UA112749C2 - Pharmaceutical compositions and methods of treatment - Google Patents

Abstract

The present invention provides pharmaceutical compositions comprising an activated potentiated form of an antibody to human cannabinoid receptor and use in the treatment of obesity and related metabolic disorders. The present invention further provides pharmaceutical compositions comprising an activated potentiated form of an antibody to human cannabinoid receptor and activated potentiated form of an antibody to protein S-100 for use in the treatment of addiction to psychoactive substances. The present invention provides methods for treating obesity and related metabolic disorders and substance abuse.

Description

FIELD OF THE INVENTION

The present invention relates to medicinal products that can be used for the treatment of obesity and related metabolic disorders, as well as addiction to psychoactive substances, in particular nicotine.

TECHNICAL LEVEL

Today, obesity is recognized as a chronic disease that requires treatment to reduce health risks. The increase in obesity is a very urgent problem because this disease carries serious risks for people's health, leading to coronary heart disease, strokes, hypertension, type 2 diabetes, dyslipidemia, sleep apnea, osteoarthritis, gall bladder disease, depression, and some forms of cancer (for example, cancer of the body of the uterus, breast, prostate and colon). The negative health consequences of obesity are the second most preventable cause of death in the US

See, M. McGinnis (MeSippis M), U.H. Foyezh (EBoyede M/N), "Actual causes of mortality in

United States", medical publication "DJAMA" (CHAMA), 270, 2207 12 (1993).

It is believed that 5-10 95 weight loss can significantly improve the condition of metabolic components, such as blood glucose, blood pressure, and lipid concentration.

To date, those prescription drugs that are available for the treatment of obesity, in general, are able to reduce weight by inducing satiety or reducing the percentage of fat absorption. Satiation is achieved by increasing the synaptic levels of norepinephrine, serotonin, or both components at once. For example, stimulation of serotonin receptors subtypes 18, 10, and 2C, as well as adrenergic receptors 1 and 2, reduces food intake by regulating satiety. Look, GA. Bray (Wgau SA), "A new era of drug treatment.

Pharmacological Treatment of Obesity: A Symposium Review", Obesity. Research C (Suppl. 4), (1995). Adrenergic agents (such as diethylpropion, benzphytamine, phendimetrazine, mazindole, and phentermine) act by modulating central norepinephrine and dopamine receptors through stimulation to the release of catecholamines.Old weight-loss drugs that were based on the action of adrenergic receptors (such as amphetamines, methamphetamines, and phenmetrazine) that actively participated in the dopamine process are no longer recommended for use because of the risk of abuse. and

Zofenfluramine and dexfenfluramine, which belong to the group of serotonergic drugs used to regulate appetite, are no longer available for use.

Unfortunately, due to the pronounced side effects and the development of addiction that occurs as a result of the use of these psychoactive substances, such a drug has not yet been invented that would be effective and safe and would have a centralized effect. Thus, there is still a need for more effective and safer methods of therapeutic treatment that could reduce or prevent obesity and all associated metabolic disorders.

In addition to obesity, there is also a need to treat such a disease as addiction to certain substances.

Tobacco addiction is one of the top 3 preventable causes of morbidity and mortality in our society, as it is responsible for thousands of deaths each year. Half of all smokers die from diseases directly related to tobacco use, and most of them are highly susceptible to disease. About 15 million smokers try to quit smoking, but every year, only one million of them manage to get rid of this bad habit.

Cigarette smoke contains a large number of very complex substances, the most important of which is nicotine, which is precisely the substance to which smokers develop addiction. Several pharmacotherapies have proven effective in the treatment of tobacco addiction. These therapies include nicotine replacement therapies in the form of chewing gum, patches, nasal sprays, and inhalers. Nicotine-free pharmacological therapies have been developed as a method of treating nicotine addiction. Possible reagents included: nicotine blockade therapy, drugs affecting serotonergic neurotransmission, antidepressants, tranquilizers, clonidine, and replacement of the sensory capacity of the respiratory tract (Rose (Nove), 1996; Chinchiripini (Sipsiiripi) et al., 1998. Oncology 12: pp. 249-256). Nicotine blockade therapy (which also refers to the use of nicotinic receptor blockers) uses compounds that take the place of nicotine receptors, which weaken the same feeling of pleasure that a person gets from tobacco (Clarke (Siagkeye), 1991. British Journal of Addiction) 86: pp. 501-505).

Despite the availability of such methods of treatment of tobacco addiction, the need for more effective methods is still relevant.

Cannabinoid receptors belong to the class of cell membrane receptors of the superfamily or protein-coupled receptor. Cannabinoid receptors are activated by three main groups of ligands, namely: (a) endocannabinoids (produced in mammals), (b) plant cannabinoids (such as THC produced in the cannabis plant), and (c) synthetic cannabinoids (such for example, as HO-210, which were first synthesized in 1988 from (18, 55)-Mupepoi). These cannabinoids exert their effects by binding to cannabinoid receptors located in the cell membrane. Endocannabinoids are participants in many physiological and pathophysiological processes. To date, most drugs used to interact with the endocannabinoid system are derived from cannabis. Cannabis is most popular as a raw material for the manufacture of products such as marijuana and hashish, and its regular use can eventually turn into an addiction.

Let's consider two characteristic cannabinoid receptors: cannabinoid receptor 1 (CRI) - a central receptor found in the brain and peripheral tissues of mammals and cannabinoid receptor 2 (CB2) - a peripheral receptor, which is found only in peripheral tissues. The SVI receptor is mainly highly expressed in several brain regions, including the limbic system (cerebellar amygdala, hippocampus), hypothalamus, cerebral cortex, cerebellum, and basal ganglia. To reflect the diversity of pharmacological effects, certain compounds acting as agonists or antagonists for one or both of these receptors were used. See, for example, R.G. Pertwee (Repmee VS), "Pharmacology of cannabinoid receptors SVI and SV2", Pharmacology. Therapy, (1997) 74: p. 129-180 and V. Di Marso (Oi Mag2o M), D. Melk (0. MeisK), T. Bisogno (T. Vizodpo) and L. De-

Petrosellis (I. OeReigoseiiv), "Endocannabinoids: endogenous ligands of cannabinoid receptors of neuromodulatory action", Neurotic tendencies (Ttepav Meigov) (1998) 21: p.521-528.

The therapeutic effect of a highly diluted (or ultralow) form of antibodies potentiated by homeopathic technology (activated potentiated form) was discovered by the inventor of this patent application, Dr. Oleg Ivanovich Epshtein. US Patent No. 7,582,294 for a drug for the treatment of benign prostatic hyperplasia, or prostatitis, by administration of an activated homeopathic form of antibodies to prostate-specific antigen (PSA).

Protein 5-100 is an acidic cytoplasmic protein found in the nervous system.

It has been suggested that protein 5-100 plays a role in causing feelings of anxiety. see

Zoe Ackermann (AsKeptapp) et al., "Increased exploratory activity and reduced response to anxiety stimulation in male mice as a consequence of protein 5100A1 deficiency," Biochemistry.

Biophysics. Protocols for 2006, 63 (11):1307-19; Diehl (Oiepi) et al., "Acute Effects of Maternal Weaning and Exposure to a PTSD Model on Behavior and 51008 Protein Levels in Sex-Different Rats." Brain Research, 2007, 144:107-16. These materials are incorporated herein by reference.

Administration of ultra-low doses of antibodies to 5-100 proteins had a sedative, anti-asthenic, anti-aggressive, anti-stress, anti-hypoxic, anti-ischemic, neuroprotective and nootropic effect. See V. Castagne (Saziadpe U), et al., "Sedative effect of ultralow-dose anti-protein 5100 antibodies in adult rats," Journal of Pharmacy. Pharmacology 2008, 60 (3):309-16;

O.I. Epstein, "Antibodies to calcium-binding protein 51008 block long-term hypersensitivity in land snails," Pharmacology. Biochemistry. Study of behavior, 2009, 94 (1):37-42; AND. Voronina et al., Chapter 8. Effect of antibodies to 5-100 proteins in anxiety-depressive disorders in experimental and clinical conditions. "Animal models in biological psychiatry", ed. A.V. Kaleff (A.M. Kaisheii), New York, New Science

Publishers, Inc. (Mem Zsiepse Rybiizneg5, Ips.), 2006, pp. 137-152. These materials are incorporated herein by reference.

The problem of obesity and dependence on certain substances remains relevant, and therefore the search for new medical drugs with the desired therapeutic effect against the above-mentioned diseases must continue.

BRIEF DESCRIPTION OF THE INVENTION

In one aspect, the invention relates to a medicinal product consisting of an activated potentiated form of an antibody to a human cannabinoid receptor. In humans, the predominant cannabinoid receptor is receptor 1 (CB1). It is anticipated that in this aspect of the invention, the activated potentiated form of the antibody fully affects the human cannabinoid receptor 1. The specific sequences presented in the detailed description of the invention directly reflect the effect of this prediction. It is assumed that the activated potentiated form of the antibody acts on the polypeptide fragment of the human cannabinoid receptor 1. The activated potentiated form of the antibody is preferably presented in the form of a mixture of homeopathic dilutions of C12, C30 and C200. In a particularly preferred embodiment, the activated potentiated form of the antibody is presented in the form of a mixture of homeopathic dilutions C12, C30 and C200 with which the solid carrier is impregnated.

It is assumed that the activated potentiated form of the human cannabinoid receptor antibody is a monoclonal, polyclonal, or natural antibody. The activated potentiated form of the human cannabinoid receptor antibody is, preferably, a polyclonal antibody. Antibody to the human cannabinoid receptor can be obtained by making successive hundredfold dilutions in combination with shaking of each solution.

According to another aspect, the invention relates to a method of treating obesity and related metabolic disorders. The specified method involves the administration of a medicinal product of any type or form provided for by this aspect of the invention. The drug can be administered to the patient in a dosage form for single or double administration from one to four times a day. In this case, twice daily administration is considered.

In another aspect, the invention relates to a method of treating nicotine addiction.

The specified method involves the administration of a medicinal product of any type or form contemplated by this aspect of the invention. The drug can be administered to the patient in a dosage form for single or double administration from one to four times a day. In this case, twice daily administration is considered.

In another aspect, the invention relates to a method of altering the anthropometric parameters of a mammal expected to benefit from such alteration. The specified method involves the administration of a medicinal product of any type or form contemplated by this aspect of the invention. According to one modification, the anthropometric parameter is waist circumference. According to another modification, the anthropometric parameter is the ratio of waist circumference to height. And according to another modification, the anthropometric parameter is the ratio of waist and hip circumferences. Various options are considered here.

In another aspect, the invention relates to a method of reducing body weight in mammals. The specified method involves the administration of a medicinal product of any type or form contemplated by this aspect of the invention. In one embodiment, the body weight is reduced by at least 5 95. In another embodiment, the body weight is reduced by at least 10-15 95. In another embodiment, the body weight is reduced by less than 15 95.

According to another aspect, the invention relates to a method of reducing the growth of a mammal's body weight.

The specified method involves the administration of a medicinal product of any type or form contemplated by this aspect of the invention. In one embodiment, body weight gain is reduced by at least 10 95 . In another embodiment, body weight growth is reduced by at least 30 95 .

In another aspect, the invention relates to a method of facilitating a reduction in food intake in a mammal expected to benefit from such reduction.

The specified method involves the administration of a medicinal product of any type or form contemplated by this aspect of the invention.

According to another aspect, the invention relates to a medicinal product, which consists of an activated potentiated form of an antibody to the human cannabinoid receptor and an activated potentiated form of an antibody to proteins 5-100. In one embodiment, the antibody to protein 5-100 is an antibody to whole protein 5-100. Protein sequences 5-100 are given in the specification. Antibodies to proteins 5-100 are mainly presented in the form of a mixture of homeopathic dilutions of C12, C30 and C200, with which a solid carrier is impregnated. The pharmaceutical composition of this aspect of the invention may include an antibody to protein 5-100, which is a monoclonal, polyclonal or natural antibody. As a rule, the antibody to the 595-100 protein is polyclonal. Antibody to protein 5-100 can be obtained by making successive hundredfold dilutions in combination with shaking of each dilution.

In another aspect, the invention relates to a method of treating a patient suffering from addiction to psychoactive substances. The specified method involves the administration of a medicinal product containing an activated potentiated form of an antibody to the human cannabinoid receptor or an activated potentiated form of an antibody to the 595-100 protein. Predominantly, the psychoactive substance is nicotine. According to the withdrawal symptom scale test (MP55 test), the introduction of the above-mentioned combinations, from the point of view of statistics, leads to a significant improvement in the ability to endure the process of giving up (quitting) smoking. Also, according to the Fagerström Nicotine Dependence Test (Radegvigot Te5i), the very introduction of the above-mentioned combinations, from a statistical point of view, leads to a significant decrease in the number of smokers among hospital patients with both moderate and severe forms of nicotine addiction.

In another aspect, the invention relates to a medicinal product used to treat patients suffering from addiction to psychoactive substances. The specified agent must be obtained in such a way that the result is the production of a) a potentiated solution of the antibody to the human cannabinoid receptor and b) a solution of the activated potentiated form of the antibody to 5-100 proteins, each of which is made by creating successive repeated dilutions and repeatedly shaking each of the resulting solution in a vertical position in accordance with the technology of manufacturing homeopathic preparations, and then combining the potentized solutions, mixing them, or impregnating the carrier with the indicated combined solution or each solution separately.

In another aspect, the invention relates to a medicinal product used for the treatment of obesity and related metabolic disorders. The specified agent must be obtained in such a way that the result is the production of a potentized solution of antibodies to the human cannabinoid receptor, made by making successive repeated dilutions and repeatedly shaking each obtained solution in a vertical position in accordance with the technology for the manufacture of homeopathic preparations, and then, optionally , impregnation of the carrier with the specified solution.

BRIEF DESCRIPTION OF SCHEMATIC IMAGES

Fig. 1 - Reflects the effect of NND antibodies to SV-1 and Sibutramine on increasing body weight and volume of food consumption.

