Artificial substance and method of its preparation

Abstract

The present invention relates to the field of pharmaceuticals, namely to method of obtaining a product, which is a series of processed solvents, possessing an activating or suppressing effect on various physicochemical or biological processes involving the initial substance using for product obtaining or molecular target associated with it, by multiple successive external vibration treatment of the initial substance, to a product obtained by this method and separation of the product into fractions, constitutes a one or more processed solvent, possessing intrinsic physicochemical properties and regulates the physicochemical and biological processes involving the initial substance or its target molecule.

Description

Artificial substance and method of its preparation

[0001] This invention relates to the field of pharmaceutics, namely, to a method for preparation of a product possessing a biological activity due to an activating or suppressing effect on various physicochemical or biological processes involving the initial substance used for product preparation, or its molecular target.

[0002] 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],

[0003] It is also known from the prior art that molecular information in ultra- highly diluted liquid (UHD signal) not only modifies the water in which the initial substance was diluted, but also can be transferred to other liquids without any contact between donor solution and recipient solution [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—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], The transfer of the UHD signal from UHD solutions to the recipient liquid has been shown, where a biologically active molecule of antibodies to interferon-gamma (IFN-gamma) was used as a molecular source in solutions [Igor Jerman, Linda Ogrizek, Vesna Pericek Krapez and Luka Jan, Physicochemical study of the molecular signal transfer of ultra-high diluted antibodies to interferon gamma. Int. J. Mol. Sci. 2023, 24], The ability of UHD to exert a distant effect was demonstrated, namely the ability to exert a modifying effect on IFN-gamma and on the solvent at a small distance of 1 to 1.5 cm [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.2020.624779; Penkov N., 2021; Novikov V.V. and Yablokova E.V., 2022).]

[0004] The technology of obtaining ultra-high dilutions by method of serial dilution in combination with controlled rhythmic influence is also known. This technology has been validated, the standard for preparing UHD was included in the Pharmacopoeia (see Pharmacopoeia XV, GPM 1.7.0001), and the terms of gradual technology and gradualized products became officially recognized. Processed dilutions of various substances, representingthe sum (mixture) of previous dilutions, acquire a special common property of exerting a direct modifying effect on the structure of the initial substance, causing conformational changes in the initial substance, which are ultimately accompanied by modification of the substance’s inherent physicochemical and biological properties [WO2012017324, US7,229,648, US4,311,897, RU2192888, 2577137, 2577136, 2536230, 2519695, 2778521, 2509572, 2531048, 2517085, 2505312, 2577299],

[0005] The author of the invention found out that as a result of vibration influence and joint incubation of the initial substance without multiple dilution (transfer of a part of the previous dilution to the subsequent one) makes it possible to obtain products (artificial substances) that have a modifying effect and exhibit biological activity. The author also developed a method for separating the obtained products into fractions possessing inherent modified physicochemical properties, including, among others, a specific modifying effect on the initial substances from which they were obtained. The obtained fractions also exert pharmacological and biological activity.

[0006] This invention had a technical purpose of developing a product exhibiting biological activity, and separating the obtained product into fractions possessing a biological efficacy determined by the initial substance and the target molecules associated with it.

[0007] The claimed invention’s technical solution consists in developing a method of obtaining a product (artificial substance) that possesses a biological (therapeutic) activity and includes multiple successive external vibration treatment of vials with activated initial substance or a processed solvent and a neutral solvent, optionally followed by incubation of vials in close contact to each other. The technical solution also consists in separating the obtained product into fractions by evaluating their physicochemical properties and / or determination of their modifying action on target molecules predetermined by the initial substance and assessed by known analytical methods [RU2643934, 2643936], The method of obtaining a product, which is a series of processed solvents - iterations, possessing an activating or suppressing effect on various physicochemical or biological processes involving the initial substance used for product obtaining or molecular target associated with this initial substance, by multiple successive external vibration treatment of the initial substance. Multiple successive external vibration treatment of the initial substance is a process including: a) external vibration treatment of vials containing the initial substance and neutral solvent to obtain form neutral solvent the first processed solvent (artificial object) - iteration zero; b) external vibration effect on vials containing the previous iteration and neutral solvent to obtain from neutral solvent the processed solvent - subsequent iteration;c) successive multiple repetitions of step b) using the processed solvent obtained at the previous step and a neutral solvent to obtain a series of processed solvents representing the final product.

[0008] A product which is a series of processed solvents - iterations, obtained by the method possessing an activating or suppressing effect on various physicochemical or biological processes involving the initial substance used for product obtaining or molecular target associated with this initial substance.

[0009] The processed solvents (hereinafter referred to as ‘iterations’) obtained as a result of external vibration treatment of vials containing a neutral solvent and the activated initial substance or a previously obtained in the same way another processed solvent exert biological and / or chemical activity, including a modifying effect characteristic of gradualized products. Depending on the exerted physicochemical properties and modifying effect assessed by known analytical methods, the iterations can be separated and classified into fractions, where each fraction possessing a specific set of measured properties by which they differ from the neutral solvent. In addition to their biological and / or chemical activity, determined by the initial substance and the target molecules associated with it, the obtained fractions can exert a modifying action aimed at one or more initial substances and / or target molecules, and can exert a distant action by modifying the physicochemical properties of the initial substances and / or its molecular target in a similar way as highly diluted substance solutions (gradualized products).

[0010] A "fraction ’ (artificial substance or artificial material object) is understood to be a processed solvent (iteration), wherein each fraction has modified physicochemical properties and / or exhibits a modifying action directed at a target molecule predetermined by the initial substance, or a combination of modified physicochemical properties and modifying action on the initial substance and the target molecule. Fraction constitutes one or more processed solvent - iterations.

[0011] The fraction has biological activity determined by the initial substance and the chemical, biological and physical processes involving this initial substance, since the fraction possessing specific physicochemical properties regulates (by activating or suppressing) the physicochemical and biological processes involving the initial substance or its target molecule. The fraction regulates processes that are carried out in different phases of these processes.

[0012] The claimed invention presents a method for obtaining the product, including:

[0013] obtaining an activated initial substance by external multiple successive vibration pre-treatment in a horizontal or vertical direction (mechanical shaking on platform) of adjacent vials with initial substance 1 and initial substance 2 for 10 seconds to 10 minutes,producing activated initial substance 1 in one vial and activated initial substance 2 in the other vial.

[0014] obtaining the first processed solvent (iteration) by joint preliminary external vibration treatment in a horizontal or vertical direction (mechanical shaking on platform) of two adjacent vials with activated initial substance or a neutral initial substance and a intact neutral solvent, for 10 seconds to 10 minutes, obtaining the processed solvent - iteration 1 (II).

[0015] Subsequently, multiple successive activations are performed using the previous processed solvent (iteration) and a neutral solvent to obtain a next iteration and then a series of processed solvents - iterations.

[0016] The method for preparing of iterations can also be accompanied by incubation of the vials with the initial substance / activated initial substance / processed solvent and neutral solvent at a small distance for 1 minute to 24 hours at room temperature, after external vibration influence. ‘Incubation’ refers to the process of holding the tubes together for a period of time.

[0017] The resulting series of iterations can be used both in a mixture, exhibiting biological or chemical effect, including the modifying action characteristic of gradualized products, or be separated into fractions having inherent physicochemical properties and biological and / or chemical activity.

[0018] A series of iterations can be obtained from an individual activated initial substance, a neutral initial substance, or from a combination of initial substances.

[0019] The time of external vibration treatment and incubation depends on the amount of initial substance and solvent and is selected from the specified range individually in each specific case. Test tubes and vials are placed next to each other, closely or at a distance.

[0020] The present invention can also be implemented as follows:

[0021] Technological processing by successive multiple dilutions of the initial substances by gradually decreasing the concentration as a result of successive dilution of 1 part of stock solution of the initial substance in 9 parts (for decimal dilution D) or in 99 parts (for centesimal dilution C) or in 999 parts (for millesimal dilution M) of neutral solvent in combination with external treatment (for example, shaking) of each obtained dilution and the use of separate containers for each subsequent dilution [V. Shvabe "Homeopathic Medicines", Moscow, 1967, pp. 14-29], A solution of the initial substance with a concentration of from 0.5 to 5.0 mg / ml is used as the stock (primary) solution.

[0022] For example, to prepare a 12-fold centesimal dilution (Cl 2) of antibodies to IFN-gamma, one part of 3.0 mg / ml stock solution of antibodies to IFN-gamma is diluted in 99parts of a neutral aqueous or aqueous-alcoholic solvent, and then shaken vertically several times (10 or more) to prepare the 1stdilution (Cl). The second dilution (C2) is similarly obtained from the 1stdilution Cl. This procedure is repeated 11 times, to obtain the C12 dilution. Thus, C12 dilution is a solution obtained by 12 successive dilutions of one part of the starting stock solution of antibodies to IFN-gamma with a concentration of 3.0 mg / ml in 99 parts of a neutral solvent in separate containers, which is equivalent to C12 dilution. Similar procedures using the appropriate dilution factor are performed to obtain C30, C50, C200 and other dilutions.

[0023] The present invention’s method of separating obtained iterations into fractions includes the following phases:1. For each obtained processed solvent (iteration) or dilution, its physicochemical properties and modifying activity are assessed by known analytical methods, including specific electrical conductivity measurement, radiometry, etc., and its modifying effect is assessed using such methods as terahertz spectroscopy, ELISA, etc.2. Based on tests results, the iterations or dilutions are classified into four fractions depending on the presence of altered physicochemical properties and / or modifying action: the first fraction has neither specific physicochemical properties nor modifying action (‘native’ fraction; the second fraction has specific physicochemical properties, but no modifying action (‘semi-native’ fraction); the third fraction has no specific physicochemical properties, but exerts a modifying action (‘semi-active’ fraction); the fourth fraction has specific physicochemical properties and exerts modifying action (‘active’ fraction).3. Each fraction’s specific biological and / or chemical activity is assessed experimentally using standard methods. Its direction depends on the initial substance and chemical, biological and physical processes involving this initial substance.

[0024] External vibration treatment is understood as horizontal or vertical mechanical shaking or their combination, or shaking using acoustics and microfluidics methods [RU2724254], or electromagnetic, ultrasound influence or other rhythmic physical action.

[0025] The fraction’s modifying effect on the target molecule is understood to be the effect exerted by the fraction on the parameters of the target molecule, namely, a change in the basic properties of the substance (target molecule) inside or outside the body after the fractions are administered.

[0026] A target molecule is understood to be the initial substance or a compound that is tropic to it, based on the ligand / substrate principle, e.g., an antigen and its antibody.

[0027] The specific physicochemical properties are understood to be a manifestation of activated initial substance’s or processed solvent’s physicochemical propertiesthat statistically significant differ from the initial substance’s or neutral solvent’s physicochemical properties.

[0028] Water, aqueous-alcohol solution, lactose or any pharmaceutically acceptable solvent or filler can be used as a neutral solvent.

[0029] Any compound with known biological or pharmaceutical activity, including low-molecular compounds, high-molecular compounds (e.g. natural, monoclonal or polyclonal antibodies), biologically active substances, organic or inorganic compounds, synthetic medicinal products, a neutral solvent, a neutral carrier processed by energy influence with transformed oscillations of bioelectric potentials of nervous tissue or brain [RU 2678979], gradualized products and neutral solvent may be used as initial substance.

[0030] The initial substance may be used in different physical forms: in solid form (e.g. a crystalline structure), in liquid form (e.g. a solution), or in gaseous form.

[0031] The initial substance may be a solid substance, a solution or a gradualized product (ultra-high dilution of the initial substance). The concentration of the initial substance in the vial may range from 1 pg / ml to 10 mg / ml, and is selected empirically in each specific case.

[0032] The claimed method also may use two or more initial substances. For example, to prepare the first activated solvent (iteration 1), the procedure may use the initial substance, or the activated initial substance obtained by preliminary external vibration treatment and joint incubation with one or more other initial substances by the procedure described above (step a).

[0033] Some examples of the implementation of this invention may include various fractions and serial numbers of iterations obtained from the initial substance or activated product that may be selected from antibodies to IFN-gamma, S-100B, histamine, bradykinin, morphine, prostate-specific antigen (PSA), tumor necrosis factor (TNF), insulin receptor, endothelial NO synthase, CD4, b2-microglobulin, HLA-DRB1. The initial substance may be also selected from phenobarbital, diazepam, sildenafil, paracetamol, morphine, diclofenac, prednisolone, sulpiride, metformin, semaglutide, glucose, cisplatin etc., or their release-active form (gradualized products).

[0034] For example, biological activity consisting in antiviral, antibacterial and immunomodulatory action, or in the treatment of pathological immune reactions is based on antibodies to IFN-gamma as initial substance; the treatment for acute or chronic diseases of the respiratory system and cough syndrome is based on the antibodies to bradykinin or histamine as initial substance; the treatment for impaired immune homeostasis is based on the antibodies to CD4 as initial substance; the effect on the central and peripheral nervous system, mental disorders, neuroses or psychoses, and mental balance recovery is based on antibodies to S100calcium -binding protein B (S-100B) as initial substance; the treatment for vascular tone impairments, neurotropic effect, anti-inflammatory and antiallergic effect, and the treatment for endothelial dysfunction is based on antibodies to endothelial NO synthase as initial substance; the pharmacological effect aimed at treating erectile dysfunction and prostate gland disorders, and the treatment of genitourinary system is based on antibodies to PSA as initial substance; inhibiting the production or enhancing the elimination of P24 HIV-1 protein is based on antibodies to P24 protein as initial substance; the potentiation of therapeutic effects by enhancing the effect of a medicinal substance in a therapeutic dose is based on the use of the same medicinal substance as initial substance; the treatment of diabetes mellitus or other glucose tolerance impairments, treatment for insulin resistance and / or lowering glucose levels is based on antibodies to beta subunit of the insulin receptor as initial substance; the treatment for vascular dystonia, dizziness of various origins, kinetoses, dysautonomia, neurological and / or behavioral developmental disorders, the treatment for vegetative-vascular dystonia is based on antibodies to S-100B protein and endothelial NO synthase as initial substances; the treatment and prevention of arterial hypertension, and the treatment of chronic heart failure is based on antibodies to the angiotensin II receptor as initial substance; the treatment of gastrointestinal disorders is based on antibodies to histamine, tumor necrosis factor-alpha and S-100B protein as initial substances; the treatment of pathological syndromes is based on initial substances that have an effect on these pathological syndromes or participate in their development.

[0035] The claimed method for preparing the product may also include an additional phase of external physical treatment at the stage of joint incubation, which increases the modifying action exerted by the final product (iteration or fraction). Such external treatment may be selected from electromagnetic radiation, geomagnetic radiation, IR radiation, temperature influence, etc.

[0036] Due to its biological activity, the claimed product presented as a mixture of processed solvents (artificial substance) or as a fraction can be used as an independent medicinal product both in liquid form as a solution, and in solid medicinal form as a pharmaceutical composition containing the technologically necessary (effective) amount of a neutral carrier saturated with the claimed product or a combination of the claimed product with an active substance, and pharmaceutically acceptable additives including lactose, microcrystalline cellulose, magnesium stearate and others, and prepared as described in W02007105981 (Al), 20.09.2007.

[0037] The claimed product can also be used as a specific fraction exerting a certain biological activity and consisting of a mixture of different iterations (activated solventsobtained at different stages of sequential activation series with external vibration treatment and joint incubation), and as a combination of several fractions.

[0038] The claimed product can be used as a combination of different fractions exerting different modifying effects and / or physicochemical properties, but representing iterations (activated solvents) with the same serial number, prepared from one activated substance.

[0039] Example 1. Example of the process for preparing iterations, using antibodies to IFN-gamma as initial substance.1) Preparing activated starting materials.

[0040] At the first phase, 50 ml solution of antibodies to IFN-gamma in water at a concentration of 25 pg / ml was poured into a 60 ml vial 1. A neutral solvent (180 ml of purified water) was poured into a 250 ml vial 2. The filled vials were placed close to each other and subjected to joint vibration on a vortex at 3000 rpm for 10 seconds, then left to incubate at room temperature for 1 minute. The vial with purified water was taken as activated initial substance 1, and the vial with the solution of antibodies to IFN-gamma was taken as activated initial substance 2.

[0041] To prepare processed solvent 1 (iteration 1), a vial with purified water (neutral solvent) in a comparable volume was placed close to the vial with activated initial substance 1. The filled vials were subjected to vibration together, on a vortex at 3000 rpm for 10 seconds, then left to incubate at room temperature for 1 minute. The vial with the initial purified water after the activation process was taken as processed solvent 1 - iteration 1 (Ii).

[0042] To obtain the processed solvent 2, a vial with purified water (neutral solvent) in a comparable volume was placed close to the vial with iteration 1. The filled vials were subjected to vibration together, on a vortex at 3000 rpm for 10 seconds, then left to incubate at room temperature for 1 minute. The vial with the initial purified water after the activation process was taken as processed solvent 2 - iteration 2 (12).

[0043] The above steps were repeated in a similar manner to prepare processed solvents 3, 4, 5, etc. (iterations 3, 4, 5...). In addition to the serial number indicating the number of previously performed operations, including joint incubation with the activated initial substance or the previously processed solvent and vibration influence (iteration number), each of the processed solvents exhibits specific physicochemical properties that may be assessed by known analytical methods and represent a basis for classifying the obtained activated initial substances (iterations) into fractions (groups), and exerts a specific modifying action directed at the target molecules.2) Methods for testing processed solvents.1. Conductometry

[0044] The conductometry method was used to assess the physicochemical properties of a series of processed solvents. To measure the specific electrical conductivity (SEC), 10 ml of the sample were placed into 15 ml test tubes and the electrode (Mettler Toledo, USA) was positioned so that the electrode membrane was completely immersed in the solution, after which the SEC was measured.

[0045] At step 1, 21 iterations (processed solvents) were prepared. The conductometry method demonstrated that the processed solvents (iterations) 4, 11, 14, 17 had significant differences compared to the water sample.2. Radiometry

[0046] The intrinsic electromagnetic radiation of the iterations was assessed using the radiometry method with a special installation consisting of a Faraday cage (an aluminum frame covered with a copper mesh), a tripod bearing a detector fixed with a clamp, a thermoshaker (BIO SAN PST-60HL-4) for heating the samples, and a TES-92 electromagnetic radiation (EMR) detector (TES Electrical Electronic Corp., Taiwan), for detecting the EMR flux density in the range from 1 pW / m2to 30.93 W / m2and a frequency range from 50 MHz to 3.5 GHz. The maximum average value (MAX AVG) was used as measurement mode.

[0047] To assess the intrinsic EMR of the iterations, the test sample (10 ml) was placed in a Petri dish, then the Petri dish with the sample was placed on a thermoshaker, and the sample was heated to a temperature of 37±1°C. After that, the detector was placed at a distance of 0.5 cm above the sample, and the Petri dish was uncovered. The measurements were performed for 10 min, with the Faraday cage closed. After 10 min, the maximum average value of EMR flux density was recorded on the device display.

[0048] Using the radiometry method, it was found that the processed solvents 6, 13, 15, 16, 20 had significant differences compared to the water sample.3. Terahertz (THz) spectroscopy

[0049] After adding the iterations, the changes in the spectral characteristics in the terahertz region of the target molecule were analyzed using a TeraPulse Lx terahertz spectrometer (TeraView, UK). In this procedure, 1 part (5 pl) of iterations or control was added to 99 parts (495 pl) of substance solution, which was a specific target for the iterations under study, then the refraction and transmission spectra were recorded. The coefficients of the equation of the Debye function describing the obtained spectra (Penkov N. and Fesenko E., 2020) and characterizing the permittivity in relaxation regions were used for data analysis.

[0050] Using terahertz spectroscopy, it was demonstrated that processed solvents (iterations) 4, 9, 13, 18, 21 had significant differences from water samples in the values of Asl (amplitude of the relaxation process Rl) or As2 (amplitude of the relaxation process R2) coefficients that shows their modifying activity.4. Enzyme-linked immunosorbent assay (ELISA)

[0051] The modifying properties of iterations were also studied using ELISA. For this procedure, the iterations were added to the target molecule (antigen), and the modifying activity was indirectly assessed by a change in the degree of antigen’s binding to monoclonal antibodies depending on their concentration.

[0052] The ELISA method demonstrated that processed solvents (iterations) 6, 7, 14, 15, 16 had significant differences compared to water samples in terms of the curve of dependence of optical density on the concentration of monoclonal antibodies to IFN-gamma after their interaction with 1 pg / ml IFN-gamma in the presence of samples.

[0053] Thus, the prepared processed solvents representing a series of iterations Ii- I21, were classified into the following fractions using the above methods: fractions with altered physicochemical properties and exhibiting a modifying effect (14, 6, 11, 13, 14, 15, 16); fractions with altered physicochemical properties, not exhibiting a modifying effect (117, 20); fractions without altered physicochemical properties but exhibiting a modifying effect (17, 9, 18, 21); fractions without altered physicochemical properties, not exhibiting a modifying effect (II, 2, 3, 5, 8, 10, 12, 19).

[0054] Example 2. The antiviral activity of the sample prepared by the claimed method was assessed using a model of influenza infection induced in mice by inoculating influenza A / California / 04 / 2009pndm (H1N1) virus adapted to mice at an infection dose causing death in 80% of the animals.

[0055] Purpose of the study: assessing the activity of the claimed product sample on a model of influenza infection in mice.

[0056] This study used 6-8-week-old sexually mature female Balb / c mice weighing 12-14 g. The animal facility has a veterinary certificate of compliance with veterinary requirements, rules and regulations issued by State Veterinary Surveillance. When forming experimental groups, each animal was assigned an individual number from 1 to 15 in each group. Animals were randomized by weight, and marked using eosin staining. The card on the cage in which the animals were kept indicated the study name, group number and administered substance.

