RU2354384C1 - Application of organic dyes as means for treatment of oncological diseases - Google Patents

Abstract

FIELD: pharmacology. ^ SUBSTANCE: essence of invention lies in application of organic dyes having in formula double N=N bond and molecular weight 400-900, from group: Sudan dark-blue, Congo red, Naphthol blue black, Sudan IV, Bismarck Brown, acid black and acid blue as means for treatment of oncological diseases with single preparation dose from 0.1 to 2 g per intake up to 3 times a day. Preferably preparation is used diluted with 10-5 to 10-7 mmole/l, in form of water solution or physiological solution, water solution of preparation is introduced through rectum, or 1-3% solution of preparation is introduced intravenously, or 1% solution of preparation is introduced by inhaling, or 1-5% ointment based on preparation is applied, or preparation is introduced in form of rectal suppositories. Wide spectrum of medicinal impact of said medications with respect to various oncological diseases (adenocarcinoma, carcinoma, melanoma, blastoma, urinary bladder cancer, kidney cancer, liver cancer, leukemia, astrocytoma, glioblastoma, etc.) is shown: size of said tumors was reduced or tumors and metastases were not found after treatment. ^ EFFECT: means are not toxic and did not cause side effects when used in pharmaceutically acceptable doses. ^ 7 cl, 5 dwg, 21 ex

Description

The invention relates to medicine, namely to drugs with a wide spectrum of action used for the treatment of cancer.

Known drug "Doxorubicin" (Doxorubicini hydrochloridum). Antitumor antibiotic anthracycline series. Synonyms: Adriablastin, Adriamycin, Rastocin, Adriacin, Doxorubicin, Farmiblastina, Hydroxydaunomycin, Rastocin. Red crystalline powder or porous mass. It is sparingly soluble in water, insoluble in alcohol. Doxorubicin has a high antitumor and anti-leukemia activity. According to the mechanism of action, it is close to rubomycin and has the ability to intercalate the DNA of cells. It has a depressing effect on blood formation. It has immunosuppressive activity. Doxorubicin is used for breast cancer, soft tissue sarcoma, osteogenic sarcoma, Ewing's tumor, lung cancer, lymphosarcoma, ovarian cancer, squamous cell carcinoma of various localization, bladder cancer, Wilms tumor, thyroid cancer, acute leukemia, lymphogranulomatosis. Enter only intravenously. Doxorubicin is a substance with a high toxicity LD 50 13-15 mg / kg When using doxorubicin, leukopenia and thrombocytopenia, stomatitis, nausea and vomiting (immediately after administration of the drug), alopecia (reversible), allergic reactions, necrosis of subcutaneous adipose tissue when the drug enters 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 process of treatment with the drug, cardiomyopathy, pain in the heart, rhythm disturbances, heart failure, decreased blood pressure may develop. For severe cardiac arrhythmias or congestive failure, doxorubicin treatment should be discontinued immediately. The use of doxorubicin is contraindicated in severe liver and kidney disorders, leukopenia (below 3.5 × 109 / l), thrombocytopenia (below 12 × 109 / l), severe concomitant heart diseases (myocarditis, myocardial infarction, significant rhythm disturbances), bleeding, tuberculosis , pregnancy, peptic ulcer of the stomach and duodenum. (Big Medical Encyclopedia. Information portal: www.province.ru.)

The closest analogue prototype is a drug based on derivatives of tri-n-aminotriphenylchloromethane. Patent No. 2257200 dated May 12, 2004. The drug has immunomodulating and antitumor activity, is effective in the treatment of many types of cancer and immunodeficiency states. However, derivatives of tri-n-aminotriphenylchloromethane are ineffective in the treatment of severe forms of cancer and have a short duration of action. The drug has a fairly low LD 50, which also limits its use in high doses.

The use of organic dyes in microbiology and histology is known as intravital and post-mortem diagnostics. For this, staining of tissues and cells using organic dyes is performed. At the same time, the tinctorial properties of microbes, cells, organelles, and tissues change. Tinctorial properties are the ability to perceive dyes and characteristically stain. The most important for identification is the use of complex (differentiating) methods, primarily the Gram method, which makes it possible to distinguish between gram-positive and gram-negative bacteria. When stained with this method, gram-positive bacteria stain blue-violet, and gram-negative bacteria become burgundy red, which reflects differences in the structure of the cell walls of the bacteria of the two groups (KMAX - 2000, Volume 2, N 2. Diseases and pathogens. I.V. Smirnov. Pathogens of human bacterial infections).

The objective of the invention is to find a drug that has a wide range of therapeutic effects in relation to various oncological diseases and does not have side effects, as well as expanding the arsenal of drugs suitable for the treatment of cancer.

The technical result, which provides a solution to the problem, consists in the use of widely available and inexpensive substances, non-toxic and not causing side effects when used in pharmaceutically acceptable doses, as a means of treating cancer, reducing treatment time, increasing the effectiveness of treatment. Such preparations include some organic dyes related to substances that can change the optical, electromagnetic polarization (linear, circular, etc.) in living tissue and serve as a kind of generators and “lenses” of coherent radiation, like a laser.

