WO2011119126A1 - Use of oxalic acid in the production of a therapeutic preparation with anti-tumour activity in relation to malignant cells, a therapeutic preparation based thereon and a method of treatment - Google Patents

Use of oxalic acid in the production of a therapeutic preparation with anti-tumour activity in relation to malignant cells, a therapeutic preparation based thereon and a method of treatment Download PDF

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WO2011119126A1
WO2011119126A1 PCT/UA2010/000015 UA2010000015W WO2011119126A1 WO 2011119126 A1 WO2011119126 A1 WO 2011119126A1 UA 2010000015 W UA2010000015 W UA 2010000015W WO 2011119126 A1 WO2011119126 A1 WO 2011119126A1
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treatment
oxalic acid
therapeutic preparation
cells
medicinal product
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PCT/UA2010/000015
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French (fr)
Russian (ru)
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Геннадий Васильевич МАЗИЛЬНИКОВ
Аркадий Петрович ШИМАНСКИЙ
Юрий Анатольевич ЛИХОДЕД
Стефания Стефановна МЕЛЬНИК
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Mazilnikov Gennadiy Vasilevich
Shimanskiy Arkadiy Petrovich
Lykhoded Yuriy Anatolevich
Melnik Stefaniya Stefanovna
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Publication of WO2011119126A1 publication Critical patent/WO2011119126A1/en

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0087—Galenical forms not covered by A61K9/02 - A61K9/7023
    • A61K9/0095—Drinks; Beverages; Syrups; Compositions for reconstitution thereof, e.g. powders or tablets to be dispersed in a glass of water; Veterinary drenches
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/194—Carboxylic acids, e.g. valproic acid having two or more carboxyl groups, e.g. succinic, maleic or phthalic acid
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/513—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim having oxo groups directly attached to the heterocyclic ring, e.g. cytosine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
    • A61K31/52—Purines, e.g. adenine
    • A61K31/522—Purines, e.g. adenine having oxo groups directly attached to the heterocyclic ring, e.g. hypoxanthine, guanine, acyclovir
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00—Medicinal preparations containing inorganic active ingredients
    • A61K33/04—Sulfur, selenium or tellurium; Compounds thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00—Medicinal preparations containing inorganic active ingredients
    • A61K33/14—Alkali metal chlorides; Alkaline earth metal chlorides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A61P35/04—Antineoplastic agents specific for metastasis

Definitions

  • oxalic acid in the manufacture of an anti-tumor drug with respect to malignant cells, a therapeutic drug based on it and a method of treatment
  • the invention relates to medicine, in particular, to the treatment of cancer and can be used as a basis for creating drugs.
  • the acids that make up these drugs are not able to induce apoptosis of a malignant cell, due to the fact that the molecules of these acids have a diffuse type of penetration into a malignant cell and cannot accumulate in it at critical concentrations necessary for apoptosis of a malignant cell.
  • the closest in technical essence to the medicinal product that is claimed is a pharmaceutical composition selected as a prototype for the prevention and treatment of cancer. It includes at least three active compounds present in the circulatory system: at least one amino acid, at least one vitamin, and at least one component selected from the group consisting of adenine, 2-deoxy-0-ribose, D mannose, D-glucosamine, malic acid, oxaloacetic acid, adenosine triphosphate and / or their pharmaceutically acceptable salts (Patent Xs 2 138 257 6 A61K31 / 195 RU).
  • a disadvantage of the known pharmaceutical composition is that malic and oxaloacetic acids are compounds that are rapidly metabolized in the mitochondria in the Rebs cycle. If these acids are used as cytolytics, a decrease in their concentration in the cells of the body will slow down the decay of tumor cells; these acids cannot accumulate in malignant cells at critical concentrations necessary for apoptosis of malignant cells.
  • the pharmaceutical composition there are no substances that accelerate the differentiation of cells.
  • a set of vitamins and amino acids accelerates the processes of unwanted growth of tumor cells. Also, it lacks compounds that slow down nucleic acid metabolism, which, as a rule, accelerates the growth of tumor cells.
  • the basis of the invention is the task of improving the method of treating cancer by creating a universal therapeutic antitumor drug, which contains a new set of its components, which, due to the systemic effect of the therapeutic drug on the process of destruction (apoptosis) of cancer cells and accelerate the differentiation of embryonic cells, provides for the prevention and treatment of cancer diseases, eliminating the postoperative use of radiation and chemotherapy that harm the body Nogo person.