[0057] The following samples were used in the study:

[0058] Sample 1 was prepared with the product prepared by the claimed method, using purified water as neutral solvent and initial substance. This sample belonged to the fraction that had no specific physicochemical properties or modifying effect (‘native’ fraction). The iteration was applied to lactose granules, and then dissolved in purified water (5% w / v).

[0059] Sample 2 - purified water (control).

[0060] Tamiflu - positive control.

[0061] The following groups were formed:

[0062] Group 1 animals were administered Sample 1 orally, 3 days before being infected, on the day of infection, and then daily for 6 days, at a volume of 20 ml / kg / day, in a single dose (n=15);

[0063] Group 2 animals were administered Sample 2 orally, 3 days before being infected, on the day of infection, and then daily for 6 days, at a volume of 20 ml / kg / day, in a single dose (n=15);

[0064] Group 3 animals were administered the comparison drug (Tamiflu) at a dose of 20 mg / kg / day (in a volume 20 ml / kg / day), first administered 4 hours before infection. Before infection and starting from the 5thday after infection, animals in this group were given the solvent (n=15).

[0065] Group 4 included viral control (untreated animals) that were given the solvent at a dose and dosing regimen identical to the experimental samples (n=15);

[0066] The treated and control animals were monitored daily for 14 full days (from the moment of infecting the animals with influenza virus). Mortality rate was recorded daily in all groups.

[0067] The activity of the compounds in a model of influenza pneumonia in mice was assessed by the following criteria: i. animal survival rate, ii. increase in mean survival duration (MSD), iii. pathogen replication in the lungs, virus titer

[0068] The mortality rate was calculated as the ratio of the number of dead animals to the total number of infected mice in the group. The animals’ MSD was calculated based on the total number of days of observation (after infection) by the formula: MSD = X f (d- 1) / n, where f was the number of mice that died on day d, the surviving mice were also included in / ; d was equal to 14 in this case; and n was the number of mice in the group. The virus titer was assessed as follows. On day 4 after influenza virus infection, 5 mice in each group were humanely sacrificed, then their lungs were removed under sterile conditions, homogenized, and resuspended in 1 ml of cold sterile 0.01 M PBS. The suspension was cleared of cell debris bycentrifugation at 2000 g for 10 min. 0.1 ml of the supernatant was used to assess the infectious titer of the virus in the MDCK cell culture. The resulting samples were stored at 4°C for no more than a week before experiments.

[0069] To assess the virus titer, MDCK cells were seeded in 96-well Costar plates at an average density of 30,000-35,000 cells per well and grown in Minimum Eagle medium (MEM) supplemented with 5% fetal calf serum, 10 mM glutamine, and antibiotics (penicillin 100 lU / ml and streptomycin 100 pg / ml) until a complete monolayer was formed. Before infection with the virus, the cell culture was washed twice with serum -free MEM. Tenfold dilutions of each virus sample from the lungs (up to 10'9) were prepared in the medium supplemented with L-(tosylamido-2-phenyl)ethyl chloromethyl ketone-treated trypsin (2 pg / ml). The resulting dilutions were used to infect the monolayers in 4 wells of a 96-well plate. After incubation at 37°C in an atmosphere containing 5% CO2 for 72 h, the cells were washed three times with PBS and fixed with 10% formaldehyde solution at a temperature of 18-23 °C for 5 min. After removing the formaldehyde solution, 100 pl of 1% crystal violet solution were added to each well of the plate and incubated at a temperature of 18-23°C for 5 min. After washing with water and drying the plate, 0.1 ml of 96% alcohol was added to the wells, the plate was incubated with slight shaking (at room temperature for 20 min), and then the optical density was measured at a wavelength of 570 nm. The wells were considered positive if the optical density in them was 20% less than the optical density in the cell control. The virus titer was assessed using the Reed and Mench method, in 4 replicates for each sample representing the material taken from one animal, and expressed as loglO TCID50 / 0.1 ml. The average titer value for five samples was then calculated.

[0070] Statistical data processing was performed by the study sponsor, with the RStudio software (2022.12.0 Build 353© 2009-2022 Posit Software, PBC), using the R package version 4.3.0. The distribution normality was assessed by Shapiro-Wilk test; the homogeneity of variances was assessed by the Bartlett test. The survival curves were compared using the Kaplan- Meier method. MSD values were compared by a permutation test with subsequent pairwise comparison. Virus titers were assessed by a permutation test with subsequent pairwise comparison. For all indicators, Holm's multiplicity correction was used.

[0071] The null hypothesis was rejected at p < 0.05.

[0072] The study results are presented in the table below.Table 1. Efficacy of samples in a model of influenza pneumonia in mice infected with adapted to mice influenza A / California / 04 / 2009pndm (H1N1) virus.

[0073] The efficacy of the samples was studied using the infectious dose of the influenza virus A / California / 04 / 2009pndm (H1N1) adapted to mice, causing the death of 80% of the mice, which corresponded to 104TCID50 / 0.1 ml. After exposure to the above dose of infection, the death of 80% of the animals was observed in the virus control group, with an average survival time of 8 days (Table 1). The average virus titer in the lungs on the 4thday after infection with the influenza A / California / 04 / 09pndm (H1N1) virus was 7.8 1g TCID50 / 0.1 ml (or 8.25 1g TCID50 / 0.1 ml by the median values), which was a cause for animals’ death from viral pneumonia or their illness.

[0074] With the therapeutic and preventive use of Sample 2, the animal mortality rate was 80%, and the average lifespan did not differ from the control group lifespan, amounting to 8.0 days. The data on clinical signs of infection in this group correlated with the data on the virus titer in the lungs, which did not statistically significantly differ from the virus titer in the lungs of untreated animals.

[0075] Sample 1 proved to be effective. The treatment with this sample reduced the animals’ mortality by 60%, increasing their life expectancy by 1.25 times (vs virus control, p> 0.05). Treatment with Sample 1 also suppressed virus replication in the animals’ lungs by more than 2 logTCIDso / O.l ml (p> 0.05) compared to the virus control: 5.85 logTCIDso / O. l ml vs 7.8 logTCIDso / 0.1 ml in the virus control group (or 5.5 vs 8.25 logTCIDso / O. l ml median values, Table 1). The Sample 1 exhibited similar pharmacological activity with the comparison drug Tamiflu (no statistically significant difference), the administration of which led to 60% survival of animals (p> 0.05), and increased their life expectancy to 14 days (p<0.05 vs virus control). The virus titer in the lungs of infected animals treated with Tamiflu was 5.4 logTCIDso / 0.1 ml vs 7.8 logTCIDso / 0.1 ml in the virus control group.

[0076] Thus, based on the results of the experiment, Sample 1 was the most effective among the assessed samples and exhibited antiviral activity meeting the preset criteria for efficacy.

[0077] Example 3. Assessment of efficacy of the product prepared by the claimed method on the model of insomnia.

[0078] Material and methods

[0079] Outbred male rats weighing 300±15 g aged 14 to 16 weeks were selected for the study.

[0080] The rats obtained from the laboratory animal nursery were kept in individual transparent polycarbonate rodent cages with natural corn cob granulate bedding Rehofix (OOO Rettenmayer Rus, Russia). The bedding was changed once a week. The cages were located in racks supplied with affluent ventilation device Bio.V.S. Vent II (Bioscape (EHRET), Germany). The cages were changed once a week. Drinking water was supplied ad libitum in standard drinking bottles. The water was completely changed twice a week. Animals were kept in controlled environments at 20-26°C and 30-70% relative humidity. Animal rooms had a 12-hour light cycle and at least 10 air changes per hour. Five groups of animals (n=10) were formed (Table 2), with a total of 50 animals at the start of the experiment.Table 2. Distribution of animals into experimental groups

[0081] All manipulations with animals were performed in accordance with Directive 2010 / 63ZEU of the European Parliament and of the Council dated 22 September 2010 on the protection of animals used for scientific purposes. The study was conducted in compliance with the principles of the European Convention for the Protection of Vertebrate Animals used for Experimental and other Scientific Purposes (Strasbourg, 1986), in accordance with good laboratory practice rules and the protocol of the bioethics commission of Saint Petersburg State Chemical-Pharmaceutical University No. Rat-AO (BI) -2020 dated 10.02.20.

[0082] Test sample

[0083] To prepare a sample of the product obtained by the claimed procedure, phenobarbital was used as the initial substance; purified water was used as a neutral solvent. This sample belongs to the fraction that has specific physicochemical properties and modifying effect. The iteration was applied to lactose granules and then dissolved in purified water (5% w / v). To prepare a placebo sample, a sample of purified water was subjected to successive vibration influence the same number of times as in the process of obtaining the sample of the product prepared by the claimed method.

[0084] Electrocorticographic electrode implantation procedure

[0085] The corticographic electrodes were made of nichrome wire with 0.5 mm diameter (for the recording and reference electrodes) and 0.16 mm diameter (for the grounding electrode). The wires were insulated using heat-shrinkable tubing, the recording (non-insulated) part being approximately 1 mm long. All electrodes were connected in a socket on a BLS-8 cable, at 2.54 mm intervals.

[0086] To perform surgical manipulations, the animals were pre-anesthetized with chloral hydrate (400 mg / kg). Before the operation, oftagel (Santen OY, Finland) was applied to the animals’ eyes to prevent cornea from drying. After preparing the skull surface (removing the muscles, fascia and periosteum, and coagulating the bleeding areas), holes of the appropriate diameters were drilled for the electrodes and fixing screws (drill insertion depth up to 1 mm). Toprevent the brain from heating, holes were drilled in short intervals. Then, corticographic electrodes were implanted.

[0087] The coordinates of the electrodes were located using the stereotaxic atlas of the rat brain by G. Paxinos, C. Watson. The recording electrodes were distributed evenly and symmetrically over the surface of the cerebral hemispheres. The frontal electrodes FP1 and FP2 were located in the primary motor cortex (AP = 0.0, ML = 2.0, DV = 1.0), the central electrodes C3 and C4 were located in the primary somatosensory cortex (AP = -4.0, ML = 2.0, DV = 1.0), and the occipital electrodes 01 and 02 were located in the secondary visual cortex (AP = -7.0, ML = 2.0, DV = 1.0). The reference electrode was installed in the nasal bone, and the ground electrode was placed under the skin in the neck area. The skull structures were additionally fixated using Villacryl C dental plastic (Zhermack, Italy). After this, the skin incision was sutured, then the sutures and the adjacent area were treated with antiseptic. After the surgery, the rats were kept in individual cages with free access to water and food throughout the study period. The condition of the animals was monitored immediately after recovery from anesthesia and then daily in the morning and evening; the sutures were treated with iodine solution if necessary. To prevent infection, the animals were administered bicillin-3 (500 U / 100 g intramuscularly) immediately after the surgery. To avoid dehydration, the rats were administered saline subcutaneously for the first 3 days after the surgery. For pain relief, ketoprofen was injected at a dose of 5 mg / kg for 3 days after the surgery.

[0088] Electrocorticogram recording

[0089] The animals’ electrocorti cographic activity was recorded no earlier than 7 days after surgery using an 8-channel encephalograph Neuron-Spectrum- 1 (Neurosoft, Russia) with a bandwidth of 0.5-35 Hz and a quantization frequency of 500 Hz. The signal was recorded simultaneously with video recording of behavior in a home cage under artificial lighting. The recording lasted for 6 hours. The sections of the recording that did not contain any artifacts were selected for further analysis.

[0090] The obtained records were analyzed using the Neuron-Spectr.NET software (Neurosoft, Russia). The ratio of theta and delta rhythm indices was calculated. Delta rhythms are characteristic of a state of slow-wave sleep, sedation, and varying degrees of metabolic / dyscirculatory disorders. Increased theta rhythm activity, especially in the leads above the hippocampus, indicates an increase in search and exploration activity.

[0091] Statistical data analysis

[0092] The obtained data were statistically processed using the GraphPad Prism 7.00 software package. The data are presented as the mean ± standard error of the mean. Thesignificance of differences between groups was assessed using the Fisher's least significant difference test (LSD-test). Differences were considered statistically significant at p <0.05.

[0093] Results and discussion

[0094] The results of the study are presented in Table 3.Table 3. The ratio of theta and delta rhythm indices in the experimental group animals in leads FP1, FP2, C3, C4, 01 and 02.- p <0.05 compared to group 2.

[0095] Group 2 rats had a statistically significantly reduced ratio of theta and delta rhythms in all leads compared to the control group (p <0.01 for all leads).

[0096] Administration of melatonin and placebo did not have a statistically significant effect on the analyzed parameters. In animals that were administered the product prepared by the claimed method (group 5), the ratios of theta and delta rhythm indices in all leads were higher (p<0.05) than in group 2 and approached the values of the control group (group 2). In group 5, an increase in the duration of REM sleep phase in animals was observed.

[0097] Thus, the test product reliably improved the ratio of theta / delta rhythm indices in animals with insomnia, which approached the values in the control group consisting of healthy animals. Based on EEG examination, it can be concluded that the test product manufactured using the claimed method proved to be more effective than the control samples.

[0098] Example 4. Effect on [3H]pentazocine standard ligand binding to the recombinant sigma 1 receptor.