The essence of the invention consists in the use of organic dyes having in the structural formula a double N = N bond and a molecular weight of 400-900 from the group: Sudan dark blue, Congo red. Naphthol dark blue, Sudan IV, Bismarck Brown, black acid and blue acid as a means for the treatment of cancer with a single dose of 0.1 mg to 2 g per dose up 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 physiological solution, an aqueous solution of the agent is administered rectally, or a 1-3% solution of the drug is administered intravenously, or a 1% solution of the drug is administered by inhalation, or 1-5% ointment based on the drug, or the drug is administered rectally in the form of suppositories.

It is known that dyes stain cancerous and healthy tissues in different ways, both posthumously and during life. Dyes, getting into the body and staining the cellular structures, change their function. This is due to the double action of dye molecules. They act as simple chemicals and as dyes with chromophores. According to the theory of Kutushov M.V., in cancer homeostasis, anisotropy changes to isotropy, which leads to a change in optical, mechanical, electromagnetic, thermal, etc. properties, this in turn leads to irreversible changes in cell structures. Ultimately, mitosis occurs, which leads to uncontrolled malignant growth of the same cells. Organic dyes, changing the tinctorial properties of cancer cells during life, restore the anisotropy and cell structure, while practically not affecting healthy cells in therapeutic doses. The therapeutic effect is determined by the fact that organic dyes, changing the tinctorial properties of organelles and structures of cancer cells, return to them the ability to coherently absorb and glow in a normal narrow range. As a result, the normal polarization properties of molecules, and especially proteins, are returned to cells and tissues. This in turn leads to the disappearance of isotropy and the restoration of anisotropy in cells and tissues. Such substances include organic dyes with a specific spatial structure. Organic dyes with N = N bonds in their formula have pronounced polarization properties. This property determines their ability to effectively intervene only in the proliferation process, without interfering with the metabolism of cancer cells.

Tryptophan is known to be uniquely sensitive to quenching by various substances. In addition to quenching with oxygen and iodide ions, tryptophan is quenched by substances such as acrylamide, succinimide, hydrogen peroxide, dichloroacetamide, pyridine hydrochloride, cysteine, chlorinated hydrocarbons, NO ₃ ^- , IO ₃ ^- , Cs ⁺ , Cu ²⁺ , Pb ²⁺ , Cd ²⁺ and Mn ²⁺ . This sensitivity to various types of quenchers is due to the tendency of the excited indole nucleus to donate electrons while in the excited state.

Proteins contain three amino acid residues that can contribute to ultraviolet fluorescence: tyrosine (Tug), tryptophan (Tgr) and phenylalanine (Phe). Protein fluorescence is usually excited at the absorption maximum at 280 nm or longer wavelengths. The maximum emission of tryptophan in water is at 348 nm and is highly dependent on polarity. (Internet. Www.enzyme.chem.msu.ru chapter 11. Protein fluorescence). According to the theory of Kutushov M.V., one of the main roles in the process of malignancy is played by a change in the absorption and luminescence of tryptophan and, as a result, a violation of polarization and anisotropy in cells. Practically established violation of the intramolecular dynamics of tryptophan in the aging process. (Mozhul V.M. et al. Article from the Belarusian Ophthalmological Journal, 2002, Internet). The therapeutic effect of dyes and the behavior of tryptophan in structures bearing the properties of cancer cells are theoretically predicted. (Kutushov M.V. Cancer is curable. - M .: Publishing House V.Sekachev. Institute for General Humanitarian Research. M: 2005, p. 127, 360). Therefore, the use of organic dyes for the treatment of cancer is determined precisely by these points.

These dyes have the lowest excitation threshold, which leads to the formation of an optical response and translates physical processes into a more ordered state. In other words, the proposed dyes most effectively restore anisotropy in cancer homeostasis, while not exerting any effect on healthy tissues that are in an anisotropic state. And finally, the last. The chromophores of these dyes covalently bind to spatially altered protein structures (D-proteins) of cancer cells located in cubic syngonies, thereby changing not only their polarization and tinctorial properties, but also normalize their physiological processes. Moreover, these dyes force cancerous structures to return to normal syngonies, which in turn returns anisotropy and dissymmetry to the cancerous homeostat.

The prerequisites for the action of dyes on the structure of malignant cells are as follows. In oncological (cancer) cells, anisotropy is impaired and, as a result, all physical processes and biochemical reactions, including and spontaneous glow of cell structures. The photoactivity of structures in the life of cells plays one of the key roles. Many biochemical reactions and cell mitosis are accompanied by photochemical reactions, which can be described as quantum mechanical phenomena. By acting on these mechanisms, it is possible to treat not only cancer, but also many other diseases. See Kutushov M.V. Cancer is curable. Ed. V.Sekachev. - M., 2005, p. 393. With cancer, spatial disturbances in the cellular structures occur, and above all, improper protein folding. As a result of this, spontaneous photoactivity of proteins is disrupted, their absorption and luminescence spectrum changes. Organic dyes predominantly from this group can serve as quantum generators (oscillators) and photon inductors in a narrow spectral range and contribute to the correction of cancer cell disorders. In addition, organic dyes, possessing such "laser" properties, are able to bring diseased tissues to physiological norms. As is known from physics, the magnitude of the limiting polarization is related to the symmetry of the molecule. With cancerous degeneration of cellular structures, the connection of oscillators with a molecule loses its rigidity. Hence, the degree of anisotropy of the molecule, and hence the degree of polarization, decreases. This circumstance determines the fact that even in the case of completely anisotropic molecules, the degree of polarization does not reach the theoretical limit. Consequently, if we introduce a dye with high polarization properties into such a system, then they should “equalize” the degree of polarization, restore the broken dissymmetry and anisotropy. Organic dyes to one degree or another have the property of generating radiation. In the emission spectra of most dyes, a number of sharp equidistant lines are observed, the distance between which depends on the properties of the resonator. The resonator has many reflective surfaces. If we allow the cell itself and its structures as resonators, then, depending on the norm and pathology, the resonant properties will change. In cancer, cellular and tissue structures are disrupted in the most severe way.