Fig. 2 - Reflects the decrease in body weight after the introduction of NND antibodies to SV-1.

Fig. C - Reflects a decrease in the patient's body weight by 5 95 or more.

DETAILED DESCRIPTION OF THE INVENTION

The definition of the invention is based on the formula of the invention, which is given at the end of this document.

Based on this formula, the following glossary contains relevant definitions of the terms used in the formulas.

The term "antibody", as used herein, means an immunoglobulin that specifically binds to, and is thus defined as associated with, a particular spatial and polar organization of another molecule. As listed, antibodies may include a complete immunoglobulin or a fragment thereof, may be natural, polyclonal, or monoclonal, and may include different classes and isotypes such as Ida, Ido, Ich, da, 4daKega, dae, and IdaZ. IdM While their fragments can include

Eab, Em and E (ab)"g, Rab" etc. The singular form "antibody" also means the plural form of this

From the term - "antibodies".

The term "activated potentiated form" or "potentiated form" as used herein in relation to antibodies means the product of homeopathic potentiation of any antibody stock solution. "HOMEOPATHIC POTENTIATION" means the use of the method of homeopathy to endow the corresponding substance of the base solution with the therapeutic effect of a homeopathic preparation. "Homeopathic potentiation" may include the implementation of successive repeated dilutions combined with external treatment methods, such as, for example, (mechanical) shaking. In other words, in accordance with the technology of manufacturing homeopathic preparations, the base solution of antibodies is subjected to successive repeated dilutions and repeated vertical shaking of each obtained solution. The preferred concentration of the antibody base solution in the solvent, which is usually water or a mixture of water and ethyl alcohol, is about 0.5 to 5.0 mg/ml. The procedure for preparing each component, that is, the antibody solution, involves the use of a mixture of three water or water-alcohol dilutions of the basic matrix solution (matrix tincture) of antibodies diluted 10072, 10090, and 100200 times, respectively, which is equivalent to hundreds of homeopathic dilutions of C12, C30, and C200.

Examples of homeopathic potentiation are described in U.S. Patent Nos. 7,572,441 and 7,582,294, which are incorporated herein by reference in their entirety and for their intended purpose. While the term "activated potentiated form" is used in the patent claims, the term "ultra-low dose (ULD)" is used in the examples.

The term "ultra-low doses" has become a professional term in this field through the research and use of homeopathically diluted and potentized forms of the substance. The term "ultra-low dose" or "ultra-low doses" are interchangeable and primarily synonymous with the term "activated potentiated form" used in the patent claims.

In other words, an antibody is considered to be in an "activated potentiated form" or in a "potentiated form" if three factors are present. First, the "activated potentiated" form of the antibody is a product of the preparation process adopted in the field of manufacturing homeopathic preparations. Secondly, the "activated potentiated" form of the antibody must have biological activity determined by methods accepted in modern pharmacology. And, thirdly, the biological activity demonstrated by the "activated potentiated form of the antibody" cannot be due to the presence of the molecular form of antibodies in the final product of the homeopathic process.

For example, an activated potentiated form of an antibody can be obtained by subjecting basic, isolated antibodies in molecular form to a series of serial dilutions in combination with external influences, such as mechanical shaking. When the concentration is reduced, external processing can also be accompanied by such processes as the influence of ultrasonic, electromagnetic or other physical factors. V. Schwabe (M. 5spuare) "Homeopathic Medicines", M., 1967, US patents Mo 7,229,648 and Mo 4,311,897, which in full form and with the purpose defined by this document, are indicated in it as references, describe those processes, which are acceptable methods of homeopathic potentiation in the field of manufacturing homeopathic preparations. The result of this procedure is a uniform reduction of the basic molecular form of antibodies in the concentration of molecules. The procedure is repeated until the desired homeopathic potency is obtained. For a particular type of antibody, the required homeopathic potencies can be determined by subjecting intermediate dilutions to biological tests according to the appropriate pharmacological model. "Homeopathic potentiation" may include the implementation of successive repeated dilutions combined with external treatment methods, such as, for example, (mechanical) shaking. In other words, in accordance with the technology of manufacturing homeopathic preparations, the base solution of antibodies is subjected to successive repeated dilutions and repeated vertical shaking of each obtained solution. The preferred concentration of the antibody base solution in the solvent, which is usually water or a mixture of water and ethyl alcohol, is about 0.5 to 5.0 mg/ml. The procedure for preparing each component, that is, the antibody solution, involves the use of a mixture of three water or water-alcohol dilutions of the basic matrix solution (matrix tincture) of antibodies diluted 10072, 10090, and 100200 times, respectively, which is equivalent to homeopathic dilutions C12, C30, and C200. Examples of obtaining the desired potency are also provided in US Pat. Nos. 7,229,648 and 4,311,897, which are hereby incorporated by reference in their entirety and for the purpose herein.

The procedure applicable to the "activated potentiated" forms of antibodies described herein is presented in more detail below.

Zo There were many contradictions regarding the treatment of research subjects with homeopathic medicines. Although the present invention is based on the application of accepted homeopathic processes to obtain "activated potentiated" forms of antibodies, from the point of view of effect on the subjects of the study, the present invention refers not only to homeopathy. The inventor of this method of application unexpectedly discovered and, in the accepted pharmacological model, fully demonstrated that the solvent, ultimately obtained as a result of carrying out several successive dilutions of the basic molecular form of the antibody, has a clearly established action, which is in no way related to by the presence of traces of the molecular form of antibodies in the target diluted. The "activated potentiated" form of antibodies referred to herein has been tested for biological activity using acceptable pharmacological models, namely in vitro ("p mio") or in vivo ("ip mimo") experiments using suitable animal model. The experiments below demonstrate the biological activity of selected models. In addition, the results of the human clinical studies presented herein below also provide evidence that the activity observed in the animal model may be readily translated to human therapy. Studies of the human body also indicate the presence of "activated potentiated forms" described in this document for the treatment of the above-mentioned diseases and disorders, which in medical practice refer to pathological conditions of the human body.

In addition, the declared "activated potentiated" form of the antibody includes only those solutions or solid drugs, the biological activity of which cannot be explained by the presence of the molecular form of antibodies remaining from the base solution. In other words, although it is assumed that the "activated potentiated" form of antibodies may contain traces of the basic molecular form of the antibody, one skilled in the art cannot with any degree of probability write down the biological activity found in the pharmacological models to the residues of the molecular form of the antibodies, because the concentration of the molecular form of antibodies remaining after serial dilutions is extremely low. Since the invention is not limited by any particular theory, the biological activity of the "activated potentiated" form of antibodies of this invention cannot be attributed to the basic molecular form of the antibody. Preference is given to the "activated potentiated form of the antibody" in liquid or solid form, in which the concentration of the molecular form of the antibody is below the limit of detection using acceptable analytical techniques such as capillary electrophoresis and High Performance Liquid Chromatography (HPLC). Particular preference is given to the "activated potentiated form of the antibody" in liquid or solid form, in which the concentration of the molecular form of the antibody is lower than Avogadro's number. In the pharmacology of molecular forms of therapeutic substances, it is a common practice to create a "dose-response" curve, in which the level of pharmacological response is displayed depending on the concentration of the drug with the active component, which is administered to the research subject or tested ip mygo. The minimum level of the drug that produces any visible response is called the threshold dose. It is especially provided that the "activated potentiated" form of antibodies contains the molecular antibody, if provided, at a concentration lower than the threshold dose determined for the molecular form of the antibody for this biological model.

The term "SVI receptor" has a general meaning in the art and may include both the natural SVI receptor and variations and altered forms thereof. The SVI receptor can originate from various sources, but the main source of its origin is the mammalian body.

The term "obese" refers to a weight range that is greater than what is considered healthy for a given height. The degree of obesity is determined by weight and height, which are used to calculate the "Body Mass Index" (BMI). An adult whose BMI is 25-29.9 is considered overweight. An adult with a BMI of 30 or higher is considered obese. The formula for determining BMI is as follows:

Weight - (height in inches) 2 x X 703 - BMI

BMI does not always accurately indicate the degree of obesity. There is increasing evidence that the prevalence of moderate obesity may be more closely related to metabolic risk than to BMI. It turns out that determining the prevalence of moderate obesity is very important for its early detection of health risks, even among people of normal weight. S.D. Sie (5 OO Nviei), H. Yoshinaga (N

Uozpipada) and T. Muto (T Myto), International Journal of Obesity Problems (2003) 27, p. 610-616. See also: H.M. Price (Rgise SM), R. Uayu (Oatsu W), E. Breeze (E Vgeegeye), S.J.

Balpitt (Viiriy Su), A.E. Fletcher (Rieispeg A) (August 2006). "Weight, shape, and mortality risk in the elderly: high waist-to-hip ratio, no

A high body mass index is associated with a greater risk of mortality" and the American Journal

sat down Myig 84 (2): 449-60. Waist circumference and its indicators, such as waist-to-hip ratio and waist-to-height ratio, were used as representative indicators of moderate obesity. Sang (Zipa) et al., "Waist Circumference and Correlation of Waist Circumference and Height in Hong Kong Chinese Children," Journal of Public Health Main BioMed Edition 2008, 8:324. Thus, measurements of anthropometric parameters such as waist circumference, waist-to-hip ratio, and waist-to-height ratio are considered indicators of obesity.

The term "waist-to-hip ratio" means the ratio of waist circumference to hip circumference. The indicator of this ratio is determined by dividing the circumference of the waist by the circumference of the hips. If this indicator is more than 0.9 in women, and more than 1.0 in men, then this indicates a high risk of cardiovascular diseases, and is a reason to start obesity treatment. Ideally, this indicator should not exceed 0.8 for women, and 0.95 for men.

The term "ratio of waist circumference and height" of a person - the indicator of such a ratio is determined by dividing a person's waist circumference by his height. For people under the age of 40, such an indicator exceeding 0.5 is critical, while for people aged 40 and under, indicators of 0.5 and 0.6 are considered critical, and for people over 50, the critical value begins with 0.6.

The term "obesity-induced metabolic disorders" refers to chronic diseases 50 that require treatment to reduce the extremely high health risks associated with obesity and the typical disorders caused by this disease, namely type 2 diabetes, cardiovascular diseases and hypertension, hyperlipidemia and fibrinolytic disorders.

The term "Fagerström test" refers to standard tests for nicotine dependence, which determine the degree of addiction to (dependence on) nicotine. See, T.F, Heatherton (Neaipepop

T.E.U, L.T. Kozlovski, (KogiIomuzkKi I.T.), R.S. Freker (EgesKeg V.S.), K.O. Fagerström (Radegvigot

K.O.), Fagerström Test for Nicotine Dependence: Analysis of the Fagerström Test Questionnaire for

Nicotine Addiction. British magazine "Dependence" 1991; 86:1119-27. The test consists of a short self-assessment report, which is measured on a ten-point scale from 0 to 10, with 10 being the highest level of dependence.

The term "Withdrawal Symptom Scale" (MRB5 test) refers to a scale developed in the early 1980s that is used to assess symptoms of cigarette withdrawal. (R. West (U/evi NE), P. Hayek (Nadek R): Evaluation of the scale of withdrawal symptoms to determine symptoms of withdrawal from cigarettes. Psychopharmacology 2004, 177 (1-2): 195-199). The main measuring element of the MRB5B5 test is a 5-point scale, which determines depressed mood, irritability, restlessness, difficulty concentrating and hunger, and a b-point scale, which determines the strength of endurance and resistance to the urge to smoke and the time spent fighting these claims.

The term "Hospital Anxiety and Depression Scale" (NAYUO5 scale) refers to a subjective scale for detecting signs of anxiety and depression in inpatients and outpatients. see

A.S., Sigmond (7idtopa, A.5.), R.P. Snaith (Zpayi V.R.), "Hospital Anxiety and Depression Scale",

Protocols of psychiatric research. 5 sapoa., 1983, Volume 67, p. 361-370.

The present invention is a medicinal product, which is used for administration to a suitable patient and which includes an activated potentiated form of antibodies to the human cannabinoid receptor.

The present invention relates to a medicinal product, which consists of an activated potentiated form of antibodies to a) the human cannabinoid receptor and to b) the 5-100 protein, which, if necessary, is used to treat patients.

According to this aspect of the invention, the drug can be in both liquid and solid form. Each activated form of antibodies of enhanced effect included in the composition of the medicinal product is made from the basic molecular form of the antibody by applying processes accepted in homeopathic practice. Base antibodies can be monoclonal or polyclonal antibodies, obtained by the results of known and used processes such as those described in Immunotechnologies, H. Frimel (a. ENGitei), M., "Medicine" (Meaiiizupa), 1987. , p. 9-33; "Human Antibodies" "Monoclonal and Recombinant Antibodies, 30 Years Later" E. Laffley (I anu E.), R. Sodoyer (Zodoueig V.) - 2005 - Volume 14. - Mo 1-2, p. 33-55, which are indicated in this document as references.

It is assumed that for the treatment of obesity and nicotine addiction, it is necessary to take 6-8 tablets per day of this medicinal product. According to one option, the method of application

The drug is prescribed to be taken 2x tablets 3 times a day. According to other methods of use - From a tablet 2 times a day; 4 tablets 2 times a day; 1 tablet 6 times a day and 2 tablets 4 times a day.

Monoclonal antibodies can be obtained, for example, using hybridoma technology (monocloning). The initial stage of the process includes immunization, which is based on principles already developed during the production of polyclonal antisera. At further stages of work, hybrid cells are produced that generate antibody clones of the same structure. their individual extraction is carried out using the same methods as in the case of preparation of polyclonal serum.

Polyclonal antibodies can be obtained by active immunization of animals. To do this, suitable animals (for example, rabbits) are given a series of injections of the appropriate antigen, either human cannabinoid receptor or protein 5-100. The immune system of animals generates appropriate antibodies, which are collected in animals in all known ways. This procedure makes it possible to produce a monospecific serum rich in antibodies.