[0099] Materials and methods[000100] Laboratory conditions for preparing iterations[000101] Iterations in each study were prepared by one operator on the same day. Temperature and humidity in the laboratory during sample preparation and subsequent measurements were controlled using a verified thermohygrometer IVA-6N (OOO NPK Microfor, Russia); temperature was 22±3 °C, humidity was 20-70 %. Vials made of transparent borosilicate glass (60, 500 ml, Glastechnik Grafenroda, Germany) were used for the preparation of iterations.[000102] Type 1 ultrapure water with a resistivity of 18.2 MQxcm (Milli-Q Integral 5, Millipore) was used as the neutral carrier for the preparation of iterations, as well as the solvent for all other reagents used in this work. The quality of purified water was monitored daily by measuring resistivity using a SevenCompact S230 conductometer (Mettler Toledo, USA) and pH using a SevenCompact S220 pH meter (Mettler Toledo, USA). For liquids, automatic pipettes of different volumes (Eppendorf, Germany; Socorex, Switzerland) and measuring glassware of accuracy class A (Borosil, India; Steklopribor, Ukraine) were used. Dry reagents were weighed using an analytical balance of accuracy class I (Pioneer PA214C, Ohaus, USA). A calibrated laboratory timer Traceable (VWR, USA) was used to measure all incubation periods. Vibration was performed using a shaker (vortex) MS 3 basic (IKA-Werke, Germany) with a standard insert.[000103] Preparing iterations[000104] The process of preparing iterations included several stages. A 60 mL vial containing a 50 mL of the initial substance (purified water or metformin solution) and a 500 mL vial containing 480 mL of purified water (neutral carrier) were rotated on a vortex for 10 seconds at 3000 rpm in close contact with each other. Thereafter, both vials were incubated for 1 minute at room temperature in close contact. Using the above-described procedure, 480 ml of iteration No.O (zero iteration) was obtained. To obtain the first iteration (Ii), the vial with iteration No.O (480 mL) was placed next to a new 500 mL vial with 480 mL neutral carrier and rotated on a vortex for 10 seconds at 3000 rpm in close contact. Both vials were then incubated for 1 minute at room temperature in close contact. After the above-described procedure, the exposed neutral carrier was taken as Ii. Then, the second iteration (L) was obtained from Ii in a similar manner. The procedure was repeated the required number of times to obtain the final iteration.[000105] In this study, iteration N26 obtained from stock solution of monoclonal antibodies to CD4 receptor (2.5 mg / mL) was used. The iterations activity was assessed by the following methods:Table 4Note: (+) there is change compared to neutral carrier.[000106] Biological model[000107] The study of the influence of the product containing iterations of antibodies to CD4 receptor (Sample 1), and the product containing ultra-low doses of antibodies to CD4 receptor (a mixture of homeopathic dilutions C12+C30+C50, Sample 2) in vitro on the [3H]pentazocine standard ligand binding to the recombinant human sigma 1 receptor was assessed using the radioligand method. Potentiated distilled water (a mixture of homeopathic dilutions C12+C30+C50, hereinafter referred to as potentiated water) was tested as a control for the test products.[000108] In the experiment, 20 pL of the test or control sample were added to the incubation medium (to assess the total binding). Then 160 pl (-200 pg protein) of Jurkat cell membrane homogenate (human leukemic T-lymphocyte line) were added, and finally 20 pl of tritiated [3H]pentazocine radioligand (15 nM) were added.[000109] To measure non-specific binding, 20 pL of unlabeled ligand (haloperidol 10 pM) were added to the incubation medium instead of the products or potentiated water.[000110] Radioactivity was measured with a scintillation counter (Topcount, Packard) using a scintillation mixture (Microscint 0, Packard) after incubation for 120 minutes at 22°C in 50 mM Tris-HCl buffer (pH = 7.4) and filtration on glass fiber filters (GF / B, Packard). Specific binding (in the experiment or control) was calculated as the difference between total binding (in the experiment or control) and non-specific binding.[000111] ResultsThe results are presented as inhibition percentage of specific binding in the control (potentiated water was used as the control) (see Table 5).Table 5. Effect of the test samples and potentiated water on the [3H]pentazocine standard radioligand binding to recombinant human sigma 1 receptorNote:% specific binding in the control = (specific binding in test / specific binding in control) * 100%; % inhibition of specific binding in the control = 100% - (specific binding in test / specific binding in control) * 100%). The results indicating inhibition above 50% represent significant effects of the test compounds. The results indicating inhibition between 25% and 50% indicate weak to moderate effects. The results showing inhibition less than 25% are considered to be minor effects of the test compound and are within background levels.[000112] Thus, the following was demonstrated under the conditions of this experimental model:1. Each of the test samples inhibited [3H]pentazocine standard radioligand binding to human recombinant sigma 1 receptor.2. Potentiated water (20 pL) added to the experimental well did not affect [3H]pentazocine standard radioligand binding to human recombinant sigma 1 receptor.[000113] Example 5. Effect on [3H]pentazocine standard radioligand binding to the recombinant human sigma- 1 receptor was assessed by the radioligand method.[000114] Materials and methods[000115] Laboratory conditions for preparing iterations[000116] Iterations in each study were prepared by one operator on the same day.Temperature and humidity in the laboratory during sample preparation and subsequent measurements were controlled using a verified thermohygrometer IVA-6N (OOO NPK Microfor, Russia); temperature was 22±3 °C, humidity was 20-70 %. Vials made of transparent borosilicate glass (60, 500 ml, Glastechnik Grafenroda, Germany) were used for the preparation of iterations.[000117] Type 1 ultrapure water with a resistivity of 18.2 MQxcm (Milli-Q Integral5, Millipore) was used as the neutral carrier for the preparation of iterations, as well as the solvent for all other reagents used in this work. The quality of purified water was monitored daily by measuring resistivity using a SevenCompact S230 conductometer (Mettler Toledo, USA) and pH using a SevenCompact S220 pH meter (Mettler Toledo, USA). For liquids, automatic pipettes of different volumes (Eppendorf, Germany; Socorex, Switzerland) andmeasuring glassware of accuracy class A (Borosil, India; Steklopribor, Ukraine) were used. Dry reagents were weighed using an analytical balance of accuracy class I (Pioneer PA214C, Ohaus, USA). A calibrated laboratory timer Traceable (VWR, USA) was used to measure all incubation periods. Vibration was performed using a shaker (vortex) MS 3 basic (IKA-Werke, Germany) with a standard insert.[000118] Preparing iterations[000119] The process of preparing iterations included several stages. A 60 mL vial containing a 50 mL of the initial substance (purified water or metformin solution) and a 500 mL vial containing 480 mL of purified water (neutral carrier) were rotated on a vortex for 10 seconds at 3000 rpm in close contact with each other. Thereafter, both vials were incubated for 1 minute at room temperature in close contact. Using the above-described procedure, 480 ml of iteration No.O (zero iteration) was obtained. To obtain the first iteration (Ii), the vial with iteration No.O (480 mL) was placed next to a new 500 mL vial with 480 mL neutral carrier and rotated on a vortex for 10 seconds at 3000 rpm in close contact. Both vials were then incubated for 1 minute at room temperature in close contact. After the above-described procedure, the exposed neutral carrier was taken as L. Then, the second iteration (L) was obtained from L in a similar manner. The procedure was repeated the required number of times to obtain the final iteration.[000120] In this study, iteration J 9 obtained from a solution of monoclonal antibodies to SIOOB protein (2.0 mg / mL) was used. The iterations activity was assessed by the following methods:Table 6.Note: (-) there is no change compared to neutral carrier.[000121] Biological model[000122] The study of the influence of the product containing the iterations of antibodies to SIOOB (Sample 1), and the product containing ultra-low doses of antibodies to SIOOB protein (a mixture of homeopathic dilutions C12+C30+C50, Sample 2) in vitro on the [3H]pentazocine standard ligand binding to human recombinant sigma 1 receptor was assessed using the radioligand method.[000123] Sigma-1 receptor is an intracellular receptor localized in the cells of the central nervous system, the cells of most peripheral tissues, and in immune-competent cells. By controlling the homeostasis of intracellular calcium, this receptor regulates intracellular signalingcascades leading to the activation of the transcription factors and to the transcription of a whole family of genes. Sigma-1 receptor is involved in the pathogenesis of various diseases, including infections and neurodegenerative disorders. Thus, drugs that affect this receptor and the effectiveness of ligands interaction with it can be considered effective for the treatment of neuroinfections, neurodegenerative and other diseases.[000124] In this experimental model, potentiated distilled water (mixture of homeopathic dilutions C12+C30+C50) (potentiated water) was used as a control.[000125] In the experiment, 20 pL of the test sample or control were added to the incubation medium (to assess total binding). Then 160 pl (-200 pg protein) of Jurkat cell membrane homogenate (human leukemic T-lymphocyte line) were added, and finally 20 pl of tritiated [3H]pentazocine radioligand (15 nM) were added. To measure non-specific binding, 20 pL of unlabeled ligand (haloperidol 10 pM) were added to the incubation medium instead of the products or potentiated water.[000126] Radioactivity was measured with a scintillation counter (Topcount, Packard) using a scintillation mixture (Microscint 0, Packard) after incubation for 120 minutes at 22°C in 50 mM Tris-HCl buffer (pH = 7.4) and filtration on glass fiber filters (GF / B, Packard). Specific binding (in the experiment or control) was calculated as the difference between total binding (in the experiment or control) and non-specific binding.[000127] Results[000128] The results are presented as inhibition percentage of specific binding in the control (potentiated water was used as control) (see Table 7).Table 7. Effect of the products and potentiated water on the binding of the standard [3H]pentazocine radioligand to the recombinant human sigma 1 receptor.Note: % specific binding in the control = (specific binding in test / specific binding in control) * 100%; % inhibition of specific binding in the control = 100% - (specific binding in test / specific binding in control) * 100%).[000129] Thus, the following was demonstrated under the conditions of this experimental model:1. Each of the test samples inhibited [3H]pentazocine standard radioligand binding to the recombinant human sigma 1 receptor and thus can be used as an effective medicine for the treatment of neuroinfections, neurodegenerative and other diseases, in particular, for the treatment of multiple sclerosis.2. Potentiated water (20 pL) added to the experimental well did not affect [3H]pentazocine standard radioligand binding to the recombinant human sigma 1 receptor.[000130] Example 6. Effect on phagocytic activity of neutrophils.[000131] Materials and methods[000132] Laboratory conditions for preparing the iterations[000133] Iterations in each study were prepared by one operator on the same day. Temperature and humidity in the laboratory during sample preparation and subsequent measurements were controlled using a verified thermohygrometer IVA-6N (OOO NPK Microfor, Russia); temperature was 22±3 °C, humidity was 20-70 %. Vials made of transparent borosilicate glass (60, 500 ml, Glastechnik Grafenroda, Germany) were used for the preparation of iterations.[000134] Type 1 ultrapure water with a resistivity of 18.2 M xcm (Milli-Q Integral 5, Millipore) was used as the neutral carrier for the preparation of iterations, as well as the solvent for all other reagents used in this work. The quality of purified water was monitored daily by measuring resistivity using a SevenCompact S230 conductometer (Mettler Toledo, USA) and pH using a SevenCompact S220 pH meter (Mettler Toledo, USA). For liquids, automatic pipettes of different volumes (Eppendorf, Germany; Socorex, Switzerland) and measuring glassware of accuracy class A (Borosil, India; Steklopribor, Ukraine) were used. Dry reagents were weighed using an analytical balance of accuracy class I (Pioneer PA214C, Ohaus, USA). A calibrated laboratory timer Traceable (VWR, USA) was used to measure all incubation periods. Vibration was performed using a shaker (vortex) MS 3 basic (IKA-Werke, Germany) with a standard insert.[000135] Preparing iterations[000136] The process of preparing iterations included several stages. A 60 mL vial containing a 50 mL of the initial substance (purified water or metformin solution) and a 500 mL vial containing 480 mL of purified water (neutral carrier) were rotated on a vortex for 10 seconds at 3000 rpm in close contact with each other. Thereafter, both vials were incubated for 1 minute at room temperature in close contact. Using the above-described procedure, 480 ml of iterationNo.O (zero iteration) was obtained. To obtain the first iteration (Ii), the vial with iteration No.O (480 mL) was placed next to a new 500 mL vial with 480 mL neutral carrier and rotated on a vortex for 10 seconds at 3000 rpm in close contact. Both vials were then incubated for 1 minute at room temperature in close contact. After the above-described procedure, the exposed neutral carrier was taken as Ii. Then, the second iteration (L) was obtained from Ii in a similar manner. The procedure was repeated the required number of times to obtain the final iteration.[000137] In this study, iteration N214 obtained from the stock solution of monoclonal antibodies to IFN-gamma (2.0 mg / mL) was used. The iteration activity was assessed by the following methods.Table 8.Note: (+) there is change compared to neutral carrier.[000138] Biological model[000139] When studying the effect of the iterations of antibodies to IFN-gamma on the phagocytic activity of neutrophils in peritoneal exudate, the neutrophils’ phagocytic activity was assessed 24 hours after the end of a 10-day course of subcutaneous administration of iterations of monoclonal antibody (AB) to IFN-gamma, and monoclonal antibody (AB) to IFN- gamma in a homeopathic dilution D60 at 0.1 mL. A sample of sheep red blood cells was used as a control.[000140] Phagocytic activity was assessed by the ability of these cells to absorb a 24h culture of S. aureus strain 209 (microbial suspension concentration 100 million / mL). In this case, the percentage of neutrophils that absorbed microbes (phagocytic index - PI), and the average number of staphylococci absorbed by one cell (phagocytic number - PN) were taken into account.[000141] ResultsTable 9. Effect of iterations on the phagocytic activity of neutrophils.[000142] The results of these experiments presented in Table 9 show that the iterations of antibodies to IFN-gamma significantly stimulate phagocytosis compared to the control group, due to an increase in the proportion of neutrophils capable of absorbing staphylococci.[000143] Example 7. Evaluation of antiretroviral activity of the iterations.[000144] Materials and methods[000145] Laboratory conditions for preparing the iterations[000146] Iterations in each study were prepared by one operator on the same day. Temperature and humidity in the laboratory during sample preparation and subsequent measurements were controlled using a verified thermohygrometer IVA-6N (OOO NPK Microfor, Russia); temperature was 22±3 °C, humidity was 20-70 %. Vials made of transparent borosilicate glass (60, 500 ml, Glastechnik Grafenroda, Germany) were used for the preparation of iterations.[000147] Type 1 ultrapure water with a resistivity of 18.2 MQxcm (Milli-Q Integral 5, Millipore) was used as the neutral carrier for the preparation of iterations, as well as the solvent for all other reagents used in this work. The quality of purified water was monitored daily by measuring resistivity using a SevenCompact S230 conductometer (Mettler Toledo, USA) and pH using a SevenCompact S220 pH meter (Mettler Toledo, USA). For liquids, automatic pipettes of different volumes (Eppendorf, Germany; Socorex, Switzerland) and measuring glassware of accuracy class A (Borosil, India; Steklopribor, Ukraine) were used. Dry reagents were weighed using an analytical balance of accuracy class I (Pioneer PA214C, Ohaus, USA). A calibrated laboratory timer Traceable (VWR, USA) was used to measure all incubation periods. Vibration was performed using a shaker (vortex) MS 3 basic (IKA-Werke, Germany) with a standard insert.[000148] Preparing iterations[000149] The process of preparing iterations included several stages. A 60 mL vial containing a 50 mL of the initial substance (purified water or metformin solution) and a 500 mL vial containing 480 mL of purified water (neutral carrier) were rotated on a vortex for 10 seconds at 3000 rpm in close contact with each other. Thereafter, both vials were incubated for 1 minute at room temperature in close contact. Using the above-described procedure, 480 ml of iteration No.O (zero iteration) was obtained. To obtain the first iteration (Ii), the vial with iteration No.O (480 mL) was placed next to a new 500 mL vial with 480 mL neutral carrier and rotated on a vortex for 10 seconds at 3000 rpm in close contact. Both vials were then incubated for 1 minute at room temperature in close contact. After the above-described procedure, the exposed neutralcarrier was taken as Ii. Then, the second iteration (I2) was obtained from Ii in a similar manner. The procedure was repeated the required number of times to obtain the final iteration.[000150] In this study, the iteration 12 prepared from a solution of polyclonal antibodies to CD4 receptor (1.8 mg / mL) was used. The iteration activity was assessed by the following methods.Table 10.Note: (+) there is change compared to neutral carrier; (-) there is no change compared to neutral carrier[000151] Biological model[000152] The antiretroviral activity of the claimed medicinal product containing the iterations of polyclonal affinity purified rabbit antibodies to CD4 receptor (Sample 1), and the medicinal product containing activated / potentiated forms of aqueous dilutions of polyclonal affinity purified rabbit antibodies to CD4 receptor in ultra-low doses (ULD), obtained by ultra- high diluting the initial matrix solution (with a concentration of 2.5 mg / mL) by 10012, 10030, 10050times, equivalent to a mixture of centesimal homeopathic dilutions C12, C30, C50 (ULD of AB to CD4, Sample 2) was assessed using the macrophages obtained from human peripheral blood mononuclear cells and infected in vitro with the HIV-l-Ba-L strain. Azidothymidine (Sigma - AZ169-100mg, lot 107 K1578) was used as a comparison drug.[000153] Human peripheral blood macrophages were obtained from human peripheral blood mononuclear cells that were isolated from the blood of two healthy seronegative donors using Ficoll-Hypaque density gradient centrifugation. Human peripheral blood mononuclear cells were grown for 3 days in RPMH640 medium (DIFCO) supplemented with 10% fetal calf serum , 1% antibiotic solution (PSN Gibco containing 50 pg / mL penicillin, 50 pg / mL streptomycin and 100 pg / mL neomycin), 15 ng / mL GM-CSF (granulocyte-macrophage colony-stimulating factor). The cells were then placed in cultural plates (150,000 cells / well in a 48-well plate) and grown for 7 days with 1 ng / mL GM-CSF and 10 ng / mL M-CSF (macrophage colony-stimulating factor) to allow the cells to fully differentiate into macrophages.[000154] The cells were infected with the HIV-l-Ba-L strain by adding 100 pL of HIV-l-Ba-L strain inoculum, equivalent to a dose of 1000 TCID50 (the dose that infects 50% of tissue culture cells).[000155] To assess the antiretroviral activity, the test samples were added to the wells 24 hours before infecting the cells with HIV-l-Ba-L strain, and on days 3, 7, 10, 14, and 17 after infection. On days 3, 7, 10, 14, and 17 after cell infection, the supernatant was collected and used to assess the effect of the products on inhibiting HIV replication.[000156] The samples were diluted with RPMI1640 medium (DIFCO) to achieve a final volume of 250 pL before adding them to wells containing 750 pL of cell culture. The ULD of AB to CD4 was diluted in RPMI1640 medium (DIFCO) by 8 times (dilution ratio 1 / 8), CD4 + ULD of AB to IFN-y with its individual components included in its composition. The comparison drug azidothymidine was diluted in RPMI1640 medium (DIFCO) to achieve a concentration of 8 nM.[000157] The efficacy of the test samples was measured by the inhibition of HIV replication, which was assessed by the enzymatic activity of HIV reverse transcriptase in supernatants of human peripheral blood macrophages using the HIV RT RetroSys kit manufactured by INNOVAGEN (lot 10-059C). To calculate the inhibition percentage of HIV replication, the supernatant of cells, to which the test samples were not added, was used as a control (Tables 11 and 12).Table 11. Antiretroviral activity of the products assessed using human peripheral blood macrophages (donor No. 1) infected with the HIV-l-Ba-L strain in vitro.Table 12. Antiretroviral activity of the products assessed using human peripheral blood macrophages (donor No. 2) infected with the HIV-l-Ba-L strain in vitro.[000158] Thus, it was shown that the antiretroviral activity of Sample 1 and Sample 2 was maintained throughout the experiment under the conditions of this experimental model. Both samples exhibited antiretroviral activity in the in vitro model of infected human peripheral blood macrophages obtained from different seronegative donors, which indicated a pronounced antiretroviral effect of Samples 1 and 2.[000159] Example 8. Investigation of the efficacy of iteration derived from polyclonal antibodies to human IFN-gamma in influenza infection in mice.[000160] Materials and methods[000161] Laboratory conditions for preparing the iterations[000162] Iterations in each study were prepared by one operator on the same day.Temperature and humidity in the laboratory during sample preparation and subsequent measurements were controlled using a verified thermohygrometer IVA-6N (OOO NPK Microfor, Russia); temperature was 22±3 °C, humidity was 20-70 %. Vials made of transparent borosilicate glass (60, 500 ml, Glastechnik Grafenroda, Germany) were used for the preparation of iterations.[000163] Type 1 ultrapure water with a resistivity of 18.2 M xcm (Milli-Q Integral 5, Millipore) was used as the neutral carrier for the preparation of iterations, as well as the solvent for all other reagents used in this work. The quality of purified water was monitored daily by measuring resistivity using a SevenCompact S230 conductometer (Mettler Toledo, USA) and pH using a SevenCompact S220 pH meter (Mettler Toledo, USA). For liquids, automatic pipettes of different volumes (Eppendorf, Germany; Socorex, Switzerland) and measuring glassware of accuracy class A (Borosil, India; Steklopribor, Ukraine) were used. Dry reagents were weighed using an analytical balance of accuracy class I (Pioneer PA214C, Ohaus, USA). A calibrated laboratory timer Traceable (VWR, USA) was used to measure all incubation periods. Vibration was performed using a shaker (vortex) MS 3 basic (IKA-Werke, Germany) with a standard insert.[000164] Preparing iterations[000165] The process of preparing iterations included several stages. A 60 mL vial containing a 50 mL of the initial substance (purified water or metformin solution) and a 500 mL vial containing 480 mL of purified water (neutral carrier) were rotated on a vortex for 10 seconds at 3000 rpm in close contact with each other. Thereafter, both vials were incubated for 1 minute at room temperature in close contact. Using the above-described procedure, 480 ml of iterationNo.O (zero iteration) was obtained. To obtain the first iteration (Ii), the vial with iteration No.O (480 mL) was placed next to a new 500 mL vial with 480 mL neutral carrier and rotated on a vortex for 10 seconds at 3000 rpm in close contact. Both vials were then incubated for 1 minute at room temperature in close contact. After the above-described procedure, the exposed neutral carrier was taken as Ii. Then, the second iteration (h) was obtained from Ii in a similar manner. The procedure was repeated the required number of times to obtain the final iteration.[000166] In this study, the iteration 14 prepared from a solution of polyclonal antibodies to IFN-gamma (2.1 mg / mL) was used. The iterations activity was assessed by the following methods.Table 13.Note: (+) there is change compared to neutral carrier; (-) there is no change compared to neutral carrier[000167] Biological model[000168] The study of the efficacy of the iteration obtained from polyclonal antibodies to human IFN-gamma in the model of influenza infection in female Balb / c mice (n=96) was conducted at the Federal Vector Research Center of Virology and Biotechnology (Koltsovo). The infection process was modeled by intranasal administration of the influenza A / California / 07 / 2009 (HlNl)v virus at a dose of 10LD50 (non-lethal infection). The study involved the iteration 14 obtained from a solution of polyclonal antibodies to IFN-gamma (Sample 1), as well as ultra-low doses (a mixture of homeopathic dilutions C12, C30, C50) of rabbit polyclonal antibodies to IFN-gamma, prepared from matrix solution with a concentration of 5.0 mg / mL and a final dilution in distilled water (Sample 2). The test samples were administered to 32 mice intragastrically at 0.2 mL / mouse (daily dose 0.4 mL / mouse) for 5 days before infection and for 8 days after infection. The comparison drug oseltamivir was administered to 32 mice intragastrically 1 hour before infection at a dose of 20 mg / kg, then twice daily at 10 mg / kg (0.2 mL / mouse) for 5 days after infection; starting from Day 6 after infection, the animals were administered distilled water twice daily at 0.2 mL / mouse instead of oseltamivir. In the control group, 20 mice were administered distilled water intragastrically twice daily at 0.2 mL / mouse. The influenza virus titer in the lungs was assessed on days 2, 4, 6, 8 after infection.[000169] As a result of the experiment, it was found that the use of both test samples in mice infected with influenza A / California / 07 / 2009(HlNl)v virus was comparable in efficacyto the use of oseltamivir and contributed to a reliable decrease in the replication of influenza virus in the lungs of mice on days 4, 6 and 8 after infection; the decrease was more than 10-fold compared to the control group (see Table 1).Table 14. Dynamics of influenza virus replication in the lungs of mice administered iteration of antibodies to IFN-gamma vs. oseltamivir, when infected with 10LD50 strain of influenza A / California / 07 / 2009(HlNl)v virus.Note: *- p<0.05 vs. control[000170] Thus, the claimed product has high antiviral efficacy in the treatment of influenza A / H1N1 caused by the strain A / Califomia / 07 / 2009(HlNl)v, not inferior to the reference drug for the treatment of influenza A, oseltamivir.[000171] Example 9. Study of the efficacy of the iterations in influenza infection in mice.[000172] Materials and methods[000173] Laboratory conditions for preparing the iterations[000174] Iterations in each study were prepared by one operator on the same day. Temperature and humidity in the laboratory during sample preparation and subsequent measurements were controlled using a verified thermohygrometer IVA-6N (OOO NPK Microfor, Russia); temperature was 22±3 °C, humidity was 20-70 %. Vials made of transparent borosilicate glass (60, 500 ml, Glastechnik Grafenroda, Germany) were used for the preparation of iterations.[000175] Type 1 ultrapure water with a resistivity of 18.2 MQxcm (Milli-Q Integral 5, Millipore) was used as the neutral carrier for the preparation of iterations, as well as the solvent for all other reagents used in this work. The quality of purified water was monitoreddaily by measuring resistivity using a SevenCompact S230 conductometer (Mettler Toledo, USA) and pH using a SevenCompact S220 pH meter (Mettler Toledo, USA). For liquids, automatic pipettes of different volumes (Eppendorf, Germany; Socorex, Switzerland) and measuring glassware of accuracy class A (Borosil, India; Steklopribor, Ukraine) were used. Dry reagents were weighed using an analytical balance of accuracy class I (Pioneer PA214C, Ohaus, USA). A calibrated laboratory timer Traceable (VWR, USA) was used to measure all incubation periods. Vibration was performed using a shaker (vortex) MS 3 basic (IKA-Werke, Germany) with a standard insert.[000176] Preparing iterations[000177] The process of preparing iterations included several stages. A 60 mL vial containing a 50 mL of the initial substance (purified water or metformin solution) and a 500 mL vial containing 480 mL of purified water (neutral carrier) were rotated on a vortex for 10 seconds at 3000 rpm in close contact with each other. Thereafter, both vials were incubated for 1 minute at room temperature in close contact. Using the above-described procedure, 480 ml of iteration No.O (zero iteration) was obtained. To obtain the first iteration (Ii), the vial with iteration No.O (480 mL) was placed next to a new 500 mL vial with 480 mL neutral carrier and rotated on a vortex for 10 seconds at 3000 rpm in close contact. Both vials were then incubated for 1 minute at room temperature in close contact. After the above-described procedure, the exposed neutral carrier was taken as Ii. Then, the second iteration (L) was obtained from Ii in a similar manner. The procedure was repeated the required number of times to obtain the final iteration.