Almost all molecules of organic dyes have a flat skeleton. Rarely, only groups of radicals go out of the common plane. Some dyes in solutions do not fluoresce, since their structure allows the rotation of radical groups around chains of conjugated bonds, but they can absorb the desired wavelength and generate photons in very narrow ranges. In solid solutions (liquid crystals), almost all dyes glow brightly. Cancer proteins are found in cubic hard syngonies; therefore, such dyes glow in them, acting as quantum generators. At the same time, dyes have a high absorption capacity in the visible region of the spectrum. Therefore, dyes mainly from the indicated group, interacting with such structures, return to them the original narrow absorption spectra, or otherwise the so-called equidistant properties. For this group of dyes, such a glow is not entirely characteristic, but they have pronounced polarizing properties, which explains their therapeutic mechanism. Thus, we can conclude that they themselves, or in conjunction with cellular structures, are capable of both suppressing the wavelength that cancerous structures “use” for their life and polarizing light and intracellular electromagnetic waves, thereby causing their death and involution of cancerous cells.

Most organic dyes can luminesce, which is a healing factor. Symmetric and asymmetric dyes are equally therapeutic agents for the treatment of various diseases. Polarized luminescence is an expression of the anisotropy of molecules. With pathology in the tissues, anisotropy and polarization are disturbed. In healthy tissues and cells there are so-called quantum dots, or elementary molecular oscillators (nanocrystals). The main characteristics of these oscillators are the frequency and orientation of the elements of the skeleton of water and protein networks of living matter. Their actions are characterized by a vector quantity. They operate in a frequency-specific mode. In pathologically altered tissues and cells where isotropy predominates, a violation of quantum-mechanical resonance occurs and concentration depolarization predominates. The generation and self-generation of light in a narrow range is a property of living tissue, proteins, glucose, metals, calcium, silicon, etc. Moreover, radiation not scattered, but strictly determined, takes part in these processes. Coherent radiation is an integral part of living matter. In diseased tissues, weakening, disruption and cessation of photon generation occur. In healthy tissues, mirror symmetry of the absorption and luminescence bands predominates. They are interconnected by a universal ratio, depending on the conditions of excitation. In diseased tissues, and especially in cancerous ones, these mechanisms are impaired. To make up for these violations, organic dyes can serve as generators of coherent radiation. Organic dyes mainly from this group are also capable of generating photons in a narrow range. The most important property of dyes is the extremely high cross-section of the maximum luminance enhancement, which is five orders of magnitude greater than that of the R-line of ruby (Stepanov B.I., Rubinov A.N. , 1968, May, pp. 45-50. Optical quantum generators based on solutions of organic dyes). Based on the universal optical and polarization properties, organic dyes with double N = N bonds were used to treat malignant tumors.

1. Naphthol dark blue (Naphthalene Blue Black) C ₂₂ H ₁₃ N ₆ O ₁₂ S ₃ Na ₃

2. Bismarck Brown mm 419.32 (Bismarck Brown Y) C ₁₈ H ₂₀ N ₈ Cl ₂

3. Sudan IV C24H20N4O 2,3-Dimethyl-4- (2-hydroxynaphthylazo) azobenzene.

4. Black acid (Acid Black 24) C36 H25 N5 06 S2 1 Naphthalenesulfonic acid, 8- (phenylamino) -5 - [(E) - [4 - [(E) - (5-sulfo-l-naphthalenyl) azo] - l-naphthalenyl] azo] -; 8-Anilino-5 - ((4 - ((5-sulfo-l-naphthyl) diazenyl) -l-naphthyl) diazenyl) -l-naphthalenesulfonic acid.

5. Sudan is navy. (Sudan Black B Blue-black)

6. Congo Ed. Mm 696.0 Congo red (synonym for Congorot) [disodium salt of 4,4'-bis- (1-amino-4-sulfo-2-naphthylazo) biphenyl].

7. Acid Blue 29. Amido Black 10B. C ₂₂ H ₁₄ N ₆ O ₉ S ₂ Na ₂ mm 616.516

Medicines obtained on the basis of these organic dyes can be taken orally in the form of a powder or tablets during or after meals, per rectum in the form of suppositories, externally in the form of suspensions and ointments, in sterile form they can be used intravenously and intramuscularly, as well as and inside the cavity introduction. Moreover, their administration in a wide range of dosages (from 10 mg to 2 g) does not cause allergic reactions and other side effects, and their effectiveness (in the treatment of relevant diseases) is higher than, for example, in a drug selected as a prototype.

Studies have shown that drugs in the form of these dyes have an antitumor effect, including against leukemia and lymphomas. This is confirmed by instrumental laboratory examinations by analyzing the blood of patients and measuring the size of the tumor before and after taking the appropriate preparations based on organic dyes.

Lanolin is used as the basis of ointments, cocoa butter is used as the basis of candles.