If desired, serum containing antibodies can be purified, for example, by affinity chromatography, fractionation by salt precipitation, or ion exchange chromatography. As a result, the purified, antibody-enriched serum can be used as a base material for the production of an activated potentiated form of antibodies.

The preferred concentration of the antibody base solution in the solvent, which is usually water or a mixture of water and ethyl alcohol, is about 0.5 to 5.0 mg/ml.

The procedure for preparing the activated potentiated form of antibodies or their combinations according to the present invention involves the use of a mixture of three water or water-alcohol dilutions of the base matrix solution of antibodies diluted 10072, 10039 and 100200 times, respectively, which is equivalent to homeopathic dilutions C12, C30 and C200. To prepare a solid dosage form, the solid carrier is treated with the necessary dilution obtained by the appropriate homeopathic process. To obtain a single unit of the medicinal product consisting of the combination of the invention, the carrier is impregnated with each separate dilution. Both methods of impregnation are suitable for preparing the desired combination of medicinal products.

According to the selected modification, the basic material used for the production of the activated potentiated form, which is part of the invention, is polyclonal,

an antibody obtained from an animal model to the corresponding antigen, namely, to the human cannabinoid receptor and/or protein 5-100.

To obtain an activated potentiated form of polyclonal antibodies to the human cannabinoid receptor, the selected antigen can be administered as an immunogen to laboratory animals, preferably rabbits. To obtain polyclonal antibodies to the human cannabinoid receptor, you can use a single molecule of the human cannabinoid receptor. Next Sequence 5EO.IO. Mo. 1 (ZEO IU MO: 1.) of the human cannabinoid receptor is considered as an accepted antigen:

ZEOLIO sequence. Mo. 1: HUMAN SVI RECEPTOR

Meb duz bek Ii tsets dz bi bez Aza dlr Tikh TV rBe aku Tv o ZY 1 yiv tiv TE yVgodyav o beu bem tTuh Uvi b1u bej dey dartiv Bii Tuyu 5 j j do dim du ie Buz biu dvo Me AT bek pub We bdu Tuk Re vk

Z 35 49 45 biv Bud re Ros yeez Tu bek re Aa Shiu bek Ruo Re biz biv yee Za po o

It was between Tnj Adi and the gray-bearer of Bkbopiv bed about Ua1i Ruye yiya AesroYah

VE What is it 15

Uvi At yi Tk piz Re Tuk Avo tsu yeh Zem bek beyu Be Buv 7 i zo siu dyapobiv sly dat tTie bij Suv biu biz Avp Re Meb do her

Z ve 180 u55 piyu bSuz BMme Meb o wai sb dey Ro dec slia biv Beo viz tre div

IP 119 115 120

Chai bEm Bek im tTvzhh vm bi TVk Ey otv Uki ep Bash AV pepy

TE 125 lo 155 ts) Uvi ee Stv Udi Tiz tsez BI Zabs Ak Cheh Bez pk Suv ju 135 i4o 145 MO

Wko bezh Tut Niz Bre ig3ye biu Zeikh im Az Uzi Vih yvr ober Beh 1581 TB 159 155 5iu bak Ma) be Be ta. Tuho uh Be goes OR Be Bzhe vi Be 156 i1u 5 189

No Akgea mu Asyayu Zek dk y5p o Mai pe tsea EBe buye Pe) SBU Tu 181 185 to iah chai TVh yia bek Re TVh Aia bas uv bru bdeh be) Re pecs TV 136 2 "05 218 dia Iie Avo du Tu Ii bek y1a No What Rho bey vya Zhuk Bu5 4 25 Hey ZB dha ysye udi Tvj Ak Bho Buv Aia vi chai Akva vve Su te Mek gav kati 285 240

Thr Tyh her yia her Teas 11 Vi and Bbey Rgo Sam without bI1U Tko for va vo rt

DvpoSuv siv buyae without biv bek Uvi Sub Bvo dev Ti le oVko Niv

ME KO dey to her dyaroby Tk o tTuk pe meh Ve tur biv opium tni Tk obet Uvi zl vh 285 vh this oivy cem Re Ich112 Uai Tuye did Tuk Meb Tut 116 vu Tho vuz

Aza Kiz zebs Ni viv chai Ak Mer ii vii dko bi Tv biv Buv kesh MU Ay 5

Shek iye iye iyeyu Piv Ttt deko bij dav bi Buv Uvi Bip omai tv

Z zah zhi tu Bho dat bio Div yko Me zvo her Aka ieo Aia fu Tk obem zi Z35 BI zav dk do a "E poozhozhyu tyu to de Metsin SechII shk toy: I chai be tli ishc Uaz) Chai pek iz ii Sue TK these RO vy Bai zag Z ZVU dao

Bi-sh tiv ' Me Za) Tk dvo" Umi vre osi Kz Mei oivoa Bush im Te

Z zbe BY 75 iipuvo TYJ UVI vve yiya ne sSuv bej Me Bbem Su would eat; two Beige pieces and 95 pieces : : KE; lay du Z ih puh poet, the same shi vi stik tka OTO Zo tv UI Ai to ie tiv Zhuk ia Bez Aha bBeg omuz AbBroshBa dk zvi 35 po 05 zhi A Yuhim dih zo Ma rf sta K gtzhkdya zahh luk ta B'i Iya niv half Re Acad pev o Mee BBe o vosopek Sue half Bi TV AtTa own cho 10 415 180 vko web baroblie Bek Me: bin yo bej yzuo dum zv Ni Vuz Nick

E E OV and: ; Ch

I am 150,435

Atch ve av Alla piz Bezh Hai Ni Ak vka yiv eva yek ssh Te he 14 scha Bo vUdsh BEK OSVVy Mai Puz Ile Av was pa tr Meye det Uli eh TE 45 45 o Zhe

ZVO lrg eh did Fiv Aza Me ale. that's what

Sequence of ZEOSMO. Mo. 2. HUMAN SV RECEPTOR?

Miss sb zhu u syh pu ih hgari s povinne i .: ro uky oyu, suka Lockk DotU ces am a shu ZHE u shcha mm I ul ZY ku ek ozh LAMI yi 5 10 o zhu ii Av» ZBK obov VE MesYE pe AshO bek Ve die besh o sheh BU i5 Z 30 tto sib u TVE Aa u dia Uk izh u tre lem Bei shu sei 3Z o 45 pa ee AT Mem SZT ABY Uvi bla UVU bed TUuh Be i3e pevy dev cho ZV vo

TE pig cho Ge vy ry s an bozha F s ion zm i; se in the same Z - K

Zei NIV Biy iz At AhO yuy Rjo bek o tTuk Bo RBa Her1e piUu Beh v 5 7o 75 i-i Bi ZU Via Ave Wbe pen Diy eh Uvi UM ve DA Suz Zv

How zo 85 o za gr zhozheiu ka fe kv ri fo be rkw HC Foemych S Yabduy Joktoh. В NA viv Uvi der veEpa on E Uvi viayu Na eV in ZE vo ekr PEDHE from Uz A ey hu yip 105 vve cem o bev buh 110 5TU Sheh Ma) tk Me Tek Be Ti biz bek 3 zen nya U yi i : h İ kov t1a To ih chai sschiu bezh tsvo Bem o tseo ALSO Aza Zi dar o dke tTshЖzhh mem Mu oceo ii21 Be 155 i 5 dho Uk Rksh BE dec tTUye vu dyin Bey Bez bi vka schu schu ho Aiya 175 140: Her o

Be ai Tnsh dev spiau iSchiye Me tTzhyu Mah men bek iv bBa Zach oBekh ih VVE iv i55 tuyu Ku Bkz Zavo Mai bi Te o tTvVk Szhyaz Sub bez ko Bgto buh be

Ibe B la 50

Z peo Be Bho bez i1e Rgo Ach oi Tu izho be dec Tk price 181 155 io Tya5 ev o RNet tiv action is reac RBe bek PTU Ti her Tk TE Tuye 015 nish Mai pe iso BUYE yva Niv bib Ni Uzi avta Zav bceo bek b1u

Niz bBip yzr Ago biv Uvi Rio biu Meb Aza Asu Meb Ako bemo Ave ev 230 o eLo

Uai dk cez div high school TV lem obiu uch di yiv Aza Uuai Bey ey «eV ay -5O 25 yiv buye Ttv o vbe RKO Myi pes liv ieo Me liz niv Zes Po dia 6 B aa 27

Tok Ta Bo bek wav oziz Uai bu Buv dyan Tse dia pe Suk et meb tsevobSuv ben i1is dev dev Mys Chai 353 Rgo Mai iiiiye Tuk dia zva for 25 320

Ben oda Hek obi bio tiv Aso bek beh viv NI nish Suv vo did lo uh 10 18

Nav tTgv pud Gud Suv Uudi Ak biUu paz bit be biz yia Buv bish 316 20 zav 330 piz div Bk Ako der bak Uai Te biz TP bis yza Avv bih Buv

With BZ zo for her TAZH Bk. TK ko dno Yabek o acOo dB ichu two em be avo sUuye

The polypeptide fragment of the human cannabinoid receptor is mainly used as an immunogen (antigen) for immunization of rabbits. For the generation of polyclonal antibodies to obtain a polypeptide fragment of the human cannabinoid receptor, it is possible to use a synthetic peptide of the human cannabinoid receptor as an immunogen (antigen). The accepted sequences (human SVI receptor) for such antigens are as follows:

Sequence BESOLO. Mo. WITH.

Siv ykga biu TO biv duv is 315 dek tiv ijeye II

ME University

Peoability of ZEOL; Mo, 4. and OBU Be bis Beye Udi Su pei Azhyu i46 be bo Pi5

In kai sha and her Azov obi Tv tuye fam in zt te

: ;

Sequence of ZEOL. Mo. 5.

Ii BZip o Azhhou BRU Tl obo ih dek her her ate Niv TBbh be biz Abe ZI" was Uvi ziv chai TBe

ZE Z2y ZY Zo

Aka Vo Ache fight Asia vho Mach 331 335 ve

Ownership of the LAND. Mo. 5.

Muth yia took betoNiya Vi U!) ika Me: iiv Biy Ako Bi Tvh biy Buv

For 18,315 wk i3e Bi TB NIV o TV back bii Av o piUu Zuv cha biv U«i TVh

ZE Za Zeu 330 krko I give both Aza Asa Me in iie deejem At Buvostnya 351 ХУ5 340 344.

EARTH sequence. Mo. 7,

Meks dec Uvi dec TE zEB ЗB

AvE ote dec action to them At pe

The sequence of ZESOMO. Mo. 8. tTvk Z be Tuk yaap obu dev ee Bach eh ENe be siz Ap bin he yvap eat fight Suv brUu pizza Ave Vice Meb der tyzh a Za 00 05 piv o Suv VEVeoMet Mi bo zvy Bresee

Me 15 114

The ZESLO sequence. Mo; 9. biv ko geo dav dai bak Mestu zr bek Ave o sSuya Ge) Biz was Ni al A25 ah 13z5 kiz OA 338 50

ZESMO sequence. Mo. 10,

Stu tvj BOY already dec o iiiie THE SAME bi Tv ypei bi Aza bi

Computer sequence. Mo. 1.

Me: TVh Aza ih Ar Azy ks bib pev Mai Rko At Azr Bio

Uki yo Ti Trg si BBa Tuk dvy Bob pek tsevo be vve VMevobuB y no 5 zo piv ja Ziy ba AV ii siv Sui Bi Zi ve) Re Me Avrotiv

Z Za 150 125 piz Sat Be MeK obai Bei Aut te 110 i12

Sequence of ZEOO. Mo. 15.

MUai in div zve Suv be) Meb 34 ha 40 tka TVk She dia Ti Uvi 116 re 45 47

Consistency: FAILED, Mo. 14. piz vva Tukh AB Puv dak dEo Bek Zed RVE was

KI: From Fr

Z yzp biz Bib ABY Ti Siv Suye pim bib bzy BBe Me Ar 12 zh 85 і0do і05 pa su re Mei tuai Be Av to pek Bil bij pcez Ada li Ata ide TO 115 zho uv Bem bek Bei Tv oba a 125 1T2k

The sequence of ZESMIU. Mo. 14. wai obi Bi dav tiv Zir Su bu Bi

Sequence of BEOIU, Mo. 15.

Siu eh Bo Be bir

It was a week ago.

BE 55 TO 75 bai dey iyee TE biz Rne Tu y puv bed pev 7 zo i VE

The sequence of ZED. Mo. 15.

Aiia tuyu duv even eV dkZ t uv Tih Aga ro was Via Uai Uki ia pe sSuz vi Mei ry glo a sho

TtTkto TE ii Aza Te Uai1 ti AMa bei ey kb be bez slu TKER 241 5-45 OVO Ka

Oh yeah

An example of the procedure for preparing basic polyclonal antibodies to the human cannabinoid receptor can be the procedure described below. 7-9 days before blood sampling, rabbits are given 1 to 3 intravenous injections of the desired antigen to increase the level of polyclonal antibodies in the circulatory system. During immunization, blood samples are taken to check the level of antibodies. As a rule, the maximum level of immune response to a soluble antigen is reached within 40-60 days after the first injection of the antigen. At the end of the first cycle of immunization, rabbits begin a 30-day rehabilitation period, after which re-immunization is carried out with 1-3 more intravenous injections.

To obtain antiserum containing the required antibodies, the blood of immunized rabbits is collected and placed in 50 ml centrifuge tubes. Clots of the product formed on the walls of the test tubes are removed with a wooden spatula, and the rod is placed in the clot in the center of the test tube. Then, the blood is placed overnight in a refrigerator at a temperature of about -40 "C. The next day, the clot on the paddle is removed, and the remaining liquid is centrifuged for 10 minutes at 13,000 revolutions per minute. The supernatant is the target antiserum. The resulting antiserum, as a rule, yellow in color. 20 95 Mam3 (weight concentration) is added to the antiserum to a final concentration of 0.02 95 and, before use, is stored in a frozen state at a temperature of -20 "C or without Mam3Z - at a temperature of -70 "C. separation of target antibodies to cannabinoid receptors from antiserum, the following sequence of solid-phase absorption is used: 10 ml of rabbit antiserum is diluted twice with 0.15 M Mass, after which 6.26 g is added

Ma2504, mix and keep for 12-16 hours at a temperature of 4 "С. The sediment is removed by centrifugation, diluted in 10 ml of phosphate buffer solution and dialyzed in the same solution overnight at room temperature. After removing the sediment, the solution is applied to the column

DEAE-cellulose, balanced with a phosphate buffer solution. The antibody fraction is determined by measuring the optical density of the eluate at 280 nm.