  • oxalic acid is used in the manufacture of a therapeutic drug, which exhibits an antitumor effect against malignant cells
  • a therapeutic drug which is an aqueous solution and contains organic acid and chloride
  • the aqueous solution contains oxalic acid as an organic acid, lithium chloride as a chloride and additionally contains dimethylxanthine, fluorouracil and sodium sulfate in the following ratio of all components (mass%):
  • distilled water to 100 a method of treating malignant tumors, which consists in taking a medicinal product inside the body and monitoring the patient’s condition according to the cytological analyzes according to the invention, in order to take a medicinal product, which is claimed, a solution is prepared by diluting 5 ml of the medicinal product in 100 ml of water, taken orally once a day for a three-month course, the patient's condition is monitored monthly, according to the results of cytological analyzes, they decide to continue and the treatment or the end, the treatment is repeated every 2-3 years.
  • Oxalic acid (dicarboxylic acid) is a colorless crystalline organic acid (C2H2O4), and its salts are found in some plants, such as sorrel and rhubarb. It is used for cleaning textile and metal products and for dyeing fabrics.
  • Oxalic acid is distinguished by metabolic resistance and duration of action; it exhibits selective action on malignant cells, without affecting healthy cells of the body, resulting in the death of malignant cells (apoptosis).
  • Lithium salts have a psychotropic effect and are used in medicine in the prevention and treatment of a number of mental illnesses. Most common in this capacity, lithium carbonate is used in psychiatry to stabilize the mood of people who suffer from bipolar disorder and frequent mood swings. On the one hand, it was found that lithium is able to regulate the activity of certain enzymes involved in the transfer of sodium and potassium ions from intercellular fluid to brain cells. On the other hand, the direct effect of lithium ions on the ionic balance of the cell is noted.
  • lithium chloride is used as a specific agent capable of inducing apoptosis of tumor cells. This is due to the fact that lithium, penetrating into the tumor cell, acidifies it excessively through the accumulation of H + protons, which easily penetrate the cell membrane, and also facilitates the entry of oxalic acid into the cell. An excess of H + protons and oxalic acid causes apoptosis of the tumor cell.
  • the claimed therapeutic drug contains a component that reduces the intensity of the nucleic acid metabolism of cells, fluorouracil. Slowing down the nucleic acid metabolism of the cell helps to slow down cell division and increase the effectiveness of the claimed therapeutic drug.
  • fluorouracil a component that reduces the intensity of the nucleic acid metabolism of cells
  • an underestimated concentration of fluorouracil is used. Dimethylxanthine was introduced to increase the content of cAMP in cells, which accelerates the process of differentiation of embryonic cells in this communication decreases the number of existing and emerging tumor cells.
  • Sodium sulfate NaHS04 is added to prevent burns to the oral mucosa.
  • oxalic acid When oxalic acid enters a patient’s body, it selectively acidifies malignant cells without affecting healthy body cells, resulting in the death of malignant cells (apoptosis), and lithium chloride, which inhibits the division of cancer cells. Fluorouracil in small concentrations inhibits the division of cancer cells by reducing the formation of nucleic acids, enhances the effect of lithium chloride. Dimethylxanthine is a phosphodiesterase inhibitor, due to which the content of cAMP increases in the malignant cells that were at the beginning of differentiation, accelerate it.
  • An aqueous solution of the claimed medicinal product is prepared by randomly mixing the necessary quantities of all components.
  • the method of using the claimed therapeutic drug is as follows and is explained by specific examples.
  • a daily dose of a medicinal product is measured - 5 ml, it is diluted in 50-100 ml of water and the patient receives the received treatment solution orally once a day for three months; every month a cytological analysis is performed on the patient.
  • the treatment is stopped and subsequently repeated according to the claimed method every 2-3 years; if cancer cells are detected by the results of cytological analyzes, the treatment is continued according to the claimed method until complete recovery.
  • cytological analyzes showed single cancer cells in the patient's body. To the patient appoint the appointment of the claimed therapeutic drug according to the method that is claimed. The patient measures the daily dose of the medicinal product - 5 ml, dilutes it in 50-100 ml of water and takes the resulting solution once a day for three months. Each month, the patient submits a cytological analysis, according to the results of which the doctor observes the dynamics of the treatment process. If according to the results of the cytological analysis after the third month of treatment no cancer cells are detected, the treatment is stopped and further repeated according to the claimed method every 2-3 years;
  • the treatment according to the claimed method is carried out for one year and then renewed every two or three years, given the fact that epigenetic growth processes tumor cells may resume after this period.
  • Oxalic acid, lithium chloride, dimethylxanthine and fluorouracil simultaneously enter the human body with a medicinal product.