Dosage forms are obtained by methods traditional for the pharmacy using conventional carriers, solvents and other auxiliary ingredients. (I.A. Muravyov, “Technology of medicines.” - M., 1980, “Pharmacist's Handbook” under the editorship of A.I. Tenzova, M., 1981).

The results of studies of the mechanism of action of the proposed drug are given in examples No. 1-5, and the possibility of its effective use for treatment is confirmed by examples No. 6-21.

Example 1

Drugs diluted with 10 ^-5 mmol / L Bismarck Brown (drug A) were introduced into the culture medium on matrices with breast adenocarcinoma MCF-7. The control group - in test tubes with the same pool of cancer cells, Doxorubicin and Digoxin were introduced. After thermostating for 3 days at a temperature of 37 ° C, an analysis of proliferative activity was carried out.

Example 2

Drugs in a dilution of 10 ^-5 mmol / L Sudan dark blue (drug C) were introduced into the culture medium on matrices with melanoma. The control group - in test tubes with the same pool of cancer cells, Doxorubicin and Digoxin were introduced. After thermostating for 3 days at a temperature of 37 ° C, an analysis of proliferative activity was carried out.

The results obtained in examples 1,2 are shown in figure 1.

The graph shows that non-toxic drugs A and C inhibit the growth of breast adenocarcinoma MCF-7 and melanoma A374 in examples 1.2 in almost the same way as the very toxic drugs Doxorubicin and Digoxin.

Example 3

In the culture medium on matrices with the experimental group ACNH (human chemoresistant renal adenocarcinoma), the drug was introduced in a dilution with 10 ^-6 mmol / L naphthol dark blue No. 11. Control group — Doxorubicin, respectively, was introduced into test tubes with the same pool of cancer cells. On the chart, this is Positive Control (PC).

After thermostating for 3 days at a temperature of 37 ° C, an analysis of proliferative activity was carried out.

Example 4

A drug diluted with 10 ^-5 mmol / L Sudan IV was introduced into the culture medium on matrices with the experimental ACNH group (human chemoresistant renal adenocarcinoma). Control group — Doxorubicin, respectively, was introduced into test tubes with the same pool of cancer cells. On the chart, this is Positive Control (PC).

After thermostating for 3 days at a temperature of 37 ° C, an analysis of proliferative activity was carried out.

The results obtained in examples 3.4 are shown in figure 2.

In test tubes of the drug-injected groups of navythol dark blue No. 11 according to example No. 3 and Sudan IV according to example No. 4, the suppression of cancer cell proliferation is very pronounced and practically corresponds to “Doxorubicin”. The results obtained suggest that the proposed drugs help to suppress the proliferation of chemoresistant cells of kidney adenocarcinoma.

Example 5

Cells of the H69AR line (chemoresistant cells of human lung carcinoma) on plastic matrices were tested for cytotoxicity with respect to black acid (Acid Black 24) No. 6 at a dilution of 10 ^-7 mmol / L.

5 fluorouracil is presented as Positive Control (PC). After thermostating for 3 days at a temperature of 37 ° C, an analysis of proliferative activity was carried out.

Example 6

H69AR cells (chemoresistant cells of human lung carcinoma) on plastic matrices were tested for cytotoxicity against blue acid 29 (Amido black 10 V) No. 11 at a dilution of 10 ^-7 mmol / L.

5 fluorouracil is presented as Positive Control (PC). After thermostating for 3 days at a temperature of 37 ° C, an analysis of proliferative activity was carried out.

Example 7

H69AR cells (chemoresistant cells of human lung carcinoma) on plastic matrices were tested for cytotoxicity with Congo red No. 15 at a dilution of 10 ^-7 mmol / L.

5 fluorouracil is presented as Positive Control (PC). After thermostating for 3 days at a temperature of 37 ° C, an analysis of proliferative activity was carried out.

The results obtained in examples 5-7 are shown in figure 3.

The data obtained indicate that these organic dyes in low doses at a dilution of up to 10 ^-7 mmol / L, tested according to examples 5-7, cause a pronounced suppression of the proliferation of chemoresistant lung carcinoma cells, and can be used, for example, for the treatment of lung cancer .

Example 8

The drug Sudan IV (substance 2) in a dilution with 10 ^-6 mmol / L was introduced into the culture medium on matrices with the experimental group MCF-7. Control groups — Doxorubicin and Digoxin, respectively, were introduced into tubes with the same pool of cancer cells. After thermostating for 3 days at a temperature of 37 ° C, an analysis of proliferative activity was carried out.

Example 9

The drug Sudan IV (substance 3) at a dilution of 10 ^-7 mmol / L was introduced into the culture medium on matrices with the experimental group MCF-7. Control groups — Doxorubicin and Digoxin, respectively, were introduced into tubes with the same pool of cancer cells. After thermostating for 3 days at a temperature of 37 ° C, an analysis of proliferative activity was carried out.

The results obtained in examples 8.9 are shown in figure 4.

The graph shows that even with large dilutions up to 10 ^-7 mmol / L, Sudan IV dye inhibits the proliferation of cancer cells much better than Doxorubicin and Digoxin.

Example 10

Patient S. 62 years. Dz: Adenocarcinoma of the pancreas.

At the onset of the disease, I felt (repeatedly) abdominal pain after eating and slight weight loss. In the neck, above the collarbone enlarged l / nodes.

After visiting the surgeon, he was directed to magnetic resonance imaging of the abdominal cavity.

