RU2775008C1 - Pharmaceutical composition with immunomodulatory, immunocorrecting, immunosuppressive, antiviral, anti-inflammatory and oncolytic activities - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: present invention relates to the field of medicine, namely to a pharmaceutical composition having immunocorrecting, antiviral activity against COVID-19 and herpetic lesions of the mucous lips and vulva, as well as anti-inflammatory and oncolytic activity against glioblastoma of the brain, light cell cancer of the left kidney with metastases to the lungs, non-Hodgkin’s lymphoma, prostate adenocarcinoma, metastatic melanoma containing a mixture of two salts: the first salt, which is a salt from the group: 5-aminophthalhydrazide of sodium, 5-aminophthalhydrazide of potassium and 5-aminophthalhydrazide of lithium, and the second salt, which is a salt from the group: bis(5-amino-1,4-dioxo-1,2,3,4-tetrahydrophthalazine-2-yl) of arsenic and bis(5-amino-1,4-dioxo-1,2,3,4-tetrahydrophthalazine-2-yl) of gold.

EFFECT: present invention provides an expansion of the arsenal and functionality of these means and the creation of an immunomodulatory agent that has an effect suppressing the growth of cancer cells, as well as an anti-inflammatory effect.

3 cl, 19 ex

Description

The invention relates to medicine, namely to drugs that affect the immune system and suppress the growth of cancer cells, as well as to the production of such drugs, and the use of derivatives of 5-aminophthalhydrazide and its salts is produced as a means for the treatment of autoimmune, oncological, infectious and viral diseases.

Known solutions related to pharmaceutical compositions with immunomodulatory, immunocorrective, immunosuppressive, antiviral, anti-inflammatory and oncolytic activities.

Known drug "Doxorubicin", (Doxorubicini hydrochloridum). Antitumor antibiotic of the anthracycline series. Synonyms: Adriablastin, Adriamycin, Rastocin, Adriacin, Farmiblastina, Hydroxydaunomycin. Red crystalline powder or porous mass. Sparingly soluble in water, insoluble in alcohol. Doxorubicin has high antitumor and antileukemic activity. The mechanism of action is close to rubomycin, it has the ability to intercalate cell DNA. It has immunosuppressive activity. Doxorubicin is used for breast cancer, soft tissue sarcomas, osteogenic sarcoma, Ewing's tumor, lung cancer, lymphosarcoma, ovarian cancer, squamous cell carcinomas of various localizations, bladder cancer, Williams' tumor, thyroid cancer, acute leukemia, lymphogranulomatosis. The disadvantages of this tool is a depressing effect on hematopoiesis, as well as a very high toxicity of LD 50 13-15 mg/kg. When using doxorubicin, leukopenia and thrombocytopenia, stomatitis, nausea and vomiting (immediately after the administration of the drug), alopecia (reversible), allergic reactions, necrosis of subcutaneous adipose tissue when the drug gets under the skin, phlebitis are possible. The use of doxorubicin must be carried out under strict hematological control. One of the characteristic toxicological features of doxorubicin is its cardiotoxic effect. In the course of treatment with the drug, cardiomyopathy, pain in the heart area, rhythm disturbances, heart failure, and a decrease in blood pressure may develop. In severe cardiac arrhythmias or congestive insufficiency, treatment with doxorubicin should be discontinued immediately. The use of doxorubicin is contraindicated in severe disorders of the liver and kidneys, leukopenia (below 3.5×109/l), thrombocytopenia (below 12×109/l). severe concomitant heart disease (myocarditis, myocardial infarction, significant arrhythmias), bleeding, tuberculosis, pregnancy. peptic ulcer of the stomach and duodenum. (Big Medical Encyclopedia, Internet, Information portal: www.province.ru).

Known drug with antitumor and immunomodulatory action, containing pharmacologically acceptable derivatives of tri-n-aminotriphenylchloromethane. The drugs of this series have immunomodulatory and antitumor activity, are effective in the treatment of many types of cancer and immunodeficiency conditions. The disadvantages of this drug are due to the fact that tri-n-aminotriphenylchloromethane derivatives are not effective in the treatment of severe forms of cancer and have a short duration of action. The drug belongs to the substances of the average level of toxicity. Its LD 50 is above 420 mg/kg of weight, which also limits its use to large doses (RU No. 2257200).

A technical solution is known for initiating the death of tumor cells with HF and microwave energy, intended for local treatment of cancer patients with tumor tissues, for their hyperthermia in all organs of the human body (RU 2739254).

Known technical solution to reduce metastasis of melanoma B-16 by introducing an injectable aqueous solution of the sodium salt of 5-amino-1,2,3,4-tetrahydrophthalazine-1,4-dione, in which an intraperitoneal injection of an aqueous solution of the sodium salt of 5-amino -1,2,3,4-tetrahydrophthalazine-1,4-dione at a dose of 40 mg salt/kg mouse once a day for 5 days (RU 2308096).

A technical solution is known to reduce the metastasis of Lewis lung carcinoma by introducing an injectable aqueous solution of the sodium salt of 5-amino-1,2,3,4-tetrahydrophthalazine-1,4-dione, characterized in that intraperitoneal administration of an injectable aqueous solution of sodium salt of 5- amino-1,2,3,4-tetrahydrophthalazine-1,4-dione at a dose of 20 mg salt/kg mouse once a day for 5 days (RU 2308097).

A technical solution for detoxification of the body in surgery for invasive bladder cancer is known, characterized in that preoperative and postoperative intramuscular administration of sodium salt of 5-amino-1,2,3,4-tetrahydrophthalazine-1,4-dione, 0.1 g each day intramuscularly, 5 injections before and 5 injections after surgery, then 10 injections every other day (RU 2370263).

Known technical solution for detoxification of the body in surgery for locally advanced hypernephroid cancer by administering a drug, characterized in that the sodium salt of 5-amino-1,2,3,4-tetrahydrophthalazine-1,4-dione is administered at 0.1 g every day intramuscularly, 7 injections before and 5 injections after surgery, then 10 injections every other day (RU 2370264)

A technical solution is known to reduce the metastasis of Lewis lung carcinoma by introducing an injectable aqueous solution of the sodium salt of 5-amino-1,2,3,4-tetrahydrophthalazine-1,4-dione, characterized in that intraperitoneal administration of an injectable aqueous solution of sodium salt of 5- amino-1,2,3,4-tetrahydrophthalazine-1,4-dione at a dose of 20 mg salt/kg once a day for 5 days (RU 2005129694)

Known technical solution consisting in the use of sodium, potassium and lithium salts of indoleacetic acid as drugs with immunomodulatory, anti-inflammatory and antitumor properties (RU 2295338).

Known technical solution for obtaining a medicinal product - 2-amino-1,2,3,4-tetrahydrophthalazine-1,4-dione sodium salt of dihydrate, including obtaining the original product, for example, 3-aminophthalhydrazide, which is subjected to a molecular rearrangement reaction followed by exposure to sodium hydroxide and endowment of the target product (RU 2138264).

Suppositories for the treatment of immunodeficiency conditions are known, made from a suppository mass, including an active principle based on interferon and a filler - a fatty base, including solid edible fat and an emulsifier tween 80 (RF patent for invention (RU 2201212, RU 50 417).

Known solid dosage forms of drugs for the treatment of immunodeficiency states, including sodium salt of 5-amino-1,2,3,4-tetrahydrophthalazine-1,4-dione (RU 52709, RU 56185).

A technical solution for the correction of the immune system is known, based on intramuscular injections of a preparation for the patient, as the latter, a drug of the phthalhydrazyl group ((5-aminophthalhydrazide) is chosen and administered in a course of 1 to 50 injections, and the dose of the drug for injection is chosen in the amount of 25 to 500 mg per 1 - 10 ml of water for injection, and the frequency of injections is prescribed from one injection per hour to one injection after 5 days, while the injections are carried out no more than 4 times a day, and after every 5 - 50 injections they take a break of 10 - 45 days, and in the time intervals between injections, the patient is examined and, based on the results of the analysis of the patient's thermometry, his general condition and laboratory data, the following injections are prescribed, while specifying the dosage of the drug and the number of injections (RU 2108806).

A technical solution is known, a drug that has a normalizing metabolism of body cells, characterized in that it contains an alkaline salt or a mixture of alkaline salts of 5-amino-2,3-dihydro-1,4-phthalazinedione (RU 2238730).