[000178] In this study, the iteration 15 prepared from a solution of polyclonal antibodies to TNF-a (2.5 mg / mL) and iteration 2 prepared from a solution of polyclonal antibodies to CD4 receptor (3.0 mg / mL) were used. The activity of the iterations was assessed by the following methods.Table 15.Note: (+) there is change compared to neutral carrier; (-) there is no change compared to neutral carrier[000179] The study of the efficacy of a medicinal product containing the iteration obtained from polyclonal antibodies to TNF-a (Sample 1), a medicinal product containing the iteration obtained from a solution of polyclonal antibodies to CD4 receptor (Sample 2), amedicinal product containing a 1 :1 mixture of the above iterations (Sample 3), a medicinal product containing an activated-potentiated form of aqueous dilutions of polyclonal antibodies to TNF-a in ultra-low doses (ULD), obtained by superdiluting the initial matrix solution (2.5 mg / mL) by 10012, 1OO30, 1OO50times, equivalent to a mixture of centesimal homeopathic dilutions C12, C30, C50 (Sample 4) or a medicinal product containing activated / potentiated forms of aqueous dilutions of polyclonal antibodies to CD4 receptor in ultra-low doses (ULD), obtained by superdiluting the initial matrix solution (2.5 mg / mL) by 10012, 1OO30, 1OO50times, equivalent to a mixture of centesimal homeopathic dilutions C12, C30, C50 (Sample 5) and a medicinal product containing a 1: 1 mixture of the above ultra-low doses (Sample 6) under conditions of influenza infection in female Balb / c mice was performed at the Federal State Budgetary Institution Research Institute of Influenza under the Ministry of Health and Social Development of Russia. Oseltamivir was used as comparison drug; the control group was administered distilled water (control).[000180] The infection process was modeled by intranasal administration of the influenza A / California / 07 / 2009swl (H1N1) virus at a dose of 10LD50 (the dose infecting 50% of tissue culture cells).[000181] The test samples were administered to mice (n=20 in each group) intragastrically at 0.2 mL / mouse twice a day (daily dose 0.4 mL / mouse) for 5 days before infection and for 10 days after infection. In addition, the test samples were added to the drinking bowls of the animals in the appropriate experimental groups. The drinking bowls were freely accessible.[000182] The comparison drug oseltamivir was administered to mice (n=20) intragastrically twice daily at a dose of 10 mg / kg (daily dose 20 mg / kg), starting from 1 hour before infection. The drug was administered for 5 days after infection with A / Califomia / 07 / 2009swl (H1N1) influenza virus. In this experimental group, the mice were administered distilled water instead of oseltamivir, intragastrically at 0.2 mL / mouse twice daily (daily dose 0.4 mL / mouse) for 4 days before infection and starting from day 6 after infection.[000183] In the control group, mice (n=20) were administered distilled water intragastrically twice daily at 0.2 mL / mouse (daily dose 0.4 mL / mouse). Throughout the study, the drinking bowls were filled with distilled water for the animals in these two experimental groups. The drinking bowls were freely available.[000184] The efficacy of the products was assessed based on the animals’ survival rate.[000185] Results[000186] The results of the study of the test samples’ antiviral activity are presented in Table 16. The statistical significance of differences between the experimental groups and the control group (distilled water) was calculated using the nonparametric chi-square criterion.Table 16. Results of the study of antiviral activity of the test samples on the model of influenza infection in female Balb / c mice infected by intranasal administration of A / Califomia / 07 / 2009swl (H1N1) influenza virus at a dose of 10LD50 (10 days after infection).- p <0.05 (significance of the difference from the control).[000187] Thus, as a result of this study, it is shown that the use of a preparation containing iteration of polyclonal antibodies to TNF-a (Sample 1) has a more pronounced antiviral effect than the use of a preparation containing a ULD of polyclonal antibodies to TNF-a (Sample 4). It has also been shown that administration of a preparation containing an iteration of polyclonal antibodies to the CD4 receptor (Sample 2) has a more pronounced antiviral effect than administration of a preparation of ULD AB to CD4 (Sample 5). The application of a preparation that is a mixture of the iterations under study (Sample 3) has a more pronounced antiviral effect than the application of a mixture of the above mentioned ULDs (Sample 6). It is also noteworthy that there are statistically significant differences in the survival rate of animals in the group receiving Sample 3 compared to the corresponding value for the control group.[000188] Example 10. Antituberculosis activity of the claimed product against Mycobacterium tuberculosis caused in guinea pigs.[000189] Materials and methods[000190] Laboratory conditions for preparing the iterations[000191] Iterations in each study were prepared by one operator on the same day. Temperature and humidity in the laboratory during sample preparation and subsequent measurements were controlled using a verified thermohygrometer IVA-6N (OOO NPK Microfor, Russia); temperature was 22±3 °C, humidity was 20-70 %. Vials made of transparent borosilicate glass (60, 500 ml, Glastechnik Grafenroda, Germany) were used for the preparation of iterations.[000192] Type 1 ultrapure water with a resistivity of 18.2 M xcm (Milli-Q Integral 5, Millipore) was used as the neutral carrier for the preparation of iterations, as well as the solvent for all other reagents used in this work. The quality of purified water was monitored daily by measuring resistivity using a SevenCompact S230 conductometer (Mettler Toledo, USA) and pH using a SevenCompact S220 pH meter (Mettler Toledo, USA). For liquids, automatic pipettes of different volumes (Eppendorf, Germany; Socorex, Switzerland) and measuring glassware of accuracy class A (Borosil, India; Steklopribor, Ukraine) were used. Dry reagents were weighed using an analytical balance of accuracy class I (Pioneer PA214C, Ohaus, USA). A calibrated laboratory timer Traceable (VWR, USA) was used to measure all incubation periods. Vibration was performed using a shaker (vortex) MS 3 basic (IKA-Werke, Germany) with a standard insert.[000193] Preparing iterations[000194] The process of preparing iterations included several stages. A 60 mL vial containing a 50 mL of the initial substance (purified water or metformin solution) and a 500 mL vial containing 480 mL of purified water (neutral carrier) were rotated on a vortex for 10 seconds at 3000 rpm in close contact with each other. Thereafter, both vials were incubated for 1 minute at room temperature in close contact. Using the above-described procedure, 480 ml of iteration No.O (zero iteration) was obtained. To obtain the first iteration (Ii), the vial with iteration No.O (480 mL) was placed next to a new 500 mL vial with 480 mL neutral carrier and rotated on a vortex for 10 seconds at 3000 rpm in close contact. Both vials were then incubated for 1 minute at room temperature in close contact. After the above-described procedure, the exposed neutral carrier was taken as Ii. Then, the second iteration (U) was obtained from Ii in a similar manner. The procedure was repeated the required number of times to obtain the final iteration.[000195] In this study, the iteration 6 prepared from a 1.8 mg / mL solution of monoclonal antibodies to HLA-DRB1 (Sample 1) and the iteration 10 prepared from 3.1 mg / mLsolution of monoclonal antibodies to P2-microglobulin (MG) (Sample 2) were used. The activity of the iterations was assessed by the following methods.Table 17.Note: (+) there is change compared to neutral carrier; (-) there is no change compared to neutral earner[000196] Biological model[000197] Anti -tuberculosis activity of the claimed medicinal product against induced Mycobacterium tuberculosis infection in guinea pigs was assessed.[000198] The study was aimed at investigating the anti -tuberculosis activity of the test samples against Mycobacterium tuberculosis on the model of experimentally induced tuberculosis in guinea pigs, in comparison with the anti-tuberculosis drug isoniazid. The study also assessed the product of technologically processing the initial substance of antibodies to HLA-DRB1 by method of successive multiple dilutions, in aqueous-alcoholic dilution C12C150 at a ratio of 2:3, monoclonal antibodies to HLA-DRB1 (Sample 3), and the product of technologically processing the initial substance of antibodies to [32-MG by the method of successive multiple dilutions, in aqueous dilution C12C150 at a ratio of 2:3, and monoclonal antibodies to [32-MG (Sample 4).[000199] Experimental groups:[000200] Group 1 : intact control, uninfected animals (n=7);[000201] Group 2: negative control (infected, untreated animals) (n=7);[000202] Group 3: animals that were administered placebo (purified water) orally 2 times a day for 5 days before infection and 6 days a week for two months, starting two weeks after infection, at a dose of 4 mL / kg (n=14);[000203] Group 4: animals that were administered placebo (purified water) orally 2 times a day for 5 days before infection and 6 days a week for two months, starting two weeks after infection, at a dose of 4 mL / kg, and 0.4 mL isoniazid at a dose of 10 mg / kg per day, 6 days a week, for two months, starting two weeks after infection (n=14);[000204] Group 5: animals that were administered Sample 1 orally 2 times a day for 5 days before infection and 6 days a week for two months, starting two weeks after infection at 4 mL / kg (n=14);[000205] Group 6: animals that were administered Sample 2 orally 2 times a day for 5 days before infection and 6 days a week for two months, starting two weeks after infection at 4 mL / kg (n=14);[000206] Group 7: animals that were administered Sample 3 orally 2 times a day for 5 days before infection and 6 days a week for two months, starting two weeks after infection at 4 mL / kg (n=14);[000207] Group 8: animals that were administered Sample 4 orally 2 times a day for 5 days before infection and 6 days a week for two months, starting two weeks after infection at 4 mL / kg (n=14).[000208] Study design[000209] This study lasted (196 days, 6.5 months): September to December: observation and treatment of experimental animals; January to March: microbiological and histological examination of diagnostic material collected at necropsy. Clinical examination, appearance, general health, and mortality rate were assessed daily before feeding the animals.[000210] The study products were administered to guinea pigs orally using a needle free syringe, at a total amount of 8 mL / kg twice a day for 5 days before infection and six days a week (daily, except Sunday) for 2 months after infection. The dose of the products was titrated once a week based on the results of weighing the animals. Water-starch suspension of isoniazid was administered to the animals at the same time and in the same way as the test samples. Isoniazid was administered at a dose of 10 mg / kg of body weight, in 0.4 mL of water-starch gruel.[000211] During the study, the survival rate, weight, growth rate of AL tuberculosis in cultures, and histological changes in the organs were assessed in all the groups of guinea pigs.Study resultsTable 18. Results of assessing the degree of damage to organs of guinea pigs.[000212] Conclusion[000213] The analysis of the data obtained during the study makes it possible to conclude that the positive therapeutic effect was equally observed in the group of animals treated with isoniazid and in the groups of animals treated with each of the test samples (Sample 1-4). Histological examination of the organs of animals in these groups showed signs of therapeutic pathomorphosis. The efficacy of the test samples against pulmonary infections was also demonstrated.[000214] Example 11. Experimental study of hypotensive effect of the claimed product.[000215] Materials and methods[000216] Laboratory conditions for preparing the iterations[000217] Iterations in each study were prepared by one operator on the same day. Temperature and humidity in the laboratory during sample preparation and subsequent measurements were controlled using a verified thermohygrometer IVA-6N (OOO NPK Microfor, Russia); temperature was 22±3 °C, humidity was 20-70 %. Vials made of transparent borosilicate glass (60, 500 ml, Glastechnik Grafenroda, Germany) were used for the preparation of iterations.[000218] Type 1 ultrapure water with a resistivity of 18.2 M xcm (Milli-Q Integral 5, Millipore) was used as the neutral carrier for the preparation of iterations, as well as the solvent for all other reagents used in this work. The quality of purified water was monitored daily by measuring resistivity using a SevenCompact S230 conductometer (Mettler Toledo, USA) and pH using a SevenCompact S220 pH meter (Mettler Toledo, USA). For liquids, automatic pipettes of different volumes (Eppendorf, Germany; Socorex, Switzerland) and measuring glassware of accuracy class A (Borosil, India; Steklopribor, Ukraine) were used. Dry reagents were weighed using an analytical balance of accuracy class I (Pioneer PA214C, Ohaus, USA). A calibrated laboratory timer Traceable (VWR, USA) was used to measure all incubation periods. Vibration was performed using a shaker (vortex) MS 3 basic (IKA-Werke, Germany) with a standard insert.[000219] Preparing iterations[000220] The process of preparing iterations included several stages. A 60 mL vial containing a 50 mL of the initial substance (purified water or metformin solution) and a 500 mL vial containing 480 mL of purified water (neutral carrier) were rotated on a vortex for 10 seconds at 3000 rpm in close contact with each other. Thereafter, both vials were incubated for 1 minute at room temperature in close contact. Using the above-described procedure, 480 ml of iterationNo.O (zero iteration) was obtained. To obtain the first iteration (Ii), the vial with iteration No.O (480 mL) was placed next to a new 500 mL vial with 480 mL neutral carrier and rotated on a vortex for 10 seconds at 3000 rpm in close contact. Both vials were then incubated for 1 minute at room temperature in close contact. After the above-described procedure, the exposed neutral carrier was taken as Ii. Then, the second iteration (h) was obtained from Ii in a similar manner. The procedure was repeated the required number of times to obtain the final iteration.[000221] The iteration 6 prepared from 2.0 mg / mL solution of monoclonal antibodies to C-terminal fragment of ATI angiotensin II receptor (Sample 1) and the iteration 3 prepared from 2.5 mg / mL solution of monoclonal antibodies to endothelial NO synthase (Sample 2) and iteration 11, obtained from a solution containing 1 : 1 mixture of monoclonal antibodies to the C-terminal fragment of ATI of angiotensin II receptor at a concentration of 2.0 mg / ml and monoclonal antibodies to endothelial NO synthase at a concentration of 2.5 mg / ml (Sample 3) were used in this study. The activity of the iterations was assessed by the following methods:Table 19.Note: (+) there is change compared to neutral carrier, (-) there is no change compared to neutral carrier[000222] Biological model[000223] The experimental study of hypotensive effect of the claimed technical solution used Samples 1-3 and a product containing an aqueous solution of activated- potentiated forms (ULD) of antibodies to the C-terminal fragment of ATi angiotensin II receptor (Sample 4), and a product containing an aqueous solution of activated-potentiated forms (ULD) of antibodies to endothelial NO synthase (Sample 5). To obtain Sample 4 and Sample 5, the initial substances were used in homeopathic dilutions C12, C30, C200. The studies were conducted on 70 male ISIAH rats (weight 300 g, age 4 months) with hereditary stress-sensitive arterial hypertension, which were divided into 7 groups of 10 animals each.[000224] The animals were administered the test samples orally at 2-2.5 mL / kg once a day for 28 days. In the positive control group, animals were administered the comparisondrug Losartan orally at 4-5 mL / kg (10 mg / kg) once a day. Group 5 was administered distilled water at 5 mL / kg. The control group animals were administered distilled water at 5 mL / kg orally, once a day for 28 days.[000225] Systolic blood pressure (SBP) was measured indirectly in the tail artery (using a cuff) twice a week, 2 to 6 hours after administration of the test samples or Losartan. Table 1 shows the changes in systolic blood pressure in ISIAH rats, measured by an indirect method.Table 20.[000226] The obtained results indicate a pronounced hypotensive effect of the test samples (Samples 1-5), compared to control sample. The test samples are not inferior in efficacy to the well-known and widely used antihypertensive drug Losartan.[000227] Example 12. Study of antidiabetic activity of drugs in a model of spontaneous insulin-independent, non-overweight diabetes mellitus in rats.[000228] Materials and methods[000229] Laboratory conditions for preparing the iterations[000230] Iterations in each study were prepared by one operator on the same day. Temperature and humidity in the laboratory during sample preparation and subsequent measurements were controlled using a verified thermohygrometer IVA-6N (OOO NPKMicrofor, Russia); temperature was 22±3 °C, humidity was 20-70 %. Vials made of transparent borosilicate glass (60, 500 ml, Glastechnik Grafenroda, Germany) were used for the preparation of iterations.[000231] Type 1 ultrapure water with a resistivity of 18.2 M xcm (Milli-Q Integral 5, Millipore) was used as the neutral carrier for the preparation of iterations, as well as the solvent for all other reagents used in this work. The quality of purified water was monitored daily by measuring resistivity using a SevenCompact S230 conductometer (Mettler Toledo, USA) and pH using a SevenCompact S220 pH meter (Mettler Toledo, USA). For liquids, automatic pipettes of different volumes (Eppendorf, Germany; Socorex, Switzerland) and measuring glassware of accuracy class A (Borosil, India; Steklopribor, Ukraine) were used. Dry reagents were weighed using an analytical balance of accuracy class I (Pioneer PA214C, Ohaus, USA). A calibrated laboratory timer Traceable (VWR, USA) was used to measure all incubation periods. Vibration was performed using a shaker (vortex) MS 3 basic (IKA-Werke, Germany) with a standard insert.[000232] Preparing iterations[000233] The process of preparing iterations included several stages. A 60 mL vial containing a 50 mL of the initial substance (purified water or metformin solution) and a 500 mL vial containing 480 mL of purified water (neutral carrier) were rotated on a vortex for 10 seconds at 3000 rpm in close contact with each other. Thereafter, both vials were incubated for 1 minute at room temperature in close contact. Using the above-described procedure, 480 ml of iteration No.O (zero iteration) was obtained. To obtain the first iteration (Ii), the vial with iteration No.O (480 mL) was placed next to a new 500 mL vial with 480 mL neutral carrier and rotated on a vortex for 10 seconds at 3000 rpm in close contact. Both vials were then incubated for 1 minute at room temperature in close contact. After the above-described procedure, the exposed neutral carrier was taken as Ii. Then, the second iteration (L) was obtained from Ii in a similar manner. The procedure was repeated the required number of times to obtain the final iteration.[000234] The iteration 34 prepared from 1.0 mg / mL solution of monoclonal antibodies to the beta chain of the insulin receptor (AB piR) (Sample 1), and the iteration 1 prepared from 3.2 mg / mL solution of monoclonal antibodies to endothelial NO synthase (Sample 2) were used in this study. The activity of the iterations was assessed by the following methods.Table 21.Note: (+) there is change compared to neutral carrier; (-) there is no change compared to neutral carrier[000235] Biological model[000236] The study was conducted at Paris Diderot University (Functional and Adaptive Biology Department, 2023). The antidiabetic activity of the products was studied in a model of spontaneous non-insulin-dependent diabetes mellitus not associated with excess weight in GK / Par rats. Goto-Kakizaki rats demonstrate mild but stable hyperglycemia after glucose absorption due to impaired glucose tolerance after a meal. These rats do not increase insulin secretion in response to glucose in vivo. In adult GK / Par rats, pancreatic insulin store is reduced by 60%, total [3-cell mass is depleted by 50%, basal glucose synthesis in the liver is increased, while muscle and fat tissues demonstrate insulin resistance.[000237] Male GK / Par rats weighing 283-314 g were divided into 7 groups of 12 animals each. The experimental groups animals were administered the iteration of piR AB (Sample 1) or the iteration of eNOs AB (Sample 2) at a dose of 2.5 mL / kg. The animals were also administered activated / potentiated forms of piR AB (Sample 3), eNOS AB (Sample 4) at a dose of 2.5 mL / kg / day (diluted with distilled water to 5 mL / kg / day). To obtain Samples 3 and 4, the original substances were used in homeopathic dilutions C12, C30, C200. Positive control group animals were administered Rosiglitazone at a dose of 5 mg / kg / day. Control animals were administered distilled water or 1% CMC solution (Rosiglitazone solvent) in equivalent doses. All samples were administered once daily, intragastrically, for 4 weeks.[000238] The basal level of fasting glucose in the blood plasma was assessed twice a week, before administering the products. The effect of the products on the rate of glucose disposal was also assessed in oral glucose tolerance test (2 g glucose / kg body weight) on the day before the first administration of the products (DO), on the first day after administration (DI) and on the day of the last administration of the products (D28) at 12:00.[000239] It was demonstrated that the use of Samples 1 and 2 for 28 days prevented the progression of diabetes mellitus and reliably reduced the level of glucose in the blood plasma by the end of the experiment compared to both Day 1 values on and the negative control (Table 22). The hypoglycemic effect of Sample 1 and Sample 2 exceeded that of Samples 3 and 4, respectively. Namely, it was shown that when Sample 3 was administered to experimental animals for 28 days, a decrease in the level of glucose in blood plasma was observed only relative to Day 1 values. Administration of Sample 4 had no significant effect on plasma glucose levels, either relative to day 1 values or relative to the negative control (purified water).[000240] By the end of the experiment, Rosiglitazone significantly reduced the plasma glucose level relative to Day 1 values. However, this effect did not significantly differ from that in the corresponding negative control group (CMC).Table 22. Effect of test products and corresponding controls on basal plasma glucose level (fasting) in male Goto Kakizaki / Par rats during 28-days administration, mg / mL, M±m[000241] The results of the oral glucose tolerance test showed that the hypoglycemic effect of Samples 1 and 2 was due to an increase in the sensitivity of peripheral tissues to glucose: the deterioration in glucose tolerance was less pronounced in the group administered these samples (Table 23). By contrast, a significant (p <0.05) decrease in the rate of glucose disposal was observed in the negative control groups (purified water for Samples 1-4 and 1% CMC solution for Rosiglitazone). Thus, the progression of diabetes mellitus was less pronounced when using Samples 1 and 2. The effect of these samples was also superior to the effect of Samples 3 and 4, respectively.Table 23. Effect of the test products on AUC value in oral glucose tolerance test with glucose load of 2 g / kg body weight in male Goto Kakizaki / Par rats before products administration (DO), on Days 1 (DI) and 28 (D28), M±mNote: * - significant difference from DO value, p <0.05; # - significant difference from the corresponding control, p <0.05.[000242] Overall, the obtained data show that the course administration of the iteration 34 obtained from the AB piR solution, and of the iteration 1 obtained from AB eNOs solution effectively reduced the level of blood glucose, increasing its disposal.[000243] Example 13. Assessment of Metabolic Activity of Cells.[000244] Materials and methods[000245] Laboratory conditions for preparing the iterations[000246] Iterations in each study were prepared by one operator on the same day. Temperature and humidity in the laboratory during sample preparation and subsequent measurements were controlled using a verified thermohygrometer IVA-6N (OOO NPK Microfor, Russia); temperature was 22±3 °C, humidity was 20-70 %. Vials made of transparent borosilicate glass (60, 500 ml, Glastechnik Grafenroda, Germany) were used for the preparation of iterations.[000247] Type 1 ultrapure water with a resistivity of 18.2 MQxcm (Milli-Q Integral 5, Millipore) was used as the neutral carrier for the preparation of iterations, as well as the solvent for all other reagents used in this work. The quality of purified water was monitored daily by measuring resistivity using a SevenCompact S230 conductometer (Mettler Toledo, USA) and pH using a SevenCompact S220 pH meter (Mettler Toledo, USA). For liquids, automatic pipettes of different volumes (Eppendorf, Germany; Socorex, Switzerland) andmeasuring glassware of accuracy class A (Borosil, India; Steklopribor, Ukraine) were used. Dry reagents were weighed using an analytical balance of accuracy class I (Pioneer PA214C, Ohaus, USA). A calibrated laboratory timer Traceable (VWR, USA) was used to measure all incubation periods. Vibration was performed using a shaker (vortex) MS 3 basic (IKA-Werke, Germany) with a standard insert.[000248] Preparing iterations[000249] The process of preparing iterations included several stages. A 60 mL vial containing a 50 mL of the initial substance (purified water or metformin solution) and a 500 mL vial containing 480 mL of purified water (neutral carrier) were rotated on a vortex for 10 seconds at 3000 rpm in close contact with each other. Thereafter, both vials were incubated for 1 minute at room temperature in close contact. Using the above-described procedure, 480 ml of iteration No.O (zero iteration) was obtained. To obtain the first iteration (Ii), the vial with iteration No.O (480 mL) was placed next to a new 500 mL vial with 480 mL neutral carrier and rotated on a vortex for 10 seconds at 3000 rpm in close contact. Both vials were then incubated for 1 minute at room temperature in close contact. After the above-described procedure, the exposed neutral carrier was taken as L. Then, the second iteration (L) was obtained from L in a similar manner. The procedure was repeated the required number of times to obtain the final iteration.[000250] This study used the iterations 1, 5 obtained from the solvent. The activity of the iterations was assessed by the following methods.Table 24.Note: (+) there is change compared to neutral carrier; (-) there is no change compared to neutral carrier; N / A - Not applicable[000251] Biological model[000252] Macrophages from intact C57B1 / 6 mice (4* 105cells / well in 50 pL) and a murine macrophage leukemia cell line, hereinafter RAW 264.7 (5* 104cells / well in 50 pL) were used in the experiment. Both cultures were provided by the Research Institute of Pharmacology and Regenerative Medicine (Tomsk, Russia) and cultured under standard conditions in a CO2 incubator (5%) at 37°C. Three groups of mouse-derived macrophages and three groups of RAW264.7 cells were treated with three different test samples (one of which was a placebo i.e. purified water) at 1 / 5 of the total volume per well (20 pL of sample + 80 pL of culture medium), followed by 48-hour incubation. The intact group treated with the medium only (100 pL) served as a control.[000253] Metabolic activity of cells after exposure to the test sample was assessed using the MTT assay in duplicate (n=5 wells for each group, 10 values in total). The MTT assay was performed according to the manufacturer's instructions. 17 pL of MTT solution (2 mg / mL) were added to 96-well plates with cells so that the final MTT concentration in each well was 200 pg / mL. The plates were then incubated for 4 hours at 37°C. The supernatants were removed and 50 pL of DMSO solution was added. Optical density (OD) was measured on a microplate reader at a wavelength of 540 nm. The results are presented as a percentage of the metabolic activity of intact control.[000254] The samples for in vitro macrophage metabolic activity assessment iterations of solvent were provided in dark glass vials as ready-to-use aqueous solutions for oral administration. In all experiments, the test samples were coded and tested blindly under identical conditions.[000255] Statistical Analysis[000256] The obtained data were analyzed and visualized using the R statistical computing environment version 4.2.2. (R Foundation for Statistical Computing, Vienna, Austria).[000257] The difference in the percentage of metabolic activity of macrophages was analyzed using Dunn's t-test.[000258] The normality of distribution was assessed using the Shapiro-Wilk test, and the homogeneity of variances was assessed using the Bartlett test.[000259] For each parameter, p-values were adjusted for the number of comparison pairs using the Holm method.[000260] Differences were considered statistically significant at p < 0.05.[000261] Results and Discussion[000262] The results are shown in Fig.l . Metabolic activity of Balb / c mice macrophages (A) and RAW 264.7 cell line (B) after incubation with the Active fraction (solvent- committed solvent) and the Native fraction (solvent-committed solvent) compared to placebo. Data are presented as mean and 95% confidence interval, dots represent individual values. N=10 in each group (5 wells measured in duplicate). Statistical significance was assessed using Dunn’s test with Holm’s correction for multiple comparisons.Metabolic activity (see Fig. 1) of healthy macrophages treated with the Active fraction of solvent iterations did not differ from the placebo level, while the administration of the Native fraction of solvent iterations resulted in a significant increase compared to the placebo level (146.1%±12.2 vs. 97.6%±4.8, p=0.002 (M±SD)). In the RAW 254.7 mice macrophage leukemia cell line, the effect was reversed: the Native fraction of solvent iterations decreased the metabolic activity of the cells compared to placebo (76.6%±2.0 vs. 91.5%±6.1, p<0.0001 (M±SD)). However, the Native fraction (solvent- committed solvent) had a similar, more pronounced effect (82.9% ± 2.5 vs. 91.5% ± 6.1, p = 0.02 (M±SD)).[000263] Example 14. Study of the antinociceptive effect.[000264] Materials and methods[000265] Laboratory conditions for preparing the iterations[000266] Iterations in each study were prepared by one operator on the same day. Temperature and humidity in the laboratory during sample preparation and subsequent measurements were controlled using a verified thermohygrometer IVA-6N (OOO NPK Microfor, Russia); temperature was 22±3 °C, humidity was 20-70 %. Vials made of transparent borosilicate glass (60, 500 ml, Glastechnik Grafenroda, Germany) were used for the preparation of iterations.