Conclusion: A picture of the volumetric formation of the pancreatic head region. Chronic pancreatitis.

He was sent to the oncology center for further examination.

A biopsy of the cervical lymph node was immediately performed.

Diagnosis - Susp.C-r of the pancreas, Mtz in the cervical lymph nodes.

Histological examination - Lymph node with Mtz of a low-grade malignant tumor, most likely of an epithelial nature, in a state of subtotal necrosis.

The result of the study: - the lymph node tissue is almost completely necrotic, only a narrow strip of tissue under the capsule is preserved. There is a group of large cells filling the marginal sinus. Cell nuclei are rounded with pedicular chromatin and 2-3 basophilic nucleoli. The cytoplasm is extensive and amphiphilic. Separate vacuoles contain mucus stained with MIC - positively. There are numerous figures of mitoses.

Histological results: tumor cells express papuntoceritin (MNF 116), EMA, CDX2, weakly express SK7. Expression of CK20, TTF-1, CK 5/6 mesothelin, PSA is negative.

Conclusion: Metastasis of low differentiated adenogenic cancer. The most likely source of metastasis is the pancreas.

P.S. The proliferative activity of tumor cells is about 70%.

After the studies, it was found that the patient has a blastoma of the pancreatic head with metastases in the left cervical lymph nodes.

Suggested treatment:

Megeis - 480 mg orally daily, for a long time.

Ftorafur - 800 mg (2 capsules) 2 times a day, daily, 3 weeks and then 3 weeks break.

After three weeks, the condition began to deteriorate sharply, and rapid weight loss also began from 95 to 72 kg. Pain - initially there was pain in the lumbar back ~ about 1.5 months, intensified in the last three weeks. Abdominal pain - occur before eating, i.e. after eating, the pain decreases. Pain in the liver appeared 3 days before the end of taking the first course of fluorofur. At the same time, the chair was slightly yellow in color - very light. He took painkillers occasionally - ketanol, but recently twice a day.

After taking the first course, fluorofura began to take an organic dye diluted in water: Bismarck Brown 200 mg three times a day 30 minutes before meals.

After 9 days from the start of treatment, the stool returned to normal and weakness decreased. After a week, the condition stabilized. Missing pain in the lower back and abdomen. A change in complexion was observed - the color became more vibrant. For 4 months, Bismarck Brown took at the beginning of treatment 200 mg in two weeks, 100 mg three times a day. After a month, a maintenance dose of 3 mg three times a day. Blood counts stabilized over 4 weeks.

After 4 months on ultrasound, the formation in the head of the pancreas decreased to 1 × 2.5 × 3 cm. Pain does not bother. Weight is stable. Control checks for 2 years did not reveal the activity of the process.

Example 11

Patient L. 58 years. Dz: Adenocarcinoma of the right ovary. Mts to the liver.

At the beginning of the disease appeared weakness and pain in the lower abdomen. After a visit to the gynecologist, she was sent for ultrasound of the abdominal cavity.

Conclusion: Volumetric formation of ovaries and liver. An operation was urgently done: hysterectomy with the right appendage.

The diagnosis of histological ovarian adenocarcinoma.

The treatment: polychemotherapy.

After six months, the condition began to deteriorate sharply, and also began rapid weight loss from 67 to 54 kg. There were pains in the lower abdomen and right hypochondrium.

From 12/29. 2002, i.e. after taking the first course of adriomycin, Naphthol Navy Blue (Naphthalene Blue Black) began to be taken, diluted in water: 300 mg, three times a day 30 minutes before meals.

After 3 days of admission, the stool returned to normal and weakness decreased. After a week, the condition stabilized. Abdominal pain is gone. After 3 weeks from the start of treatment, the dose of the drug was reduced to 100 mg, and after another two weeks to 5 mg per dose. For 6 months I took the proposed dyes with short interruptions. Blood counts stabilized over 5 weeks.

After 6 months on ultrasound, the formation in the liver decreased to 1.3 × 1.2 × 1.0 cm. Pain does not bother. Weight is stable. Control checks for 5 years did not reveal any changes.

Example 12

Patient H., 64 years old. Diagnosis: Cancer of the bladder. MTS in the pelvic bone. Two years ago, a bladder resection was performed for cancer. At the time of treatment, complaints of pain, bloody urine and frequent urination. On CT at the mouth of the projection of the right ureter, a tumor formation of 2 × 3 × 3 cm in the mouth of the left 2 × 2 × 1 cm. In the wing of the left iliac bone there are 3 tumor formations with uneven contours, with a diameter of 1.3 to 1.5 cm. severity, pallor of the skin, blood in the urine. Treatment with the drug has been started according to the scheme of 40 drops of Sudan IV-1% solution in half a glass of water through the mouth and in the form of a 3% solution of 20 drops at a time for microclyster. The course lasted 4 months. During treatment, the tumor decreased in size to 0.1 × 0.1 × 0.1 cm. Metastases in the pelvic bone decreased by 40%. In the second week from the start of treatment, bleeding and pain decreased. Three weeks after the start of treatment, the dose of the drug was reduced to 4 drops of 1% solution at a time. The number of drops of a 3% solution for microclysters was also reduced to 2 drops per reception. Blood tests during treatment returned to normal at 4 weeks. Conducted a full course of treatment with the drug for 6 months. During therapy, a tumor in the bladder and metastases in the pelvis disappeared. Weight restored.