A technical solution is known, which is bis (5-amino-1,4-dioxo-1,2,3,4-tetrahydrophthalazin-2-yl) zinc, in the form of a dihydrate, in the form of a solid amorphous substance, in the form of a crystalline substance for treatment skin diseases for the manufacture of a pharmaceutical composition for the treatment of skin diseases, for topical, rectal, vaginal, oral use, for the treatment of traumatic skin lesions by stimulating regeneration and due to anti-inflammatory action, for the treatment of wound infections of the skin, thermal burns or chemical or sunburn of the skin, inflammatory diseases of the skin and is an inflammation of allergic genesis, immunological genesis and / or idiopathic inflammation or dermatosis or herpes in the form of a ready-made dosage form for topical use and is a gel, foam, ointment or cream, or the said finished dosage form is granules, tablets , pills, dragees, lozenges, syrup, potion and / or psules (RU 2577849, prototype).

The disadvantages of the known solutions are the lack of effectiveness of the immunosuppressor and the limited arsenal of drugs to restore: cellular and humoral immunity.

The technical problem to be resolved by the present technical solution is to increase the effectiveness of the agent, the properties of the immunosuppressor and expand the arsenal of drugs to restore: cellular and humoral immunity.

The technical result, which provides a solution to the problem posed, consists in expanding the arsenal and functionality of these agents and creating an immunomodulatory agent for the specified purpose, which has an inhibitory effect on the growth of cancer cells, as well as an anti-inflammatory effect.

At the same time, the technical result is based on the fact that the claimed agent is a controlled, temporary immunosuppressant. It inhibits (reversibly for 6–8 hours) hyperactive macrophages, reduces the synthesis of TNF, interleukin 1, the production of reactive oxygen species and other acute phase proteins responsible for the development of toxic and diarrheal syndrome. Normalizes the functional state of macrophages, leads to the restoration of their antigen-presenting and regulatory functions. By increasing the functional antibacterial activity of neutrophilic granulocytes, it enhances phagocytosis and increases the nonspecific defense of the body. EFFECT: invention allows to expand the arsenal of agents having a wide range of therapeutic effects and not causing side effects. At the same time, the claimed agent has a polymorphism of action, namely, luminescent properties to increase the level of anisotropy in the cytoplasm of damaged cells and at the same time promotes immunomodulation, namely, temporary suppression (controlled immunosuppression) of the metabolism of hyperactive macrophages.

Immunomodulating agent, also has an anti-inflammatory effect. It inhibits (reversibly for 6-8 hours) hyperactive macrophages, reduces the synthesis of TNF, interleukin 1, the production of reactive oxygen species and other acute-phase proteins responsible for the development of toxic and diarrheal syndrome. Normalizes the functional state of macrophages, leads to the restoration of their antigen-presenting and regulatory functions. By increasing the functional antibacterial activity of neutrophilic granulocytes, it enhances phagocytosis and increases the nonspecific defense of the body.

The agent can be used in the following diseases: autoimmune diseases: ulcerative colitis, Crohn's disease, total alopecia, rheumatoid arthritis, acute and chronic inflammatory diseases, viral and bacterial lesions, purulent-septic complications and sepsis, accompanied by intoxication and / or diarrhea, purulent surgical diseases (burns, recurrent trophic ulcers, chronic osteomyelitis, peritonitis, purulent pleurisy); frequent recurrent diseases of the respiratory tract and ENT organs of bacterial and viral etiology. Accompanying chemotherapy and radiation in oncological diseases. Intramuscular and intravenous forms, as well as tablet forms. For external use ointments, creams and rectal suppositories, inhalations.

The essence of the invention lies in the fact that the pharmaceutical composition, which has immunomodulatory, immunocorrective, immunosuppressive, antiviral, anti-inflammatory and oncolytic activities, contains a mixture of two salts: the first salt, which is an alkali metal 5-aminophthalhydrazide, and the second salt, which is a bis(5-amino -1,4-dioxo-1,2,3,4-tetrahydrophthalazin-2-yl) element from the group: zinc, arsenic or gold.

Preferably, the first salt is a salt from the group: sodium 5-aminophthalhydrazide, potassium 5-aminophthalhydrazide and lithium 5-aminophthalhydrazide, and the second salt is a salt from the group: bis(5-amino-1,4-dioxo-1,2, 3,4-tetrahydrophthalazin-2-yl) zinc, bis(5-amino-1,4-dioxo-1,2,3,4-tetrahydrophthalazin-2-yl) arsenic and bis(5-amino-1,4- dioxo-1,2,3,4-tetrahydrophthalazin-2-yl) gold.

Preferably, the mixture contains in wt %:

- the first salt - 60-70%;

- the second salt - 30-40%.

Preferably, the composition is made in a dosage form from the group: tablets, powder for injection , ointment , suppositories for rectal use.

Preferably, the composition is designed to be used in a course of up to 20 days.

Preferably, the composition is designed to be used in the following order: in the acute period of the disease, the initial dose is 0.2 g, then 0.1 g 2-3 times a day (every 4-6 hours); in chronic diseases - 0.1 g 2 times a day (after 6-8 hours).

The essence of the invention consists in the use of 5-amino-1,2,3,4-tetrahydrophthalazine-1,4-dione (alkali metal salts - sodium, potassium and lithium) as well as (zinc, arsenic and gold) as a means for the treatment of inflammatory , viral, autoimmune and oncological diseases, with a single dosage of the drug from 0.1 mg to 10 g per reception from 1 to 3 times a day. Preferably, the agent is used in a dilution from 10-5 to 10-7 mmol / l in the form of an aqueous solution or saline, or a 1-3% solution of the agent is administered intravenously, or a 1% solution of the agent is administered by inhalation, or a 1-5% ointment is used for the basis of the agent, or the agent is administered rectally in the form of suppositories. A wide range of therapeutic effects of these drugs has been shown in relation to various oncological diseases (adenocarcinoma, carcinoma, melanoma, blastoma, astrocytoma, glioblastoma, etc.): the size of these tumors decreased or tumors and metastases were not detected after treatment. At the same time, the agents are not toxic and did not cause side effects when used in pharmaceutically acceptable doses.

The chemical structure of the product

Mixtures of 5-amino-1,2,3,4-tetrahydrophthalazine-1,4-dione (alkali metal salts - sodium, potassium and lithium) and Bis (5-amino-1,4-dioxo-1,2,3, 4-tetrahydrophthalazin-2-yl), zinc, gold, arsenic.

The ratio of the number of components in wt. or about %;

The first salt from the group: 5-aminphthalhydrozide sodium, 5-aminphthalhydrozide potassium and 5-aminphthalhydrozide lithium, mixed with the second salt from the group: bis(5-amino-1,4-dioxo-1,2,3,4-tetrahydrophthalazine-2 -yl) zinc, bis(5-amino-1,4-dioxo-1,2,3,4-tetrahydrophthalazin-2-yl) arsenic and bis(5-amino-1,4-dioxo-1,2,3 ,4-tetrahydrophthalazin-2-yl) gold.

The mixture contains in wt % the first salt - 60-70%; the second salt - 30-40%.

The composition is used intramuscularly, rectally, in the acute period of the disease, the initial dose is 0.2 g, then 0.1 g 2-3 times a day (every 4-6 hours); in chronic diseases - 0.1 g 2 times a day (after 6-8 hours) until the symptoms of intoxication and / or diarrhea disappear. The course of treatment is up to 20 days.

Chronic recurrent viral infection - rectally, 0.1 g daily for 10 days, postoperative purulent-septic complications - 0.1 g every other day, course - 15-20 suppositories.

Before administration, the powder in a vial is diluted with 2-3 ml of water for injection or 0.9% NaCl solution in compliance with asepsis requirements.

In experiments according to examples 1-6 in vitro shows the mechanism of apoptosis of cancer cells with the help of the proposed agent. In vitro (from Latin - “in glass”) is a technology for performing experiments, when experiments are carried out “in a test tube” - outside a living organism.

Example #1.

In the test tubes of the experimental group with A375 cancer cells (metastasizing human melanoma) in a buffer solution (10 ml), the drug was introduced at a dilution of 10 ^-11 mmol / l, respectively, in the form of a zinc salt solution of 3-aminophthalhydrazide

In addition, the drug Doxorubicin 10 ^-5 mmol/l, in a buffer solution, was introduced into the tubes with the same pool of cancer cells in the same dilution, respectively.

At the same time, a control group was also formed from the same number of tubes and with the same components, except for cancer cells, instead of which fibroblasts were placed in the tubes of this group.

After incubation for 3 days at a temperature of 37 ⁰ C, the contents of the test tubes described above were analyzed.

Consideration of the obtained results showed:

In the test tubes of the experimental group with the drug, the nuclei are large, formed and filled with chromatin, while the mitochondrial membranes are almost completely destroyed, and the picture is approximately the same for all variants of the drug used; 60%) by their destruction, no changes were detected in the cells in the test tube with saline.

In the test tubes of the control group, the mitochondrial membranes were swollen, but their integrity was preserved.

The data obtained indicate that the proposed drug causes apoptosis of cancer cells, and in particular the destruction of the membranes of mitochondria of cancer cells, or, in other words, the drug enhances the ability of cell mitochondria to produce enzymes that cause apoptosis of cancer cells.