  • oxalic acid When oxalic acid enters the patient’s body, it selectively acidifies the malignant cells, without affecting the healthy cells of the patient’s body, resulting in the death of malignant cells (apoptosis); lithium chloride inhibits the division of cancer cells.
  • Fluorouracil in small concentrations inhibits the division of cancer cells due to the formation of nucleic acids and enhances the effect of lithium oxalate.
  • Dimethylxanthine is an inhibitor of phosphodiesterase, due to which the content of cAMP in the cell increases, and in malignant cells that were at the stage of differentiation, it accelerates.
  • the inventive therapeutic drug reduces the risk of the transformation of healthy cells into malignant and reduces the speed and volume of development of metastases.
  • the claimed therapeutic drug in contrast to existing antitumor drugs, is not toxic.
  • Tests of the antitumor activity of the claimed therapeutic drug according to the claimed method was carried out on a suspension culture of Raja tumor cells, C57B1 / 6 mice, and rats; antiproliferative activity of the claimed medicinal product was carried out on a Raji cell culture and on C57B1 / 6 mice.
  • Table 1 shows an example of the use of the claimed medicinal product.
  • Table 2 shows the number of Raji Lewis lung carcinoma cell culture cells (3LL carcinoma) that remained alive (live treated cells) after three days of incubation.
  • Figure 1 shows a graph of the dependence of the number of living treated cells on the concentration of the drug in comparison with the number of living cells that have not been processed.
  • the vertical axis shows the percentage of the number of living treated cells, the horizontal axis shows the concentration of the drug.
  • composition of the claimed therapeutic drug allows you to comprehensively stop the tumor process.

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  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
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  • Animal Behavior & Ethology (AREA)
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Abstract

The invention relates to medicine, in particular to means for the treatment of oncological diseases and may be used as the basis for creation of therapeutic preparations. Oxalic acid is used in the production of a therapeutic preparation which exhibits anti-tumour activity in relation to malignant cells. A therapeutic preparation contains oxalic acid as an organic acid, and lithium chloride as a chloride, and additionally contains dimethylxanthine, fluorouracil and sodium thiosulphate with the following ratio of all components (wt.%): oxalic acid 0.2-3.2, lithium chloride 0.2-3.1, dimethylxanthine 0.1-1.8, fluorouracil 0.1-1.8, sodium thiosulphate 0.2-3.1, distilled water to 100. A method for treatment of malignant tumours comprises taking the therapeutic preparation internally, for which purpose 5 ml of the therapeutic preparation is diluted in 50-100 ml of water, it is taken perorally once daily during a three-month course, the condition of the patient is checked monthly and a decision on whether to continue the course of treatment or to terminate it is taken on the basis of the results of cytological analyses; the treatment is repeated every 2-3 years.

Description

Применение щавелевой кислоты в производстве лечебного препарата противоопухолевого действия по отношению к злокачественным клеткам, лечебный препарат на его основе и способ лечения  The use of oxalic acid in the manufacture of an anti-tumor drug with respect to malignant cells, a therapeutic drug based on it and a method of treatment
Изобретение относится к медицине, в частности, к средствам лечения онкологических заболеваний и может быть использовано в качестве основы для создания лекарственных препаратов. The invention relates to medicine, in particular, to the treatment of cancer and can be used as a basis for creating drugs.
Известно использование в клинической онкологии противоопухолевых препаратов, в которых применяются, например:  Known use in clinical oncology of anticancer drugs in which are used, for example:
водный раствор уксуса 9% (Патент UA N° 30769 А, 6 А61К 31/00);  an aqueous solution of vinegar 9% (Patent UA N ° 30769 A, 6 A61K 31/00);
аскорбиновая кислота (Патент RU Л 2 377 007, 6 А61К 31/00);  ascorbic acid (Patent RU L 2 377 007, 6 A61K 31/00);
никотиновая кислота (Патент RU 2 257 899, 7 А61 31/455).  nicotinic acid (Patent RU 2 257 899, 7 A61 31/455).
Кислоты, которые входят в состав этих препаратов, не в состоянии индуцировать апоптоз злокачественной клетки, из-за того, что молекулы этих кислот имеют диффузный тип проникновения в злокачественную клетку и не могут накапливаться в ней в критических концентрациях, необходимых для апоптоза злокачественной клетки.  The acids that make up these drugs are not able to induce apoptosis of a malignant cell, due to the fact that the molecules of these acids have a diffuse type of penetration into a malignant cell and cannot accumulate in it at critical concentrations necessary for apoptosis of a malignant cell.