Example 13

Patient G. 32 years. Diagnosis: clear cell cancer of the left kidney. Three years ago, the left kidney was removed and preventive chemotherapy was performed. When examining on CT in the projection of the left kidney, the tumor formation is 3.5 × 5.4 × 3.7 cm, as well as four tumor-like circular formations with a diameter of 2.0 to 2.3 cm in the left lung. The condition is severe dyspnea, cyanosis, ascites, adynamia. Treatment has been prescribed, including the use of an antitumor drug. The drug Acid black (Acid Black 24) was administered through the mouth in the form of a drink, 30 drops of a 1% solution three times a day and in the form of microclysters. After 4 weeks of treatment, shortness of breath and pain decreased. Blood tests during treatment returned to normal within 3 months. Then, a second course of the drug was carried out, which was administered at night into the rectum in the form of 1% suppositories, and inhaled 7 drops of 1% solution per 10 ml of distilled water once a day for 6 months. During therapy, the tumor in the right kidney and metastases in the lungs disappeared. The phenomena of ascites disappeared in the third week from the start of treatment. Weight restored. Blood and urine tests are normal.

Example 14

Patient F., 22 years old. Diagnosis: Acute myeloid leukemia. According to the patient, there were a lot of white blood cells, few red blood cells and platelets. In addition, many white blood cells were blast cells. A bone marrow examination confirmed the diagnosis. Therefore, four years ago chemotherapy was performed for acute leukemia. A year later, a relapse occurred. Complaints of fever, weakness, and nausea. Blood tests at the beginning of treatment: red blood cells 2.8, white blood cells 20 thousand, platelets 60 thousand. The state of moderate severity, pallor of the skin, an increase in cervical lymph nodes. The treatment with the Congo mouth preparation was started according to the scheme of 20 drops of a 1% solution per half a glass of water through the mouth and in the form of microclysters. The drug was also administered intravenously at 100 mg twice a week. The course lasted 3 months. During treatment, lymph nodes are not determined, no complaints. Bone marrow puncture showed the absence of immature forms. Blood tests during treatment returned to normal within 2 months. Conducted a full course of treatment with the drug for 6 months. During therapy, the weight is restored. There are no complaints.

Example 15

Patient V., 44 years old. Diagnosis: Astrocytoma of the brain on the right. Relapse. A year and a half ago, a tumor was extirpated due to brain astrocytoma. When handling complaints of headaches, dizziness, nausea, vomiting. On an MRI of the right frontotoparietal region, a tumor with irregular edges of 3.5 × 2.4 cm is determined. The condition is moderate, pallor of the skin. Facial asymmetry is noted. The patient is prescribed Sudan dark blue 250 mg per 500 ml of physiological saline in sterile form intravenously. Procedure for 60 minutes. Subsequent procedures were carried out in exactly the same sequence 3 times a week. The course lasted 5 months. During treatment, the tumor decreased in size to 1.3 × 2.5 cm. After two infusions of drugs, nausea and pain decreased, the asymmetry of the face disappeared. In the following months, a single injection of the drug was carried out every three weeks. On CT after 12 months of treatment, the tumor is not detected.

Example 16

Patient S. 51 years old. Diagnosis: Multiforme glioblastoma of the brain on the right. Relapse. Two years ago, the tumor was extirpated due to glioblastoma of the brain. Complaints of headaches, nausea, vomiting. On an MRI in the projection of the p / operative scar in the substance of the brain, a tumor with uneven edges of 2.7 × 3.5 cm is determined. The condition is moderate, pallor of the skin. The patient was prescribed Acid Blue black 100 mg per 500 ml of physiological saline in sterile form intravenously. Procedure for 60 minutes. Subsequent procedures were carried out in exactly the same sequence 2 times a week. The course lasted 3 months. During treatment, the tumor decreased in size to 0.18 × 0.21 cm. After two infusions of drugs, nausea and pain decreased. For 6 months, a single injection of the drug was carried out every two weeks. On CT after 14 months of treatment, the tumor is not detected.

Example 17

Patient M., 62 years old. Diagnosis: Primary liver cancer. 4 years ago, a portion of the right lobe of the liver with a tumor was resected for hepatoma. Complaints of pain in the right hypochondrium, shortness of breath, ascites, periodic stool retention. The state of moderate severity, low nutrition, yellowness of the skin. An ultrasound scan identifies a tumor in the left lobe of the liver with uneven edges 4 × 5 cm. The patient underwent umbilical vein surgery. For two weeks, twice a day, a sterile preparation Sudan, dark blue, 2 g, dissolved in 100 ml of physiological saline, was introduced into the catheter. Subsequent procedures were carried out in exactly the same sequence 2 times a week. Only the drug was administered intravenously. The course lasted 3 months. During treatment, the tumor in the region decreased in size to 0.5 × 0.7 cm. After 4 months, a connective tissue scar of 0.4 × 0.3 cm remained at the tumor site in the liver. During treatment with the drug, a positive trend was observed in the analyzes blood.