Example #2.

In 4 test tubes of the experimental group with MSF-7 cancer cells (breast adenocarcinoma) in a buffer solution (10 ml), the drug was introduced at a dilution of 10 ^-9 mmol / l, respectively, in the form of a solution of the lithium salt of 5-aminophthalhydrazide

The control group - in test tubes with the same pool of cancer cells, respectively, were introduced into one saline solution, and into the others, Fluorouracil.

In the test tubes of both groups, cytochrome-C titers were determined, which are 1:14000,

After incubation for a day at a temperature of 37 ⁰ C, the contents of the test tubes described above were analyzed.

Consideration of the obtained results showed:

In the test tubes of the experimental group with the administered drug, the cytochrome-C titer for the test tube with cholesteryl acetate sensitized TiO2 (rutile) was 1:2000.

In test tubes with Fluorouracil, the titer is 1:12000 and 1:9600, respectively. In a test tube with physiological saline, no particular changes in titer were noted.

The results obtained give reason to believe that the proposed drug contributes to the restoration of anisotropy. This leads to the release of the “aggressive” cytochrome-C protein from the membranes of the mitochondria of cancer cells, which triggers the mechanism of DNA destruction, which in turn causes apoptosis of cancer cells.

Example #3

In a test tube (10 ml) with transthyretin (protein) of blood plasma (pH -7.0), concentration of 0.05 mmol / ml, 4 drops of a 0.1% aqueous solution of sodium salt 5 aminophthalhydrazide were introduced

The test tube is placed in a thermostat (incubator) with a temperature of 37 ⁰ C.

After 15 min. transthyretin concentration and plasma pH were measured.

Transthyretin is not determined, pH is 6.0.

It follows that this drug acts on protein denaturation not as an acid, but as a drug that changes the structure of the polymer.

This property determines the therapeutic effect of this drug in the treatment of cancer.

Example number 4.

The blood of a patient with prostate cancer (10 ml) was centrifuged.

Part of the obtained plasma was dried and photographed in a polarizing microscope. An aqueous solution of the potassium salt of aminophthalhydrazide was introduced into another part of the same plasma, and the resulting mixture was also photographed in a polarizing microscope.

Results: Light scattering occurs in the first composition, birefringence is observed in the second.

These data suggest that this drug restores anisotropy in cancerous structures and normalizes protein folding that was altered in cancer.

Example #5

The filtrate from sarcoma 45 (5 ml) was placed in a quartz cuvette, and spectrophotometry was performed.

Then a solution of a solution of an arsenic salt solution of 5-aminophthalhydrazide was added to this filtrate,

the preparation was cooled to 10°C, and re-spectrophotometry was performed.

Results: In the images without the drug, the absorption spectrum is in the region of 278 nm, and the emission is in the region of 417 nm; in the images after the administration of the drug, there is a shift in the absorption spectrum of the far part of UV radiation to 281 nm, and luminescence, respectively, to 422 nm. From the literature it is known that the shift is 2-3 nm. in the UV part of the spectrum indicates large changes in the structure of organic molecules.

The data obtained indicate, firstly, that protein structures are disturbed in the serum of cancer patients, since Normally, the absorption and emission bands of protein structures are 280 and 420 nm, respectively. Secondly, the regulatory effect of the drug on structural changes in the proteins of cancer cells is clearly shown.

Example No.6

The blood of a patient with prostate cancer (10 ml) was centrifuged.

Part of the obtained plasma was dried and photographed in a polarizing microscope. An aqueous solution of the potassium salt of aminophthalhydrazide was introduced into another part of the same plasma, and the resulting mixture was also photographed in a polarizing microscope.

Results: Light scattering occurs in the first composition, birefringence is observed in the second.

These data suggest that this drug restores anisotropy in cancerous structures and normalizes protein folding that was altered in cancer.

Below are examples 7-18 in vivo - special cases of treatment of patients using the claimed composition. those. conducting experiments on (or inside) living tissue in a living organism.

Example #7.

The patient is 64 years old. Diagnosis: Psoriasis. For treatment, an ointment was used, which includes: zinc salt or a mixture of alkaline salts of 5-amino-2,3-dihydro-1,4-phthalazinedione with an ointment base in the form of vaseline oil and distilled water in the following ratio of components in wt. %: arsenic salt of 5-amino-2,3-dihydro-1,4-phthalazinedione or a mixture of alkaline salts of 5-amino-2,3-dihydro-1,4-phthalazinedione - 1.0-50.0; medical vaseline - 10.0-20.0; vaseline oil - 5.0-10.0, water - the rest, and lithium or potassium salt of 5-amino-2,3-dihydro-1,4-phthalazinedione is used as an alkaline salt, and 5-amino alkaline salts are used as a mixture -2,3-dihydro-1,4-phthalazinedione, a mixture of sodium and zinc salts of 5-amino-2,3-dihydro-1,4-phthalazinedione, composed at an equal ratio of components, is used. This ointment restores the cell membrane to its normal state, normalizes and regulates intracellular and intercellular metabolic processes, which, in turn, contributes to the normalization of metabolism and the relief of inflammation in the shortest possible time.

Example number 8.

Patient C 49 years old. Diagnosis: Rheumatoid arthritis. Salts of 5-aminophthalhydrazide were used for treatment. As a therapeutic agent, an ointment is used, which includes: an alkaline salt or a mixture of alkaline salts of 5-amino-2,3-dihydro-1,4-phthalazinedione in saline. with the following ratio of components in wt. %: zinc salt of 5-amino-2,3-dihydro-1,4-phthalazinedione or a mixture of alkaline salts of 5-amino-2,3-dihydro-1,4-phthalazinedione - 1.0-50.0; solution 10.0-20.0; vaseline oil - 5.0-10.0, water - the rest, moreover, sodium or potassium salt of 5-amino-2,3-dihydro-1,4-phthalazinedione is used as an alkaline salt, and 5-amino alkaline salts are used as a mixture -2,3-dihydro-1,4-phthalazinedione, a mixture of sodium and potassium salts of 5-amino-2,3-dihydro-1,4-phthalazinedione, composed at an equal ratio of components, is used. This ointment brings the cell membrane, which is disturbed due to the disease, to a normal state, normalizes and regulates intracellular and intercellular metabolic processes.

Example #9.

Patient V., 43 years old. Diagnosis: Glioblastoma of the brain. Headache complaints. Stopped, inadequate. On CT scan of the brain, interconnected foci are noted: 3x4 and 2x3 cm in the right fronto-parietal region. According to the patient and relatives, 2 years ago there was an operation for a brain tumor. A year and a half later, headaches and slurred speech appeared. CT showed a recurrence at the site of surgery. Reoperation and chemotherapy were refused. Treatment was prescribed, including the use of a drug based on a 1% solution of the zinc salt of aminophthalhydrazide

The first course of treatment with 5-aminophthalhydrazide lithium salt, 35 drops of a 1% solution per glass of water three times a day through the mouth, in the afternoon an additional microclyster 10 drops of a 1% solution per 30 ml. water, and at night a 1% suppository with methylene blue 1% solution. Within a week, the condition was basically unchanged, however, the patient noted that after the administration of the drug, a decrease in drowsiness and headaches was observed for several hours. On the third week after the start of treatment, the patient's condition improved. According to relatives, he became more adequate. Three months after the start of treatment with the drug, CT showed a decrease in the tumor in the brain. After a year of treatment, the condition improved significantly, became adequate. On the control CT, at the site of the tumor, small formations 1x1x2 cm with signs of calcification are determined. Analyzes (what indicators?) blood levels returned to normal during treatment.

Example #10

Patient L, 43 years old. D-h: Clear cell carcinoma of the left kidney with lung metastases.

Three years ago, the left kidney was removed and prophylactic chemotherapy was performed for clear cell carcinoma. When examined on CT in the projection of the left kidney, a tumor-like formation was 3.2 x 4.4 x 3.4 cm, as well as four tumor-like round formations with a diameter of 3.0 to 3.5 cm in the left lung. The condition is severe: shortness of breath, cyanosis, weakness, severe pain syndrome, which can be stopped only by the introduction of large doses of morphine and omnopon. Treatment was prescribed, including the use of a drug: 10% solution of zinc salt of 5-aminophthalhydrazide. The drug was administered through the mouth in the form of drinking 12 drops of a 1% solution three times a day and in the form of microclysters. Inhalations of the drug twice a week. After 4 weeks of treatment, shortness of breath decreased, the pain syndrome disappeared on the third day from the start of treatment. After that, the patient refused narcotic analgesics. Blood tests (hemoglobin, leukocytes, ESR) returned to normal within 3 months during treatment. Next, a second course was carried out with the potassium salt preparation of 5-aminophthalhydrazide , which was injected into the rectum in the form of 1% suppositories ( 100 mg.) and inhaled 1% solution for 15 minutes, for 6 months. During therapy, the tumor in the right kidney and metastases in the lungs disappeared. Weight restored.