Наиболее близким по технической сути к лечебному препарату, который заявляется, является выбраный в качестве прототипа фармацевтический состав для профилактики и лечения раковых заболеваний. Он включает по меньшей мере три активных соединения, присутствующих в кровеносной системе: по меньшей мере одну аминокислоту, по меньшей мере один витамин и по меньшей мере один компонент, выбранный из группы, которая состоит из аденина, 2-деокси-0-рибози, D-маннозы, D-глюкозамина, яблочной кислоты, щавелевоуксусной кислоты, аденозинтрифосфата и /или их фармацевтически приемлемых солей (Патент Xs 2 138 257 6 А61К31/195 RU). The closest in technical essence to the medicinal product that is claimed is a pharmaceutical composition selected as a prototype for the prevention and treatment of cancer. It includes at least three active compounds present in the circulatory system: at least one amino acid, at least one vitamin, and at least one component selected from the group consisting of adenine, 2-deoxy-0-ribose, D mannose, D-glucosamine, malic acid, oxaloacetic acid, adenosine triphosphate and / or their pharmaceutically acceptable salts (Patent Xs 2 138 257 6 A61K31 / 195 RU).
Недостатком известного фармацевтического состава является то, что яблочная и щавелевоуксусная кислоты - соединения, которые быстро метаболизуются в митохондриях в цикле ребса. Если эти кислоты используются в качестве цитолитиков, снижение их концентрации в клетках организма будет замедлять процессы распада опухолевых клеток, эти кислоты не могут накапливаться в злокачественных клетках в критических концентрациях, необходимых для апоптоза злокачественных клеток. В фармацевтическом составе отсутствуют вещества, ускоряющие дифференцировку клеток. Набор витаминов и аминокислот ускоряет процессы нежелательного роста опухолевых клеток. Также в нем отсутствуют соединения, замедляющие нуклеиновый обмен, что, как правило, ускоряет процессы роста опухолевых клеток.  A disadvantage of the known pharmaceutical composition is that malic and oxaloacetic acids are compounds that are rapidly metabolized in the mitochondria in the Rebs cycle. If these acids are used as cytolytics, a decrease in their concentration in the cells of the body will slow down the decay of tumor cells; these acids cannot accumulate in malignant cells at critical concentrations necessary for apoptosis of malignant cells. In the pharmaceutical composition there are no substances that accelerate the differentiation of cells. A set of vitamins and amino acids accelerates the processes of unwanted growth of tumor cells. Also, it lacks compounds that slow down nucleic acid metabolism, which, as a rule, accelerates the growth of tumor cells.
В основу изобретения поставлена задача усовершенствования способа лечения онкозаболеваний путем создания универсального лечебного противоопухолевого препарата, который содержит новую совокупность его составляющих, что, за счет системности действия лечебного препарата на процесс уничтожения (апоптоз) раковых клеток и ускорения дифференцировку эмбриональных клеток, обеспечивает профилактику и лечение онкологических заболеваний, устраняя послеоперационное использование облучения и химиотерапию, которые наносят вред организму больного человека.  The basis of the invention is the task of improving the method of treating cancer by creating a universal therapeutic antitumor drug, which contains a new set of its components, which, due to the systemic effect of the therapeutic drug on the process of destruction (apoptosis) of cancer cells and accelerate the differentiation of embryonic cells, provides for the prevention and treatment of cancer diseases, eliminating the postoperative use of radiation and chemotherapy that harm the body Nogo person.