The isolated unpurified antibodies are purified using affinity chromatography by adding the obtained cannabinoid receptor antibodies located on the insoluble matrix of the chromatographic carrier, followed by release with concentrated aqueous solutions of salts.

The resulting buffer solution is used as a starting solution for the homeopathic dilution process, which is used to prepare activated

From potentiated forms of antibodies. The preferred concentration of the starting matrix solution of antigen-purified rabbit polyclonal antibodies to the cannabinoid receptor is 0.5-5.0 mg/ml, preferably 2.0-3.0 mg/ml.

Protein 5100, responsible for the functioning of the brain, expressed by neurons and glial cells (astrocytes and oligodendrocytes), directly or through interaction with other proteins, performs a number of functions in the central nervous system aimed at maintaining the normal functioning of the brain, in particular, it concerns the processes of learning and memory , growth and viability of neurons, regulation of metabolic neural processes in tissues, etc. To obtain polyclonal antibodies to protein 5-100, this protein is used, the physical and chemical properties of which are described in the article by M.V. Starostina, S.M. Sviridova, Neurospecific protein 5-100, "Progress of modern biology", 1977, Volume 5, p. 170-178; in the book of M.B. Shtarka (M.V. 5Magk), "Antigens of the protein responsible for the work of the brain and the functions of neurons", "Medicine", 1985; p. 12-14. Protein 5-100 is isolated from the brain tissue of a bull according to the following method:

With the help of special shredders, the brain tissue of a bull frozen in liquid nitrogen is turned into powder; - proteins are isolated in a ratio of 1:3 (weight/volume) using a buffer for extraction with homogenization; - the homogenate is heated for 10 minutes at a temperature of 60 °C, and then cooled to 4 °C in an ice bath; - heat-resistant (thermolabile)) proteins are removed by centrifugation; - fractionation with ammonium sulfate is carried out in several stages, followed by the removal of sediment proteins; - the fraction containing protein 5-100 is precipitated using 100 95 saturated ammonium sulfate, to which pH is added dropwise to the 4.0 mark; the required fractions are collected by centrifugation; - the precipitate is dissolved in a minimal amount of buffer solution containing EDTA and mercaptoethanol, dialyzed with deionized water and lyophilized; - fractionation of acidic proteins is followed by chromatography on ion exchange media -

DEAE-cellulose OE-52, and then DEAE-sefadex A-50;

- the collected and dialyzed fractions containing 5-100 proteins are divided by molecular weight by sludge filtration on Sephadex C1-100; - purified protein 5-100 is dialyzed and lyophilized.

The molecular weight of brain-specific purified protein 5-100 is 21,000 0.

Due to the high concentration of aspartic and glutamic acids, the brain-specific protein 5-100 is highly acidic and occupies the extreme position of the anode during electroendosmosis in the discontinuous buffer system of polyacrylamide gel, which facilitates its identification.

Polyclonal antibodies to protein 5-100 can also be obtained by a method similar to that described for obtaining antibodies to the cannabinoid receptor, using an adjuvant.

The whole molecule of protein 5-100 can be used as an immunogen (antigen) for immunization of rabbits: and

Sequence of ZEOLO. Mo. 17 - Bovine protein 51008 meh back pis rey sii iz dia mvi Uvi vii pet iv ver o wai RE

No bz tuyu sheh biu Aha bij bib y Buv Viv buye Beo Muz: Buv 23 . 25 Bize eh ish ey Tu bij Baev ii dp AzZpoosiy ey bek Ni pe Bey

Ba: 35 : 40 45. iz pich yi uv biz div biy Uvi Uai Avv o gub wau Mee pat tne y5 5 sh5 KO ivo Yazo dev derobiu AYU bZiu Biy buh Ayayu gav bi Bib tse meh i same to 5 kid be uli diya Meb i1v tih Tvk via bue Nizh bib rve ZVe 016 tk vo vh ha

No sconces

The sequence of ZESMIU. Mo. 18 - Human protein 51008 me Sei bij fBEch bi PU dia ShMezh UT Vii bec Ii du Uvi RVE

A: in her i5 n sz tuye eh biu hu zZiy zi Ar vuye No buye em was MUue 18 her 25 Za

Bek sy Bey Buv blo bab yiye Ai Av bib iBO bek Nu pe pev sh-iz zi i1i18 BU piz biv ooiiz chai hai vo buh uv MES Z TAH ib vo BO vo ivn vvb Aza dvo biu Ar opiu Piv was dvor rve p) bi fire fur

BI EV lo 75 ia Eve chi yta Mezh Ma Tv tah liv Su NEB ii VNe EE sli t «yat VI 85 Zo niv shchi Ne . 31 29

FAILURE sequence. Mo. T9 - Human bipok ZTO0D1

Mas Ziu Beh bi sie b tah Biy meh bib tyh infantry At cha 1 5 16 15 vne nia dia nuye Zak piu bez Zish bZiu abroruv tuye bu Evu bek 16 a 28 for:

There was a bin baby There was a si benoibn M Zhe Si ben bek b1u Ve zi 35 Ei 4 yiv der aka ip puh dya" Uvi bar Aza li vro zuz uv meb was sich betso dz Biy dam spi bvrobiUu bic Uvi dev obye bil vich Tut 8 ve 7 5

Uvi chai web uv Asia uza ev Tikh Uh dia Sub Ai Azy sve rae

TV Zich zay BE

FAILURE sequence. Mo. 20 - Bovine protein 5TO0DI

Mas siu bezh o ev cm Te Za Mebobiv TAH yny. Bi Ava ЖЖ zve nish div Ni bek bi pu 013 15 Avro was TUYU There was shShem vek 15 28 dya 3

But they sat with them; buz bij zey Be) bij So Z1chz Bez bek su pe

Z KI 10 a ivtspoda" diva liy Bu spirodiv dZrodav Uvi Avrobuv Ua Mes Buv 45 M ZE voliy yny o AzZYU i Azaobiu ee pis Ua AYU Epesyera bip tukh viiy e5 ha 75

Mai Mak vo Mai Aiya div be Tv bvi yiya Su Ai Bap ore VVE tt an dev por 9 za

To obtain antiserum, brain-specific protein 5-100 or its mixture, proteins 5-100 (antigens) in a complex with methylated bovine serum albumin as a heat carrier with complete Freund's adjuvant is prepared and added to the isolated brain-specific protein 5-100 , which is administered subcutaneously to laboratory animals - rabbits in the back region in the amount of 1-2 ml. On the 8th and 5th days, re-immunization is carried out. Blood sampling (for example, from the ear vein) is carried out on the 26th and 28th days.

The obtained titer of antiserum 1:500-1:1000, forms one band of precipitation with extract of nervous tissue, but does not react with extracts of heterologous organs and forms a single peak of precipitation both with pure protein 5-100 and with extract of nervous tissue, indicating that the antiserum obtained is monospecific.

The activated potentiated form of the antibodies of this invention can be obtained by homeopathic potentiation using a base solution. As a rule, the method of proportional reduction of concentration is used, which involves the serial dilution of 1 part of each preliminary solution (starting from the base) in 9 parts (for decimal dilution), or in 99 parts (for hundredth dilution), or in 999 parts (for thousandth dilution ) neutral solvent, starting from the concentration of the base solution of antibodies in the solvent, preferably water or a water-alcohol mixture, in a volume from 0.5 to approximately 5.0 mg/ml, in combination with external influence. As a rule, external influence means repeated vertical shaking (dynamization) of each dilution. Separate containers are used for each subsequent dilution until the required activity level or dilution factor is reached. This method is generally accepted in homeopathic practice. For an example, see V. Schwabe (U. Zspugabe) "Homeopathic Medicines", M., 1967, p. 14-29, which is incorporated herein by reference.

For example, to prepare a 12-percent dilution (denoted C12), one part of the basic matrix solution of antibodies to the human cannabinoid receptor with a concentration of 3.0 mg/ml is diluted in 99 parts of a neutral aqueous or aqueous-alcohol solution (mostly, 1595 ethyl alcohol), and then shaken many times (10 or more) in a vertical position to produce the first hundredth dilution (denoted as C1).

The second hundredth dilution (C2) is obtained from the first hundredth dilution of C1. To prepare the 12th hundredth dilution (C12), this procedure is repeated 11 times. Thus, the 12th hundredth dilution (C12) is a solution obtained as a result of 12 serial dilutions of one part of the basic matrix solution of antibodies to the human cannabinoid receptor with a concentration of 3.0 mg/ml in 99 parts of a neutral solvent in different containers, which is equivalent to one hundredth homeopathic breeding C12. Analogous procedures with the appropriate dilution factor are carried out to obtain dilutions of SZO and C200. To test for activity, intermediate dilutions can be tested using any biological model you need. Preferred activated potentiated forms for the antibodies included in the invention are a mixture of dilutions of C12, C3Z0O and C200 for each activated potentiated form. When using a mixture of different homeopathic dilutions (mainly hundreds)

From the active substance as biologically active liquid components, each component of the medicinal product (for example, C12, C30, C200) is prepared separately according to the above-mentioned procedure until the moment of obtaining the next to the last dilution (for example, until the moment of obtaining C11, C29 and C199, respectively ), and then one part of each component is added to the containers, observing the composition of the mixture, and mixed with the required amount of solvent (for example, with 97 parts for hundredth dilution).

You can use the active substance as a mixture of various homeopathic dilutions, for example, decimal and/or hundredths (020, C30, C100 or C12, C30, C50, etc.), the effectiveness of which is determined experimentally by testing the dilution in a suitable biological model, for example , in the models described in the "Examples" section of this document.

During the reduction of potentiation and concentration, vertical shaking can be replaced by the external influence of ultrasound, electromagnetic fields or any similar external factor acceptable for use in homeopathic practice.

As a rule, the medicinal product provided by this invention can be both in liquid and solid form. If the medicinal product includes two antibodies, then its liquid form contains a mixture of two antibodies, preferably in a 1:11 ratio of activated potentiated form of antibodies to the human cannabinoid receptor and activated potentiated form of antibodies to protein 5-100. The best liquid carrier is water or water-alcohol mixtures.

The solid form of the medicinal product according to the present invention can be obtained by impregnating the solid form with a mixture of an activated potentiated form of an aqueous or aqueous-alcohol solution of active components. If the medicinal product includes two antibodies, the active components are mixed, as a rule, in a ratio of 1:11 and used in a liquid medicinal form. Alternatively, the carrier may be successively impregnated with each required dilution. Both methods of impregnation are acceptable.

As a rule, the drug in solid form is prepared from granules of a pharmaceutically acceptable carrier, which has previously been saturated with water or water-alcohol dilution of the activated potentiated form of antibodies. The solid dosage form can be in any form known in the pharmaceutical industry, namely, in the form of tablets, capsules, lozenges, etc. As inactive pharmaceutical ingredients, you can use glucose, sucrose, maltose, starch, isomaltose, isomalt and other mono-oligo- and polysaccharides used in the production of pharmaceutical preparations, as well as technological mixtures of the above inactive pharmaceutical ingredients with other pharmaceutically acceptable fillers, such as , for example, as isomalt, crospovidone, sodium cyclamate, sodium saccharin, anhydrous citric acid, etc., including lubricants, leavening agents, binders and dyes. The preferred carriers are lactose and isomalt. The composition of the pharmaceutical dosage form may additionally include standard pharmaceutical fillers such as, for example, microcrystalline cellulose and magnesium stearate.

An example of obtaining a standard solid dosage form is presented below. To prepare a solid form for oral administration, 100-300 μm lactose granules are impregnated with aqueous or water-alcohol solutions of an activated potentiated form of antibodies to the human cannabinoid receptor and/or an activated potentiated form of antibodies to the protein 5-100 in the ratio of 1 kg of antibody solution to 5 or 10 kg of lactose (from 1:5 to 1:10). To carry out impregnation, lactose granules are subjected to saturation by irrigation in a fluidized boiling bath (for example, "Nyship Riyuyar", produced by the company Nyyip StrN), followed by drying with the help of a heated air flow at a temperature below 40"C. A certain calculated number of dried granules (from 10 to 34 parts by weight), saturated with the activated potentiated form of antibodies, are placed in a mixer and mixed with 25-45 parts by weight of "unsaturated" pure lactose (used to reduce costs, simplify and speed up the technological process without reducing the effectiveness of treatment), together with 0.1- 1 parts by weight of magnesium stearate, and from 3 to 10 parts by weight of microcrystalline cellulose.

The resulting tableted mass is evenly mixed and tableted by direct semi-dry pressing (for example, under a Korsh - ХИ 400 tableting press) to form 150 to 500 mg of round pills with a weight of preferably 300 mg. After tableting, we get 300 mg tablets saturated with a water-alcohol solution (3.0-6.0 mg/tablet) in combination with an activated potentiated form of antibodies. Each component of the combination used to impregnate the carrier is presented in the form of a mixture of hundreds of homeopathic dilutions, mainly C12, SZO and C200.

While the invention is not limited by any particular theory, it is believed that the activated potentiated antibody form described herein does not contain the molecular form of the antibody in an amount sufficient for the biological activity that is characteristic of such

From the molecular form. The biological activity of the medicinal product presented by this invention and its combinations is clearly demonstrated in the examples attached to this document.

The drug, which includes an activated potentiated form of antibodies to the human cannabinoid receptor, can be used to treat patients suffering from obesity and related metabolic disorders.