Example number 11.

Patient T., 53 years old. Diagnosis: Bilateral pneumonia. Coronavirus. Covid 19.

Complaints of pain in the muscles, chills, dry cough, impaired urination. On CT "ground glass" in both lungs, the lesions are 4x5x4 cm. The state of moderate severity, high temperature 39.5 dyspnea, pallor of the skin. Treatment with a powder preparation was started: a mixture of sodium and zinc salts of 5-aminophthalhydrazide in a ratio of 50/50, 100 mg each. per 100 ml of water. Reception twice a day 30 minutes before meals.

In addition, the chest and pharynx were processed using the Kutushov meander. The course lasted 1 week. During the treatment, the foci of inflammation decreased in size to 1.2x0.9x0.3 cm. In the second week from the start of treatment, the lung fields were clear, saturation returned to normal, the patient breathes on his own. Blood tests during treatment returned to normal within 2 weeks.

Example #12

Patient D., 33 years old. Diagnosis: Crohn's disease. Two years ago, a resection of 20 cm of the small intestine was performed due to swelling and inflammation of the terminal part of the small intestine. Complaints of abdominal pain, nausea, vomiting. On NMRI in the projection of the p / surgical scar in the substance of the brain, a tumor with uneven edges 3.8 x2.9 cm is determined. The state of moderate severity, pallor of the skin. The patient was prescribed 5-aminophthalhydrazide sodium salt 100 mg. dissolved in 2.0 ml of saline. The first two days intramuscularly 100 mg twice a day . The remaining three days, 1 injection is also intramuscularly 100 mg. once a day. Subsequent procedures were carried out in exactly the same sequence 2 times a week. The course lasted 3 months. During the treatment, the pain disappeared. After two infusions of the drug intramuscularly 100 mg. once a day , decreased tenesmus, nausea and pain. Within 6 months, a single injection of the drug was carried out every two weeks. No complaints for 2 years.

Example #13

Patient T., 44 years old. Diagnosis: Rheumatoid arthritis. Complaints of pain in the joints, swelling and limitation of movement. The state of moderate severity, reduced nutrition, yellowness of the skin, swelling of large joints. Blood tests indicate the presence of nonspecific inflammation. ESR 50 mm/h. For two weeks, once a day, it was intravenously administered in sterile saline (150 ml. A mixture of potassium and zinc salts of 5-aminophthalhydrazide, 50 mg each.

During the treatment, the swelling of the joints decreased, the pain syndrome is less. Movement in the joints returned to normal. In the process of treatment with the drug, there was a positive trend in blood tests.

Results of general blood tests

Basic. indicators 10.11.20 01/16/20 12.02.20 07/27/20 red blood cells
Hemoglobin
platelets
Leukocytes
Basophils 0-1%
Eosinophils 0-5
Pal.nuclear 1-6%
Segment nuclear 45-70
Lymphocytes 18-40%
Monocytes 2-9%
ESR 1-15mmh 3.22
74
315
7.2
one
one
one
21
9
fifteen
fifty 3.60
80
362
7.8
-
2
one
44
16
4.3
twenty 4.37
117
286
5.8
-
2
-
63
23
four
12 4.67
123
310
6.7
one
one
-
65
37
9
8.5

The results of biochemical blood tests

Main characteristics Sod. fine 11/14/20 12/22/20 14.02.20 07/27/20 total protein
Creatinine
Urea
Cholesterol
Bilirubin
general
Bilirubin
straight
Bilirubin indirect
Amylase
Chlorine
Sodium
Potassium
Calcium ionization.
Calcium total
Iron syv.
AST
ALT
Phosphatase alkali.
LDH
65.0-85.0 hl
44-110
1.66-8.3
2.90-6.54
8.5-20.5
up to 25%

up to 25%
up to 100 El
95-110.0
135.0-147.0
3.5-6.0
0.98-1.30
2.1-2.55
8.8-27.0
5-40 Ate
5-40 Ate
up to 104 El
225-450 El
43.43
98.0
7.2
6.21
11.0

3.0

8.0

82
107.2
114.0
114.20
3.8
2.72

19.4
314.3
190.4
554.5

665.8
5.71
879 49.90
83
6.4
5.62
24.2

22.3

11.9

96
102
140
115.3
4.9
2.32

13.4
395.8
224.7
432.9

426
5.48
556 78
79
4.1
5.75
8.4

3.3

5.1

84
89
102.8
114.31
4.8
2.28

18.0
138.0
94.4
103.8

154.2
4.55
332 64.34
67
2.6
7.03
8.0

2.0

6.0

90
78.0
110.0
134.2
4.9
2.15

17.7
64.4
43.7
30.4

40
6.7
362

There are currently no complaints.

Example 14

Patient T., 58 years old. Diagnosis: non-Hodgkin's lymphoma. Cachexia. A full course of polychemotherapy was performed 2.5 years ago. Six months ago, tumor-like formations appeared on the neck and under the jaw. An x-ray showed mediastinal enlargement. At the time of treatment, complaints of shortness of breath, weakness, sweating. Condition of moderate severity, low nutrition, pale skin. In the submandibular region on the left there is a tumor-like formation 4x6 cm. On both sides of the neck there are tumor-like formations 3x4, 4x4 cm. The treatment was carried out according to the scheme. 1.0 ml of 1% solution of gold salt, 5-aminophthalhydrazide, dissolved in 150 ml of sterile saline three times a week. The course lasted 1.5 months. After 12 days from the start of treatment, the patient's submandibular lymph nodes completely disappeared. Within a month, the tumors in the neck decreased in size to 0.3x0.4 cm. After 1.5 months, none of the lymph nodes was detected. Blood tests Hemoglobin, erythrocytes, leukocytes and urine are normal. Weight restored. There are no complaints.

Example 15

Patient T., 55 years old. D-z: cirrhosis of the liver. Ascites. 2 years ago, jaundice and ascites appeared. Completed a detox course. 1 year after the treatment pain in the lower abdomen, tenesmus appeared. At the time of treatment, he complains of severe weakness, persistent abdominal pain, cough, shortness of breath, ascites, and stool retention. Severe condition, malnutrition, pale skin with a cyanotic tint, abdomen with signs of ascites. In blood tests, there is a decrease in the number of erythrocytes, hemoglobin, leukocytes, albumin, an increase in ALT and AST. On computed tomography in the right lobe of the liver, an irregularly shaped 3x4 cm formation with uneven edges is determined. The patient was prescribed the potassium salt of 5-aminophthalhydrazide in the form of intravenous infusions, microclysters and drinking. The infusion solution is 100 mg. sterilized powder of potassium salt of 5-aminophthalhydrazide dissolved in 250 ml. physiological solution. Infusions were carried out weekly for 2 months. Enemas are a mixture of 200 gr. lithium salt of 5-aminophthalhydrazide ligated with methylene blue 1.5% solution 5.0 ml. To enhance therapy, the drug was taken orally in the form of 10.0 ml of 1% per 200 ml. boiled water 20 minutes before meals three times a day. After 10 days from the start of treatment, the patient's pain completely disappeared, and appetite appeared. At the third week of treatment, shortness of breath decreased. In the course of treatment, the tumor in the area of the anastomosis decreased in size to 0.2x0.3 cm. After 3 months, a monthly break was made, and then the therapy continued for 2 months. During treatment, liver metastases and a tumor in the anastomosis area are not detected. There is a pronounced gradual improvement in blood counts, directly related to drug treatment.

Blood test results

Main indicators 9.09.03 11/14/03 29.12.03 23.01.04 red blood cells
Hemoglobin
platelets
Leukocytes
Basophils 0-1%
Eosinophils 0-5
Pal.nuclear 1-6%
Segment nuclear 45-70

Lymphocytes 18-40%
Monocytes 2-9%
ESR 1-15 mmh 3.20
74
120
9.2
one
one
0
2

35
13
36 3.84
90
210
12.0
-
2
one
6
49
four
12 4.44
115
326
5.2
-
2
-
6
58
7
ten 4.87
128
440
5.3
one
one
2
5
69
9
12

The results of biochemical blood tests

Main
indicators Sod.norm 01.03.19 09/14/19 12/29/19 01/23/20 total protein
Creatinine
Urea
Cholesterol
Bilirubin total
Bilirubin direct
Bilirubin indirect
Amylase
Chlorine
Sodium
Potassium
Calcium ionization.
Calcium
general
Iron syv.
AST
ALT
Phosphatase alkali.
LDH
65.0-80 g 85.0 g/l
44-110
1.66-8.3
2.90-6.54
8.5-20.5
up to 25%
up to 25%

up to 100 El
95-110.0
135.0-147.0
3.5-6.0
0.98-1.30
2.1-2.55

8.8-27.0
5-40
5-40 Ate
up to 104
225-450 El 51.23

118.0
8.2
6.21
11.0

3.0
8.0

82
107.2
114.0
114.20
3.8
2.72

19.4
314.3
190.4
265.7
465.8
623 62.26

89
7.4
5.62
24.2

22.3
11.9

96
102
140
115.3
4.9
2.32

13.4
395.8
104.7
125.8
326
332 65

74
3.1
5.75
8.4

3.3
5.1

84
89
102.8
114.31
4.8
2.28

18.0
138.0
54.8
45.7
69.2
242 82.53

69
2.9
7.03
8.0

2.0
6.0

90
78.0
110.0
134.2
4.9
2.15

17.7
64.4
42.9
29.5
79
228

Weight restored. No complaints for 2 years.