Поставленная задача решается за счет того, что щавелевая кислота применяется в производстве лечебного препарата, который проявляет противоопухолевое действие относительно злокачественных клеток, лечебный препарат, который представляет собой водный раствор и содержит органическую кислоту и хлорид, согласно изобретению, водный раствор в качестве органической кислоты содержит щавелевую кислоту, в качестве хлорида - литий хлористый и дополнительно содержит диметилксантин, фторурацил и серноватистокислый натрий при следующем соотношении всех компонентов, (масс %): The problem is solved due to the fact that oxalic acid is used in the manufacture of a therapeutic drug, which exhibits an antitumor effect against malignant cells, a therapeutic drug, which is an aqueous solution and contains organic acid and chloride, according to the invention, the aqueous solution contains oxalic acid as an organic acid, lithium chloride as a chloride and additionally contains dimethylxanthine, fluorouracil and sodium sulfate in the following ratio of all components (mass%):
щавелевая кислота 0,2 - 3,2  oxalic acid 0.2 - 3.2
литий хлористый 0,2 - 3, 1  lithium chloride 0.2 - 3, 1
диметилксантин 0,1 - 1,8  dimethylxanthine 0.1 - 1.8
фторурацил од - 1,8  fluorouracil od - 1.8
серноватистокислый натрий 0,2 - 3, 1  sodium sulfate 0.2 - 3, 1
вода дистиллированная до 100, способ лечения злокачественных опухолей, который заключается в принятии внутрь организма лечебного препарата и контроле состояния больного по цитологическим анализам, согласно изобретению, для принятия лечебного препарата, который заявляется, готовят раствор, для чего разбавляют 5 мл лечебного препарата в 50-100 мл воды, перорально принимают его один раз в сутки в течение трехмесячного курса, контроль состояния больного проводят ежемесячно, по результатам цитологических анализов принимают решение о продолжении курса лечения или его окончание, лечение повторяют через каждые 2-3 года.  distilled water to 100, a method of treating malignant tumors, which consists in taking a medicinal product inside the body and monitoring the patient’s condition according to the cytological analyzes according to the invention, in order to take a medicinal product, which is claimed, a solution is prepared by diluting 5 ml of the medicinal product in 100 ml of water, taken orally once a day for a three-month course, the patient's condition is monitored monthly, according to the results of cytological analyzes, they decide to continue and the treatment or the end, the treatment is repeated every 2-3 years.
Щавелевая кислота (дикарбоновая кислота) -бесцветная кристаллическая органическая кислота (С2Н2О4), ее соли содержатся в некоторых растениях, таких как щавель и ревень. Используется для чистки текстильных и металлических изделий и для окрашивания тканей.  Oxalic acid (dicarboxylic acid) is a colorless crystalline organic acid (C2H2O4), and its salts are found in some plants, such as sorrel and rhubarb. It is used for cleaning textile and metal products and for dyeing fabrics.
Щавелевая кислота отличается метаболической стойкостью и длительностью действия, обнаруживает выборочное действие на злокачественные клетки, не влияя на здоровые клетки организма, в результате чего происходит отмирание злокачественных клеток (апоптоз). Oxalic acid is distinguished by metabolic resistance and duration of action; it exhibits selective action on malignant cells, without affecting healthy cells of the body, resulting in the death of malignant cells (apoptosis).
Соли лития имеют психотропное действие и используются в медицине при профилактике и лечении ряда психических заболеваний. Наиболее распространенный в этом качестве, карбонат лития применяется в психиатрии для стабилизации настроения людей, которые страдают биполярным расстройством и частыми перепадами настроения. С одной стороны, установлено, что литий способен регулировать активность некоторых ферментов, принимающих участие в переносе из межклеточной жидкости в клетки мозга ионов натрия и калия. С другой стороны, отмечено непосредственное влияние ионов лития на ионный баланс клетки.  Lithium salts have a psychotropic effect and are used in medicine in the prevention and treatment of a number of mental illnesses. Most common in this capacity, lithium carbonate is used in psychiatry to stabilize the mood of people who suffer from bipolar disorder and frequent mood swings. On the one hand, it was found that lithium is able to regulate the activity of certain enzymes involved in the transfer of sodium and potassium ions from intercellular fluid to brain cells. On the other hand, the direct effect of lithium ions on the ionic balance of the cell is noted.
В заявляемом изобретении литий хлористый используется в качестве специфического средства, способного индуцировать апоптоз опухолевых клеток. Это происходит из-за того, что литий, проникая в опухолевую клетку, избыточно закисляет ее посредством накопления протонов Н+, которые легко проникают через клеточную мембрану, а также облегчает поступление в клетку щавелевой кислоты. Избыток протонов Н+ и щавелевой кислоты вызывает апоптоз опухолевой клетки.  In the claimed invention, lithium chloride is used as a specific agent capable of inducing apoptosis of tumor cells. This is due to the fact that lithium, penetrating into the tumor cell, acidifies it excessively through the accumulation of H + protons, which easily penetrate the cell membrane, and also facilitates the entry of oxalic acid into the cell. An excess of H + protons and oxalic acid causes apoptosis of the tumor cell.