As shown in the examples attached to this document, the introduction of the activated potentiated form of antibodies presented by this invention leads to a decrease in body weight, slowing down the growth of body weight, helps to reduce the amount of the upper type of obesity and facilitates the process of reducing the volume of food consumption.

According to one modification, the present invention relates to a method of treating obesity and associated metabolic disorders by administering drugs containing an activated potentiated form of antibodies to the human cannabinoid receptor, preferably cannabinoid receptor 1.

According to another modification, the present invention provides a method of promoting a reduction in food intake in a research subject who is expected to benefit from such reduction by administering a medicament containing an activated potentiated form of antibodies to a human cannabinoid receptor, preferably cannabinoid receptor 1.

Another modification of the present invention provides methods for changing anthropometric parameters such as waist circumference, waist-to-hip ratio, and waist-to-height ratio. According to the modification used to reduce the waist circumference, the subject of the study is administered drugs containing an activated potentiated form of antibodies to the human cannabinoid receptor, namely receptor 1, in the volume that will be sufficient to achieve the goal.

Accordingly, according to one modification, the waist circumference of the subject of the study is reduced by at least 1 95, while according to other modifications - by 1.5 95, 2 Ов, 2.5 Ую, З У or 3.5 95, if to compare the waist circumference of the subject of the study before the introduction of drugs containing an activated potentiated form of antibodies to the human cannabinoid receptor.

Accordingly, according to one modification, the waist circumference of the subject of the study is reduced by at least 1 cm, while according to other modifications - by 2 cm, 3 cm or 4 cm, when comparing the waist circumference of the subject of the study before the administration of drugs containing activated potentiated form of antibodies to the human cannabinoid receptor.

Another modification of the invention provides methods for reducing the body weight of the research subject. According to this modification, the research subject is administered drugs containing an activated potentiated form of antibodies to the human cannabinoid receptor, namely receptor 1, in the volume that will be sufficient to achieve the set goal.

Accordingly, according to one modification, the body weight of the research subject is reduced by at least 15 95, while according to other modifications - by 5 95, 10 95, or 15 95, when comparing the body weight of the research subject before the administration of drugs , containing an activated potentiated form of antibodies to the human cannabinoid receptor.

Another modification of the invention provides methods for slowing down the growth of the subject's body weight. According to this modification, the subject of the study is administered drugs containing an activated potentiated form of antibodies to the human cannabinoid receptor, namely receptor 1, in the volume that will be sufficient to achieve the set goal.

Accordingly, according to one modification, the growth of the body weight of the research subject slows down by at least 60 95, while according to other modifications - by 10 95, 25 Fo, 30 U», 50 95 or 60 95, if comparing the body weight of sub the object of the study before the introduction of drugs containing an activated potentiated form of antibodies to the human cannabinoid receptor.

A drug containing an activated potentiated form of antibodies to the human cannabinoid receptor and an activated potentiated form of antibodies to protein 5-100 can be used to treat patients suffering from addiction to psychoactive substances, mainly nicotine addiction.

The applicant unexpectedly discovered that the combination of an activated potentiated form of antibodies to the human cannabinoid receptor and an activated potentiated form of antibodies to the 5-100 protein is useful in the treatment of substance abuse.

In one modification, the combination of an activated potentiated form of antibodies to the human cannabinoid receptor and an activated potentiated form of antibodies to the 5-100 protein is effective in the treatment of nicotine addiction.

Administration of a medicinal product containing an activated potentiated form of antibodies to

Human cannabinoid receptor 1 and activated potentiated form of anti-protein antibody 5-100 for the treatment of patients with nicotine dependence improves quality of life measures assessed by criteria such as depression and anxiety.

It has been experimentally shown that the administration of a medicinal product containing an activated potentiated form of antibodies to human cannabinoid receptor 1 and an activated potentiated form of antibodies to protein 5-100 for the treatment of patients with nicotine dependence improves the ability to more easily and painlessly tolerate the process of quitting (quitting) smoking , 1 was proved by the analysis of MP55 test results.

Also, it was experimentally shown that the administration of a combination of antibody forms to patients with mild nicotine dependence from » 4, as determined by the Fagerström test on

Nicotine Addiction, as a result, leads to a reduction of smoking by at least 23 95 during 4 weeks; 3695 in 8 weeks and not less than 41 95 in 12 weeks. In addition, it was experimentally shown that the introduction of a combination of antibody forms to patients with a mild form of nicotine addiction leads to a statistically significant decrease in the initial average number according to the Fagerström test to at least the mark of 1.34:0.14.

Also, it was experimentally shown that the administration of a combination of antibody forms to patients with severe nicotine dependence from » 7, as determined by the Fagerström test on

Nicotine Addiction, as a result, leads to a reduction of smoking by at least 11 95 within 4 weeks; 2295 in 8 weeks and not less than 30 95 in 12 weeks. In addition, it was experimentally shown that the introduction of a combination of forms of antibodies to patients with a severe form of nicotine dependence leads to a statistically significant decrease in the initial average number according to the Fagerström test to at least the mark of 4.42:0.30.

According to a certain modification, the separate introduction of two separately manufactured dosage forms, each of which contains one of the activated potentiated forms of antibodies of this medicinal product, is also considered.

Next, the invention is illustrated by examples.

EXAMPLES EXAMPLES.

The effect of ultra-low doses of polyclonal rabbit antibodies to the human cannabinoid receptor type 1 (NND Anti-SVI1 (SHO Apii-SVI1)), purified on the antigen obtained by hyperdilution of the basic matrix solution in 10072, 10030, 100200 times (a mixture of hundreds of homeopathic dilutions of C12, C30 and C200) on the functioning of the type 1 cannabinoid receptor was tested ip myo in two modes: in the mode of agonists and antagonists.

Agonist Mode:

Before plating in the wells of the plate (96-well plate, volume 250 μl), cells were maintained in Hanks' balanced salt buffer solution (Invitrogeni) containing 20 mM HERE5 (BI-2-pdroxy1-ethylpiperazine-Me2-ethanesulfonic acid) (pH - 7.4). Cells were pre-incubated for 10 minutes at room temperature with the addition of 20 μl of NND solution

Anti-SV1. After preliminary incubation, the adenylate cyclase activator MKNA77 was added.

Cells were incubated for 10 minutes at 37 "C and lysed. A fluorescent acceptor (SAME, labeled 02) and a luminescent donor (SAME antibody, labeled with European cryptate) were added to the wells.

As a baseline control, the cell suspension was pre-incubated in the presence of Hanks' balanced salt buffer solution (20 μl) and not NND Anti-SVI. As a stimulated control, the cell suspension was pre-incubated in the presence of the reference agonist SR 55940 (20 μl) and not the NND Anti-SVI1.

Functional activity (CAME concentration) was determined by the homogeneous method using time-resolved fluorescence (TMR). The fluorescence intensity according to the basic control was taken as fundamental, so its value was calculated from the fluorescence intensity according to experimental indicators (NND Anti-SV1) and control indicators (SR 55940):

The determined specific reaction of the cell to the introduction of NND Anti-SVI was calculated according to the following formula: fluorescence intensity in the experiment (NND Anti-SVI) - fluorescence intensity of the basic control.

The determined specific response of the cell to the introduction of the reference agonist (SR 55940) was calculated according to the following formula: the fluorescence intensity of the control (SR 55940) - the fluorescence intensity of the basic control.

The results were expressed as a percentage of the specific response of the cell to the introduction of the reference agonist compared to the stimulated control:

The percentage of the reaction of the reference agonist - (determined specific reaction/specific reaction to

From the introduction of the reference agonist in the control) X 100 95).

Antagonist Mode:

Prior to plating in the wells of the plate (96-well plate, volume 250 μl), cells were maintained in Hanks' balanced salt buffer solution (Invitrogeni) containing 20 mM NERB5 (IR-2-hydroxy-ethylpiperazine-Me2-ethanesulfonic acid) (pH - 7.4). Cells were pre-incubated for 5 minutes at room temperature with the addition of 20 μl of NND solution

Anti-SVI1. After adding the reference agonist SR 55940 to the wells, the cells were incubated for 10 minutes at room temperature. Then, adenylate cyclase activator was added to the wells

MKNA77. The cells were incubated for 10 minutes at a temperature of 37 "C and lysed. A fluorescent acceptor (CAME, labeled 02) and a luminescent donor (antibodies

SAME, marked with a European cryptate).

As a basic control, the cell suspension was pre-incubated in the presence of the reference antagonist AM 281 (20 μl) and not NND Anti-SV1. The reference agonist SR 559408 was not added to the baseline control. As a stimulated control, the cell suspension was pre-incubated in the presence of Hanks' balanced salt buffer solution) containing 20 mM NEREZ (M-2-hydroxy-ethylpiperazine-Me2-ethanesulfonic acid) (pH - 7.4) and the reference agonist SR 55940 (20 μl).

Functional activity (CAME concentration) was determined by the homogeneous method using time-resolved fluorescence (TMR). The fluorescence intensity according to the basic control was taken as fundamental, so its value was calculated from the fluorescence intensity according to experimental indicators (NND Anti-SV1) and control indicators (SR 55940):

The determined specific reaction of the cell to the introduction of NND Anti-SVI was calculated according to the following formula: fluorescence intensity in the experiment (NND Anti-SVI) - fluorescence intensity of the basic control.

The determined specific response of the cell to the introduction of the reference agonist (SR 55940) was calculated according to the following formula: the fluorescence intensity of the control (SR 55940) - the fluorescence intensity of the basic control.

The results were expressed as a percentage of the inhibition of the specific response of the cell to the introduction of the reference agonist in the control:

Percentage of inhibition of the reaction of the reference agonist - 10095 - ((determined specific reaction/specific reaction to the introduction of the reference agonist in the control) x100 Ob).

As a result of the study, it was shown (see Table 1) that NND Anti-CB1 changes the functional activity of the cannabinoid receptor type 71, which was proven by determining the intracellular concentration of SAMe.

Cannabinoid receptor type 1 agonist activity was demonstrated on the test substance, namely ultra-low doses of antibodies to cannabinoid receptor type 1 (mixtures of homeopathic dilutions of C12, C30 and C200). Compared to the potency of the standard agonist SR 55940, which is taken as 100 95, the potency of the studied agonist is 21 95.

Table 1.

ГRecepto | Finish chewing | Bmist in Agonist Mode | Antagonist mode. (sh

Ir on substance: punches! (volumes) (the total job is Standa 5 | The standard of the reaction wells of rt inhibitors |

About mkl ned antagonie o Anti- and vynni nia Z Venvovny o

I Recento | NNDoOAnty- 1095. ka I 0 INND o dAnti-: 7 (all | | (OSVROomaye, effect and | agonist, : rash of action! and : : which ! and : ! is ( : ! | 215 in! : : o : comparable 3!! is | io a rash of action! : : | schi | : - standard

WE Aa AND CANOES with and Her. toshgOoNNEshtTa.

EXAMPLE 2.

The substance under study is presented in the form of an aqueous solution of polyclonal rabbit antibodies to the human cannabinoid receptor type 1 (NND Anti-SVI), purified on the antigen obtained by hyperdilution of the basic matrix solution in 10072, 10030, 100200 times (a mixture of hundreds of homeopathic dilutions of C12, S30O and C200 ).

For the study, 40 male mice of the C57B1 line were used (their weight at the beginning of the study was 13.5-15.5 g). 10 mice received standard feed on a regular basis (standard diet); 30 mice received standard food with high-calorie supplements (high-calorie diet) and, at the same time, either distilled water (control dose - 0.4 ml/mouse) or Sibutramine (Meridia, capsules 10 mg, manufactured by the company

Arroy StrnN, Germany) (10 mg/kg) or NND Anti-SVI (0.4 ml/mouse). All solutions were administered intragastrically once a day for 5 months. Before the introduction of the studied substances, the volume of food consumption by mice was measured. In the future, such measurement was carried out every week. The volume of food consumption was determined as the average amount of food (in grams) consumed by a mouse 1 and 2 months after the study, and as the average amount of food per 10 g of mouse body weight.

Over the entire period of observation, mice that followed a low-calorie diet consumed an average of 1595 less food than mice that followed a high-calorie diet (Table 2). Both Sibutramine and NND Anti-SVI1 contributed

By reducing food consumption. The effectiveness of Sibutramine was higher, as for a week the volume of food consumption decreased by 19.3 95 (p "0.05), while with NND Anti-SVI1, this indicator was 9.395 in relation to the control (p" 0, 05). Table 2 shows the results of the study, in particular, the effect of NND Anti-SVI1 and Sibutramine on the volumes of food consumption in C57B1 mice (average indicators for 5 months of observation), M x m.

Table 2

Nutritional regimes Volume of food consumption Volume of food consumption (and 10 g (g/mouse) per day" mass tiparu day

Standard feeding mode 2.3 Beats 142 1.55 zhk 0.05

A high-caporic nutritional regime for distributed water Zahi Ba OVOoBA

A high-caporic diet - pibutramine and 16 128 mg

A high-caporic diet of NNID Anti-SVi Evil and TAYA kov 7 yubtatiastically significant differences from the control ed. oh

Also, statistically significant differences from the standard diet at 0.05

In the twentieth week of the experiment, mice on a high-fat diet that received NND Anti-SVI consumed much more food compared to the first week of the experiment (See Fig. 1). Fig. 1 shows the effect of NND Anti-CB1 and Sibutramine on the increase in body weight of C57B1 mice and the volume of food consumption per 10 g of weight after the last 20th week of the experiment.

Compared to the control, mice receiving NND Anti-SVI1 showed a slowdown in body weight growth by 51.2 95. Sibutramine, in turn, at the last twentieth week of the experiment, reduced body weight by 51.5 95 compared to the control group

EXAMPLE 3.

The substance under investigation is presented in the form of an aqueous solution of polyclonal rabbit antibodies to the human cannabinoid receptor type 1 (NND Anti-SVI), purified on the antigen obtained by hyperdilution of the basic matrix solution in 10072, 10030, 100200 times (a mixture of hundreds of homeopathic dilutions of C12, SZ30 and 200 ).