Example #16.

Patient T., 75 years old.

When addressing complaints of cramps during urination and retention and redness of urine. During the examination: ultrasound of 03/01/2019 - prostate 95 cm ³ , tumor with fuzzy contours 34 x 40 mm ² . PSA from 04/02/2019 - 14.9 mg / ml.

Needle biopsy - adenocarcinoma of the prostate.

Diagnosis: Adenocarcinoma of the prostate.

He refused surgery and chemotherapy.

The patient was treated with the zinc salt of 5-aminophthalhydrazide.

From 04/09/2019, for 20 days, the patient took the drug - a powder of 300 mg x 2 times a day with meals, with 50 mg. rhodamine 6G. At night, a suppository with a 2% preparation was administered rectally. To increase efficiency, 250 ml of a 4% solution of sodium bicarbonate was injected intravenously 2 hours after the administration of the drug. During this period, pain during urination decreased, urine color returned to normal, ultrasound examination of the prostate volume decreased by 40%, the tumor acquired a clear outline, dimensions 12 x 10 mm ² . Then therapy was continued by taking 300 mg x 2 times a day for two weeks with meals, respectively, 300 mg. and lithium salt of 5 aminophthalhydrazide, 100 mg each. and also prescribed therapeutic enemas with the drug daily at bedtime, 2.0 g in 50 ml of boiled water.

During the subsequent examination, according to the patient's words, the final disappearance of the symptoms of the disease (dragging during urination, urinary retention, etc.) was noted. On the control ultrasound, the prostate is 33 cm ³ , the tumor has decreased to 4 x 4 mm ² . PSA dated September 19, 2019 - 2.0 mg / ml.

Within 2 years of recurrence is not observed.

Example #14.

Patient S., 44 years old.

In 2019, she discovered a massive rash on her labia. Diagnosed - Herpetic lesions of the mucous membranes of the lips and vulva. She suffered from a herpetic lesion of the upper lip since 2010, when rashes appeared on the lips with discharge in the form of an ichor.

Diagnosis: Recurrent herpetic lesions of the mucous lips and genitals. Was treated with Zovirax - no effect.

Due to the ineffectiveness of continuing with antiviral drugs, treatment with the drug was carried out. Salts of 5-aminophthalhydrazide were used for treatment. As a therapeutic agent, an ointment is used, which includes: an alkaline salt or a mixture of alkaline salts of 5-amino-2,3-dihydro-1,4-phthalazinedione in saline. with the following ratio of components in wt. %: gold salt of 5-amino-2,3-dihydro-1,4-phthalazinedione or a mixture of alkaline salts of 5-amino-2,3-dihydro-1,4-phthalazinedione - 1.0-50.0; solution 10.0-20.0; vaseline oil - 5.0-10.0, water - the rest, and sodium or arsenic salt of 5-amino-2,3-dihydro-1,4-phthalazinedione is used as an alkaline salt, and 5-amino alkaline salts are used as a mixture -2,3-dihydro-1,4-phthalazinedione, a mixture of sodium and potassium salts of 5-amino-2,3-dihydro-1,4-phthalazinedione, composed at an equal ratio of components, is used. This ointment brings the cell membrane, which is disturbed due to the disease, to a normal state, normalizes and regulates intracellular and intercellular metabolic processes. On the 3rd day after the start of treatment, the pain decreased, the rash decreased. On the 5th day, complete recovery. Currently healthy.

Example #17.

Big G. 56 years old. In June 2018, he was diagnosed with pulmonary tuberculosis. Nowhere was treated, took herbal medicine. Complaints of cough, hemoptysis and chest pain. On the radiograph, there are several rounded lesions 2x2x3 cm in both lungs. Results: general blood test dated June 19, 2018: hemoglobin -76, leukocytes - 11.5, lymphocytes - 38. The rest of the parameters are within the normal range. The treatment of lithium salt 5 with aminophthalhydrazide 200 mg is proposed. intravenously in sterile saline ligated with methylene blue 50 mg. Inhalations daily 1.0 gr. drug dissolved in 10 ml. water in inhalation. Treatment according to this scheme continued for 3 months. On the second day after taking the pain became dull and on the fifth day they disappeared and did not recur. Hemoptysis stopped on the second week from the start of treatment.

On CT scan after 3 months, tumor-like formations and infiltration are not detected. Results. Complete blood count dated December 26, 2018: hemoglobin -134, leukocytes - 4 thousand, lymphocytes - 43. The rest of the parameters are within the normal range. There are currently no complaints. Weight 79 kg.

Example #18.

Patient L. 45 years old. Dz: Melanoma of the left thigh, metastasis to the inguinal lymph node. In the region of the left thigh, a dark brown neoplasm 4x5x3 cm. irregular shape, with perifocal edema. In the left inguinal region, an enlarged lymph node, soldered to the surrounding tissues. The histological diagnosis was metastatic melanoma. Treated with 10% solution of 5-aminophthalhydrazide arsenic salt per 20.0 ml of sterile saline. Daily treatment of the tumor was carried out in the form of 5% gold 5-aminophthalhydrazide ointment, based on cocoa butter. Within 2 months, the size of the tumor decreased by 80%. The lymph node is not defined. After 3 months, hyperpigmentation and a primary tumor 2x3x2 cm are determined at the site of the tumor. She has no complaints. There are no relapses for 3 years.

In each case, with an established pathogenetic factor, the degrees of disturbance of the microbiocenosis of a particular biotope were recorded using a set of methods for assessing the levels of colonization resistance factors, namely, normal microflora, opportunistic microflora, immunoglobulins - G, M, A, secretory immunoglobulin A and sc component; and depending on the degree of violation of microbiocenosis, the state of mucosal immunity was assessed and in 97% of cases a favorable effect was found on the overall improvement of metabolism, increased secretory and motor functions of the gastrointestinal tract, regulation of the functional activity of the pancreas, liver and gallbladder, with eradication of the pathogen or chronization with the persistence of the pathogen, i.e. the immunomodulatory, immunocorrective and immunosuppressive effects of the agent were confirmed.

In addition, the ability of DCA to induce apoptosis in breast cancer cell cultures has been convincingly proven. It was shown that in cultured rat mammary adenocarcinoma cells, switching of the glycolytic phenotype upon exposure to DCA correlated with inhibition of proliferation without any increase in cell death. A positive effect from the use of the drug in 90 patients is noted in 67% of cases, and the study also included patients with metastatic forms of cancer in whom traditional methods of therapy were ineffective.

In order to study the effect of the declared funds 2019-2021. practical use was carried out in the following, described below in a brief form, cases 1-72 of its implementation for the treatment of oncological diseases of various organs.

A positive result of the application of the claimed composition was considered to be the complete disappearance of the symptoms of the disease or a significant decrease (at least 70%) in the size of the tumor and / or metastases within 25-45 days of its use, confirmed by computed tomography data, accompanied by restoration of the patient's weight and elimination of pain.

1. A composition was used in which the first salt is sodium 5-aminophthalhydrazide 70% and the second salt is bis(5-amino-1,4-dioxo-1,2,3,4-tetrahydrophthalazin-2-yl)zinc 30%, taken in the form of tablets, was used to treat oncological diseases of the gastrointestinal tract and kidneys (hereinafter referred to as the gastrointestinal tract) with a positive result in 4 patients.

2. A composition was used in which the first salt is sodium 5-aminophthalhydrazide 70% and the second salt is arsenic bis(5-amino-1,4-dioxo-1,2,3,4-tetrahydrophthalazin-2-yl) A 30% dose in the form of tablets was used to treat gastrointestinal cancers with a positive result in 4 patients.

3. A composition was used in which the first salt is sodium 5-aminophthalhydrazide 70% and the second salt is bis(5-amino-1,4-dioxo-1,2,3,4-tetrahydrophthalazin-2-yl) gold thirty%. administration in the form of tablets, was used for the treatment of oncological diseases of the gastrointestinal tract with a positive result in 3 patients.