В отличие от прототипа, заявляемый лечебный препарат содержит составляющую, которая снижает интенсивность нуклеинового обмена клеток, - фторурацил. Замедление нуклеинового обмена клетки способствует замедлению деления клетки и усилению эффективности действия заявляемого лечебного препарата. Для уменьшения скорости нуклеинового обмена клетки, который является обязательным условием опухолевого процесса, используется заниженная концентрация фторурацила. Диметилксантин введен с целью увеличения содержания в клетках цАМФ, которая ускоряет процесс дифференцировки эмбриональных клеток, в этой связи уменьшается количество существующих и возникающих опухолевых клеток. Серноватистокислый натрий NaHS04 добавляется для предотвращения ожогов слизистой оболочки рта. Unlike the prototype, the claimed therapeutic drug contains a component that reduces the intensity of the nucleic acid metabolism of cells, fluorouracil. Slowing down the nucleic acid metabolism of the cell helps to slow down cell division and increase the effectiveness of the claimed therapeutic drug. To reduce the rate of nucleic acid metabolism of the cell, which is a prerequisite for the tumor process, an underestimated concentration of fluorouracil is used. Dimethylxanthine was introduced to increase the content of cAMP in cells, which accelerates the process of differentiation of embryonic cells in this communication decreases the number of existing and emerging tumor cells. Sodium sulfate NaHS04 is added to prevent burns to the oral mucosa.
Щавелевая кислота, при попадании в организм больного, избирательно закисляет злокачественные клетки, не влияя на здоровые клетки организма, в результате чего происходит отмирание злокачественных клеток (апоптоз), а литий хлористый, который тормозит деление раковых клеток. Фторурацил в небольших концентрациях тормозит деление раковых клеток за счет снижения образования нуклеиновых кислот, усиливает действие лития хлористого. Диметилксантин - это ингибитор фосфодиэстеразы, за счет чего увеличивается содержание цАМФ и в злокачественных клетках, которые находились в начале дифференцировки, ускоряют ее.  When oxalic acid enters a patient’s body, it selectively acidifies malignant cells without affecting healthy body cells, resulting in the death of malignant cells (apoptosis), and lithium chloride, which inhibits the division of cancer cells. Fluorouracil in small concentrations inhibits the division of cancer cells by reducing the formation of nucleic acids, enhances the effect of lithium chloride. Dimethylxanthine is a phosphodiesterase inhibitor, due to which the content of cAMP increases in the malignant cells that were at the beginning of differentiation, accelerate it.
Водный раствор заявляемого лечебного препарата готовится произвольным смешиванием необходимых количеств всех компонентов.  An aqueous solution of the claimed medicinal product is prepared by randomly mixing the necessary quantities of all components.
Способ использования заявляемого лечебного препарата является следующим и объясняется конкретными примерами.  The method of using the claimed therapeutic drug is as follows and is explained by specific examples.
Для лечения отмеряют суточную дозу лечебного препарата - 5 мл, разбавляют ее в 50-100 мл воды и полученный лечебный раствор больной перорально принимает один раз в сутки в течение трех месяцев; каждый месяц больному проводят цитологический анализ.  For treatment, a daily dose of a medicinal product is measured - 5 ml, it is diluted in 50-100 ml of water and the patient receives the received treatment solution orally once a day for three months; every month a cytological analysis is performed on the patient.
Если по результатам цитологических анализов не обнаружены раковые клетки, лечение прекращают и в дальнейшем повторяют согласно заявляемому способу через каждые 2-3 года; при выявлении по результатам цитологических анализов раковых клеток, лечение продолжают согласно заявляемому способу до полного выздоровления.  If according to the results of cytological analyzes no cancer cells are detected, the treatment is stopped and subsequently repeated according to the claimed method every 2-3 years; if cancer cells are detected by the results of cytological analyzes, the treatment is continued according to the claimed method until complete recovery.
Рассмотрим послеоперационный случай: цитологические анализы показали одиночные раковые клетки в организме больного. Больному назначают прием заявляемого лечебного препарата согласно способу, который заявляется. Больной отмеряет суточную дозу лечебного препарата - 5 мл, разбавляет ее в 50-100 мл воды и принимает полученный раствор один раз в день в течение трех месяцев. Каждый месяц больной сдает цитологический анализ, по результатам которого врач наблюдает за динамикой процесса лечения. Если по результатам цитологического анализа после третьего месяца лечения не выявлены раковые клетки, лечение прекращают и в дальнейшем повторяют его согласно заявляемому способу через каждые 2-3 года; Consider the postoperative case: cytological analyzes showed single cancer cells in the patient's body. To the patient appoint the appointment of the claimed therapeutic drug according to the method that is claimed. The patient measures the daily dose of the medicinal product - 5 ml, dilutes it in 50-100 ml of water and takes the resulting solution once a day for three months. Each month, the patient submits a cytological analysis, according to the results of which the doctor observes the dynamics of the treatment process. If according to the results of the cytological analysis after the third month of treatment no cancer cells are detected, the treatment is stopped and further repeated according to the claimed method every 2-3 years;
При выявлении раковых клеток лечение продолжают до полного выздоровления.  If cancer cells are detected, treatment is continued until complete recovery.
