WO2011119126A1 - Utilisation de l'acide oxalique dans la fabrication d'une préparation médicinale qui possède une action antitumorale vis-à-vis des cellules malignes, préparation médicinale sur cette base et procédé de traitement - Google Patents

Utilisation de l'acide oxalique dans la fabrication d'une préparation médicinale qui possède une action antitumorale vis-à-vis des cellules malignes, préparation médicinale sur cette base et procédé de traitement Download PDF

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Publication number
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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WO
WIPO (PCT)
Prior art keywords
treatment
oxalic acid
therapeutic preparation
cells
medicinal product
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PCT/UA2010/000015
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English (en)
Russian (ru)
Inventor
Геннадий Васильевич МАЗИЛЬНИКОВ
Аркадий Петрович ШИМАНСКИЙ
Юрий Анатольевич ЛИХОДЕД
Стефания Стефановна МЕЛЬНИК
Original Assignee
Mazilnikov Gennadiy Vasilevich
Shimanskiy Arkadiy Petrovich
Lykhoded Yuriy Anatolevich
Melnik Stefaniya Stefanovna
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
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Application filed by Mazilnikov Gennadiy Vasilevich, Shimanskiy Arkadiy Petrovich, Lykhoded Yuriy Anatolevich, Melnik Stefaniya Stefanovna filed Critical Mazilnikov Gennadiy Vasilevich
Publication of WO2011119126A1 publication Critical patent/WO2011119126A1/fr

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Classifications

    • 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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  • Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Epidemiology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Inorganic Chemistry (AREA)
  • Oncology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

L'invention concerne la médecine et notamment les moyens de traitement de maladies cancéreuses et peut s'utiliser en tant que base (5) pour créer des préparations médicinales. L'acide oxalique s'utilise dans la fabrication d'une préparation médicinale qui possède une action antitumorale vis-à-vis des cellules malignes; la préparation médicinale comprend en tant qu'acide organique de l'acide oxalique, en tant que chlorure du chlorure de lithium et comprend en outre de la diméthylxanthine, du fluoruracile et du thiosulfate de sodium, avec un rapport suivant des composants, en % en masse : acide oxalique 0,2 - 3,2, chlorure de lithium 0,2 - 3,1, diméthylxanthine 0,1 - 1,8, fluoruracile 0,1 - 1,8, thiosulfate de sodium 0,2 - 3,1, eau distillée jusqu'à 100. L'invention concerne également un procédé de traitement de tumeurs malignes consistant l'administration pérorale la préparation du médicament; 5 ml de préparation médicinal sont dissous dans 50 à 100 ml d'eau et administrés péroralement une fois par jours dans le cadre d'un traitement durant trois mois. L'état du malade est surveillé mensuellement. Sur la base des analyses cytologiques on prend la décision de continuer le traitement ou de l'arrêter. Le traitement est répété tous les 2 ou 3 ans.
PCT/UA2010/000015 2010-03-25 2010-03-26 Utilisation de l'acide oxalique dans la fabrication d'une préparation médicinale qui possède une action antitumorale vis-à-vis des cellules malignes, préparation médicinale sur cette base et procédé de traitement WO2011119126A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
UAA201003471A UA98666C2 (ru) 2010-03-25 2010-03-25 Лекарственный препарат на основе щавелевой кислоты, проявляющий противоопухолевое действие в отношении злокачественных клеток, и способ лечения
UAA201003471 2010-03-25

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WO2011119126A1 true WO2011119126A1 (fr) 2011-09-29

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UA (1) UA98666C2 (fr)
WO (1) WO2011119126A1 (fr)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2013074055A1 (fr) * 2011-11-16 2013-05-23 ШИМАНСКИЙ, Аркадий Петрович Способ оздоровления и омоложения организма человека и фармацевтическая композиция для его осуществления
RU2712443C1 (ru) * 2018-12-14 2020-01-29 Федеральное государственное бюджетное учреждение науки институт химии растворов им. Г.А. Крестова Российской академии наук Сокристаллическая форма 1-[5-(4-хлорфениламино)-1,2,4-тиадиазол-3-ил]-пропан-2-ола

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6133317A (en) * 1995-11-15 2000-10-17 Hart; Francis J. Oxalic acid or oxalate composition and method of treatment
WO2004026319A2 (fr) * 2002-09-17 2004-04-01 Centre National De La Recherche Scientifique Compositions pharmaceutiques utilisees pour le traitement de cancers
WO2005117915A1 (fr) * 2004-06-03 2005-12-15 F. Hoffmann-La Roche Ag Traitement avec de l'oxaliplatine et un inhibiteur egfr
WO2008106721A1 (fr) * 2007-03-02 2008-09-12 University Of Wollongong Compositions et procédés permettant d'administrer des agents anticancéreux
US20090214669A1 (en) * 2004-07-23 2009-08-27 Jacques Alain Bauer Combination anticancer therapy and pharmaceutical compositions therefore

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6133317A (en) * 1995-11-15 2000-10-17 Hart; Francis J. Oxalic acid or oxalate composition and method of treatment
WO2004026319A2 (fr) * 2002-09-17 2004-04-01 Centre National De La Recherche Scientifique Compositions pharmaceutiques utilisees pour le traitement de cancers
WO2005117915A1 (fr) * 2004-06-03 2005-12-15 F. Hoffmann-La Roche Ag Traitement avec de l'oxaliplatine et un inhibiteur egfr
US20090214669A1 (en) * 2004-07-23 2009-08-27 Jacques Alain Bauer Combination anticancer therapy and pharmaceutical compositions therefore
WO2008106721A1 (fr) * 2007-03-02 2008-09-12 University Of Wollongong Compositions et procédés permettant d'administrer des agents anticancéreux

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
ZHANG W. V. ET AL.: "Early gene response in lithium chloride induced apoptosis", APOPTOSIS, vol. 10, no. 1, 2005, pages 75 - 90, XP019204653, DOI: doi:10.1007/s10495-005-6063-x *

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2013074055A1 (fr) * 2011-11-16 2013-05-23 ШИМАНСКИЙ, Аркадий Петрович Способ оздоровления и омоложения организма человека и фармацевтическая композиция для его осуществления
RU2712443C1 (ru) * 2018-12-14 2020-01-29 Федеральное государственное бюджетное учреждение науки институт химии растворов им. Г.А. Крестова Российской академии наук Сокристаллическая форма 1-[5-(4-хлорфениламино)-1,2,4-тиадиазол-3-ил]-пропан-2-ола

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