4. A composition was used in which the first salt is potassium 5-aminophthalhydrazide 70% and the second salt is bis(5-amino-1,4-dioxo-1,2,3,4-tetrahydrophthalazin-2-yl)zinc 30%, taken in the form of tablets, was used to treat gastrointestinal cancers with a positive result in 4 patients.

5. A composition was used in which the first salt is potassium 5-aminophthalhydrazide 70% and the second salt is arsenic bis(5-amino-1,4-dioxo-1,2,3,4-tetrahydrophthalazin-2-yl) A 30% dose in the form of tablets was used to treat gastrointestinal cancers with a positive result in 4 patients.

6. A composition was used in which the first salt is potassium 5-aminophthalhydrazide 70% and the second salt is: bis(5-amino-1,4-dioxo-1,2,3,4-tetrahydrophthalazin-2-yl) gold 30%. administration in the form of tablets, was used for the treatment of oncological diseases of the gastrointestinal tract with a positive result in 6 patients.

7. A composition was used in which the first salt is lithium 5-aminophthalhydrazide 70% and the second salt is: bis(5-amino-1,4-dioxo-1,2,3,4-tetrahydrophthalazin-2-yl) zinc 30%, taken in the form of tablets, was used to treat gastrointestinal cancers with a positive result in 5 patients.

8. A composition was used in which the first salt is lithium 5-aminophthalhydrazide 70% and the second salt is arsenic bis(5-amino-1,4-dioxo-1,2,3,4-tetrahydrophthalazin-2-yl) A 30% dose in the form of tablets has been used to treat gastrointestinal cancers with a positive result in 3 patients.

9. A composition was used in which the first salt is lithium 5-aminophthalhydrazide 70% and the second salt is: bis(5-amino-1,4-dioxo-1,2,3,4-tetrahydrophthalazin-2-yl) gold 30%. administration in the form of tablets, was used for the treatment of oncological diseases of the gastrointestinal tract with a positive result in 5 patients.

10. A composition was used in which the first salt is sodium 5-aminophthalhydrazide 60% and the second salt is bis(5-amino-1,4-dioxo-1,2,3,4-tetrahydrophthalazin-2-yl)zinc 40%, taken in the form of tablets, was used to treat gastrointestinal cancers with a positive result in 6 patients.

11. A composition was used in which the first salt is sodium 5-aminophthalhydrazide 60% and the second salt is arsenic bis(5-amino-1,4-dioxo-1,2,3,4-tetrahydrophthalazin-2-yl) 40% of the intake in the form of tablets, was used to treat gastrointestinal cancers with a positive result in 5 patients.

12. A composition was used in which the first salt is sodium 5-aminophthalhydrazide 60% and the second salt is bis(5-amino-1,4-dioxo-1,2,3,4-tetrahydrophthalazin-2-yl) gold 40%. administration in the form of tablets, was used for the treatment of oncological diseases of the gastrointestinal tract with a positive result in 4 patients.

13. A composition was used in which the first salt is potassium 5-aminophthalhydrazide 60% and the second salt is bis(5-amino-1,4-dioxo-1,2,3,4-tetrahydrophthalazin-2-yl)zinc 40%, taken in the form of tablets, was used to treat gastrointestinal cancers with a positive result in 4 patients.

14. A composition was used in which the first salt is potassium 5-aminophthalhydrazide 60% and the second salt is arsenic bis(5-amino-1,4-dioxo-1,2,3,4-tetrahydrophthalazin-2-yl) 40% of the intake in the form of tablets, was used to treat gastrointestinal cancers with a positive result in 5 patients.

15. A composition was used in which the first salt is potassium 5-aminophthalhydrazide 60% and the second salt is: bis(5-amino-1,4-dioxo-1,2,3,4-tetrahydrophthalazin-2-yl) gold 40%. administration in the form of tablets, was used for the treatment of oncological diseases of the gastrointestinal tract with a positive result in 4 patients.

16. A composition was used in which the first salt is lithium 5-aminophthalhydrazide 60% and the second salt is: bis(5-amino-1,4-dioxo-1,2,3,4-tetrahydrophthalazin-2-yl) zinc 40%, taken in the form of tablets, was used to treat gastrointestinal cancers with a positive result in 3 patients.

17. A composition was used in which the first salt is lithium 5-aminophthalhydrazide 60% and the second salt is arsenic bis(5-amino-1,4-dioxo-1,2,3,4-tetrahydrophthalazin-2-yl) 40% of the intake in the form of tablets, was used to treat gastrointestinal cancers with a positive result in 3 patients.

18. A composition was used in which the first salt is lithium 5-aminophthalhydrazide 60% and the second salt is: bis(5-amino-1,4-dioxo-1,2,3,4-tetrahydrophthalazin-2-yl) gold 40%. administration in the form of tablets, was used for the treatment of oncological diseases of the gastrointestinal tract with a positive result in 6 patients.

19. A composition was used in which the first salt is sodium 5-aminophthalhydrazide 70% and the second salt is bis(5-amino-1,4-dioxo-1,2,3,4-tetrahydrophthalazin-2-yl)zinc 30%, in the form of suppositories, was used for the treatment of oncological diseases of the anorectal region with a positive result in 3 patients.

20. A composition was used in which the first salt is sodium 5-aminophthalhydrazide 70% and the second salt is arsenic bis(5-amino-1,4-dioxo-1,2,3,4-tetrahydrophthalazin-2-yl) A 30% dose in the form of suppositories was used for the treatment of oncological diseases of the anorectal region with a positive result in 7 patients.

21. A composition was used in which the first salt is sodium 5-aminophthalhydrazide 70% and the second salt is bis(5-amino-1,4-dioxo-1,2,3,4-tetrahydrophthalazin-2-yl) gold thirty%. administration in the form of suppositories, was used for the treatment of oncological diseases with a positive result in 5 patients.

22. A composition was used in which the first salt is potassium 5-aminophthalhydrazide 70% and the second salt is bis(5-amino-1,4-dioxo-1,2,3,4-tetrahydrophthalazin-2-yl)zinc 30%, in the form of suppositories, was used for the treatment of oncological diseases of the anorectal region with a positive result in 5 patients.

23. A composition was used in which the first salt is potassium 5-aminophthalhydrazide 70% and the second salt is arsenic bis(5-amino-1,4-dioxo-1,2,3,4-tetrahydrophthalazin-2-yl) 30% supplementation in the form of suppositories was used for the treatment of oncological diseases of the anorectal region with a positive result in 5 patients.

24. A composition was used in which the first salt is potassium 5-aminophthalhydrazide 70% and the second salt is: bis(5-amino-1,4-dioxo-1,2,3,4-tetrahydrophthalazin-2-yl) gold 30%. reception in the form of suppositories, was used for the treatment of oncological diseases of the anorectal region with a positive result in 3 patients.

25. A composition was used in which the first salt is lithium 5-aminophthalhydrazide 70% and the second salt is: bis(5-amino-1,4-dioxo-1,2,3,4-tetrahydrophthalazin-2-yl) zinc 30%, taken in the form of suppositories, was used to treat cancer of the anorectal region with a positive result in 4 patients.

26. A composition was used in which the first salt is lithium 5-aminophthalhydrazide 70%, and the second salt is arsenic bis(5-amino-1,4-dioxo-1,2,3,4-tetrahydrophthalazin-2-yl) 30% supplementation in the form of suppositories was used for the treatment of oncological diseases of the anorectal region with a positive result in 3 patients.

27. A composition was used in which the first salt is lithium 5-aminophthalhydrazide 70% and the second salt is: bis(5-amino-1,4-dioxo-1,2,3,4-tetrahydrophthalazin-2-yl) gold 30%. reception in the form of suppositories, was used for the treatment of oncological diseases of the anorectal region with a positive result in 4 patients.

28. A composition was used in which the first salt is sodium 5-aminophthalhydrazide 60% and the second salt is zinc bis(5-amino-1,4-dioxo-1,2,3,4-tetrahydrophthalazin-2-yl) 40%, in the form of suppositories, was used for the treatment of oncological diseases of the anorectal region with a positive result in 4 patients.

29. A composition was used in which the first salt is sodium 5-aminophthalhydrazide 60% and the second salt is arsenic bis(5-amino-1,4-dioxo-1,2,3,4-tetrahydrophthalazin-2-yl) 40% supplementation in the form of suppositories was used for the treatment of oncological diseases of the anorectal region with a positive result in 3 patients.

30. A composition was used in which the first salt is sodium 5-aminophthalhydrazide 60% and the second salt is bis(5-amino-1,4-dioxo-1,2,3,4-tetrahydrophthalazin-2-yl) gold 40%. reception in the form of suppositories, was used for the treatment of oncological diseases of the anorectal region with a positive result in 5 patients.