С целью профилактики при хронических заболеваниях гастритом, панкреатитом и другими болезнями, при которых возникает риск перерождения здоровых клеток в раковые, лечение по заявляемому способу проводят на протяжении одного года и затем возобновляют его через каждые два или три года, учитывая то, что эпигенетические процессы роста опухолевых клеток могут возобновиться через этот срок.  In order to prevent chronic diseases of gastritis, pancreatitis and other diseases in which there is a risk of the transformation of healthy cells into cancer cells, the treatment according to the claimed method is carried out for one year and then renewed every two or three years, given the fact that epigenetic growth processes tumor cells may resume after this period.
С лечебным препаратом в организм человека одновременно поступают щавелевая кислота, литий хлористый, диметилксантин и фторурацил. Щавелевая кислота при попадании в организм больного избирательно закисляет злокачественные клетки, не оказывая воздействия на здоровые клетки организма больного, вследствии чего происходит отмирание злокачественных клеток (апоптоз); литий хлористий тормозит деление раковых клеток. Фторурацил в малых концентрациях тормозит деление раковых клеток за счет образования нуклеиновых кислот и усиливает действие оксалата лития. Диметилксантин является ингибитором фосфодиэстеразы, за счет чего в клетке увеличивается содержание цАМФ, и в злокачественных клетках, которые находились на стадии начала дифференцировки, она ускоряется. Заявляемый лечебный препарат снижает опасность превращения здоровых клеток в злокачественные и снижает скорость и объем развития метастазов. Кроме того, заявляемый лечебный препарат, в отличие от существующих противоопухолевых препаратов, не является токсичным. Oxalic acid, lithium chloride, dimethylxanthine and fluorouracil simultaneously enter the human body with a medicinal product. When oxalic acid enters the patient’s body, it selectively acidifies the malignant cells, without affecting the healthy cells of the patient’s body, resulting in the death of malignant cells (apoptosis); lithium chloride inhibits the division of cancer cells. Fluorouracil in small concentrations inhibits the division of cancer cells due to the formation of nucleic acids and enhances the effect of lithium oxalate. Dimethylxanthine is an inhibitor of phosphodiesterase, due to which the content of cAMP in the cell increases, and in malignant cells that were at the stage of differentiation, it accelerates. The inventive therapeutic drug reduces the risk of the transformation of healthy cells into malignant and reduces the speed and volume of development of metastases. In addition, the claimed therapeutic drug, in contrast to existing antitumor drugs, is not toxic.
Пример 1  Example 1
Испытания противоопухолевой активности заявляемого лечебного препарата согласно заявляемому способу проводили на суспензионной культуре опухолевых клеток Раджи, мышах С57В1/6, и на крысах; антипролиферативную активность заявляемого лечебного препарата, проводили на клеточной культуре Раджи и на мышах С57В1/6.  Tests of the antitumor activity of the claimed therapeutic drug according to the claimed method was carried out on a suspension culture of Raja tumor cells, C57B1 / 6 mice, and rats; antiproliferative activity of the claimed medicinal product was carried out on a Raji cell culture and on C57B1 / 6 mice.
В Таблице 1 приведен пример использования заявляемого лечебного препарата.  Table 1 shows an example of the use of the claimed medicinal product.
Таблица 1  Table 1
Figure imgf000009_0001
Из Таблицы 1 следует, что наибольшее уменьшение количества опухолевых клеток происходит при обработке их лечебным препаратом с содержанием всех компонентов по 3 составу.
Figure imgf000009_0001
From Table 1 it follows that the greatest decrease in the number of tumor cells occurs when they are treated with a therapeutic drug containing all components of 3 composition.
В таблице 2 приведенно количество клеток клеточной культуры Раджи карциномы легких Льюиса (карцинома 3LL), которые остались живыми (живые обработанные клетки) через трое суток инкубации.  Table 2 shows the number of Raji Lewis lung carcinoma cell culture cells (3LL carcinoma) that remained alive (live treated cells) after three days of incubation.
Таблица 2  table 2
Figure imgf000010_0001
Figure imgf000010_0001
На фиг.1 приведен график зависимости количества живых обработанных клеток от концентрации лечебного препарата по сравнению с количеством живых клеток, которые 'не были обработаны. По вертикальной оси приведен процент количества живых обработанных клеток, по горизонтальной оси - концентрации лечебного препарата. Figure 1 shows a graph of the dependence of the number of living treated cells on the concentration of the drug in comparison with the number of living cells that have not been processed. The vertical axis shows the percentage of the number of living treated cells, the horizontal axis shows the concentration of the drug.