[000267] Type 1 ultrapure water with a resistivity of 18.2 M xcm (Milli-Q Integral 5, Millipore) was used as the neutral carrier for the preparation of iterations, as well as the solvent for all other reagents used in this work. The quality of purified water was monitored daily by measuring resistivity using a SevenCompact S230 conductometer (Mettler Toledo, USA) and pH using a SevenCompact S220 pH meter (Mettler Toledo, USA). For liquids, automatic pipettes of different volumes (Eppendorf, Germany; Socorex, Switzerland) and measuring glassware of accuracy class A (Borosil, India; Steklopribor, Ukraine) were used. Dry reagents were weighed using an analytical balance of accuracy class I (Pioneer PA214C, Ohaus, USA). A calibrated laboratory timer Traceable (VWR, USA) was used to measure all incubation periods. Vibration was performed using a shaker (vortex) MS 3 basic (IKA-Werke, Germany) with a standard insert.[000268] Preparing iterations[000269] The process of preparing iterations included several stages. A 60 mL vial containing a 50 mL of the initial substance (purified water or metformin solution) and a 500 mL vial containing 480 mL of purified water (neutral carrier) were rotated on a vortex for 10 seconds at 3000 rpm in close contact with each other. Thereafter, both vials were incubated for 1 minuteat room temperature in close contact. Using the above-described procedure, 480 ml of iteration No.O (zero iteration) was obtained. To obtain the first iteration (Ii), the vial with iteration No.O (480 mL) was placed next to a new 500 mL vial with 480 mL neutral carrier and rotated on a vortex for 10 seconds at 3000 rpm in close contact. Both vials were then incubated for 1 minute at room temperature in close contact. After the above-described procedure, the exposed neutral carrier was taken as Ii. Then, the second iteration (U) was obtained from Ii in a similar manner. The procedure was repeated the required number of times to obtain the final iteration.[000270] In this study, the iterations 1, 5 obtained from the solvent were used. The activity of the iterations was assessed by the following methods.Table 25.Note: (+) there is change compared to neutral carrier; (-) there is no change compared to neutral carrier; N / A - Not applicable[000271] Biological model[000272] Male Balb / c mice (n=30) were obtained from Rappalovo nursery (St. Petersburg, Russia) and divided into 3 groups depending on body weight. In each group, animals were orally administered either a placebo (purified water) or the test samples in the form of aqueous solutions (10 mL / kg / day via tube, for 5 days), with the last administration on the day of testing. The experiment was approved by the Ethics Committee of the Research Institute of General Pathology and Pathophysiology, record No. 5 dated 10.10.2023.[000273] Fifteen minutes after the last injection of test samples, the mice were subcutaneously injected with 20 pL of 2% formalin solution into the plantar surface of the left hind paw using a 100 pL Hamilton syringe connected to a 30-gauge needle. A mouse was placed in a transparent observation chamber. After a 5-min adaptation period, the intensity of the pain response was assessed for the next 50 minutes (5 consecutive 10-min intervals) by the latency of the first pain response, the number of episodes of licking or twitching the injected paw.[000274] The samples for the formalin test (solvent-committed iterations) were provided in dark glass vials as ready-made aqueous solutions for oral administration. In all experiments, the test samples were coded and tested blindly under the same conditions.[000275] Statistical analysis[000276] The obtained data were analyzed and visualized using the R statistical computing environment version 4.2.2. (R Foundation for Statistical Computing, Vienna, Austria).[000277] The groups were compared pairwise using the two-tailed Mann-Whitney U-test or the two-tailed Student / Welch t-test, depending on the normality of the data distribution in the groups and the homogeneity of variances.[000278] The normality of distribution was assessed using the Shapiro-Wilk test, and the homogeneity of variances was assessed using the Bartlett test.[000279] For each parameter, p-values were adjusted for the number of comparison pairs using the Holm method.[000280] Differences were considered statistically significant at p < 0.05.[000281] Results and discussion[000282] The obtained results are presented in Fig. 2. Number of paw twitches during the 20-30 min of the test in response to formalin-induced pain. Active = Active fraction , n=l 1, Native = Native fraction of solvent iterations, n=l 1. For the placebo group, n=8. Data are presented as mean and 95% confidence interval, dots represent individual values. Statistical significance was assessed using Welch's t-test with Holm's correction for multiple comparisons.[000283] The most pronounced pain response was observed between 20 and 30 min of the experiment, while the number of post-injection paw twitches showed significant differences between the experimental groups. Active fraction of solvent iterations demonstrated a significant antinociceptive effect, reducing the mean number of pain responses by 74.4%. Native fraction of solvent iterations showed a less pronounced reduction in the number of pain reactions (by 57.2% compared to placebo, p=0.066).[000284] Example 15. Effectiveness of the claimed product in the treatment of influenza virus.[000285] Materials and methods[000286] Laboratory conditions for preparing the iterations[000287] Iterations in each study were prepared by one operator on the same day. Temperature and humidity in the laboratory during sample preparation and subsequent measurements were controlled using a verified thermohygrometer IVA-6N (OOO NPK Microfor, Russia); temperature was 22±3 °C, humidity was 20-70 %. Vials made of transparent borosilicate glass (60, 500 ml, Glastechnik Grafenroda, Germany) were used for the preparation of iterations.[000288] Type 1 ultrapure water with a resistivity of 18.2 MQxcm (Milli-Q Integral 5, Millipore) was used as the neutral carrier for the preparation of iterations, as well as the solvent for all other reagents used in this work. The quality of purified water was monitored daily by measuring resistivity using a SevenCompact S230 conductometer (Mettler Toledo, USA) and pH using a SevenCompact S220 pH meter (Mettler Toledo, USA). For liquids, automatic pipettes of different volumes (Eppendorf, Germany; Socorex, Switzerland) and measuring glassware of accuracy class A (Borosil, India; Steklopribor, Ukraine) were used. Dry reagents were weighed using an analytical balance of accuracy class I (Pioneer PA214C, Ohaus, USA). A calibrated laboratory timer Traceable (VWR, USA) was used to measure all incubation periods. Vibration was performed using a shaker (vortex) MS 3 basic (IKA-Werke, Germany) with a standard insert.[000289] Preparing iterations[000290] The process of preparing iterations included several stages. A 60 mL vial containing a 50 mL of the initial substance (purified water or metformin solution) and a 500 mL vial containing 480 mL of purified water (neutral carrier) were rotated on a vortex for 10 seconds at 3000 rpm in close contact with each other. Thereafter, both vials were incubated for 1 minute at room temperature in close contact. Using the above-described procedure, 480 ml of iteration No.O (zero iteration) was obtained. To obtain the first iteration (Ii), the vial with iteration No.O (480 mL) was placed next to a new 500 mL vial with 480 mL neutral carrier and rotated on a vortex for 10 seconds at 3000 rpm in close contact. Both vials were then incubated for 1 minute at room temperature in close contact. After the above-described procedure, the exposed neutral carrier was taken as Ii. Then, the second iteration (L) was obtained from Ii in a similar manner. The procedure was repeated the required number of times to obtain the final iteration.[000291] In this study, the iterations (1, 7) obtained from the solvent were used. The activity of the iterations was assessed by the following methods.Table 26.Note: (+) there is change compared to neutral carrier; (-) there is no change compared to neutral carrier; N / A - Not applicable[000292] Lactose powder was coated with the samples using the fluidized bed saturation method.[000293] Biological model[000294] Influenza infection was induced in 7-9 week-old female BALB / c mice (n=100) obtained from SMC STEZAR, Russia. All the procedures were approved by the Ethics Committee of the LI. Mechnikov Research Institute of Vaccines and Serums. The animals were divided into five groups comparable in body weight (within 10% tolerance, n=20 each). Group 1 mice were administered Tamiflu (Hoffmann-La Roche) orally 4 hours before infection (20 mg / kg / day, divided into 2 doses), then the dosing was repeated for 4 days. The mice in Groups 2 and 3 were administered the test samples (dissolved in purified water) intragastrically at 20 mL / kg / day 3 days before infection and for 6 days after infection. The mice in Group 4 were administered a placebo (intact lactose dissolved in purified water). The mice in Group 5 were administered distilled water based on the dosing regimen used for the test samples.[000295] Influenza infection[000296] Mice were anesthetized with ether and then infected intranasally with mouse-adapted influenza A / California / 04 / 2009 (HlNlpdm2009) virus (provided by the WHO National Influenza Center, A. Smorodintsev Research Institute of Influenza, Ministry of Health of the Russian Federation, St. Petersburg). For this experiment, an infectious dose of LD80 (25 pL in each nostril - 104TCIDso / 0.1 mL) was used.[000297] Animals were examined daily, their body weight was measured in the morning on the day of infection (day 0) and every other day until the end of the experiment (on days 2, 4, 6, 8, 10, 12, 14 after infection). On the day 4 after infection, 7 mice from each group were sacrificed by cervical dislocation, their lungs were isolated and used to estimate the virus titer. The virus titer was assessed using the Reed and Muench method and expressed as log 10 TCIDso / O.l mL.[000298] The remaining animals (n=13 per group) were observed for survival (the primary efficacy endpoint) for further 14 days.[000299] The test samples for the murine influenza model were provided as lactose- based powder in Falcon polypropylene tubes. Prior to intragastric administration, the test samples were dissolved in purified water by the following procedure: 1.25 g of the test sample was placed in a sterile polypropylene tube, and then purified water (15 mL) was added. The polypropylene tube containing the diluted test sample was gently mixed by inversion. Additional 10 mL of purified water was then added to the resulting solution (total 25 mL). The resulting solutions were mixed prior to each administration.[000300] Statistical analysis[000301] The obtained data were analyzed and visualized using the R statistical computing environment version 4.2.2. (R Foundation for Statistical Computing, Vienna, Austria).[000302] Differences in virus titer were analyzed using Dunn's t-test. The Kaplan- Meier method was used to estimate the survival of mice in the influenza infection model.[000303] Normality of distribution was assessed using the Shapiro-Wilk test, and homogeneity of variances was assessed using the Bartlett test.[000304] For each parameter, p-values were adjusted for the number of comparison pairs using the Holm method. Differences were considered statistically significant at p < 0.05.[000305] Results and discussion[000306] The obtained results are shown in Fig. 3. Survival of mice in a model of influenza infection. Native = solvent-committed solvent, Placebo = placebo, Active = solvent- committed solvent, Tamiflu = Tamiflu treatment, Control = distilled water administration. n=13 for survival analysis and n=7 for virus titer analysis, in each group. Statistical significance was assessed using the Kaplan-Meier method (survival) and Dunn's test (virus titer) with Holm's correction for multiple comparisons.[000307] In both control groups (placebo or distilled water), experimental influenza virus challenge resulted in high mortality of mice (Figure 3, A). The use of standard antiviral treatment Tamiflu resulted in a significant increase in survival rate (p=0.018 vs. placebo), and a similar trend was demonstrated for the Native treatment group (solvent-committed solvent) with the endpoint survival rate of 46.1% (p=0.63 vs. placebo).[000308] The value of influenza virus titer in the lungs confirmed the survival results, as the number of viral particles was reduced by Tamiflu (p=0.004 vs. placebo). A strong shift in the same direction was also observed in the Native solvent-committed solvent group (p=0.07 vs. placebo). Although these results are not statistically significant, they provide further evidence of the solvent iterations’ pharmacological activity.[000309] Example 16. Effect of the claimed product on the toxic dose of paracetamol.[000310] Materials and methods[000311] Laboratory conditions for preparing iterations[000312] Iterations in each study were prepared by one operator on the same day.Temperature and humidity in the laboratory during sample preparation and subsequent measurements were controlled using a verified thermohygrometer IVA-6N (OOO NPKMicrofor, Russia); temperature was 22±3 °C, humidity was 20-70 %. Vials made of transparentborosilicate glass (60, 500 ml, Glastechnik Grafenroda, Germany) were used for the preparation of iterations.[000313] Type 1 ultrapure water with a resistivity of 18.2 M xcm (Milli-Q Integral 5, Millipore) was used as the neutral carrier for the preparation of iterations, as well as the solvent for all other reagents used in this work. The quality of purified water was monitored daily by measuring resistivity using a SevenCompact S230 conductometer (Mettler Toledo, USA) and pH using a SevenCompact S220 pH meter (Mettler Toledo, USA). For liquids, automatic pipettes of different volumes (Eppendorf, Germany; Socorex, Switzerland) and measuring glassware of accuracy class A (Borosil, India; Steklopribor, Ukraine) were used. Dry reagents were weighed using an analytical balance of accuracy class I (Pioneer PA214C, Ohaus, USA). A calibrated laboratory timer Traceable (VWR, USA) was used to measure all incubation periods. Vibration was performed using a shaker (vortex) MS 3 basic (IKA-Werke, Germany) with a standard insert.[000314] Preparing the stock solutions of substances used for obtaining the iterations[000315] The 1 mg / mL stock solution of paracetamol was prepared by adding 5 mL of a freshly opened Paracetamol-Alium solution for infusions (OOO PFK ALIUM, Russia) with a concentration of 10 mg / mL to 45 mL of purified water, then mixing by inverting the bottle ten times.[000316] Obtaining the iterations[000317] The process of preparing iterations included several stages. A 60 mL vial containing a 50 mL of the initial substance (purified water or metformin solution) and a 500 mL vial containing 480 mL of purified water (neutral carrier) were rotated on a vortex for 10 seconds at 3000 rpm in close contact with each other. Thereafter, both vials were incubated for 1 minute at room temperature in close contact. Using the above-described procedure, 480 ml of iteration No.O (zero iteration) was obtained. To obtain the first iteration (Ii), the vial with iteration No.O (480 mL) was placed next to a new 500 mL vial with 480 mL neutral carrier and rotated on a vortex for 10 seconds at 3000 rpm in close contact. Both vials were then incubated for 1 minute at room temperature in close contact. After the above-described procedure, the exposed neutral carrier was taken as Ii. Then, the second iteration (L) was obtained from Ii in a similar manner. The procedure was repeated the required number of times to obtain the final iteration.[000318] In this study, the iterations obtained from the solvent (iterations 2, 3) or paracetamol (iterations 2, 5) were used. The activity of the iterations was assessed by the following methods.Table 27.Note: (+) there is change compared to neutral carrier; (-) there is no change compared to neutral carrier; N / A - Not applicable[000319] Biological model[000320] Fertilized eggs of Brachidanio rerio fish were obtained from breeding of wild-type hybrids and treated with placebo (purified water), or Active and Native fraction of solvent iterations, or Active and Native fractions of paracetamol iterations (n=20 or more per experimental group) or incubated in water for the intact control group (n=39).[000321] The fertilized eggs were incubated under controlled conditions in a solution of test samples (2 mL per well) or paracetamol (500 mg / 1). The incubation solutions were renewed daily. Larval viability was recorded as the main indicator of toxicity after 24, 48, 72, 96 and 120 h of incubation.[000322] Statistical analysis[000323] The obtained data were analyzed and visualized using the R statistical computing environment version 4.2.2. (R Foundation for Statistical Computing, Vienna, Austria).[000324] Survival analysis was performed using the Kaplan-Meier method with Holm's correction for multiple comparisons. Differences were considered statistically significant at p < 0.05.[000325] Results and discussion[000326] The obtained results are shown on Fig. 4. Survival of Brachidanio rerio fish eggs exposed to a toxic dose of paracetamol vs. eggs tested with the test samples. Native (par) = Native fraction of paracetamol iterations (n = 21), Active (par) = Active fraction ofparacetamol iterations (n = 20), Placebo = Placebo (n = 20), Native (sol) = Native fraction of solvent iterations (n=21), Active (sol) = Active fraction of solvent iterations (n=22), Control = intact control group (n=39). Statistical significance was assessed by the Kaplan-Meier method with Holm's correction for multiple comparisons.[000327] Figure 4 shows the ability to counteract the toxic effect of paracetamol iterations in Active fraction (p=0.048 vs. placebo) and Active fraction of solvent iterations (p=0.005 vs. placebo). Using these iterations resulted in a significant increase in Brachidanio rerio egg survival.[000328] Example 17. Study of the ability to counteract the development of metabolic syndrome and pathological fat formation in mice.[000329] Materials and methods[000330] Laboratory conditions for preparing the iterations[000331] Iterations in each study were prepared by one operator on the same day. Temperature and humidity in the laboratory during sample preparation and subsequent measurements were controlled using a verified thermohygrometer IVA-6N (OOO NPK Microfor, Russia); temperature was 22±3 °C, humidity was 20-70 %. Vials made of transparent borosilicate glass (60, 500 ml, Glastechnik Grafenroda, Germany) were used for the preparation of iterations.[000332] Type 1 ultrapure water with a resistivity of 18.2 MQxcm (Milli-Q Integral 5, Millipore) was used as the neutral carrier for the preparation of iterations, as well as the solvent for all other reagents used in this work. The quality of purified water was monitored daily by measuring resistivity using a SevenCompact S230 conductometer (Mettler Toledo, USA) and pH using a SevenCompact S220 pH meter (Mettler Toledo, USA). For liquids, automatic pipettes of different volumes (Eppendorf, Germany; Socorex, Switzerland) and measuring glassware of accuracy class A (Borosil, India; Steklopribor, Ukraine) were used. Dry reagents were weighed using an analytical balance of accuracy class I (Pioneer PA214C, Ohaus, USA). A calibrated laboratory timer Traceable (VWR, USA) was used to measure all incubation periods. Vibration was performed using a shaker (vortex) MS 3 basic (IKA-Werke, Germany) with a standard insert.[000333] Preparing iterations[000334] The process of preparing iterations included several stages. A 60 mL vial containing a 50 mL of the initial substance (purified water or metformin solution) and a 500 mL vial containing 480 mL of purified water (neutral carrier) were rotated on a vortex for 10 seconds at 3000 rpm in close contact with each other. Thereafter, both vials were incubated for 1 minuteat room temperature in close contact. Using the above-described procedure, 480 ml of iteration No.O (zero iteration) was obtained. To obtain the first iteration (Ii), the vial with iteration No.O (480 mL) was placed next to a new 500 mL vial with 480 mL neutral carrier and rotated on a vortex for 10 seconds at 3000 rpm in close contact. Both vials were then incubated for 1 minute at room temperature in close contact. After the above-described procedure, the exposed neutral carrier was taken as Ii. Then, the second iteration (U) was obtained from Ii in a similar manner. The procedure was repeated the required number of times to obtain the final iteration.[000335] In this study, we used U (iteration No. 6) obtained using purified water as initial substance (hereinafter referred to as Sample 1) and I4 (iteration No. 4) obtained using semaglutide solution as initial substance (1 mg / ml) (hereinafter referred to as Sample 3). The activity of iterations was determined by methods listed in Table 28.Table 28.Note: (+) there is change compared to neutral carrier, (-) there is no change compared to neutral carrier[000336] The study was conducted in a model of diet-induced metabolic syndrome in mature C57B1 / 6 mice (6 groups of 13 each). In the first group, rats received a standard diet (STD), in the second - STD and a placebo drug (purified water, Sample 2), in the third - a high- fat diet (HFD), in the fourth - HFD and Sample 1 (iteration No. 6 of purified water), in the fifth - HFD and Sample 2, in the sixth - HFD and Sample 3 (iteration No. 4 of semaglutide solution (1 mg / ml). Animals received HFD for 10 weeks. During the entire study, animals in HFD groups received standard synthetic complete food, manufactured at the research center according to the recipe AIN-93G, with the addition of rendered pork fat (lard). The drinking water for the animals in HFD groups was replaced with an 8% fructose solution. Animals of the first and second groups received standard synthetic complete food and water throughout the study. Experimental samples were administered to animals orally in the form of an aqueous solution daily for 10 weeks immediately from the start of the experimental diet-induced metabolic syndrome modeling.[000337] During the experiment, the body weight and body weight gain of laboratory animals in the control and experimental groups, as well as indicators of food and water consumption were monitored. At the end of the administration of experimental samples (10 weeks after the start of the experiment), mice of all groups were subjected to humane euthanasia by CO2 asphyxia with immediate collection of blood serum for biochemical analyzes and epididymal adipose tissue for histological examination. 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).[000338] The effectiveness of experimental samples against obesity was assessed by the body weight of the animals at the end of the experiment, as well as by the weight of epididymal adipose tissue.[000339] 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 analysis of variance and Dunn's test. Holm's correction for multiple comparisons was used. Differences between groups were considered statistically significant at p<0.05.[000340] The experiment showed that animals on a high-fat diet experienced a statistically significant increase in body weight and epididymal fat mass. Administration of Sample 1 resulted in a significant reduction in body weight (20% compared to placebo) as well as epididymal fat (59%). In the group treated with Sample 3, the epididymal fat mass was higher than in the placebo-treated group by 37%. The results of the study are presented in Table 29.Table 29. Results of determining body weight at the end of the experiment and visceral fat weightNote: * - differences are significant compared to groups maintained on standard diet, #- differences are significant compared to groups “high-fat diet” and “high-fat diet + Sample 2[000341] Thus, the Sample 1 (iteration No. 6 of purified water) demonstrated the ability to counteract the development of metabolic syndrome and pathological fat formation in mice, while Sample 3 (iteration No. 4 of semaglutide) increased the epididymal fat weight gain.[000342] Example 18.[000343] The blinded randomised comparative clinical trial determined the efficacy and safety of the claimed medicinal product - native fraction of iterations of phenobarbital, in the form of oral lozenge tablets in the treatment of sleep disorders and insomnia.[000344] The study included 10 outpatients aged 18 years and older with a diagnosis of chronic insomnia according to the International Classification of Sleep Disorders version 3 criteria: a. difficulty falling asleep, maintaining sleep or waking up earlier than expected; b. adequate facilities and time for sleeping; c. impaired daytime functioning due to sleep disturbance; d. sleep disturbance and associated daytime symptoms are present 3 or more times per week; e. sleep / wake problems are not explained by the presence of another sleep disorder; f. a sleep disorder meeting the criteria for insomnia has been present for more than 3 months.[000345] Patients taking medications affecting sleep, refusing or unable to discontinue these medications at least 1 week before the study and for the entire study period; patients with a history of drug, alcohol, or substance abuse; previously diagnosed endogenous mental illness; and patients working shift work were excluded. Patients suffering from decompensated somatic diseases were also not included in the study.[000346] At the start of the study (before starting the study drugs), we collected complaints, anamnesis, objective examination, patients filled out a questionnaire to assess falling asleep and sleep quality (the maximum number of points on the questionnaire - 30, a higher number of points indicates more pronounced insomniac disorders, Fig. 8) in the electronic patient diary (EPD) after instruction on working with the EPD by the doctor. If inclusion criteria were met and no non-inclusion criteria were met, patients were randomised using a random number table into one of two groups:• Group 1 (n=5): patients took native fraction of iterations of phenobarbital 1 tablet once a night (before bed at 21 : 00) for 5 days. This was followed by a ‘washout’ period of 2 days during which patients did not native fraction of iterations of phenobarbital. After 2 days, patients started taking the comparison drug (Zolpidem) 1 tablet once at bedtime (before bed at 21 :00) for 5 days;• Group 2 (n=5): patients took native fraction of iterations of phenobarbital 1 tablet once in the morning (after waking up) for 5 days followed by a 2-day ‘washout’ period. At the end of the 2 days, patients were started on the comparison drug (Zolpidem) 1 tablet once in the morning (upon waking) for 5 days.[000347] Blinded study design implied that the patient had no knowledge of the study drug being taken. After completion of the study medication, a washout period of 2 days occurred for patients in both groups. The study design is shown in Fig.5 A.[000348] During the study, patients used the EPD on their own on a daily basis: they filled out a questionnaire to assess falling asleep and sleep quality after taking the study drug, and during the ‘wash-out’ period - before 12:00. The doctor supervised the prescribed therapy, assessed the safety of the treatment administered and the degree of patients' adherence to the investigational therapy, and the completion of the EPD. In total, patients were observed in the study for 15 days.[000349] Primary criterion for assessing effectiveness:• change in scores on the sleepiness and sleep quality questionnaire after 5 days of therapy.[000350] Safety assessment criterion:• presence and nature of adverse events (AEs), relation to drug intake, outcome;[000351] In the 1 week prior to inclusion in the study, as well as during the study, any therapy that could affect patients' sleep and inhibition-excitation processes in the CNS was not allowed.[000352] Patients of both groups had no differences in clinical and demographic characteristics. The mean age of patients in group 1 (n=5) was 52.6±11.7 years, in group 2 (n=5) - 61.4±9.3 years (p=0.29). Males were 60% in group 1 and 20% in group 2, females were 40% and 80%, respectively (p=0.52). The initial severity of insomniac disorders in group 1 and group 2 was comparable and reached 15.2±3.1 points and 17.8±4.8 points, respectively (Table 1).[000353] Results on the evaluation of efficacy and safety[000354] Efficacy evaluation. The therapeutic response (change in scores on the Sleepiness and Sleep Quality Questionnaire) to native fraction of iterations of phenobarbital 1 tablet once at bedtime (before bed at 21 :00) for 5 days and 1 tablet once in the morning (upon awakening) for 5 days was manifested as a reduction in the time to fall asleep, a reduction in the number of nocturnal awakenings and an improvement in the quality of night sleep compared to the response to the comparison drug on similar regimens.[000355] Insomnia therapy with native fraction of iterations of phenobarbital for 5 days resulted in a statistically significant reduction in scores on the Sleepiness and Sleep Quality Questionnaire from 16, 2±3.1 points on Day 0 to 13.0±2.0 points on Day 5 (A 3.2 points) inGroup 1 and from 17.8±4.8 points on Day 0 to 12.8±2.1 points on Day 5 (A 5.0 points) in Group 2 (Factor ‘Day’ F=1.42, p=0.2474; factor ‘Group*Day’ F=1.00, p=0.4199; covariate ‘Day 0’ F=21.5, p=0.0003), whereas comparison drug therapy increased from 11.4±3.3 points on day 8 to 9.8±3.1 points on day 12 (A 1.6 points) in group 1 and from 11.8±3.1 points on day 8 to 8.8±1.7 points on day 12 (A 3.0 points) in group 2 (factor ‘Day’ F=2.41, p=0.0656; ‘Group*Day’ factor F=1.53, p=0.2113) (Table 30, Fig. 6 Change in scores on the Sleepiness and Sleep Quality Questionnaire after 5 days of therapy with native fraction of iterations of phenobarbital and the comparison drug).Table 30. Change in scores on the Sleepiness and Sleep Quality Questionnaire after 5 days of therapy with native fraction of iterations of phenobarbital and the comparison drugNote. Mean Sl) - mean value and its standard deviation, n - number of patients.[000356] Analysis of the results of therapy with the studied drugs according to the questionnaire for assessment of falling asleep and sleep quality revealed a statistically significant advantage of native fraction of iterations of phenobarbital 1 tablet once at night (before going to bed, at 21 :00) for 5 days and 1 tablet once in the morning (after waking up) for 5 days in the form of decreasing the time of falling asleep, improving the quality of night sleep, reducing the number of night awakenings with the impossibility of subsequent falling asleep and reducing sleepiness during the day compared to therapy with the comparison drug (p=0,0007).