31. A composition was used in which the first salt is potassium 5-aminophthalhydrazide 60% and the second salt is bis(5-amino-1,4-dioxo-1,2,3,4-tetrahydrophthalazin-2-yl)zinc 40%, suppositories, was used to treat anorectal cancers with a positive result in 2 patients.

32. A composition was used in which the first salt is potassium 5-aminophthalhydrazide 60%, and the second salt is arsenic bis(5-amino-1,4-dioxo-1,2,3,4-tetrahydrophthalazin-2-yl) 40% supplementation in the form of suppositories was used for the treatment of oncological diseases of the anorectal region with a positive result in 2 patients.

33. . A composition was used in which the first salt is potassium 5-aminophthalhydrazide 60%, and the second salt is: bis(5-amino-1,4-dioxo-1,2,3,4-tetrahydrophthalazin-2-yl) gold 40 %. reception in the form of suppositories, was used for the treatment of oncological diseases of the anorectal region with a positive result in 3 patients.

34. A composition was used in which the first salt is lithium 5-aminophthalhydrazide 60% and the second salt is: bis(5-amino-1,4-dioxo-1,2,3,4-tetrahydrophthalazin-2-yl) zinc 40%, taken in the form of suppositories, was used to treat oncological diseases of the anorectal region with a positive result in 3 patients.

35. A composition was used in which the first salt is lithium 5-aminophthalhydrazide 60%, and the second salt is arsenic bis(5-amino-1,4-dioxo-1,2,3,4-tetrahydrophthalazin-2-yl) 40% supplementation in the form of suppositories was used for the treatment of oncological diseases of the anorectal region with a positive result in 3 patients.

36. A composition was used in which the first salt is lithium 5-aminophthalhydrazide 60% and the second salt is: bis(5-amino-1,4-dioxo-1,2,3,4-tetrahydrophthalazin-2-yl) gold 40%. reception in the form of suppositories, was used for the treatment of oncological diseases of the anorectal region with a positive result in 4 patients.

37. A composition was used in which the first salt is sodium 5-aminophthalhydrazide 70% and the second salt is zinc bis(5-amino-1,4-dioxo-1,2,3,4-tetrahydrophthalazin-2-yl) 30%, taken in the form of injections, was used to treat oncological diseases of the internal organs, including the lungs, brain and spinal cord, with a positive result in 3 patients.

38. A composition was used in which the first salt is sodium 5-aminophthalhydrazide 70%, and the second salt is arsenic bis(5-amino-1,4-dioxo-1,2,3,4-tetrahydrophthalazin-2-yl) 30% in the form of injections, was used to treat oncological diseases of the internal organs, including the lungs, brain and spinal cord, with a positive result in 4 patients.

39. A composition was used in which the first salt is sodium 5-aminophthalhydrazide 70% and the second salt is bis(5-amino-1,4-dioxo-1,2,3,4-tetrahydrophthalazin-2-yl) gold thirty%. administration in the form of injections, was used to treat oncological diseases of internal organs, including the brain and spinal cord, with a positive result in 2 patients.

40. A composition was used in which the first salt is potassium 5-aminophthalhydrazide 70% and the second salt is bis(5-amino-1,4-dioxo-1,2,3,4-tetrahydrophthalazin-2-yl)zinc 30%, taken in the form of injections, was used to treat oncological diseases of the internal organs, including the lungs, brain and spinal cord, with a positive result in 4 patients.

41. A composition was used in which the first salt is potassium 5-aminophthalhydrazide 70% and the second salt is arsenic bis(5-amino-1,4-dioxo-1,2,3,4-tetrahydrophthalazin-2-yl) 30% in the form of injections, was used to treat oncological diseases of the internal organs, including the lungs, brain and spinal cord, with a positive result in 3 patients.

42. A composition was used in which the first salt is potassium 5-aminophthalhydrazide 70%, and the second salt is: bis(5-amino-1,4-dioxo-1,2,3,4-tetrahydrophthalazin-2-yl) gold 30 %. administration in the form of injections, was used to treat oncological diseases of internal organs, including the lungs, brain and spinal cord, with a positive result in 3 patients.

43. A composition was used in which the first salt is lithium 5-aminophthalhydrazide 70%, and the second salt is: bis(5-amino-1,4-dioxo-1,2,3,4-tetrahydrophthalazin-2-yl) zinc 30%, taken in the form of injections, was used to treat oncological diseases of the internal organs, including the lungs, brain and spinal cord, with a positive result in 4 patients.

44. A composition was used in which the first salt is lithium 5-aminophthalhydrazide 70% and the second salt is arsenic bis(5-amino-1,4-dioxo-1,2,3,4-tetrahydrophthalazin-2-yl) 30% in the form of injections, was used to treat oncological diseases of the internal organs, including the lungs, brain and spinal cord, with a positive result in 4 patients.

45 . A composition was used in which the first salt is lithium 5-aminophthalhydrazide 70%, and the second salt is: bis(5-amino-1,4-dioxo-1,2,3,4-tetrahydrophthalazin-2-yl) gold 30 %. administration in the form of injections, was used to treat oncological diseases of internal organs, including the lungs, brain and spinal cord, with a positive result in 5 patients.

46. A composition was used in which the first salt is sodium 5-aminophthalhydrazide 60% and the second salt is bis(5-amino-1,4-dioxo-1,2,3,4-tetrahydrophthalazin-2-yl)zinc 40%, taken in the form of injections, was used to treat oncological diseases of the internal organs, including the lungs, brain and spinal cord, with a positive result in 4 patients.

47. A composition was used in which the first salt is sodium 5-aminophthalhydrazide 60% and the second salt is arsenic bis(5-amino-1,4-dioxo-1,2,3,4-tetrahydrophthalazin-2-yl) 40% in the form of injections, was used to treat oncological diseases of the internal organs, including the lungs, brain and spinal cord, with a positive result in 4 patients.

48. A composition was used in which the first salt is sodium 5-aminophthalhydrazide 60% and the second salt is bis(5-amino-1,4-dioxo-1,2,3,4-tetrahydrophthalazin-2-yl) gold 40%. administration in the form of injections, was used to treat oncological diseases of internal organs, including the lungs, brain and spinal cord, with a positive result in 4 patients.

49. A composition was used in which the first salt is potassium 5-aminophthalhydrazide 60% and the second salt is bis(5-amino-1,4-dioxo-1,2,3,4-tetrahydrophthalazin-2-yl)zinc 40%, taken in the form of injections, was used to treat oncological diseases of the internal organs, including the lungs, brain and spinal cord, with a positive result in 4 patients.

50. A composition was used in which the first salt is potassium 5-aminophthalhydrazide 60% and the second salt is arsenic bis(5-amino-1,4-dioxo-1,2,3,4-tetrahydrophthalazin-2-yl) 40% in the form of injections, was used to treat oncological diseases of the internal organs, including the lungs, brain and spinal cord, with a positive result in 3 patients.

51. . A composition was used in which the first salt is potassium 5-aminophthalhydrazide 60%, and the second salt is: bis(5-amino-1,4-dioxo-1,2,3,4-tetrahydrophthalazin-2-yl) gold 40 %. administration in the form of injections, was used to treat oncological diseases of internal organs, including the lungs, brain and spinal cord, with a positive result in 4 patients.

52. A composition was used in which the first salt is lithium 5-aminophthalhydrazide 60%, and the second salt is: bis(5-amino-1,4-dioxo-1,2,3,4-tetrahydrophthalazin-2-yl) zinc 40%, taken in the form of injections, was used to treat oncological diseases of the internal organs, including the lungs, brain and spinal cord, with a positive result in 3 patients.

53. A composition was used in which the first salt is lithium 5-aminophthalhydrazide 60%, and the second salt is arsenic bis(5-amino-1,4-dioxo-1,2,3,4-tetrahydrophthalazin-2-yl) 40% in the form of injections, was used to treat oncological diseases of the internal organs, including the lungs, brain and spinal cord, with a positive result in 4 patients.

54 . A composition was used in which the first salt is lithium 5-aminophthalhydrazide 60%, and the second salt is: bis(5-amino-1,4-dioxo-1,2,3,4-tetrahydrophthalazin-2-yl) gold 40 %. administration in the form of injections, was used to treat oncological diseases of internal organs, including the lungs, brain and spinal cord, with a positive result in 4 patients.

55. A composition was used in which the first salt is sodium 5-aminophthalhydrazide 70% and the second salt is bis(5-amino-1,4-dioxo-1,2,3,4-tetrahydrophthalazin-2-yl)zinc 30%, used in the form of an ointment, was used for the treatment of oncological diseases of the external surfaces with a positive result in 4 patients.

56. A composition was used in which the first salt is sodium 5-aminophthalhydrazide 70% and the second salt is arsenic bis(5-amino-1,4-dioxo-1,2,3,4-tetrahydrophthalazin-2-yl) 30% use in the form of an ointment, was used for the treatment of oncological diseases of the external surfaces with a positive result in 4 patients.