ЗАМЕНЯЮЩИЙ ЛИСТ (ПРАВИЛО 26) SUBSTITUTE SHEET (RULE 26)
Из приведенных таблицы 2 и графика следуют выводы: From the above table 2 and the graph, the conclusions follow:
- инкубация клеточной культуры Раджи в суспензии с добавлением заявляемого лечебного препарата через трое суток дала снижение опухолевых клеток до (10,0 - 1 1,7)% практически независимо от концентрации лечебного препарата в пределах (1 - 10) мМоль, это свидетельствует о четко выраженной системности действия заявляемого лечебного препарата,  - incubation of the Raji cell culture in suspension with the addition of the claimed medicinal product after three days resulted in a decrease in tumor cells to (10.0 - 1.7)% almost regardless of the concentration of the medicinal product in the range of (1 - 10) mmol, this indicates clearly pronounced systemic effects of the claimed therapeutic drug,
- увеличение концентрации лечебного препарата при обработке живых клеток не приводит к увеличению количества погибших опухолевых клеток, что свидетельствует о системности действия лечебного препарата и о том, что оптимальная доза лечебного препарата находится в пределах отмеченных концентраций всех компонентов лечебного препарата;  - an increase in the concentration of the drug during the processing of living cells does not lead to an increase in the number of dead tumor cells, which indicates the consistency of the action of the drug and that the optimal dose of the drug is within the marked concentrations of all components of the drug;
9 9
ЗАМЕНЯЮЩИЙ ЛИСТ (ПРАВИЛО 26) - свойства заявляемого лечебного препарата являются наиболее приемлемыми для лечения онкозаболеваний. SUBSTITUTE SHEET (RULE 26) - the properties of the claimed medicinal product are the most acceptable for the treatment of cancer.
Таким образом состав заявляемого лечебного препарата позволяет всесторонне останавливать опухолевый процесс.  Thus, the composition of the claimed therapeutic drug allows you to comprehensively stop the tumor process.

Claims

ФОРМУЛА ИЗОБРЕТЕНИЯ CLAIM
1. Применение щавелевой кислоты в производстве лечебного препарата противоопухолевого действия по отношению к злокачественным клеткам. 1. The use of oxalic acid in the manufacture of a therapeutic drug with an antitumor effect in relation to malignant cells.
2. Лечебный препарат, который представляет собой водный раствор и содержит органическую кислоту и хлорид,, отличающийся тем, что водный раствор в качестве органической кислоты содержит щавелевую кислоту, в качестве хлорида - литий хлористый и дополнительно содержит диметилксантин, фторурацил и серноватистокислый натрий при следующем соотношении всех компонентов, (масс %):  2. A medicinal product, which is an aqueous solution and contains organic acid and chloride, characterized in that the aqueous solution contains oxalic acid as an organic acid, lithium chloride as a chloride and additionally contains dimethylxanthine, fluorouracil and sodium sulfate in the following ratio all components (mass%):
щавелевая кислота 0,2 - 3,2  oxalic acid 0.2 - 3.2
литий хлористый 0,2 - 3,1  lithium chloride 0.2 - 3.1
диметилксантин од - 1,8  dimethylxanthine od - 1.8
фторурацил од - 1,8  fluorouracil od - 1.8
серноватистокислый натрий 0,2 - 3,1  sodium sulfate 0.2 - 3.1
вода дистиллированная до 100  distilled water up to 100
3. Способ лечения злокачественных опухолей, который заключается в принятии внутрь организма лечебного препарата и контролировании состояния больного по результатам цитологических анализов, отличающийся тем, что для принятия лечебного препарата, по п.2, готовят раствор, для чего разбавляют 5 мл лечебного препарата в 50-100 мл воды, перорально принимают его один раз в сутки в течение трехмесячного курса, контроль состояния больного проводят ежемесячно, по результатам цитологических анализов принимают решение продолжать курс лечения или закончить его, лечение повторяют через каждые 2-3 года.  3. A method of treating malignant tumors, which consists in taking a medicinal product inside the body and monitoring the patient’s condition according to the results of cytological analyzes, characterized in that for taking the medicinal product, according to claim 2, a solution is prepared, for which 5 ml of the medicinal product is diluted in 50 -100 ml of water, taken orally once a day for a three-month course, the patient is monitored on a monthly basis, according to the results of cytological analyzes, they decide to continue the treatment or chit him, the treatment is repeated every 2-3 years.
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