33 male mice of the C57B1 line were used for the study (their weight at the beginning of the study was 13.0920.738 g). Mice were fed a modified diet with a high (45–95) fat content and, at the same time, they were given either distilled water (control dose - 0.2 ml/mouse) or Sibutramine (10 mg/kg) or NND Anti-SVI (0.2 ml/mouse). All NND solutions

Anti-SVI1 was administered intragastrically once a day for 2 months. Before the introduction of the substances under study (at the beginning of the study), the weight of the mice was measured on the electronic scales of RNiirbe Sysip NA 239016 and, subsequently, such measurements were carried out weekly.

The increase in body weight of mice was estimated as a percentage of the initial weight.

6 weeks after the administration of the solutions, the Anti-SVI1 NLDs slowed down the increase in body weight in mice fed a high-fat diet. Table C shows the average weekly (in grams) body weight of C57B16 mice fed a high-fat diet and NND Anti-SVI1 (0.2 ml/mouse) or

Sibutramine (1Omg/kg) M x m. Table C shows the dynamics of body weight increase in mice.

Table 3.

Group Body weight (grams), weeks of recovery 0 1 y C 4 5 b 7 8

Pistillate 12.18 185.27 45:27 1800 188 1727 9018 2055 2145 water 30501 30582 0488 50972 0569 0557 20501 0608 0857

And up to 254 25a With 453 41.8 55.7 sh8.? 784 spot weight

Sibutramine 13.82 345 8:73 19582 2018 20.91 89.36 23654 92.81

Phone: 0954 0474 0407 30501 05784 563 02 ONCE at

Ж жк жх until -2nd 214 34 45.1 513 18 t 55.8. initial weight

NNADAnty- 13527 15.15 17.55 1984 2018 2018 19852 21.54 25.00

SVI ОБ ЖО182 0882 0453 30493 жЖ0ОА?3 0501 0354 з04А67 ж жкж жк жж

A yes 21.8 Z14 47.8 BA BI 4943 530 55.5 initial weight

Note: " - p«0.05 compared to the control group as vro compared to the control group

Anti-SVI1 NLDs have been shown to slow weight gain in mice fed a high-fat diet, reducing food intake, and are no less effective than the widely used weight-loss agent, Sibutramine.

EXAMPLE 4. 300 mg tablets saturated with a water-alcohol solution (b mg/tablet) of an activated potentiated form of polyclonal rabbit antibodies to the human cannabinoid receptor type 1, purified on the antigen obtained by hyperdilution of the base matrix solution in 10072, 10030, 100200 times (a mixture of hundreds of homeopathic dilutions C12, C30 and C200).

The study involved 80 subjects (20 men and 60 women) aged 20 to 69 years (mean age 40,221.26 years), 68.7 96 of whom were overweight or obese (grade 1-II) . Study subjects (SD) were given 1 tablet 2 times a day. Table 4 shows the demographic and anthropometric parameters of the patients included in the study. Data from all subjects who participated in the study (M-80) were included in the safety analysis. During the entire period of observation, the study subjects had a good tolerability of the solutions. No side effects were detected. All study subjects completed the treatment within the time limit specified by the study protocol; no patient was prematurely withdrawn from the study. When assessing the impact of NND Anti-

SVI on the change in the body weight of the subjects of the study (SD), it was established that the use of the drug led to a decrease in the body weight of 56 (70 Fo) patients. In 24 (30 Fo) patients, the weight remained unchanged or slightly increased. However, it should be noted that among such patients, 14 (17.5 95) had a normal weight at the beginning of the study (BMI "25 kg/m2).

Table 4

Larameter Indicator

Age Mem 40255 (number of years)

Height (bm.) Mam 167.1 50595

Weight kg) MEM 80.3 51.85

Gender Male 70 SD (2556) zhzhvocha bo SD eX

Mio 0 8 Mem Z. 20505 dtp sh- shi sia 1 25-28.99 2 sp) Masatila exceeded

I ate it before obesity

OMmtokyM? 003 -BsDFVKI 0 Obesity is stulann.

So 00853989 1 BODY 01 Obesity By degree

In patients who responded to treatment, a statistically significant decrease in body weight was observed (p «0.001). Only after 15 days of introduction of NND Anti-SVI, the reduction in body weight was 1.1 kg (1.3 95), and in a month this figure was 1.9 kg (2.2 95) from the initial value (Fig. 2).

In patients who responded to treatment, a statistically significant (P «0.001) reduction in waist and hip circumference was observed as early as one (1) week after the start of NND-

Anti-SVI, and at the end of treatment these figures were 2.395 and 2.7 96, respectively. In table 5

Figure 2 shows the dynamics of waist and hip circumference changes.

Table 5 ШШШШШШШЩchatkovi, torom role 15 22 for zosh ШШШ I gave

Around the waist, see. . . detours 93 | defects OB | OB | bak sho re Z let

And from | pl! a kavny s a KO V ES of the initial i and ! And indicator, | ! !

Thigh circumference, om. 8 thirds of the site rttntknt about Mzhmosm | pvc 10 8k about w | 109 at 108.75 | 108.35 | 10815 | 1078Х 1758 web tya Ton voi gubata tva BV a vid Toboyu 146006 | 191 yes r 5 you initial and | and

Its indicator, | and ! And about | AI code of OI in comparison with the initial indicator; b x vdo 0001 compared to 3. the initial indicator

When assessing the feeling of hunger in patients using the visual analog scale (VAS), the greatest intensity of the feeling of hunger was observed in the evening hours. At the end of the 1st month after the introduction of NND Anti-SVI1, the level of feeling hungry in the evening decreased significantly (p «0.001) from 49.4x53.75 to 42,024.32 points. Also noticeable was the tendency to decrease the feeling of hunger in the morning and afternoon periods (from 20.5253.23 to 13.6:21.78 points in the morning hours and from 44.73.45 to 27.353.72 points in the daytime). Although the data on the morning feeling of hunger at the end of the treatment did not reach a statistically significant value, the observation of which could be related to the moderate initial values, such dynamics cannot remain unnoticed.

Thus, the conducted clinical studies of NND Anti-SVI confirmed the high tolerability of the studied solution, which also did not show any side effects.

EXAMPLE 5.

Fagerström Test for Nicotine Dependence

In this example, the test itself is presented. The relevant data are listed below. Test

Fagerström for nicotine addiction is a test for assessing the degree (intensity) of nicotine addiction. See T.F. Heatherton (Neaiiepop T.E.), L.T. Kozlovsky, (KogIombKi

G.T.), R.S. Freker (EgesKeg V.S.), K.O. Fagerström (Radegvigot K.O.), Fagerström Test for Nicotine Dependence: Analysis of the Fagerström Test for Nicotine Dependence.

British magazine "Dependence" 1991; 86:1119-27. In the studies described below, patients answered all questions in full. The total number of points indicates the degree of nicotine dependence. The degree of nicotine dependence is assessed according to the following scale: less than 4 - minor dependence; 4-6 - medium degree of dependence; and 7th - a high degree of dependence.

Table 6.

I. When do you smoke your first cigarette after waking up? o More than a minute 0/0 11111113 o After31-bb'minutes 1111 pa in pet tn kp iv, Is it difficult for you to refrain from smoking in those places where smoking is prohibited, for example, at meetings, in. book, in cinemas, etc.? 00

No shk sho SHE and pi

SVC Sho po

V. Which of the cigarettes, in order of smoking, is the most difficult for you

Refuse itD

Odrankova 00000002 on tn

Anything else! 30000000 ooo pin (I. How many cigarettes do you burn per day.d//-/:/ ОСС

ZFabolesshei/////11O a S ot or more B 5. Do you smoke more in the early hours of the morning or at any other time

IN

Yes ША П2 ОО ОО ОО 2 D«yuYUKe 6. Do you poop even when you are sick and you should

SHOULD YOU STAY IN THE NZHKU? 00000000 family nausea

And S

EXAMPLE 6.

Withdrawal symptom scale test (MP55 test)

In this example, the test itself is presented. The relevant data are listed below. In the studies described below, patients who quit smoking answered 12 questions (on a scale of 1 to 5 points per answer) describing and rating their feelings over the past 24 hours (questions 1-7), the desire to smoke (questions 8-9 ) and manifestation of physical symptoms (questions 10-12). Patients circled only one number when answering each question. The summary of the results can be divided into three domains (M - questions 1-7, C - questions 8-9 and P - questions 10-12) or summarized by the total number of points, which can vary from the minimum (12) to the maximum (60) points, reflecting the manifestation of smoking cessation symptoms.

Table 7

Please describe, in a numerical equivalent, your condition for the last 25 hours (Circle a circle and write one number opposite each question)

Go Ne | Ulpetky | Enough | Very | Extremely felt the form strongly | very strong

How.--"STICKNESS. sleepy vni nan fen nn 2. excitement SHE | 2 | "M NI a PA Z ; : : di tt nt : 3... Irritability. 02000 ash tree SYA 5. Sensation of topod ERI SHY SHE ZY v. Deterioration and II r! CI 4 | 5

A. How long did you have the urge to smoke in the last 24 hours? (Circle only one pattern)

There was no such thing 0 Not very good Less | Bigger and Almost / Such a feeling! desire | For a long time) a part of a part always (constant shu pnya: days - DAYS and M pnya and 7.6 Ш Ш Ше і | z 4 | 5

Q. How strong was your desire to smoke? (Circle only one number) and , and in There was no such | Me Moderately Pai |slie Extremely ionic ---INFUSION 80800 SMLE STRONG o330000O.| STRONG STRONG

Have you experienced any of the following symptoms in the past 74 hours? (Circle only one number p m ! t. Pain in nn nn ny shi sha v shi 719, Cough; pain in 1 ! 21 Z 4 | 5 ky shi V VOK VOK MN she

R. West (M/ezvi N), P. Hayek (Na|eK R): Evaluation of the Withdrawal Symptom Scale to determine symptoms of withdrawal from cigarettes. Psychopharmacology 2004, 177(1-2): 195-199), is incorporated herein by reference.

EXAMPLE 7.

Hospital anxiety and depression scale (NAOB scale)

In this example, the test itself is presented. The relevant data are listed below. "Hospital anxiety and depression scale" (NAYUO5 scale) refers to a subjective scale for detecting signs of anxiety and depression in inpatients and outpatients. See, A.S.

Sigmond (7idtopa, A.5.), R.P. Snaith (Zpayi V.R.), "Hospital Anxiety and Depression Scale",

Protocols of psychiatric research. 5th edition, 1983, Volume 67, p. 361-370. - is indicated in this document as reference material.

Method of use: the patient is given a questionnaire form of the scale, which contains the following instruction: "Scientists believe that emotions play an important role in the occurrence of most diseases.

If your doctor knows more about your medical history, he can help you much better.

This questionnaire is designed to help your doctor understand your condition. Do not pay attention to the numbers and letters on the left side of the questionnaire. Read each statement carefully and in the space on the left place an "X" next to the answer that most closely corresponds to the state in which you were a week ago. You should not think too long about this or that statement. Your first reaction will always be the best."

The scale includes 14 statements divided into 2 subsections: "anxiety" (questions under odd numbers - 1, 3, 5, 7, 9, 11, 13) and "depression" (questions under even numbers - 2, 4, 6, 8, 10, 12, 14).

There are 4 answer options for each statement, reflecting the strength of feeling or emotion, thereby characterizing the severity of symptoms from 0 (no symptoms) to C (maximum presence of certain symptoms).

When interpreting the results, the total score for each subscale is taken into account.

The results are divided into C domains: 0-7 - means "normal state" (absence of pronounced symptoms of anxiety and depression); 8-Yu - means "state of subclinical anxiety/depression" and 11 and above - means "state of clinical anxiety/depression".

Table 8 (1) I detect voltage, for example, sheneya.dD 111

So feavidyidH 1111111 V

SENATE 0000 2

Goa From INJECTION 00000000 nn nn

F | What I used to get extraordinary pleasure from: E pleasure, that works on me and now Hey - just like that

With | I'm afraid that something bad will happen to me: and M sha Ben nn, S --- ABSOLUTELY NOT! 4 |I am easily distracted and I always try | AND

To see something funny in a vision or other event and : | --- POSSIBLE Yes 1 in s -- 6 -- «- 0- Zh

S---TTLYAK, LE NE UNN MU SENS 8 /(Anxious thoughts are spinning in the main head. 33000001 wholesale pcs with mm in soslytimestimesuiG 111111 in

SOIDSHLYSHEEYINKOLY nn tn son gyaudobromunastroiid 77777711

SOO1LLUDUZHE FROM KO 000 odn shcha

Go bavkoly 0 0 ОО со0Ш127tovraktichnozavzhdi.id with Sy

T...It's easy for me to sit down and relax -0001 (In iIt seems to me that I have started (-apa) to do everything

A. I feel a bit of internal tension and nausea. nn

Goren does not have such a feeling at all ДГ 30311100 y ---although А ХССС Ь ОО Фр -шсппvery frequent З pgt (46 I clearly monitor my health 00303. nt g - does she spend as much time as I had to 2 Y - Maybe I began to pay less attention to my 1 and take care of my health the way I used to | 0 3 before Ying I gy I feel restless, as if I need

I En and ssh POSSIBLE Yes 800,000 shk 1 Y

0000 2 I feel that my actions (beliefs, interests) can bring me pleasure in life

Shshevne

Soy Always b. ;

And I feel better than before 10101010. I feel it at all/ 0000000. From day 113 I have unexpected feelings of panic and - very often - I have no such feeling at all. 14 I can get pleasure from a good book, o-.Vadiochy television programid -/: 77111111 -- YIVKOMY | n M PO - very rarely i

A.S. Sigmond (7idtopa, A.5.), R.P. Snaith (Zpipe AR), "Hospital Scale of Anxiety and 5 Depression" Protocols of Psychiatric Research. bsapa., 1983, Volume 67, p. 361-370. - is indicated in this document as reference material.

EXAMPLE 8.

