 :9 ratio.

[0205] Note: * statistically significant differences from intact water, p < 0.05. $ - control measurements ("intact water + intact water") were carried out on the day of the study of the corresponding iteration ("vibrational iterations of the ECA-water (group 1) + intact water"). The data are normalized to the corresponding values obtained for intact water. The values are represented as Mean ± SD.

[0206] The magnitude and direction of the changes depended on the characteristics of the electrical signal used to prepare the initial substance of the vibrational iterations. Thus, each studied vibrational iteration caused changes in the radiation power of tested mixtures: both studied fractions of iterations obtained from the substance "ECA-water 0.8 V" reduced the radiation power, and vibrational iterations obtained from other substances increased this parameter. It can also be seen from Table that mixtures of intact water with both fractions from a row of vibrational iterations "ECA-water 0.8 V", vibrational iterations "ECA-water 0.8 V, 12.6 Hz" and vibrational iterations "ECA-water 8 V" have a lower scattering intensity than a similar control mixture, whereas as a mixture of intact water with Semi-native fraction of vibrational iterations "ECA-water 0 V" has a high scattering intensity. A similar (but not fully corresponding) situation was observed with the size of optical heterogeneities: mixtures of intact water with both fractions of vibration iterations "EC A- water 0.8 V" and "ECA-water 0.8 V, 12.6 Hz", as well as with Active fraction of vibrational iterations "ECA-water 8 V, 12.6 Hz" and Semi-Native fraction of vibrational iterations "ECA-water 0 V" contain optical heterogeneities of a smaller size than the control, whereas mixtures of intact water with Semi-Native fraction of vibrational iterations "ECA-water 8 V" and "ECA-water 8 V, 12.6 Hz" contain optical heterogeneities of a larger size than the control.

[0207] The electrical conductivity of the mixtures decreases with the addition of both fractions from the series of vibrational iterations "ECA-water 0.8 V" and "ECA-water 8 V".

[0208] The signal intensity attenuation coefficient (according to oscillography data) decreased under the action of both fractions from a row of vibrational iterations of "ECA-water 8 V, 12.6 Hz" and increased under the action of the Active fraction of vibrational iterations "ECA-water 0.8 V, 12.6 Hz".

[0209] It is important to note that the Active, Native and Semi-Native fractions of vibrational iterations of ECA-water obtained by any electrical treatment (0.8 V; 0.8 V, 12.6 Hz; 8 V; 8 V, 12.6 Hz) in studied mixtures with intact water (1 : 9) have no effect on the value of the dielectric constant de i of the resulting mixture compared with the control (Table ). However, the value of ds i of a mixture of intact water with both Active and Semi-Native fractions of vibrational iterations of "ECA-water 0 V" increased.

[0210] Conclusions

[0211] 1. The study of vibrational iterations of ECA-water has shown that they follow the general pattern of post-vibration activity, and they can be classified into fractions that differ from each other in physico-chemical properties. The obtained result indicates the universality of the vibration treatment mechanisms, that is, the possibility of their implementation regardless of the nature of the initial substance.

[0212] 2. The use of an electrical signal with a constant voltage of 0.8 V for the preparation of the initial substance makes it possible to obtain a wide variety of fractions of vibrational iterations. Using an electrical signal with a constant voltage of 8 V or an alternating voltage of 8 V, 12.6 Hz allows you to obtain a larger number of vibration iterations related to the Semi-Native fraction. This result emphasizes that the mechanisms of formation of post- vibrational activity are sensitive to the magnitude and nature of external influences, which may indicate their plasticity.

[0213] 3. Adding vibrational iterations of ECA-water in the volume ratio 1 :9 to intact water leads to a change in physico-chemical parameters of intact water. The magnitude of differences depends on the parameters of the electrical signal used to generate ECA-water.

Claims

Claims1. A method of obtaining a drug, which is an artificial material object - iteration, modifying effect of external physical factors on the organism, by successive external vibration treatment of a neutral carrier and a product of vibration treatment of a neutral carrier with a physical factor.

2. A method according to claim 1, wherein the modifying effect consists in a protective effect, i.e., a weakening of the physical factor impact on the organism, and is provided by selecting the appropriate task of the fraction of the physical factor iterations.

3. A method according to claim 1, wherein the modifying effect consists in an enhancement of the physical factor impact on the organism and is provided by selecting the appropriate task of the fraction of the physical factor iterations.

4. A method according to claim 1, wherein the physical factor is selected from temperature exposure, radiation, sound exposure, and field exposure.

5. A method according to claim 3, wherein radiation includes laser, ionizing, thermal, electromagnetic radiation.

6. A method according to claim 3, wherein the fields include an electric, magnetic field.

7. A method according to claim 1, wherein the successive vibration treatment is a process including a) external vibration treatment of test tubes containing a neutral carrier processed with a physical factor and a neutral carrier, with obtaining from the neutral carrier the primary artificial object, ‘iteration zero’; b) external vibration treatment of the previous iteration and neutral carrier to obtain from the neutral carrier the subsequent iteration;8. A method according to claims 1, 7, wherein the neutral carrier is water or an aqueous- alcoholic solution, lactose or a pharmaceutically acceptable carrier.

9. A method according to claim 7, wherein the vibration treatment may be horizontal or vertical mechanical shaking.

10. A method according to claim 7, wherein the vibration treatment is accomplished by electromagnetic, ultrasonic, acoustic effect or other rhythmic physical effects.

11. A method according to claim 7, wherein a neutral carrier processed with a physical factor is a neutral carrier exposed to a physical factor.12 An artificial object obtained using the method according to claim 1, which is a neutral carrier subjected to vibration treatment in the presence of neutral carrier processed with a physical factor or a preceding iteration, having protective effect.

13. A method for obtaining a fraction of a product obtained using the method according to claim 1, having specific activity, including:1) preliminary separation of the obtained iterations into fractions depending on the physical -chemi cal properties they acquire after vibration treatment, which are different from the properties of neutral carrier,2) determination of specific modifying activity for each fraction using standard methods.

14. A method according to claim 13, wherein the physical-chemical properties are evaluated using generally accepted analytical methods.

15. A method according to claim 13, wherein the separation into fractions is based on the presence of physical-chemical properties altered compared to the neutral carrier.

16. A method according to claim 13, wherein the determination of specific activity is accomplished by determining the biological (pharmacological) activity of the fraction using methods generally accepted in experimental biology.

17. A method according to claim 14, wherein the analytical method is any generally known validated analytical method for determining physical-chemical properties of the substance.

18. A method according to claim 17, wherein the evaluation of specific electrical conductivity (SEC), radiometry, terahertz spectroscopy, immunoassay (ELISA), pH measurement, determination of the amount of dissolved oxygen, dynamic light scattering, high- resolution thermography is selected as the analytical method.

19. A method according to claim 13, wherein iterations for further experimental determination of the biological (pharmacological) action are selected from two fractions that markedly differ in their physico-chemical properties both from the neutral carrier and from each other - in the presence or absence of a modifying effect on the organism.

20. A drug product containing a drug obtained using the method according to claim 1, exerting protective effect on the body against external physical factors.

21. A drug product according to claim 20, wherein the physical factor is selected from temperature exposure, radiation, sound exposure, and field exposure.

22. A drug product according to claim 21, wherein radiation includes laser, ionizing, thermal, and electromagnetic radiation.

23. A drug product according to claim 21, wherein the fields include an electric, and magnetic field.

24. A drug product according to claim 20, wherein the organism is an animal or human body.

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