[000357] All patients (n=10) after the first taking of native fraction of iterations of phenobarbital, regardless of the regime of administration before bedtime or after awakening, noted a decrease in the difficulties of sleep initiation and maintenance, a reduction in the number of nighttime early morning awakenings with the inability to fall asleep, increased satisfaction with the quality of nighttime sleep and lengthening of total sleep duration, minimisation of the negative impact of sleep disorders on daily life in the form of increased efficiency and concentration, improved memory and us Short periods of treatment did not require gradual withdrawal of the drug, which was confirmed by the absence of ‘ricochet’ insomnia when patients were monitored during ‘washout’ periods.[000358] It should be noted that against the background of taking native fraction of iterations of phenobarbital no patient's condition worsened, whereas taking the comparison drug in the evening caused worsening of sleep quality and falling asleep, so it is necessary to pay attention to the positive effect of native fraction of phenobarbital on the quality of daily life of patients.[000359] Safety assessment. A total of 8 AEs were detected in 4 patients, including 2 AEs in 2 patients in Group 1 and 6 AEs in 2 patients in Group 2.[000360] Native fraction of iterations of phenobarbital (Group 2): patient 01-002- LTS on day 1 showed onset of headache in the evening (n=l); patient 01-008-DEI on day 3 and day 4 showed onset of somnolence after 16:00 and 17:00 (n=2). The AEs resolved with recovery. A cause-and-effect relationship of the AEs to the ingestion of native fraction of iterations of phenobarbital was not present in all cases in the opinion of the study physicians.[000361] Comparison drug (Group 1): patient 01-009-NDI on day 12 showed reduction of snoring (n=l); group 2: patient 01-002-LTS on day 9 registered toothache on the left side (n=l). The AEs resolved with recovery. In the opinion of the study physicians, there was no causal relationship of the AEs with the intake of the investigational comparator drug in all cases.[000362] On Day 6 (‘washout’ period) in Group 2, Patient 01-008-DEI had drowsiness (n=l), Patient 01-002-LTS had minor intermittent malaise headaches (n=l). On day 13 (‘washout’ period) in group 1, patient 01-005-CGV showed more vigour in the morning (n=l). The AEs resolved with recovery. In the opinion of the study physicians, there was no causal link between the AEs and the intake of the investigational drug in all cases. All patients in the study groups completed the treatment within the time limits set by the study protocol, there were no early dropouts.[000363] Thus, in patients with a diagnosis of chronic insomnia, monotherapy with native fractions of iterations of phenobarbital 1 tablet once a day both at night (before bedtime, at 21 :00) and in the morning (after waking up) for 5 days contributed to a statistically significant reduction in sleep disturbances and improvement of sleep quality compared to therapy with a comparison drug (p=0.0007). Native fractions of iterations of phenobarbital had a significant positive effect on the time of falling asleep, number of night awakenings, duration of night sleep against the background of improvement of subjective feeling of quality of night sleep in comparison with the therapy with the comparison drug, which improves the quality of life of patients and reduces the level of social maladaptation without the development of ‘ricochet’ insomnia.[000364] Example 19.[000365] The comparative clinical study determined the efficacy and safety of the claimed medicinal product, made in the form of oral drops of native fraction of iterations of benzodiazepine, in the treatment of sleep disorders and insomnia.[000366] The study included 10 outpatients aged 18 years and older with a diagnosis of chronic insomnia according to the International Classification of Sleep Disorders version 3 criteria.[000367] Patients taking medications affecting sleep, refusing or unable to stop taking these medications at least 1 week before the study and for the entire study period; patients with a history of drug, alcohol, or substance abuse; previously diagnosed endogenous psychiatric diseases; and patients working on a shift schedule were not included. Patients suffering from decompensated somatic diseases were also not included in the study.[000368] At the start of the study (before starting the study drugs), complaints, anamnesis, objective examination were collected, patients filled out the questionnaire for assessment of falling asleep and sleep quality (maximum number of points - 30, a higher number of points indicates more pronounced disturbances of falling asleep and sleep quality) in the EPD (Fig. 8) after being instructed in the use of the EPD by a physician. If inclusion criteria were met and no non-inclusion criteria were met, patients were started on native fraction of iterations of benzodiazepine 10 drops every 2 hours 6 times a day for 1 day, followed by completion of a questionnaire to assess falling asleep and sleep quality after the last drug administration. This was followed by a ‘washout’ period of 4 days during which patients did not take native fraction of iterations of benzodiazepine. After 4 days, patients started taking the comparison drug (Zolpidem) at 10 drops every 2 hours 6 times daily for 1 day, with completion of a questionnaire to assess falling asleep and sleep quality before starting the drug and after finishing the drug on the same day. The study design is shown in Fig. 5B.[000369] During the study, patients used the EPD on their own on a daily basis: they filled out a questionnaire to assess falling asleep and sleep quality after taking the study drug, and during the ‘wash-out’ period - before 12:00. The physician monitored the prescribed therapy, assessed the safety of the ongoing treatment and the degree of patients' adherence to the investigational therapy, and the completion of the EPD. In total, patients were observed in the study for 9 days.[000370] Primary criterion for assessing effectiveness:• change in the number of scores on a questionnaire to assess falling asleep and sleep quality after 1 day of therapy.[000371] Safety assessment criterion:• presence and nature of AEs, relationship to drug intake, outcome.[000372] In the 1 week before inclusion in the study, as well as during the course of the study, any therapy that could affect patients' sleep and inhibition-excitation processes in the CNS was not permitted.[000373] The average age of the patients was 57.0±11.7 years, among whom there were 40% men and 60% women. The baseline severity of insomniac disorders reached 13.3±3.5 points on the Sleepiness and Sleep Quality Questionnaire (Table 31).[000374] Results on efficacy and safety assessment[000375] Efficiency assessment. No statistically significant difference was found in the assessment of the sleeping effect after taking native fraction of iterations of benzodiazepine 10 drops every 2 hours 6 times a day for 1 day compared with the comparison drug. The change in scores on the Sleepiness and Sleep Quality Questionnaire during therapy with native fraction of iteration of benzodiazepine did not reach statistical significance (from 13.3±3.5 points on day 1 before starting native fraction of iteration of benzodiazepine to 12.3±3.8 points on day 2, A 1.0 point). Administration of the comparison drug was not associated with a statistically significant change in scores (from 13.4±4.5 points on day 6 to 10.7±2.8 points on day 7, A 2.7 points) (Table 31, Fig. 7 Change in scores on the Sleepiness and Sleep Quality Questionnaire after 1 day of therapy with native fraction of iterations of benzodiazepine and a comparison drug).Table 31. Change in scores on the Sleepiness and Sleep Quality Questionnaire after 1 day of therapy with native fraction of iterations of benzodiazepine and a comparison drugNote. Mean Sl) - mean value and its standard deviation, n - number of patients.[000376] In patients after native fraction of iterations of benzodiazepine and the comparison drug, no soporific effect in the form of improvement of falling asleep and quality of night sleep was observed. A few patients noted a mild anxiolytic effect in the form of a feeling of calmness while taking native fraction of iterations of benzodiazepine.[000377] Safety assessment. A total of 7 AEs in 4 patients were identified.[000378] Native fraction of iterations of benzodiazepine: in patient 01-011-FEA on day 1 after administration of the investigational drug, the appearance of headache was noted (n=l). The AE resolved with recovery. According to the opinion of the investigators, there was no causal relationship between the AE and the study drug administration.[000379] On Day 2 (‘washout’ period), Patient 01-014-CGV was slightly overexcited (n=l) and Patient 01-017-NDI was drowsy in the evening hours (n=l). On day 3 (‘washout’ period), patient 01-014-CGV showed fatigue in the evening (n=l). On Day 4 (‘washout’ period), Patient 01-017-NDI had drowsiness in the evening after 6pm, so went to bed earlier than usual (n=l). On day 5 and day 7 (‘washout’ periods), patient 01-018-ENV had persistent sleepiness (n=l) and somnolence (n=l), respectively.[000380] The AEs resolved with recovery. In the opinion of the physicians- researchers, there was no cause-and-effect relationship between AEs and the intake of the investigational drug in all cases. Thus, in patients with the presence of a diagnosis of chronic insomnia, monotherapy with native fraction of iterations of benzodiazepine compared to the comparison drug of 10 drops every 2 hours 6 times daily for 1 day did not have a significant sleeping effect compared to the comparison drug against a favourable safety profile.[000381 ] Example 20.[000382] Materials and methods[000383] Laboratory conditions for preparing the iterations[000384] Iterations in each study were prepared by one operator on the same day. Temperature and humidity in the laboratory during sample preparation and subsequent measurements were controlled using a verified thermohygrometer IVA-6N (OOO NPK Microfor, Russia); temperature was 22±3 °C, humidity was 20-70 %. Vials made of transparent borosilicate glass (60, 500 ml, Glastechnik Grafenroda, Germany) were used for the preparation of iterations.[000385] Type 1 ultrapure water with a resistivity of 18.2 MQxcm (Milli-Q Integral 5, Millipore) was used as the neutral carrier for the preparation of iterations, as well as the solvent for all other reagents used in this work. The quality of purified water was monitored daily by measuring resistivity using a SevenCompact S230 conductometer (Mettler Toledo, USA) and pH using a SevenCompact S220 pH meter (Mettler Toledo, USA). For liquids, automatic pipettes of different volumes (Eppendorf, Germany; Socorex, Switzerland) and measuring glassware of accuracy class A (Borosil, India; Steklopribor, Ukraine) were used. Dry reagents were weighed using an analytical balance of accuracy class I (Pioneer PA214C, Ohaus, USA). A calibrated laboratory timer Traceable (VWR, USA) was used to measure all incubationperiods. Vibration was performed using a shaker (vortex) MS 3 basic (IKA-Werke, Germany) with a standard insert.[000386] Preparing iterations[000387] The process of preparing iterations included several stages. A 60 mL vial containing a 50 mL of the initial substance (purified water or metformin solution) and a 500 mL vial containing 480 mL of purified water (neutral carrier) were rotated on a vortex for 10 seconds at 3000 rpm in close contact with each other. Thereafter, both vials were incubated for 1 minute at room temperature in close contact. Using the above-described procedure, 480 ml of iteration No.O (zero iteration) was obtained. To obtain the first iteration (L), the vial with iteration No.O (480 mL) was placed next to a new 500 mL vial with 480 mL neutral carrier and rotated on a vortex for 10 seconds at 3000 rpm in close contact. Both vials were then incubated for 1 minute at room temperature in close contact. After the above-described procedure, the exposed neutral carrier was taken as L. Then, the second iteration (L) was obtained from L in a similar manner. The procedure was repeated the required number of times to obtain the final iteration.[000388] In this study, we used the mixture (1 : 1 v / v) of L (iteration No. 3) and L (iteration No. 4) both obtained using Diazepam solution as initial substance (1 mg / ml) (hereinafter referred to as Sample 1). The activity of iteration was determined by methods listed in Table 32.Table. 32Note: (+) there is change compared to neutral carrier; (-) there is no change compared to neutral carrier[000389] In the study we determined the neurotropic activity of Sample 1 using generally accepted methodological approaches - study of animal behavior in the test “Elevated cruciform maze”. White male Wistar rats (n=21) were used in the study.[000390] Sample 1 was administered to 11 rats intragastrically at a dose of 5 ml / kg / day for 7 days. In the control group 10 rats were intragastrically administered purified water at a dose of 5 ml / kg / day for 7 days.[000391] Behavioral responses of rats using the indicated test were examined before administration of Sample 1 or control and the day after the last administration of Sample 1 or control (values on day 8).[000392] The “Elevated Cross Maze” test setup consists of 4 sleeves 0.5 m long and 10 cm wide, fastened together at right angles. Two opposite arms are surrounded on three sides by 40 cm high walls, the other two are open. The maze is located 0.5 m above the floor and its entire surface is evenly illuminated by two fluorescent lamps (20 W) located 60 cm above the level of the arms. Animals were placed on the central platform of the maze with their tails facing the open arm and the latent period of the animal's exit from the central platform, the time of staying in the open and closed arms, and the number of hanging off the edges of the maze were visually evaluated for 3 minutes.[000393] The obtained data were expressed as mean (M) and standard error of mean (SEM). Statistical analysis of differences between groups was performed using the Mann- Whitney criterion. The Wilcoxon test was used to determine the statistical significance of the data obtained on the 8th day of the experiment from the baseline. Differences were considered statistically significant at p < 0.05.[000394] The results showed that Sample 1 increased the latent period of the animal leaving the central site by 85.3% compared to baseline values, and the time spent in closed arms was also increased by 7% (p<0.05) compared to baseline values. The time in open arms decreased by 56.4% (p<0.05) and 66% (p<0.05), respectively, compared to baseline values and compared to values in the control (Table 33).Table 33.Note: * p < 0.05 compared to baseline; ** p < 0.01 compared to baseline; # p < 0.05 compared to the values of the control group on the 8th day.[000395] Thus, the claimed drug exhibits a pronounced sedative effect.[000396] Example 21.[000397] Materials and methods[000398] Laboratory conditions for preparing the iterations[000399] Iterations in each study were prepared by one operator on the same day. Temperature and humidity in the laboratory during sample preparation and subsequent measurements were controlled using a verified thermohygrometer IVA-6N (OOO NPK Microfor, Russia); temperature was 22±3 °C, humidity was 20-70 %. Vials made of transparent borosilicate glass (60, 500 ml, Glastechnik Grafenroda, Germany) were used for the preparation of iterations.[000400] Type 1 ultrapure water with a resistivity of 18.2 MQxcm (Milli-Q Integral 5, Millipore) was used as the neutral carrier for the preparation of iterations, as well as the solvent for all other reagents used in this work. The quality of purified water was monitored daily by measuring resistivity using a SevenCompact S230 conductometer (Mettler Toledo, USA) and pH using a SevenCompact S220 pH meter (Mettler Toledo, USA). For liquids, automatic pipettes of different volumes (Eppendorf, Germany; Socorex, Switzerland) and measuring glassware of accuracy class A (Borosil, India; Steklopribor, Ukraine) were used. Dry reagents were weighed using an analytical balance of accuracy class I (Pioneer PA214C, Ohaus, USA). A calibrated laboratory timer Traceable (VWR, USA) was used to measure all incubation periods. Vibration was performed using a shaker (vortex) MS 3 basic (IKA-Werke, Germany) with a standard insert.[000401] Preparing iterations[000402] The process of preparing iterations included several stages. A 60 mL vial containing a 50 mL of the initial substance (purified water or metformin solution) and a 500 mL vial containing 480 mL of purified water (neutral carrier) were rotated on a vortex for 10 seconds at 3000 rpm in close contact with each other. Thereafter, both vials were incubated for 1 minute at room temperature in close contact. Using the above-described procedure, 480 ml of iteration No.O (zero iteration) was obtained. To obtain the first iteration (Ii), the vial with iteration No.O (480 mL) was placed next to a new 500 mL vial with 480 mL neutral carrier and rotated on a vortex for 10 seconds at 3000 rpm in close contact. Both vials were then incubated for 1 minute at room temperature in close contact. After the above-described procedure, the exposed neutral carrier was taken as Ii. Then, the second iteration (U) was obtained from Ii in a similar manner. The procedure was repeated the required number of times to obtain the final iteration.[000403] In this study, we used the mixture (1 : 1 v / v) of I5 (iteration No. 5) and I7 (iteration No. 7) both obtained using diclofenac solution as initial substance (3 pg / ml) (hereinafter referred to as Sample 1). The activity of iteration was determined by methods listed in Table 34.Table 34.Note: (+) there is change compared to neutral carrier; (-) there is no change compared to neutral earner[000404] The aim of the study was to investigate anti-inflammatory activity of the claimed preparation in a study model of carrageenan-induced inflammation in rats in comparison with the anti-inflammatory drug indomethacin (Merck, USA).[000405] Experimental groups[000406] Group 1, male Wistar rats, received Sample 1 intragastrically for five days before induction of inflammation (last injection 1 h before induction) at a dose of 7.5 ml / kg / day (n=10);[000407] Group 2 - control, male Wistar rats, received purified water intragastrically for five days before induction of inflammation (last injection - 1 h before induction) at a dose of 7.5 ml / kg / day (n=10);[000408] Group 3, male Wistar rats, received indomethacin intragastrically at a dose of 10 mg / kg (in 7.5 ml / kg / day of purified water).[000409] Research design[000410] Animals were modeled inflammatory reaction by subplantar (under the plantar or plantar aponeurosis of the hind left paw) injection of 0.1 ml of 1% carrageenan solution (Sigma, USA). 1 hour after phlogogen injection, the animal was euthanized (animals were placed in a CO2 chamber until loss of consciousness and respiratory arrest), disarticulation in the ankle joints of the inflamed and healthy limb was performed. The mass of the right and left limbs was determined on the electronic scales Adventurer™ FR3130 (Ohaus, Switzerland). The magnitude of withdrawal was determined by the difference between the masses of the inflamed and healthy limbs of the animal. The anti-inflammatory effect was assessed by the reduction of edema and expressed as a percentage of control.[000411] Statistical analysis of the results was performed using the Kraskell-Wallis test with Tukey's post-hoc test. Differences were considered statistically significant at p < 0.05.[000412] Research resultsTable 35.difference from the indomethacin group is statistically significant, p < 0.05.[000413] The claimed drug reduced swelling mass by 31.4% compared to control, while indomethacin reduced it by 57.4%.[000414] Conclusion[000415] Thus, the claimed drug, which is a mixture (1 : 1 v / v) of 15 (iteration No. 5) and 17 (iteration No. 7) both obtained using diclofenac solution as initial substance (1 mg / ml), showed a pronounced anti-inflammatory activity in modeling carrageenan-induced inflammation in rats, reducing the mass of paw swelling.[000416] Example 22. Aqueous iterations, metformin iterations, and glucose iterations affect the rate of glucose utilization in mice[000417] Materials and methods[000418] Preparation of the initial substance, C6 glucose trituration.[000419] 1 g of lactose monohydrate was weighed and ground in a mortar with a pestle to fill the pores. Three 33 g portions of lactose powder and three 0.33 g portions of glucose were weighed. 33 g of lactose was placed in the mortar, then 0.33 g of glucose was added and the mixture was triturated with a pestle for 3.5 minutes. The resulting mixture was transferred to an evaporation bowl. The process was repeated twice and then all three mixtures were combined in the evaporation bowl. This mixture was taken as the first trituration of glucose powder, which was transferred into a 250 mL polypropylene flask. To obtain the second trituration of glucose, three new lactose portions of 33 g each were weighed. 33 g of lactose was added into a mortar followed by 0.33 g of the first trituration of glucose, and the mixture was triturated for 3.5 minutes. The resulting mixture was transferred to an evaporation bowl. Theprocess was repeated two more times, and all three mixtures were combined in the evaporation bowl, resulting in the second glucose trituration, which was transferred into a 250 mL polypropylene flask. The procedure was repeated six times until the sixth (C6) glucose trituration was obtained.[000420] Laboratory conditions for preparing the iterations[000421] Iterations in each study were prepared by one operator on the same day. Temperature and humidity in the laboratory during sample preparation and subsequent measurements were controlled using a verified thermohygrometer IVA-6N (OOO NPK Microfor, Russia); temperature was 22±3 °C, humidity was 20-70 %. Vials made of transparent borosilicate glass (60, 500 ml, Glastechnik Grafenroda, Germany) were used for the preparation of iterations.[000422] Type 1 ultrapure water with a resistivity of 18.2 M xcm (Milli-Q Integral 5, Millipore) was used as the neutral carrier for the preparation of iterations, as well as the solvent for all other reagents used in this work. The quality of purified water was monitored daily by measuring resistivity using a SevenCompact S230 conductometer (Mettler Toledo, USA) and pH using a SevenCompact S220 pH meter (Mettler Toledo, USA). For liquids, automatic pipettes of different volumes (Eppendorf, Germany; Socorex, Switzerland) and measuring glassware of accuracy class A (Borosil, India; Steklopribor, Ukraine) were used. Dry reagents were weighed using an analytical balance of accuracy class I (Pioneer PA214C, Ohaus, USA). A calibrated laboratory timer Traceable (VWR, USA) was used to measure all incubation periods. Vibration was performed using a shaker (vortex) MS 3 basic (IKA-Werke, Germany) with a standard insert.[000423] Preparing aqueous iterations[000424] The process of preparing iterations included several stages. A 60 mL vial containing a 50 mL of the initial substance (purified water or metformin solution) and a 500 mL vial containing 480 mL of purified water (neutral carrier) were rotated on a vortex for 10 seconds at 3000 rpm in close contact with each other. Thereafter, both vials were incubated for 1 minute at room temperature in close contact. Using the above-described procedure, 480 ml of iteration No.O (zero iteration) was obtained. To obtain the first iteration (Ii), the vial with iteration No.O (480 mL) was placed next to a new 500 mL vial with 480 mL neutral carrier and rotated on a vortex for 10 seconds at 3000 rpm in close contact. Both vials were then incubated for 1 minute at room temperature in close contact. After the above-described procedure, the exposed neutral carrier was taken as Ii. Then, the second iteration (U) was obtained from Ii in a similar manner. The procedure was repeated the required number of times to obtain the final iteration.[000425] Preparing lactose iterations[000426] Two 10 mL vials with 5 g of initial substance powder in each of them were placed closely together and vibrated on a vortex for 10 seconds at 3000 rpm in close contact. Both vials were then incubated for 1 minute at room temperature in close contact. Then, to obtain the first iteration (II), one of the vials containing the initial substance that had undergone the first step described above was taken as the effector and placed close to a 250 mL polypropylene flask containing 100 g of intact lactose (neutral carrier) and vibrated on a vortex for 10 seconds at 3000 rpm in close contact. Both, the vial and flask, were then incubated for 1 minute at room temperature in close contact, after which the flask with intact lactose was taken as II of the initial substance. To obtain the second iteration (12), the flask with II was placed close to a new 250 mL polypropylene flask containing 100 g of intact lactose and vibrated on a vortex for 10 seconds at 3000 rpm in close contact. Both flasks were then incubated for 1 minute at room temperature in close contact, after which the flask containing intact lactose was taken as the 12 of the initial substance. Next, 13 were obtained from 12 in a similar manner.[000427] Iteration (No.3) obtained from two C6 glucose triturations, iteration (No.7) obtained from purified water, and iterations (No. l, 6) obtained from metformin solution (1 mg / mL) were used in this study. The activity of the iterations was determined using the following methods.Table 36.Note:(-) there is no change compared to neutral carrier(+) there is change compared to neutral carrier[000428] Research methodology[000429] The study was performed on adult male Balb / c mice. Baseline glucose levels (DO) were measured 3-5 days after the animals were received. A change of bedding within 24 hours before the measurement was not performed to avoid the effect of stress on glucose levels. 13-15 h before the test, all animals were subjected to food deprivation.[000430] Administration of Native of water and Native of glucose triturations (5% water solution of lactose iteration) to animals was performed intragastrically once in the volume of 10 ml / kg immediately after the first measurement of glucose level. 30 minutes later 20% glucose solution at a dose of 2 g / kg was administered intragastrically. Blood glucose levels were assessed 15, 60 and 90 minutes after the glucose load.[000431] Aqueous metformin iterations (Active and Native) were administered intragastrically in the volume of 10 ml / kg for three days, with the last administration after the first glucose measurement and 30 minutes before the glucose load. The next blood glucose measurement was performed 15 minutes after glucose solution administration. A total of 4 time points were used for measurement: fasting, 15, 30, and 60 minutes after administration. Metformin (MF, single oral administration at a dose of 350 mg / kg) was used as a reference drug.[000432] Glucose levels were measured using a Contour TS glucometer and test strips (Ascensia Diabetes, Basel, Switzerland). The animal was placed under the grate with its tail stretched between the bars, and one of the lateral tail veins was punctured with a lancet The blood drop was collected on a test strip, the result was read and recorded in the protocol. Based on the measurements, an area under the curve (AUC) of the blood glucose level was calculated:where a is the initial value on the y-axis; b is the next value on the y-axis; f(a) is the value on the x-axis, corresponding to the point a; f(b) is the value on the x-axis, corresponding to the point b.[000433] ResultsTable 37. Results of the glucose tolerance test after administration of Native of water and Native of glucose triturations.Note: intact animals did not receive any preparations and glucose loadTable 38. Results of the glucose tolerance test after administration of metformin iterations.Note: intact animals did not receive any preparations or glucose loadTable 39. Area under the curve of the blood glucose level after administration of metformin iterations.Note: intact animals did not receive any preparations or glucose load[000434] Conclusions1. Native of lactose iteration of triturations C6 of glucose powder and Native of water had unidirectional hypoglycemic effects on the peak of glucose load (15 minutes after glucose administration).2. Native of aqueous iteration of MF significantly increased glucose levels compared to water (placebo) throughout the experiment, whereas Active of aqueous iteration of MF increased glucose levels only at 30 minutes after glucose load. Thus, metformin iterations had a similar hyperglycemic effect, opposite in direction to that of metformin at the therapeutic dose.[000443] Example 23. Evaluating the effects of iterations on physico-chemical processes involving the substance used to produce the iterations.[000444] Materials and methods[000445] Laboratory conditions for preparing the iterations[000446] Iterations in each study were prepared by one operator on the same day. Temperature and humidity in the laboratory during sample preparation and subsequent measurements were controlled using a verified thermohygrometer IVA-6N (OOO NPK Microfor, Russia); temperature was 22±3 °C, humidity was 20-70 %. Vials made of transparent borosilicate glass (60, 500 ml, Glastechnik Grafenroda, Germany) were used for the preparation of iterations.[000447] Type 1 ultrapure water with a resistivity of 18.2 MQxcm (Milli-Q Integral 5, Millipore) was used as the neutral carrier for the preparation of iterations, as well as the solvent for all other reagents used in this work. The quality of purified water was monitored daily by measuring resistivity using a SevenCompact S230 conductometer (Mettler Toledo, USA) and pH using a SevenCompact S220 pH meter (Mettler Toledo, USA). For liquids, automatic pipettes of different volumes (Eppendorf, Germany; Socorex, Switzerland) and measuring glassware of accuracy class A (Borosil, India; Steklopribor, Ukraine) were used. Dry reagents were weighed using an analytical balance of accuracy class I (Pioneer PA214C, Ohaus, USA). A calibrated laboratory timer Traceable (VWR, USA) was used to measure all incubation periods. Vibration was performed using a shaker (vortex) MS 3 basic (IKA-Werke, Germany) with a standard insert.