57. A composition was used in which the first salt is sodium 5-aminophthalhydrazide 70% and the second salt is bis(5-amino-1,4-dioxo-1,2,3,4-tetrahydrophthalazin-2-yl) gold thirty%. use in the form of an ointment, was used to treat oncological diseases of the external surfaces with a positive result in 4 patients.

58. A composition was used in which the first salt is potassium 5-aminophthalhydrazide 70% and the second salt is bis(5-amino-1,4-dioxo-1,2,3,4-tetrahydrophthalazin-2-yl)zinc 30%, used in the form of an ointment, was used for the treatment of oncological diseases of the external surfaces with a positive result in 3 patients.

59. A composition was used in which the first salt is potassium 5-aminophthalhydrazide 70%, and the second salt is arsenic bis(5-amino-1,4-dioxo-1,2,3,4-tetrahydrophthalazin-2-yl) 30% use in the form of an ointment, was used for the treatment of oncological diseases of the external surfaces with a positive result in 6 patients.

60. A composition was used in which the first salt is potassium 5-aminophthalhydrazide 70% and the second salt is: bis(5-amino-1,4-dioxo-1,2,3,4-tetrahydrophthalazin-2-yl) gold 30%. use in the form of an ointment, was used to treat oncological diseases of the external surfaces with a positive result in 5 patients.

61. A composition was used in which the first salt is lithium 5-aminophthalhydrazide 70%, and the second salt is: bis(5-amino-1,4-dioxo-1,2,3,4-tetrahydrophthalazin-2-yl) zinc 30%, used in the form of an ointment, was used for the treatment of oncological diseases of the external surfaces with a positive result in 3 patients.

62. A composition was used in which the first salt is lithium 5-aminophthalhydrazide 70% and the second salt is arsenic bis(5-amino-1,4-dioxo-1,2,3,4-tetrahydrophthalazin-2-yl) 30% use in the form of an ointment, was used for the treatment of oncological diseases of the external surfaces with a positive result in 5 patients.

63 . A composition was used in which the first salt is lithium 5-aminophthalhydrazide 70%, and the second salt is: bis(5-amino-1,4-dioxo-1,2,3,4-tetrahydrophthalazin-2-yl) gold 30 %. use in the form of an ointment, was used to treat oncological diseases of the external surfaces with a positive result in 3 patients.

64. A composition was used in which the first salt is sodium 5-aminophthalhydrazide 60% and the second salt is bis(5-amino-1,4-dioxo-1,2,3,4-tetrahydrophthalazin-2-yl)zinc 40%, used in the form of an ointment, was used for the treatment of oncological diseases of the external surfaces with a positive result in 4 patients.

65. A composition was used in which the first salt is sodium 5-aminophthalhydrazide 60% and the second salt is arsenic bis(5-amino-1,4-dioxo-1,2,3,4-tetrahydrophthalazin-2-yl) 40% use in the form of an ointment, was used for the treatment of oncological diseases of the external surfaces with a positive result in 5 patients.

66. A composition was used in which the first salt is sodium 5-aminophthalhydrazide 60% and the second salt is bis(5-amino-1,4-dioxo-1,2,3,4-tetrahydrophthalazin-2-yl) gold 40%. use in the form of an ointment, was used to treat oncological diseases of the external surfaces with a positive result in 5 patients.

67. A composition was used in which the first salt is potassium 5-aminophthalhydrazide 60% and the second salt is bis(5-amino-1,4-dioxo-1,2,3,4-tetrahydrophthalazin-2-yl)zinc 40%, used in the form of an ointment, was used for the treatment of oncological diseases of the external surfaces with a positive result in 6 patients.

68. A composition was used in which the first salt is potassium 5-aminophthalhydrazide 60%, and the second salt is arsenic bis(5-amino-1,4-dioxo-1,2,3,4-tetrahydrophthalazin-2-yl) 40% use in the form of an ointment, was used for the treatment of oncological diseases of the external surfaces with a positive result in 3 patients.

69. A composition was used in which the first salt is potassium 5-aminophthalhydrazide 60%, and the second salt is: bis (5-amino-1,4-dioxo-1,2,3,4-tetrahydrophthalazin-2-yl) gold 40%. use in the form of an ointment, was used to treat oncological diseases of the external surfaces with a positive result in 3 patients.

70. A composition was used in which the first salt is lithium 5-aminophthalhydrazide 60% and the second salt is: bis(5-amino-1,4-dioxo-1,2,3,4-tetrahydrophthalazin-2-yl) zinc 40%, used in the form of an ointment, was used for the treatment of oncological diseases of the external surfaces with a positive result in 5 patients.

71. A composition was used in which the first salt is lithium 5-aminophthalhydrazide 60% and the second salt is arsenic bis(5-amino-1,4-dioxo-1,2,3,4-tetrahydrophthalazin-2-yl) 40% use in the form of an ointment, was used for the treatment of oncological diseases of the external surfaces with a positive result in 4 patients.

72 . A composition was used in which the first salt is lithium 5-aminophthalhydrazide 60%, and the second salt is: bis(5-amino-1,4-dioxo-1,2,3,4-tetrahydrophthalazin-2-yl) gold 40 %. use in the form of an ointment, was used to treat oncological diseases of the external surfaces with a positive result in 3 patients.

Given the significant amount of positive results when using the claimed composition, and their excess over negative results by an average of 3 times (75%), the likelihood of an erroneous judgment about achieving a real positive result from its use is very small.

The generalized results of the studies, in essence, really confirmed that the claimed agent is a controlled, temporary immunosuppressant. It inhibits (reversibly for 6–8 hours) hyperactive macrophages, reduces the synthesis of TNF, interleukin 1, the production of reactive oxygen species and other acute phase proteins responsible for the development of toxic and diarrheal syndrome. Normalizes the functional state of macrophages, leads to the restoration of their antigen-presenting and regulatory functions. By increasing the functional antibacterial activity of neutrophilic granulocytes, it enhances phagocytosis and increases the nonspecific defense of the body. EFFECT: invention makes it possible to expand the arsenal of agents that have a wide range of therapeutic effects and do not cause side effects. At the same time, the claimed agent has a polymorphism of action, namely, luminescent properties to increase the level of anisotropy in the cytoplasm of damaged cells and at the same time promotes immunomodulation, namely, temporary suppression (controlled immunosuppression) of the metabolism of hyperactive macrophages.

Immunomodulating agent, also has an anti-inflammatory effect. Inhibits (reversibly for 6–8 hours) hyperactive macrophages, reduces the synthesis of TNF, interleukin 1, the production of reactive oxygen species and other acute phase proteins responsible for the development of toxic and diarrheal syndrome. Normalizes the functional state of macrophages, leads to the restoration of their antigen-presenting and regulatory functions. By increasing the functional antibacterial activity of neutrophilic granulocytes, it enhances phagocytosis and increases the nonspecific defense of the body.

The agent can be used in the following diseases: autoimmune diseases: ulcerative colitis, Crohn's disease, total alopecia, rheumatoid arthritis, acute and chronic inflammatory diseases, viral and bacterial lesions, purulent-septic complications and sepsis, accompanied by intoxication and / or diarrhea, purulent surgical diseases (burns, recurrent trophic ulcers, chronic osteomyelitis, peritonitis, purulent pleurisy); frequent recurrent diseases of the respiratory tract and ENT organs of bacterial and viral etiology. It is advisable to accompany chemotherapy and radiation in oncological diseases. Easily implemented injection forms, as well as tablet forms. For external use, ointments, creams, suppositories and rectal suppositories, inhalations are not excluded.

Thus, the invention allows to expand the arsenal of agents that have a wide range of therapeutic effects and do not cause side effects.

Claims (4)

1. Pharmaceutical composition with immunocorrective, antiviral activity against COVID-19 and herpetic lesions of the mucous membranes of the lips and vulva, as well as anti-inflammatory and oncolytic activity against glioblastoma of the brain, clear cell carcinoma of the left kidney with lung metastases, non-Hodgkin's lymphoma, prostate adenocarcinoma , metastatic melanoma, containing a mixture of two salts: the first salt, which is a salt from the group: sodium 5-aminophthalhydrazide, potassium 5-aminophthalhydrazide and lithium 5-aminophthalhydrazide, and the second salt, which is a salt from the group: bis (5-amino-1 ,4-dioxo-1,2,3,4-tetrahydrophthalazin-2-yl) arsenic and bis(5-amino-1,4-dioxo-1,2,3,4-tetrahydrophthalazin-2-yl) gold. 2. The composition according to claim 1, characterized in that the mixture contains in wt.%: first salt 60-70 second salt 30-40 3. The composition according to any one of claims 1-2, characterized in that it is made in a dosage form from the group: tablets, powder for injection solution, ointment, suppositories for rectal use.