A comparative, double-blind, placebo-controlled clinical trial evaluating the combination of ultra-low-dose anti-protein 5-100 antibodies and ultra-low-dose anti-receptor antibodies

SVI and ultra-low doses of antibodies to the SVI receptor in the treatment of moderate nicotine dependence and obesity.

For the study, 300 mg tablets saturated with a water-alcohol solution (b mg/tab) of the NND of polyclonal rabbit antibodies to the brain-specific protein 5-100 (NND Anti-

C100) and cannabinoid receptor type 1 (NND Anti-SVI), each of which is obtained by hyperdilution of the base matrix solution in 10072, 10030, 100200 times (a mixture of hundreds of homeopathic dilutions of C12, C30 and C200) (NND Anti-5i00 Ж NND Anti- SVI1). In addition, the study used 300 mg tablets saturated with a water-alcohol solution (6 mg/gb)

NND of polyclonal rabbit antibodies to cannabinoid receptor 1 (NND Anti-SVI), obtained by hyperdilution of the basic matrix solution in 10072, 10030, 100200 times (a mixture of hundreds of homeopathic dilutions C12, C30 and 200). 59 patients who have a desire to quit smoking were included in a comparative, double-blind, placebo-controlled study of the effectiveness of the combination NND Anti-5100 u- NND

Anti-SVI and anti-SVI in the treatment of nicotine addiction. 22 patients were included in the active drug group, in which they were given NND Anti-5100 4 NND Anti-SVI, 1 tablet C times a day. 17 patients were included in the group of the comparative drug, in which they were given NND Anti-

SVI, 1 tablet C times a day. 20 patients were included in the placebo group and received 1 tablet C times a day (namely, a tablet of granulated lactose and other auxiliary substances without active components). Treatment lasted 12 weeks. All three groups were compared based on initial demographic, anthropometric and clinical laboratory test results. According to the Fagerström test, all patients had a slight nicotine dependence (less than 4 points), that is, the patients smoked for more than one year and had the first (1) degree of obesity (body mass index (BMI) - 30.0-34.9 kg/m2).

All patients who took part in the study completed the treatment within the period specified by the study protocol; no patient was withdrawn from the study prematurely.

Data analysis showed that the number of patients who quit smoking increased among those patients who received NND Anti-5100 i- NND Anti-SVI1 and NND Anti-SVI (Table 9). In a group

From NND Anti-5100 i- NND Anti-SVI, the number of patients who quit smoking already after 4 weeks of treatment was 23 90; after 8 weeks - 36 9o, and at the end of the 12-week course of treatment - 41 95. In the NND Anti-SVI group, the corresponding indicators were 12 95, 2495 and 29 95 (against 5 95, 5905 Her 10 Ob, respectively, in the placebo group ). The difference in the effectiveness of treatment according to the main parameter of effectiveness in comparison with placebo therapy was 31 95 (for the NND Anti-5100--01 0 group) and 19 95 (for the NND Anti-SVI group), and, from the point of view of statistics, this is quite a significant achievement.

Evaluation of the effectiveness of NND Anti-5100 and NND Anti-SVI showed a significant reduction in nicotine dependence, both in the entire group and in the subgroup of patients who could not quit smoking.

The initial total average score on the Fagerström test was 2.67-0.14. After 12 weeks of treatment, it decreased to 1.33240.14, and the decrease was statistically significant, not only compared to baseline, but also compared to the placebo group. Patients who received NND Anti-SVI and who did not quit smoking also demonstrated positive dynamics in relation to the manifestation of their nicotine dependence, which at the end of 3 months of treatment was significantly lower compared to the initial levels of dependence and placebo.

Analysis of data on the scale of withdrawal symptoms (MPO5 test) showed that nicotine withdrawal symptoms gradually decreased among patients who quit smoking, reaching minimum values 12 weeks after the start of treatment in both groups NLD Anti-5100 4 NLD Anti-CB1 and NLD Anti - SVI (Table 9). The lowest overall score was recorded in the group of NND Anti-5100 and NND Anti-SVI, which proves the fact that the use of the combination of NND Anti-5100 and NND

Anti-SV1I and NND Anti-SVI allows you to make the process of quitting smoking easier and painless, including in comparison with only the group of NND Anti-SVI.

Table C

The dynamics of the main indicators depending on the form of treatment

And Period | NND Anti-5100 « NND Anti-SV Ppacebo and

NND Anti-SV1 | (Me5E) (MEBE) pisha ME) r poet Fagerström, yut baliv (n number of smokers) and ue3 anal AV KATA AD nna kVA azh mAlenya la - dn ENN

Initial 2.640100 (pe22 2652012 (pe17) 2.0520.11 (pe20

Initial 2675014 (pe12) 2bbzhOIYA4 (pe12) | oYubBOM1(pe18) ""Elyzhniv VO Zh(mon) 115013) 1 Zob, about nn. 1 percent of patients who quit smoking, in close proximity to 00 3bB(peB) 00000120) 00005900) bweeks 300 ZbO6(pe8) ! A 596 (pi

Tatyzhniv I (p-10 2996 (pEV 1095 (p2).

Symptom withdrawal scale and test MROZ5), number of points (n-- number of days and nights of sleepers who QUIT SMOKING) For ah1.25 (pev) 33.0059.00 (mon-2 Sat (mon) and V weeks | 28, Tezh 02 (mon. 25.5042.22 (mon4) | ZA (mon) 3 weeks 485 and mon 208016 (pe) and Z NO BO (a

NH Questionnaire scale of anxiety and depression (NAV scale), number of points pin osn - -4l - Number of interviewed patients) Fr. p

Initial 11.7340.36 (p522) | 110.50 (p517) 104 (pe20).. p. Yatyzhny 08080 10.3250.32 (22) 10.470.30 (Fri.17, 11.95:20.45 (Fri.20) o Yaltyzhniv 6695033 (Fri.22) | 9, 8820.32 (p517) 12.5550.95 (Fri.20). and Lyltyzhniv, | 70 46'Я (peda 84120357) | 120550. 18 (p520)

Note: I statistically significant difference compared to 5 ppacebo group; ed co. a statistically significant difference between the bodies of NAD Anti 500 NNYA Anti-SV' and NAD Anti-OB, but also a statistically significant difference in comparison with the initial data.

The first degree of obesity was found in all groups of patients included in the study. At regular time intervals, all patients of the studied groups were measured!MT.

The results of the study are presented in Table 10.

Tabpinya 10

Average difference between initial and current weight (in kg); measured at each visit;

And Period | NND Anti-9100 with NND | nndantisVi 00 Placebo še

My children Goa MaZE) ip 2: MUBE) nm NI NN PI VN EK ZK i same week | ш0 2Я0Б 00000 0031 0Я0a sleds pttltuye tr lyue 77 o5oY close 30300002 0002006 00100010 licks 000000 ss TO -otyzhniv 00 VOYE 00 OVO SOY

Zatyzhniv 000yaoyuyut 0017 zvo vv

Note: To determine the statistical significance of a change. two-sided Student's tests in Dunnett's modification were used to compare weight indicators at the control visit (visit 0) with the indicators of all subsequent visits. Significant differences (p<0.05) are marked with an asterisk.

As a result of the 12-week course of treatment, body weight in both study groups significantly decreased compared to the placebo group. During the 3rd month of therapy, about half of the patients (52 95 and

47 9U5) in both study groups reduced their weight by 5 95 or more in comparison with their initial weight (compared to 15 95 patients of the placebo group, with an indicator of p "0.05) (Fig. 3).

The assessment of the safety of the treatment, which was carried out on the basis of records of adverse events (AEs) during the treatment period and observations of laboratory indicators, showed that the combination of NND Anti-5100 and NND Anti-SVI and NND Anti-SVI were very well tolerated by patients. The safety analysis includes data from all patients who participated in the study (M - 59). No negative effect of treatment on the central nervous system was found; indicators of psychiatric consequences were absent. This conclusion was confirmed by monitoring indicators according to the Hospital scale of anxiety and depression (Table 9). Combination of NND Anti-5100 --

NND Anti-SVI demonstrated a positive effect on symptoms of anxiety and depression, which were significantly reduced at the end of treatment compared to both baseline and placebo groups. No AEs were detected. Laboratory indicators, including general and biochemical blood tests and clinical urine analysis, did not show significant deviations from the norms.

Thus, the study showed the effectiveness and safety of the NND Anti-5100 combination --

NND Anti-SVI1 and NND Anti-SVI for the treatment of nicotine addiction. The effectiveness of the treatment was proven by the high percentage of patients who quit smoking, the reduction of withdrawal symptoms during therapy, and the relief of nicotine dependence in those patients who could not quit smoking.

All observed performance indicators were statistically significant compared to the placebo group. The effectiveness of the combination of NND Anti-5100 and NND Anti-SV1 exceeds the effectiveness of NND Anti-SV1 alone. The safety profile was impeccable for both the combination of NND Anti-5100 and NND Anti-SVI and NND Anti-SVI. And the combination of NND Anti-

With 100 days of NND Anti-SVI1 and NND Anti-SVI alone did not lead to the appearance of clinical symptoms of anxiety and/or depression. In addition, a decrease in body weight was recorded in patients who were diagnosed with 1 degree of obesity.

EXAMPLE 9.

A comparative, double-blind, placebo-controlled clinical trial evaluating the combination of ultra-low-dose anti-protein 5-100 antibodies and ultra-low-dose anti-receptor antibodies

SVI and ultra-low doses of antibodies to the SVI receptor in the treatment of severe nicotine dependence.

Zo For the study, 300 mg tablets saturated with a water-alcohol solution (b mg/tab) of NND polyclonal rabbit antibodies to brain-specific protein 5-100 (NND Anti-5100) and cannabinoid receptor type 1 (NND Anti-SVI) were used, each with which are obtained by hyperdilution of the basic matrix solution in 10072, 10030, 100200 times (a mixture of hundreds of homeopathic dilutions of C12, C30 and C200) (NND Anti-5100 and NND Anti-SVI1). In addition, the study used 300 mg tablets saturated with a water-alcohol solution (6 mg/gb)

NND of polyclonal rabbit antibodies to cannabinoid receptor type 1 (NND Anti-SVI), obtained by hyperdilution of the basic matrix solution in 10072, 10030, 100200 times (a mixture of hundreds of homeopathic dilutions C12, C30 and 200).

To evaluate the effectiveness of the combination of NND Anti-5100 and NND Anti-SVI1 in the treatment of severe nicotine addiction, 61 patients were included in a comparative, double-blind, placebo-controlled study, randomly divided into three groups: 18 patients were included in the first group (they were given NND Anti-5100 same NND Anti-SVI, 1 tablet 4 times a day), 22 patients were included in the second group (they were given NND Anti-SVI, 1 tablet 1 time a day) and 21 patients were included in the third group, in which patients received 1 tablet 4 times a day (namely, a tablet of granulated lactose and other auxiliary substances without active components).

Treatment lasted 12 weeks. All three groups were compared on baseline demographic, physical, and clinical laboratory test scores. According to the preliminary data of the Fagerström test, severe nicotine addiction was noted in all patients (» 7 points), that is, the patients smoked for more than three years. During monthly visits, patients were monitored and their physical condition and laboratory test results were checked (Fagerström test, Hospital Anxiety and Depression Scale test, (MRBO5Y test). All patients who quit smoking passed the MRBOB test. All patients participating in the study completed the treatment within the period determined by the study protocol; no patient was withdrawn from the study prematurely. The results of the study are presented in Table 11:

Zo

Table 11

Dynamics of the main indicators depending on the form of treatment

Period NND Anti-8100 » NNYA Anti-SV1 Placebeo

NNYA Anti-SVi (MeEZE) (ME (MEVE

Fagerinström test, number of points (p is the number of smokers)

Initial 8.785026 (pe18) 8.553025 (pe) 8.520 4 (ve)

Initial 3.920534 (pe15). ATO 417) 8ATO o (pe 20)

Tatyzhniv 45050952 (pe12) VL150,267 (ph17) 8.730233 (pe19)

Part of patients who started to smoke, 4 weeks T195 pd) 96 (pev) 595 (pe) 8 weeks old 1495 (pa) (pe)

T2 weeks Zo95 (Abu VZ (p-5) TO (la)

Scale of withdrawal symptoms (ME55 test), number of points - the number of smokers who quit smoking) 4 weeks Ba, 3zh1.2 (pe) Ba OKO 50 (pa) 5441) 8 weeks ab, 75je1.89 (pea) 47335087 (ve ) Sat (n i2 weeks ZU OV (pev) adek veB) Z, OKO (pe)

Hospital scale of anxiety and depression scale НАЮ5Vast points (p.- angle of surveyed patients)

Initial 12515035 (pe 18) 195.50:30.29 (pe) 14.8150.38 (per) 4 weeks FOR OU (pe 15) 11.85:50.25 (phe2) 15.0550.47 (pe) 8 weeks 9.5650.30 (8218) 10803022 (peg2i 13245039 (pe) 1 weeks 720 (le 18) 9.500, 19 (groin 12674023 (pe)

Note:

Zh is a statistically significant difference in porn with the ppaceyoe test, but it is statistically significant: the difference between the groups NN Anti-8100 I-NUD Anti SVI and "NND Anti OV, re;

I" statistically significant difference in comparable initial data re,

In the NND Anti-5100 -- NND Anti-SVI group, the number of patients who quit smoking already after 4 weeks of treatment was 11 95; after 8 weeks - 22 95, and at the end of the 12-week course of treatment -

ZO 96. In the NND Anti-SVI group, the corresponding indicators were 9 95, 14 95 and 23 95 (against 5 95, 5 95 and 95, respectively, in the placebo group).

After the introduction of NND Anti-5i00 and NND Anti-SVI, the manifestations of nicotine dependence significantly decreased, both in all groups and in the subgroup of patients who could not quit smoking (see Table 11). their initial average scores on the Fagerström test were 8.92:50.34, and after 12 weeks of treatment, these indicators almost halved to 4.5020.26. In addition, the reduction was 10 statistically significant not only in comparison with the initial indicators, but also in comparison with the indicators of the NND Anti-SVI group and placebo.