General blood test results The main 11/12/02 01/19/03 05/14/03 04/17/05 Indicators Red blood cells 3.43 3.65 4.43 4.78 Hemoglobin 72 83 116 125 Platelets 130 343 265 410 White blood cells 11.3 7.9 6.8 6.0 Basophils 0-1% 2 one 0 one Eosinophils 0-5 2 one 2 3 Pal. nuclear 1-6% 7 3 2 four Segm. nuclear 45-70 23 43 56 65 Lymphocytes 18-40% 10 12 eighteen 34 Monocytes 2-9% 5 12 3 four ESR 1-15 mmh 34 23 5,0 7

Results of biochemical blood tests Main characteristics Sod. fine 11/12/02 01/19/03 05/14/03 04/17/05 Total protein 63.0- 45.49 65.90 68 75.64 Creatinine 85.0 78.0 93 99 67 Urea 44-110 7.1 6.5 4.6 2.5 Cholesterol 1.66-8.3 6.23 5.23 4.75 6.03 Common bilirubin 2.90-6.54 13.0 23.21 8.42 8.24 Bilirubin 8.5-20.5 13.0 21.3 14.3 12.0 straight before 6.0 12.9 15.1 16,0 Bilirubin 25% 92 91 81 70 indirect up to 25% 106.21 105 109 98.0 Amylase up to 100 ate 114.0 141 142.8 144.0 Chlorine 95-110.0 4.20 4.3 4.31 4.2 Sodium 135.0- 3.8 1.9 1.8 1,2 Potassium 147.0 2.72 2,31 2.12 2.45 Calcium ionizir. 3,5-6,0 19.0 17.4 28.0 27.7 Total calcium 0.98-1.30 431.3 495.8 238.4 164.4 Iron syv. 2.1-2.55 191.4 124.71 54,4 23.72 ACT 8.8-27.0 532.5 334.34 101.8 43,2 ALT 5-40 ate 765.8 324 454.2 448.1 Phosphatase slit. 5-40 ate LDH up to 104 Ate 225-450 Ate

No complaints at this time.

Example 18

Patient S. 55 years. Dz: Hodgkin's lymphoma. Cachexia. 3.5 years ago, a full course of polychemotherapy was performed for enlarged cervical lymph nodes. Six months ago, tumor-like formations appeared on the neck (4 × 10 cm) and under the jaw (2 × 3 cm). An X-ray revealed an expansion of the mediastinum. At the time of treatment, complaints of shortness of breath, weakness, sweating. The state of moderate severity, low nutrition, pale skin. In the submandibular region on the left, a tumor formation of 2 × 4 cm. On both sides of the neck, tumor formations of 4 × 13 cm and 5 × 14 cm. Congo red treatment was carried out according to the scheme: 50 drops, a 1% dye solution dissolved in 150 ml of water was taken through the mouth three times a day. The course lasted 4 months. After 20 days from the start of treatment, the patient completely reduced submandibular lymph nodes. Within a month, tumors in the neck area decreased in size to 3.2 × 4.3 cm. After 3 months, no lymph nodes were detected. Blood and urine tests are normal. Weight restored. There are no complaints.

Example 19

Patient J. 47 years. Dz: Mesothelioma of the pleura of the right lung. The patient has shortness of breath, excruciating cough and pain in the right lung. From the anamnesis it is known that 2.5 years ago the patient developed a dry cough. After computed tomography, the diagnosis was established: Exudative pleurisy of the right lung. However, antibiotic therapy did not give a positive result. A puncture and cytology of exudate were performed, as well as a fragment of the pleura. Based on cytology and histology, a diagnosis of parietal pleural mesothelioma was made. The patient underwent a full course of chemotherapy. Improvement temporarily came, but the growth of the neoplasm continued. Six months ago, tumor-like formations appeared on the neck and under the jaw. CT scan revealed an expansion of the tumor area and an increase in the amount of exudate. At the time of treatment, complaints of shortness of breath, chest pain, weakness and sweating. The state of moderate severity, low nutrition, pale skin. The treatment with Acid Black 24 was started according to the scheme: 50 drops of a 1% dye solution dissolved in 150 ml of water was taken by mouth three times a day and daily dye inhalations of 3-4 drops per 10 ml of distilled water. The course lasted 2 months. After 10 days from the start of treatment, the patient completely disappeared pain. Within a month, shortness of breath and coughing passed. Submandibular l / nodes disappeared at 3 weeks from the start of treatment. After 2 months from the start of treatment, a control CT scan was performed with contrast. The pleura on the right is slightly thickened, there is no exudate. Blood and urine tests are normal. Weight restored. There are no complaints.

Example 20

Patient G. 51 years. Dz: non-Hodgkin lymphoma. Cachexia. 4 years ago, the cervical lymph nodes suddenly enlarged and shortness of breath appeared. A full course of chemotherapy was carried out. Lymph nodes decreased. However, six months ago, tumor-like formations appeared on the neck and under the jaw. An X-ray revealed an expansion of the mediastinum. At the time of treatment of complaints of shortness of breath, sweating weakness. The state of moderate severity, low nutrition, pale skin. In the submandibular region on the left, a tumor formation of 3 × 2.8 cm. On the neck on both sides, tumor formation of 3 × 2, 4 × 3 cm. Treatment with the preparation of acid blue 29 (Amido Black 10B) was carried out according to the scheme of 50 drops 1% dye solution, dissolved in 150 ml of water, was taken by mouth three times a day. The course lasted 4 months. After 12 days from the start of treatment, the patient's submandibular lymph nodes completely disappeared. Within a month, tumors in the neck area decreased in size to 0.1 × 0.25 cm. After 4 months, no lymph nodes were detected. Blood and urine tests were normal. Weight restored. There are no complaints.