[000448] Preparing iterations[000449] The process of preparing iterations included several stages. A 60 mL vial containing a 50 mL of the initial substance (purified water or metformin solution) and a 500 mL vial containing 480 mL of purified water (neutral carrier) were rotated on a vortex for 10 seconds at 3000 rpm in close contact with each other. Thereafter, both vials were incubated for 1 minute at room temperature in close contact. Using the above-described procedure, 480 ml of iteration No.O (zero iteration) was obtained. To obtain the first iteration (Ii), the vial with iteration No.O (480 mL) was placed next to a new 500 mL vial with 480 mL neutral carrier and rotated on a vortex for 10 seconds at 3000 rpm in close contact. Both vials were then incubated for 1 minute at room temperature in close contact. After the above-described procedure, the exposed neutral carrier was taken as Ii. Then, the second iteration (L) was obtained from Ii in a similar manner. The procedure was repeated the required number of times to obtain the final iteration.[000450] Iteration (No.5) obtained from sodium thiosulfate solution (Sample 1) was used in this study. Physico-chemical properties of iteration and its modifying effect on sodium thiosulfate solution were determined by the following methods.Table 40.Note: (-) no change compared to neutral carrier; N / A - Not applicable[000451] Decomposition reaction of sodium thiosulfate[000452] The effect of the test sample (sodium thiosulfate iteration) on the kinetics of the chemical reaction was evaluated in a well reproducible model reaction between sodiumthiosulfate and sulfuric acid. This reaction causes the solution to become cloudy and yellow colored: finely dispersed colloidal sulfur is formed, due to which the rate of the reaction can be estimated by the change in turbidity of the solution over time.[000453] Na2S2C>3 (0.1 M) solution was diluted 2-fold with the test sample to a concentration of 0.05 M. Dilution was performed in 20 mL glass vials by adding 2.5 mL of each solution.[000454] 1.5 mL of H2SO4 solution (0.05 M) was added to a quartz cuvette with a lid (Hellma 100-QS, optical path 10 mm, volume 3500 pL) by pipette, followed by 1.5 mL of Na2S2C>3 solution (0.05 M). Immediately, the cuvette was covered with a lid and the contents were mixed by a single inversion. The cuvette was then immediately placed in the spectrophotometer and the measurement of the time dependence of the optical density of the solution was started. The optical density was measured at X740 nm (selected experimentally) using a UV-1800 spectrophotometer, (Shimadzu) in kinetics mode for 5 minutes. Temperature (22°C) and humidity (37%) in the room were monitored using thermohygrometer (Testo 605-H1, TESTO AG, Germany)).[000455] Using the test sample, 6 replicates of the reaction were performed and, accordingly, 6 kinetic curves of the dependence of optical density on time were recorded. The kinetics data were fitted with a linear regression method, and the reaction rate was determined as the tangent (a) of the angle of the straight line slope. All solutions used in the study were prepared by the same operator and tested on the same day.[000456] Statistical analysis[000457] The obtained data were analyzed and visualized using the environment for statistical computing R version 4.2.2. (R Foundation for Statistical Computing, Vienna, Austria). Normality of distribution was assessed using the Shapiro-Wilk test. Groups were compared using the Mann-Whitney U-test. Differences were considered statistically significant at p<0.05.[000458] Effect of iterations on the decomposition reaction of sodium thiosulfate.Table 41.* - significant differences from neutral carrier (purified water) (p < 0.05).[000459] Table 41 presents the results of the effect of the test sample on the decomposition rate of sodium thiosulfate. When Sample 1 was added, an increase in the chemical reaction rate by 8.2% was observed compared to the neutral carrier (purified water) (p < 0.05).[000460] Thus, based on the data obtained, it can be concluded that iterations of one of the components of a chemical reaction can have a statistically significant effect on its rate.[000461] Example 24.[000462] Materials and methods[000463] Laboratory conditions for preparing iterations[000464] Iterations in each study were prepared by one operator on the same day. Temperature and humidity in the laboratory during sample preparation and subsequent measurements were controlled using a verified thermohygrometer IVA-6N (OOO NPK MICROFOR, Russia); temperature was 22±3 °C, humidity was 20-70 %. Vials made of transparent borosilicate glass (60, 500 ml, Glastechnik Grafenroda, Germany) were used for the preparation of iterations.[000465] Type 1 ultrapure water with a resistivity of 18.2 M xcm (Milli-Q Integral 5, Millipore) was used as the neutral carrier for the preparation of iterations, as well as the solvent for all other reagents used in this work. The quality of purified water was monitored daily by measuring resistivity using a SevenCompact S230 conductometer (Mettler Toledo) and pH using a SevenCompact S220 pH meter (Mettler Toledo). For liquids, automatic pipettes of different volumes (Eppendorf, Germany; Socorex, Switzerland) and measuring glassware of accuracy class A (Borosil, India; Steklopribor, Ukraine) were used. 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 periods. Vibration was performed using a shaker (vortex) MS 3 basic (IKA-Werke, Germany) with a standard insert.[000466] Preparing iterations[000467] The process of obtaining iterations included several stages. A vial with a capacity of 60 ml with a freshly prepared stock solution of the initial substance in a volume of 50 ml and a vial with a capacity of 500 ml with neutral carrier (purified water) in a volume of 480 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, 480 ml of iteration 0 (Io) was obtained.[000468] Next, a 480 ml vial with Io (35 ml) was placed adjacent to a new 500 ml vial with 480 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.[000469] In this study, we used the mixture (1 : 1 v / v) of L (iteration No. 6) and I9 (iteration No. 9) both obtained using Morphine (Sigma, USA) solution as initial substance (3 pg / ml) (hereinafter referred to as Sample 1). The activity of iteration was determined by methods listed in Table 42.Table 42.Note: (+) there is change compared to neutral carrier[000470] Analgesic activity was investigated after a 5-day intragastric administration of Sample 1 on the “Hot Plate” and “Paw Pressure” models.[000471] The data for the animals used in the study are shown in Table 43.Table 43.1. Animals were divided into 2 groups using body weight as the inclusion criterion so that individual weights did not differ by more than ±20% from the mean. Each group contained 10 animals.2. Group 1- Experimental. Sample 1 was administered intragastrically to the animals for 5 days at a rate of 10 ml / kg via an atraumatic metal probe.3. Group 2 - Control. Animals were intragastrically injected with purified water at a rate of 10 ml / kg for 5 days using an atraumatic metal probe.[000473] On day 5 (the end of the 5-day course of sample administration), 1 hour after the last injection, the animals were subjected to the paw pressure test and 2 hours later to the hot plate test.[000474] To assess analgesic activity in the 'paw pressure' test, each female rat that was to receive test samples was removed from the holding cage and the animal's paw was placed on a small platform under a cone-shaped pusher in an appropriate manner. The researcher then used a foot pedal to gradually increase the pressure on the rat's paw until it resisted and the paw jerked back. At the same time, the researcher released the pedal and the level of pressure at which the animal felt pain was recorded on a measuring scale (in g / mm2) using an analgesimeter (Ugo Basile, Italy).[000475] Studies to assess temperature sensitivity of rats were performed using the classic hot / cold plate test. Each animal studied was tested only once in the hot / cold plate setup, as repeated placement on the thermostatted plate contributes to bias in the results due to the immediate response to touching the surface. In addition, to reduce the likelihood of thermal damage to the animal's paw pads, the maximum duration of the test is not to exceed 60 seconds, and if the animal shows no activity during this time, it is removed from the hot surface and the latent response time is taken to be 60 seconds. The hot / cold plate apparatus (UgoBasile, Italy) consists of a thermostatically controlled, electrically heated surface surrounded by a transparent cylinder 15 cm in diameter. Temperature sensitivity was determined by the occurrence of motor responses of restlessness to thermal irritation: paw licking and jumping. For this purpose, a temperature of 55°C was set on the apparatus. At the moment the animal was placed on the plate, the "start" button on the instrument panel was pressed and the latent period (in seconds) of the nociceptive response in the animal was determined. That is, the time interval from the moment the animal was placed on the hot plate to the moment it licked its hind leg and jumped up was recorded. After these behavioural responses, the timer of the apparatus was stopped, the latency period was recorded and the animal was removed from the hot surface of the apparatus.[000476] Samples were considered effective if Group 1 (Sample 1) showed a statistically significant reduction in pain sensitivity compared to Group 2 (Control) in the paw pressure and hot plate tests.[000477] Descriptive statistics were applied to all data: the mean and standard error of the mean were calculated and presented in summary tables. The analysis was carried outseparately for each indicator. Statistical analysis was performed using the program Statist! cal 2.0.Differences from control were considered statistically significant at p < 0.05.[000478] Results[000479] The results of the Paw Pressure Test are shown in Table 44.Table 44. Results of the “Paw Pressure” test (M±m).* - Differences from Control are statistically significant (p <0.05).[000480] The presented data show that the values of the Analgesia Scale Index in animals treated with Sample 1 were 29% higher than in the Control group. Thus, animals treated with Sample 1 were less sensitive to pain than the Control group.[000481] The results of the hot plate test are presented in Table 45.Table 45. Results of the « Hot Plate » (M±m).[000482] The latency of the start of the first licking of the hind leg was 63.3% longer in animals receiving Sample 1 compared to the Control. As for the parameter "time of first jump up", the animals receiving Sample 1 had a 44.5% longer jump up time compared to the control. Thus, the animals receiving Sample 1 showed less thermosensitivity compared to the Control.[000483] Conclusions1. A clinically significant difference between groups was found in the paw pressure test. Animals receiving Sample 1 had a lower sensitivity to pain compared to the Control.2. A clinically significant intergroup difference was found in the Hot Plate test. Animals receiving Sample 1 showed lower thermosensitivity compared to the Control.[000484] Therefore, based on the results obtained, it can be concluded that the tested drug has analgesic activity.[000485] Example 25.[000486] Materials and methods[000487] Laboratory conditions for preparing the iterations[000488] Iterations in each study were prepared by one operator on the same day. Temperature and humidity in the laboratory during sample preparation and subsequent measurements were controlled using a verified thermohygrometer IVA-6N (OOO NPK Microfor, Russia); temperature was 22±3 °C, humidity was 20-70 %. Vials made of transparent borosilicate glass (60, 500 ml, Glastechnik Grafenroda, Germany) were used for the preparation of iterations.[000489] Type 1 ultrapure water with a resistivity of 18.2 M *cm (Milli-Q Integral 5, Millipore) was used as the neutral carrier for the preparation of iterations, as well as the solvent for all other reagents used in this work. The quality of purified water was monitored daily by measuring resistivity using a SevenCompact S230 conductometer (Mettler Toledo, USA) and pH using a SevenCompact S220 pH meter (Mettler Toledo, USA). For liquids, automatic pipettes of different volumes (Eppendorf, Germany; Socorex, Switzerland) and measuring glassware of accuracy class A (Borosil, India; Steklopribor, Ukraine) were used. Dry reagents were weighed using an analytical balance of accuracy class I (Pioneer PA214C, Ohaus, USA). A calibrated laboratory timer Traceable (VWR, USA) was used to measure all incubation periods. Vibration was performed using a shaker (vortex) MS 3 basic (IKA-Werke, Germany) with a standard insert.[000490] Preparing iterations[000491] The process of preparing iterations included several stages. A 60 mL vial containing a 50 mL of the initial substance (purified water or metformin solution) and a 500 mL vial containing 480 mL of purified water (neutral carrier) were rotated on a vortex for 10 seconds at 3000 rpm in close contact with each other. Thereafter, both vials were incubated for 1 minute at room temperature in close contact. Using the above-described procedure, 480 ml of iteration No.O (zero iteration) was obtained. To obtain the first iteration (Ii), the vial with iteration No.O (480 mL) was placed next to a new 500 mL vial with 480 mL neutral carrier and rotated on a vortex for 10 seconds at 3000 rpm in close contact. Both vials were then incubated for 1 minute at room temperature in close contact. After the above-described procedure, the exposed neutral carrier was taken as Ii. Then, the second iteration (U) was obtained from Ii in a similar manner. The procedure was repeated the required number of times to obtain the final iteration.[000492] In this study, we used I4 (iteration No. 4) obtained using Prednisolone (Sigma, USA) solution as initial substance (100 pg / ml) (hereinafter referred to as Sample 1). The activity of iteration was determined by methods listed in Table 46.Table 46.Note: (+) there is change compared to neutral carrier.[000493] To investigate the effect of sample 1 on the development of immediate- type hypersensitivity reactions, the severity of anaphylactic reactions in Balb / c mice (sexually mature males weighing 18-21 g) was assessed in response to sensitisation with a heterogeneous protein - normal horse serum (HS).[000494] Sensitisation schedule: HS at 1 / 10 dilution was administered p / v 0.3 ml once daily, 5 times with an interval of 4 days. The permissive HS of drug at 1 / 10 dilution was administered intravenously, 0.5 ml, on day 7 after the last sensitising injection.[000495] The following picture of shock was observed: in the first minutes after administration of a permissive dose of HS, excitement was observed, followed by depression. In 10-15 minutes, partial paresis of the limbs, cyanosis, clonic convulsions, and labored breathing appeared. Between convulsions, the animal would lie in the 'frog' position. Death occurred in 30- 40 min or recovery in 2 h.[000496] The results were evaluated according to the following criteria: no response; + - depressed state, eyes covered; ++ - cyanosis, mild convulsions, depressed state; +++ - cyanosis, clonic convulsions, depressed state, marked paralysis, 'frog' position; ++++ - lethal outcome.[000497] Sample 1, Control (purified water) and HS were administered as follows:[000498] Group 1.On days 1, 4, 8, 12 and 16, HS sensitisation was performed p / k 0.3 ml; from day 1 to day 10 - administration of Sample 1 (0.2 ml per os);on day 23 (on day 7 after the last HS administration) - administration of a permissive dose of HS and recording of the results.[000499] Group 2.On days 1, 4, 8, 1 2 and 16, HS sensitisation was performed p / k 0.3 ml; from day 1 to day 10 - administration of Control (0.2 ml per os); on day 23 (on day 7 after the last HS administration) - administration of a permissive dose of HS and recording of the results.[000500] Group 3.On days 1, 4, 8, 12 and 16, HS sensitisation was carried out p / k 0.3 ml; from the 14th to the 23rd day - administration of Samplel (0.2 ml per os); on the 23rd day (on the 7th day after the last HS administration) - administration of the authorising dose of HS and recording of the results.[000501] Group 4.On days 1, 4, 8. 1 2nd and 16th day HS sensitisation was performed p / k 0.3 ml; from day 14 to day 23 - administration of Control (0.2 ml per os); on day 23 (on day 7 after the last HS administration) - administration of a permissive dose of HS and recording of the results.[000502] Results[000503] In the groups where the course of Sample 1 was started simultaneously with sensitisation (*), pronounced statistically significant differences were observed between the control and experimental groups. In the control group, no mice survived, whereas in the experimental group, 5 out of 8 animals survived, and in 2 animals the shock manifestations were moderate, without development of pronounced paralysis, allowing its severity to be rated as ++. In the groups in which the course of Sample 1 was administered in the last 10 days before the administration of the permissive dose (**), there was a non-significant decrease in lethality in the experimental group compared with the control group (from 85.7% to 50.0%). The results are shown in Table 47.Table 47.Notes: ! - in all groups a permissive dose of drug was administered on day 7 after the last sensitising injection. * - Sample 1 (or Control) was administered from day 1 to day 10 of sensitisation. ** - the course of Sample 1 (or Control) administration was conducted from the 14th to the 23rd day of sensitisation. - no reaction; + - depressed state, eyes covered; ++ - cyanosis, insignificant convulsions, depressed state; +++ - cyanosis, clonic convulsions, depressed state, pronounced paralyses, ‘frog’ position; ++++ - lethal outcome.# - p < 0.05 when compared to the corresponding Control.[000504] It follows from the above data that the use of the claimed invention in prophylactic application significantly reduces the severity of immediate type hypersensitivity allergic reactions in the form of anaphylactic shock.[000505] Example 26.[000506] A single blind, placebo-controlled, randomised trial was conducted to determine the efficacy and safety of a claimed drug product, manufactured as an iteration of the substance sildenafil (I3+I7+I9, active fraction), in the treatment of erectile dysfunction (ED).[000507] Men aged 25-65 years with mild to moderate erectile dysfunction (11-20 IIEF-5 scores) who had not previously received drug therapy for erectile dysfunction were included in the study. Patients were then randomised to the drug or placebo group using a random number generator. The drug or placebo was administered according to a single schedule: 10 drops twice a day for 4 weeks. The effect was assessed after 4 weeks based on the dynamics of the mean score of the IIEF -5 questionnaire. Data are presented as mean and standard deviation. Patient proportions were compared by Fisher's exact test, between groups by Wilcoxon test, within groups ('before' vs. 'after') by paired t-test.[000508] Forty-two patients were included: 20 in the drug group and 21 in the placebo group. The mean age of the patients was 47.5±10.5 years in the drug group and 47.8±9.6 years in the placebo group. Initial ED severity did not differ between groups.[000509] During the four weeks of treatment, ED severity decreased significantly in the drug group and remained almost unchanged in the placebo group. The differences between the groups were statistically significant (Table 48).[000510] In the drug group, after 4 weeks of therapy, 45% of patients showed absence of objective signs of ED (more than 20 points on the IIEF -5 scale). There were no such patients in the placebo group.Table 48. Mean IIEF-5 scores in drug / placebo groups, before and after 4 weeks of therapy.[000511] No adverse events were reported in any group during the 4 weeks of treatment.[000512] The study demonstrated the efficacy and safety of iterations of sildanafil in the treatment of erectile dysfunction.[000513] Example 27.[000514] The efficacy and safety of the claimed medicinal product, manufactured as an iteration (12+110, Semi-native fraction) of a substance of the drug Sulpiride (the Drug), in the treatment of Irritable Bowel Syndrome (IBS) was determined in a single blind, placebo- controlled, randomised trial.[000515] Outpatients of both sexes aged 18-60 years with IBS exacerbation diagnosed according to Rome IV criteria (2016) were included in the study.[000516] Study inclusion criteria.[000517] Outpatients of both sexes with a diagnosis of IBS according to the Rome IV criteria (2016). Recurrent abdominal pain or discomfort with a frequency of at least 2 days per week at the time of enrolment. Age between 18 and 60 years inclusive. Intensity of abdominal pain / discomfort of at least 30 mm (max 100 mm - most severe pain, 0 - no pain) on a visual analogue scale (VAS).[000518] Study design.[000519] In the screening phase, anamnesis and complaints were taken, and objective, laboratory and instrumental examinations, including colonoscopy and ultrasound of the abdominal and pelvic organs, were carried out to rule out causes of pathological symptoms other than irritable bowel syndrome. The initial severity of the main symptoms of IBS was assessed. If the inclusion criteria were met, patients were randomised (envelope method was used) into one of two groups. Patients in group 1 (drug group) received the investigational drug 2 tablets twice a day for 8 weeks, and patients in group 2 (placebo group) received placebo according to the investigational drug schedule. During the subsequent treatment period, patientsmade two visits to the medical centre, during which their condition was assessed, objective and laboratory examinations, tests and questionnaires were performed, concomitant therapies, possible adverse events and compliance were recorded. If necessary, patients in both groups were allowed to take a laxative (Guttalax®), an anti diarrhoeal agent (Smecta®) for constipation and diarrhoea, respectively, and Noshpa® for severe spastic abdominal pain. These medicines were provided to patients throughout the study.[000520] The efficacy of the drug was assessed by:• The proportion of patients with a 30% or greater reduction in pain / discomfort after 8 weeks of therapy (according to VAS);• Dynamics of mean scores on the anxiety and depression subscale of the Hospital Anxiety and Depression Scale (HADS) after 8 weeks of treatment;[000521] Results[000522] Sixty-four patients were included, 32 in the drug group and 32 in the placebo group. The mean age was 47.5±10.5 years in the drug group and 47.8±9.6 years in the placebo group.[000523] The initial intensity of the pain syndrome according to VAS was 54.6±18.5 in the drug group and 55.8±14.4 in the placebo group (differences between the groups were not significant, p=0.444). On average, VAS pain severity decreased by 31.5±14.3 and 10.8±11.6 points in the drug and placebo groups, respectively, after 8 weeks of treatment. The differences between baseline and post-treatment scores were statistically significant in both groups (p<0.0001). The differences between the groups were also significant (p<0.0001).[000524] The proportion of patients with a 30% or greater reduction in VAS was 53.1% (17) in the drug group and 6.3% (2) in the placebo group. The differences between the groups were statistically significant (p<0.0001).[000525] The effect on anxiety and depression in patients with IBS was assessed using the HADS scale. The drug significantly reduced the severity of anxiety and depressive symptoms, significantly better than the placebo group (Tables 49, 50).Tab e 49, Change in mean score on the Anxiety subscale of the HAPS scaleTable 50, Change in mean score on the Depression subscale of the HAPS scale[000526] Taking the study drug for 8 weeks significantly reduced the main symptoms of irritable bowel syndrome and the severity of the pain syndrome, as well as the severity of anxiety and depression.[000527] Example 28. In vitro evaluation of the antitumour activity of the claimed drug against mastocytoma P-815.[000484] Materials and methods[000485] Laboratory conditions for preparing iterations[000486] Iterations in each study were prepared by one operator on the same day. Temperature and humidity in the laboratory during sample preparation and subsequent measurements were controlled using a verified thermohygrometer IVA-6N (OOO NPK Microfor, Russia); temperature was 22±3 °C, humidity was 20-70 %. Vials made of transparent borosilicate glass (60, 500 ml, Glastechnik Grafenroda, Germany) were used for the preparation of iterations.[000487] Type 1 ultrapure water with a resistivity of 18.2 MQxcm (Milli-Q Integral 5, Millipore) was used as the neutral carrier for the preparation of iterations, as well as the solvent for all other reagents used in this work. The quality of purified water was monitored daily by measuring resistivity using a SevenCompact S230 conductometer (Mettler Toledo, USA) and pH using a SevenCompact S220 pH meter (Mettler Toledo, USA). For liquids, automatic pipettes of different volumes (Eppendorf, Germany; Socorex, Switzerland) and measuring glassware of accuracy class A (Borosil, India; Steklopribor, Ukraine) were used. Dry reagents were weighed using an analytical balance of accuracy class I (Pioneer PA214C, Ohaus,USA). A calibrated laboratory timer Traceable (VWR, USA) was used to measure all incubation periods. Vibration was performed using a shaker (vortex) MS 3 basic (IKA-Werke, Germany) with a standard insert.[000488] Preparing iterations[000489] The process of preparing iterations included several stages. A 60 mL vial containing a 50 mL of the initial substance (purified water or metformin solution) and a 500 mL vial containing 480 mL of purified water (neutral carrier) were rotated on a vortex for 10 seconds at 3000 rpm in close contact with each other. Thereafter, both vials were incubated for 1 minute at room temperature in close contact. Using the above-described procedure, 480 ml of iteration No.O (zero iteration) was obtained. To obtain the first iteration (Ii), the vial with iteration No.O (480 mL) was placed next to a new 500 mL vial with 480 mL neutral carrier and rotated on a vortex for 10 seconds at 3000 rpm in close contact. Both vials were then incubated for 1 minute at room temperature in close contact. After the above-described procedure, the exposed neutral carrier was taken as L. Then, the second iteration (L) was obtained from L in a similar manner. The procedure was repeated the required number of times to obtain the final iteration.[000490] In this study, we used L (iteration No. 3) obtained using Cisplatin (Cisplatin NeoCorp, Hexal AG, Germany) solution as initial substance (1 mg / ml) (hereinafter referred to as Sample 1). The activity of iteration was determined by methods listed in Table 51. Table 51.[000491 ] Note: (+) there is change compared to neutral carrier.[000492] The study was conducted on P-815 mastocytoma cell culture. The following groups were formed in the experiments (n=10 in each group): first group - intact (complete culture medium), second - with addition of comparison drug cisplatin (1 / 5 volume of well), third - with addition of Sample 1 (cisplatin iterations) (1 / 5 volume of well), fourth - with addition of Sample 2 (placebo) (1 / 5 volume of well), fifth - with the addition of a comparison drug in combination with Sample 1 (cisplatin dissolved in Sample 1, injection volume 1 / 5 of the well), sixth - with the addition of a comparison drug in combination with Sample 2 (cisplatin dissolved in Sample 2, injection volume 1 / 5 of the well).[000493] Cell concentration and viability were counted before seeding the cells onto the plates. The cell concentration for seeding was 5xl04cells / well. The P-815 cell line wascultured in DMEM and EFV medium (containing a mixture of antibiotic and antifungal agent, sodium pyruvate and glutamine) at 37°C and 5% CO2. To 50 pL of cells, a mixture of 30 pL substance + culture medium and 70 pL complete culture medium (CCM) or a mixture of 30 pL substance + culture medium and 70 pL CCM with cisplatin (20 pMol / L) was added. To the wells where no experimental images were added, 100 pL PCS (control) or 100 pL PCS with cisplatin (20 pMol / L) was added. Co-incubation was then performed for 48 hours without changing the medium. After 48 hours, the MTT assay was performed. Incubation of cells with different samples was performed in separate plates. Each plate contained control wells (nutrient medium, values taken as 100%) and wells with added cisplatin.[000494] MTT assay[000495] Four hours before the end of tumour cell culture, MTT (3-[4,5- dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) solution (Serva, USA) was added to the wells at a final concentration of 200 pg / ml. The supernatant was then removed from the wells and the precipitate was dissolved with dimethyl sulfoxide (Sigma, USA). The absorbance of the resulting solutions was measured using a Titertek Multiscan MCC spectrophotometer (Labsystems, Finland) at a wavelength of 540 nm.[000496] For statistical processing of the results, normality of distribution was assessed by the Shapiro-Wilk test and homogeneity of variance by the Bartlett test. Groups were compared using T-test, analysis of variance, Kraskell-Wallis test, permutation test. Hill's multiple correction was applied. The null hypothesis was rejected when p <0.05.[000497] To express the metabolic activity values as percentages, the formula was used: (OD of experimental sample) / (OD of medium without added sample and / or cisplatin) *100%.[000498] Administration of cisplatin at a concentration of 20 pmol / L resulted in a significant decrease in the metabolic activity of the cells. Addition of sample 1 to P-815 mastocytoma cell culture resulted in a statistically significant decrease in tumour cell metabolic activity compared to the placebo group (Table 52).[000499] Administration of sample 1 or placebo together with cisplatin at a dose of 20 pmol / L did not affect the metabolic activity of P-815 mastocytoma cells compared to the corresponding values in groups incubated with cytostatic supplementation alone.Table 52. Effect of the tested samples on the metabolic activity of P-815 mastocytoma (n=10) incubated without cytostatic agent and with the addition of cisplatin at a dose of 20 pmol / L (data are presented as percentage of control, as mean±SE).Note: * - statistically significant differences compared to placebo, p < 0.05; n=10; # - statistically significant differences compared to medium without cisplatin.[000500] Sample 1 demonstrated the ability to inhibit the metabolic activity of tumour cells compared to placebo.