When the combination of NND Anti-5100 and NND Anti-SVI was administered, patients also had a statistically significant reduction in withdrawal symptoms compared to both the NND Anti-SVI1 group (at p "0.05) and the placebo group (p "0.005) based on the data of the MRUOB5 test with the achievement of minimum indicators after 12 weeks from the start of treatment.

A safety assessment was also conducted. The safety analysis included data from all patients who participated in the study (M-61). This assessment was based on adverse event data and laboratory test results. The results of the study showed not only good tolerability of the combination of NND Anti-5100 4 NND Anti-SVI and separately NND Anti-

SVI, but also the absence of any adverse events associated with medication. No negative effect of treatment on the central nervous system was found; indicators of psychiatric consequences were absent. This conclusion was confirmed by monitoring indicators according to the Hospital scale of anxiety and depression (Table 11). Combination of NND Anti-5100 and NND Anti-

SVI demonstrated a positive effect on symptoms of anxiety and depression, which were significantly reduced at the end of treatment compared to both baseline and placebo. No AEs were detected. Laboratory indicators, including general and biochemical blood tests and clinical urine analysis, did not show significant deviations from the norms.

Thus, the study showed the effectiveness and safety of the NND Anti-5100 combination --

From NND Anti-SVI for the treatment of severe nicotine addiction. After completing a 12-week course of treatment, almost a third of smokers were able to free themselves from nicotine addiction. As shown in

Table 11, the effectiveness of the combination of NND Anti-5100 and NND Anti-SVI, from a statistical point of view, significantly exceeds the effectiveness of placebo. The combination of NND Anti-5100 and NND Anti-SVI significantly increased the ability of patients to more easily and painlessly endure the process of quitting smoking.

When NND Anti-5100 and NND Anti-SVI were administered to patients who could not quit smoking during the study, the manifestations of nicotine addiction, in comparison with the NND Anti-SVI and placebo groups, were significantly reduced.

The combination of NND Anti-5100 and NND Anti-SVI and separately NND Anti-SVI1 had an excellent safety profile and did not affect the work of the central nervous system in any way.

EXAMPLE 10.

Study of the effect of ii) a combination of NLD polyclonal rabbit antibodies to brain-specific protein 5-100 (NND Anti-5100) and NND antibodies to cannabinoid receptor type 1 (NND Anti-SVI), each of which was obtained by hyperdilution of the base matrix solution in 10072, 10030, 100200 times (mixture of hundreds of homeopathic dilutions of C12, C30, C200) (NND Anti-5100 i- NND Anti-SVI), i) separately NND

Anti-SVI, and others) separately NND Anti-5i00, on locomotor activity of mice, the purpose of which is to evaluate their antinicotinic qualities.

40 white outbred male mice (weighing 22-25 g, age 1.5 months) were used for the study. 10 mice were intact. The remaining mice were injected with nicotine subcutaneously for 4 days at a dose of 0.3 mg/kg. Before the administration of nicotine (an hour before), mice were injected intragastrically with either distilled water (control 0.4 ml/mouse), or NND Anti-5100 (0.4 ml/mouse), or

NND Anti-SVI (0.4 ml/mouse), or a combination of NND Anti-5100 and NND Anti-SVI1 (0.4 ml/mouse).

30 minutes after the last dose of nicotine, the "Open field" test was performed.

The animals were placed in the center of the Tgybsap photo-sensor installation (manufactured by Sotsroitstp,

USA), where the movement activity of animals in vertical and horizontal positions was recorded for two minutes. The model of the "Open field" test allows to evaluate the influence of compounds (component solutions) on the locomotor activity of animals (H.K. Gershenfield (N.K. SegzpepiivYi),

P.E. Neumann (Mdytapp R.E.), S. Mathis (Mayiz S), J.N. Crowley (Stamlu U.M.), H. Lee (Ii H), SM.

Paul (Rush 5.M.). Cell mapping of quantitative signs of mouse behavior in the "Open field" chamber. Genetics of behavior. -1997 - Vol. 27. - Mo. 3. - p. 201-209. This material is complete

In the form and with the purpose defined by this document, it is indicated in this document as a reference). Installation parameters: size 270 x 270 x Zbomm, the field is divided into 64 squares, 2.5 x 2.5, 3 25 mm apertures located on the platform, lighting with a 150 W lamp.

Nicotine is an alkaloid found in plants of the nightshade family, mainly in tobacco, and has psychotropic properties. The effect of nicotine is considered indirect, as it is carried out through peripheral and central M-choline receptors. Depending on the dose, getting alkaloids into the human body can lead to symptoms of anxiety and depression, euphoria, excitement or, on the contrary, calmness. In addition, long-term use of nicotine leads to addiction.

Drugs used to facilitate the process of quitting smoking, among other things, are aimed at eliminating pathological changes in the psycho-emotional state of a person, which helps patients with a pathological addiction to tobacco to get rid of this harmful addiction.

In this study, the introduction of nicotine led to an increase in the motor activity of mice: the activity time increased by 8.2 95 (p «0.05), the distance traveled - by 5.1 95, the number of examined apertures - by 78.2 95 (p « 0.05), the time of the reaction study - by 76.9 95, while the time of the immobile state, on the contrary, decreased by 13.5 95 (p "0.05) in comparison with intact animals.

Separately, NND Anti-5100 did not have a significant effect on the studied parameters of the control group. NND Anti-SVI reduced the time of locomotor activity and the distance traveled of mice in the experimental group to the level of intact mice. However, Anti-SVI1 NNDs have no effect on immobility period, number of apertures, and response period. At the same time, combined input

NND Anti-SVI and NND Anti-5100 led to a decrease in mobility time and, accordingly, to an increase in immobility time to the level of intact animals, to a significant reduction in the distance traveled (by 29.2 95 in comparison with the control and by 25.5 95 in comparison with intact animals) and to a certain decrease in activity (the number of apertures fell by 15.3 95, reaction time decreased by 17.4 Ob).

Thus, the introduction of NND Anti-SVI and the combination of NND Anti-SV1 and NND Anti-5100 contributes to the elimination of changes in the behavior of animals caused by the introduction of nicotine. Using a combination

NND Anti-SVI1 and NND Anti-5100 were more effective compared to the introduction of only NND

Anti-SVI1.

Table 12

The effect of drugs on the locomotor activity of the muscles ("Open: field" test). M w m:

Chado's Elapsed Time (time of mobility, distance, immobility, investigated responses sec. see aperture

Group ntactny 7a121,a 3933519, 45.0x5.0 5.521. 2606

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Anti-5100

Group NND, ToAK1NE ZbbZzh19 451 9.8 For me

Anti-SV1

NID Tako group call 45.5:29 831.5 Z.8307

Anti-5100

NNI Anti-ST

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Claims (44)

FORMULA OF THE INVENTION 1. A medicinal product for the treatment of obesity and related metabolic disorders and/or nicotine addiction, which contains antibodies in an activated potentiated form to the human cannabinoid receptor type 1 in a mixture of three homeopathic dilutions C12, C30 and C200. 2. Medicinal product according to claim 1, which is characterized by the fact that said antibodies in an activated potentiated form are antibodies to the entire human cannabinoid receptor type 1. 3. Medicinal product according to claim 2, which is characterized by the fact that the entire human cannabinoid receptor type 1 has the sequence 5EO IU MO:1. 4. Medicinal product according to claim 1, which is characterized by the fact that said antibodies in an activated potentiated form are antibodies to polypeptide fragments of the human cannabinoid receptor type 1. 5. Medicinal product according to claim 4, which is characterized by the fact that the indicated polypeptide fragment of human cannabinoid receptor type 1 is selected from the group consisting of sequences presented in ZEO IU MO:3-16. 6. Medicinal product according to claim 1, which is characterized by the fact that the indicated antibodies in an activated potentiated form are presented in the form of a mixture of homeopathic dilutions C12, C30 and C200, with which a solid carrier is impregnated. 7. Medicinal product according to claim 1, which is characterized by the fact that said antibodies in an activated potentiated form to human cannabinoid receptor type 1 are monoclonal, polyclonal or natural antibodies. 8. Medicinal product according to claim 7, which is characterized by the fact that said antibodies in an activated potentiated form to the human cannabinoid receptor type 1 are polyclonal antibodies. 9. Medicinal product according to claim 1, which is characterized by the fact that antibodies to human cannabinoid receptor type 1 are obtained by performing successive hundredfold dilutions in combination with shaking of each dilution. Zo 10. Medicinal product according to clauses of formula 1, which is characterized by the fact that it additionally contains an activated potentiated form of antibodies to protein 5-100 in the form of a mixture of homeopathic dilutions C12, C30, C200. 11. The drug according to claim 10, which is characterized in that the antibodies to the protein 5-100 are antibodies to the whole protein 5-100. 12. Medicinal product according to claim 11, which is characterized by the fact that the specified whole protein 5-100 consists of the sequence given in ZEO IU MO:17. 13. Medicinal product according to claim 10, which is characterized by the fact that said antibodies to protein 5-100 are presented in the form of a mixture of homeopathic dilutions C12, C30, C200, with which a solid carrier is impregnated. 14. The drug according to claim 10, which is characterized in that the antibody to the protein 5-100 is a monoclonal, polyclonal or natural antibody. 15. The drug according to claim 14, which is characterized in that the antibody to protein 5-100 is a polyclonal antibody. 16. The drug according to claim 13, which is characterized by the fact that the antibody to the protein 5-100 is obtained by making successive hundredfold dilutions in combination with shaking of each dilution. 17. Method of treatment of obesity and related metabolic disorders, which is characterized by the fact that the medicine according to claim 1 is administered. 18. The method according to claim 17, which is characterized by the fact that the specified drug is administered to the patient in the form of a single or double dosage from once a day to four times a day. 19. The method of claim 18, wherein the dosage form(s) are administered twice a day. 20. A method of changing the anthropometric parameters of mammals expected to benefit from such changes, which is characterized by administering the drug according to claim 1. 21. The method according to claim 20, which differs in that the specified anthropometric parameter is waist circumference. 22. The method according to claim 20, which differs in that the indicated anthropometric parameter is the ratio of waist circumference to height. 23. The method according to claim 20, which differs in that the specified anthropometric parameter is the ratio of the circumference of the waist and hips. 24. The method according to claim 21, characterized in that the waist circumference is reduced by at least 1 What 25. The method according to claim 21, which is characterized by the fact that the waist circumference is reduced by at least 2 What 26. The method according to claim 21, which is characterized by the fact that the waist circumference is reduced by at least Z What 27. The method according to claim 21, characterized in that the waist circumference is reduced by at least 1 cm. 28. The method according to claim 21, which is characterized by the fact that the waist circumference is reduced by at least 3 cm. 29. The method of reducing the body weight of a mammal, which differs in that the medicine according to claim 1 is administered. 30. The method according to claim 29, which is characterized by the fact that the body weight is reduced by at least 5 95. 31. The method according to claim 29, which is characterized by the fact that the body weight is reduced by at least 10 95. 32. The method according to claim 29, which is characterized by the fact that the body weight is reduced by at least 15 95. 33. The method according to claim 29, which is characterized by the fact that the body weight is reduced by less than 15 95. 34. The method of slowing down the increase in the body weight of a mammal, which is characterized by the fact that the medicine according to claim 1 is administered. 35. The method according to claim 34, which is characterized in that the increase in body weight is slowed down by at least 10,905. 36. The method according to claim 34, which is characterized by the fact that the increase in body weight is slowed down by at least 30 95. 37. A method of facilitating the process of reducing food intake in a mammal expected to benefit from such reduction, characterized in that the drug of claim 1 is administered. 38. A method of treating a patient suffering from nicotine addiction, which is characterized by the fact that the drug according to claim 12 is administered. 39. The method according to claim 38, which is characterized in that the drug is administered, which results in a statistically significant improvement in the ability to tolerate the smoking cessation process, as determined by the data of the MP55 test. 40. The method of claim 38, wherein the drug is administered which results in a statistically significant reduction in the frequency of smoking among inpatients with moderate nicotine dependence as determined by the Fagerström test. 41. The method of claim 38, wherein the drug is administered which results in a statistically significant reduction in the frequency of smoking among inpatients with severe nicotine dependence, as determined by the Fagerström test. 42. The method of treating addiction to nicotine, which differs in that the medicine according to claim 10 is administered. 43. Medicinal product used for the treatment of patients suffering from nicotine addiction, which is characterized by the fact that the specified product is obtained in such a way that the result is the production of a) a potentiated solution of antibodies in an activated potentiated form to the human cannabinoid receptor type 1 in a mixture of three homeopathic dilutions C12, C30 and C200, and b) a potentiated solution of antibodies in an activated potentiated form to protein 5-100 in the form of a mixture of homeopathic dilutions C12, C30, C200, each of which is made by performing successive repeated dilutions and multiple shaking of each obtained solution in a vertical position in accordance with the technology of manufacturing homeopathic preparations, and then combining the potentized solutions by mixing them or impregnating the carrier with the specified combined solution or each solution separately. 44. Medicinal product used for the treatment of obesity and related digestive disorders, characterized in that said product is prepared in a manner that results in the production of a potentiated solution of antibodies in an activated potentiated form to the human cannabinoid receptor type 1 in a mixture of three homeopathic dilutions C12, C30 and C200, made by making successive repeated dilutions and repeatedly shaking each obtained solution in a vertical position in accordance with the technology of manufacturing homeopathic preparations, and then, optionally, impregnating the carrier with the specified solution. Ду ренни нени нтнюттня still | | And 180.9 to her; w 160 louse aa a mouth a o p. 4 stump J. "h g. x ! I х ЖООЯ40 Зонты ethno oknttttttnnntisnchnn VIJ - still an increase I: In her mass type Ks M I in I . B in 758 and ak 50 repejzhtkttietechnn In neon tive et ptn kt inet CHEN same same same same same t ZHE same t UK Ya p Mp i same tt SL on drit tt -. 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