Example 21

Patient T., 49 years old. Dz: Adenocarcinoma of the colon. MTS to the liver. Ascites. 3 years ago, a large bowel resection was performed with an end-to-end anastomosis. He completed a full course of chemotherapy. 1.5 years after treatment, pain appeared in the lower abdomen, tenesmus. At the time of treatment, she complains of severe weakness, constant abdominal pain, cough, shortness of breath, ascites, and stool retention. The condition is serious, of poor nutrition, the skin is pale with a cyanotic tinge, the abdomen with signs of ascites. In blood tests, there is a decrease in the number of red blood cells, hemoglobin, white blood cells, albumin, an increase in ALT and ACT. On computed tomography in the right lobe of the liver, 2 neoplasms of irregular shape 3 × 4 cm and 4 × 5 with uneven edges are determined. In the area of the anastomosis, a volumetric formation of 4 × 5.4 cm and free fluid in the abdominal cavity are determined. The patient is prescribed a drug in the form of intravenous infusions, microclysters and drinking. The infusion solution is 200 mg of sterilized Naftol dark blue dissolved in 500 ml of physiological saline. Infusions were carried out weekly for 3 months. Enema is a mixture of 20 grams of Naftol dark blue and Bismarck Brown in 1500 ml of boiled water. Enema was taken three times a week for 2 months. To enhance therapy, the drug was taken by mouth in the form of a 1% solution in 200 ml of boiled water 20 minutes before meals three times a day. After 10 days from the start of treatment, the patient completely disappeared pain and appetite. In the third week of treatment, shortness of breath decreased. During treatment, the tumor in the anastomotic area decreased in size to 0.2 × 0.3 cm. After 3 months, a month break was made and then the treatment continued for 2 months. During treatment, metastases in the liver and tumor in the area of the anastomosis are not determined. Marked gradual improvement in blood counts is noted, which is directly related to drug treatment.

Blood test results DOS indicators 10/10/05 11/24/05 12/09/05 01/09/06 Red blood cells 2.81 3.84 4.43 4.23 Hemoglobin 72 114 114 124 Platelets 120 210 226 345 White blood cells 14.2 11.0 6.2 5.5 Basophils 0-1% one - - one Eosinophils 0-5 one 2 2 one Pal. nuclear 1-6% 0 3 2 2 Segm. nuclear 45-70 28 64 62 70 Lymphocytes 18-40% eleven 24 32 39 Monocytes 2-9% 10 3.2 5.3 7.9 ESR 1-15 mmh 34 5 23 12

Results of biochemical blood tests DOS indicators Sod. fine 10/09/05 11/24/05 12/09/05 01/09/06 Total protein 65.0- 51.34 61.23 70.56 87.98 Creatinine 85.0 hl 112.0 99 54 64 Urea 44-110 8.9 7.1 3,7 8.9 Cholesterol 1.66-8.3 7.21 7.62 6.74 7.43 Common bilirubin 2.90-6.54 19.44 14.9 9.42 8.33 Bilirubin 8.5-20.5 12.0 32,3 31.3 12,4 straight up to 25% 18.0 14.9 15.4 16.78 Bilirubin up to 25% 95 93 54 91 indirect up to 100 ate 107,2 104 109 118.0 Amylase 95-110.0 144.0 144 143.8 144.9 Chlorine 135.0- 4.20 5.3 4.33 4.2 Sodium 147.0 3.8 1.9 1.8 1.32 Potassium 3,5-6,0 2,32 2.12 2.18 2.25 Calcium ionization. 0.98-1.30 12,4 13.3 18.1 17.1 Total calcium 2.1-2.55 313.1 325.8 238.8 44,4 Iron syv. well 8.8-27.0 490.4 404.7 254.8 42.9 ACT 5-40 ate 265.7 245.8 145.7 39.5 ALT 5-40 ate Phosphatase slit. up to 104 Ate

There are no complaints for 2 years. No tumors were detected in control images. There are no relapses. Weight restored.

Thus, drugs were found that have a wide range of therapeutic effects in relation to various oncological diseases and do not have side effects.

At the same time, effective, widely available and inexpensive substances that are not toxic and do not cause side effects when used in pharmaceutically acceptable doses are used as a means for treating cancer, treatment periods are shortened, and treatment efficiency is increased.

Claims (7)

1. The use of organic dyes having in the formula a double N = N bond and a molecular weight of 400-900 from the group: Sudan dark blue, Congo red, Naphthol dark blue, Sudan IV, Bismarck Brown, black acid and blue acid, as a means for the treatment of cancer, with a single dosage of 0.1 mg to 2 g per dose up to 3 times a day. 2. The use according to claim 1, characterized in that the tool is used in dilution from 10 ^-5 to 10 ^-7 mmol / l in the form of an aqueous solution or physiological solution. 3. The use according to any one of claims 1 and 2, characterized in that the aqueous solution is administered rectally. 4. The use according to any one of claims 1 and 2, characterized in that a 1-3% solution of the drug is administered intravenously. 5. The use according to any one of paragraphs.1 and 2, characterized in that a 1% solution of the drug is administered by inhalation. 6. The use according to any one of claims 1 and 2, characterized in that apply 1-5% ointment based on the funds. 7. The use according to any one of claims 1 and 2, characterized in that the agent is administered rectally in the form of suppositories.

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