Claims

Claims1. A method of obtaining a product, which is a series of processed solvents, possessing an activating or suppressing effect on various physicochemical or biological processes involving the initial substance using for product obtaining or molecular target associated with it, by multiple successive external vibration treatment of the initial substance.

2. The method according to claim 1, wherein the multiple successive external vibration treatment of the initial substance is a process including: a) external vibration treatment on test tubes containing the initial substance and neutral solvent to obtain form neutral solvent the first artificial object - iteration zero; b) external vibration effect on test tubes containing the previous iteration and neutral solvent to obtain from neutral solvent the processed solvent - subsequent iteration; c) successive multiple repetitions of step b) using the processed solvent obtained previously and a neutral solvent to obtain a series of processed solvents representing the final product.

3. The method according to claim 1, wherein the initial substance may be used in an aggregate state selected from liquid, solid, gaseous state.

4. The method according to claim 1, wherein the initial substance selected from low- molecular compounds, high-molecular compounds, biologically active substances, organic or inorganic compounds, synthetic medicinal products, a neutral carrier processed by energy influence with transformed oscillations of bioelectric potentials in nervous tissue or brain, gradual products and neutral solvent.

5. The method according to claim 1, wherein a neutral solvent is water, water- alcohol solution, lactose or any pharmaceutically acceptable solvent.

6. The method according to claim 1, wherein the initial substance is one or more substances.

7. The method according to claim 1, wherein the external vibration treatment may be horizontal or vertical mechanical shaking.

8. The method according to claim 1, wherein the external vibration treatment is accomplished by electromagnetic, ultrasonic, acoustic or other rhythmic physical action.

9. The method according to claim 1, wherein the external vibration treatment is carried out within 10 sec - 10 min.

10. The method according to claim 1, wherein the external vibration treatment is followed by a subsequent co-incubation of the tubes together for 1 minute to 24 hours.

11. The method according to claim 1, in addition comprising an external physical influence selected from electromagnetic influence, temperature, infrared radiation.

12. A product which is a series of processed solvents, obtained by the method to claim 1, possessing an activating or suppressing effect on various physicochemical or biological processes involving the initial substance using for product obtaining or molecular target associated with it.

13. A method for separating the obtained products to claim 12, which constitutes a series of processed solvents, into fractions, including: a) measurement of chemical-physical properties and modifying activity of obtained processed solvents by analytical methods; b) separation of processed solvents into fractions, depending on the presence of altered physicochemical properties and / or modifying action; c) determination of specific biological and / or chemical activity for each fraction using standard methods.

14. The method according to claim 13, wherein analytical method is any known analytical method for determining the physical and chemical properties of a substance.

15. The method according to claim 13, wherein analytical method is selected from electrical conductivity (SEC), radiometry, terahertz spectroscopy, immunoassay (ELISA).

16. Fraction, obtained by the method to claim 13, constitutes a one or more processed solvent, possessing intrinsic physicochemical properties and regulates the physicochemical and biological processes involving the initial substance or its target molecule.

17. Fraction according to claim 16, wherein the regulation of processes activating or suppressing of processes.

18. Fraction according to claim 16, wherein the regulation of processes is carried out in different phases of these processes.

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