RU2354369C2 - Application of rhodamine 6g as medication for treatment of malignant neoplasms and amyloidoses - Google Patents

Abstract

FIELD: pharmacology.

SUBSTANCE: claimed invention relates to field of medications, in particular, to application of Rhodamine 6G in form of 9-(2-etoxycarbonyl)phenyl)-3,6-bis(ethylamino)2,7-dimegylxantyl chloride with chemical formula C₂₈H₃₁N₂O₃CI as medication for amyloidoses treatment.

EFFECT: describes Rhodamine 6G application with novel purpose.

5 cl, 4 tbl, 17 ex

Description

The invention relates to medicine, namely to medicines used to treat amyloidosis and cancer.

The known drug “Fluorouracil”, which is a white or slightly yellowish, slightly soluble in water and alcohol crystalline powder, is an antimetabolite, the antitumor activity of which is determined by its conversion in cancer cells into a competitive inhibitor of the enzyme involved in the synthesis of nucleic acids (Mashkovsky M.D. Medicines, Moscow, New Wave LLC, Publisher SB Divov, 2002, v.2, p.425).

This drug by intravenous injection is used for inoperable and recurrent cancer of the stomach, cancer of the colon and rectum, breast, ovaries, and pancreas, however, the drug has high toxicity and when it is used, inhibition of hematopoiesis, diarrhea, loss of appetite, and vomiting may occur. ulcerative stomatitis. In addition, this drug is contraindicated in the general serious condition of the patient, gastric ulcer and duodenal ulcer, severe functional liver failure.

Known drug melphalan used to treat amyloidosis. At the same time, intermittent schemes are used to treat amyloidosis, since melphalan is a toxic drug and, among the long-term consequences of its use, the development of a second tumor (acute leukemia) or myelodysplastic syndrome is possible. A more gentle regimen is the use of melphalan every 4-6 weeks, in 7-day courses (0.15 mg / kg body weight) in combination with prednisone (0.8 mg / kg body weight). The treatment is long, at least 1 year. The treatment results are worse in patients with chronic heart failure (CHF) and significantly better in patients with nephrotic syndrome. So, in patients who responded to treatment, the life expectancy may be 5 years.

Also known is the drug "Colchicine" for the treatment of amyloidosis. However, the drug has very pronounced side effects, and it does not have a sufficient therapeutic effect (see Internet, website www.bsmu.by A.E. Makarevich et al. Cardiac amyloidosis: pathomorphology, clinic, diagnosis, differential diagnosis, treatment. Belarusian State Medical University, 10th clinical hospital in Minsk).

Doxorubicin (an antitumor antibiotic) - one of the most effective known anticancer drugs ceases to act at 10 ^-7 mmol / L. Its LD 50 (half lethal dose) is 13-15 mg / kg, which corresponds to substances with very high toxicity (Internet, website http://medvrach.ru/).

Closest to the claimed purpose and action is a drug with antitumor and immunomodulatory effects, characterized in that it contains pharmacologically acceptable derivatives of tri-n-aminotripenylchloromethane, for example, its tetramethyl, pentamethyl and hexamethyl derivatives (RU No. 2257200, 2004, prototype) .

The disadvantages of this drug are the short duration, low efficacy in the treatment of a number of tumors, low efficacy in the treatment of amyloidosis and relative toxicity.

It is known that Rhodamine 6G is used as a red dye, which is used for dyeing leather, paper, soap, as an analytical reagent for determining a number of metals, and in medicine and biology as a dye for microscopy (TU 6-09-2463-82).

It is known to use Rhodamine as an auxiliary component of a seed dressing composition (RU No. 2282961, 2006).

The objective of the invention is to find an affordable and inexpensive drug with a wide range of therapeutic effects.

The technical result, which provides a solution to the problem, consists in creating a drug with a wide range of applications for cancer and amyloidosis, reducing toxicity and side effects when used in pharmaceutically acceptable doses, reducing doses and treatment time, increasing the effectiveness of treatment.

The invention consists in the use of Rhodamine 6G in the form of 9- (2-ethoxycarbonyl) phenyl) -3,6-bis (ethylamino) 2,7-dimethylxanthyl chloride having the chemical formula C ₂₈ H ₃₁ N ₂ O ₃ .Cl as funds for the treatment of malignant neoplasms and amyloidosis with a dosage of 1 mg to 2 g.

As a tool for the treatment of malignant neoplasms and amyloidosis, Rhodamine 6G (equivalently, Rhodamine 6G) can be used as a solution in water, or in physiological saline, or in alcohol. In various applications, Rhodamine 6G solution is taken orally before or after a meal, or Rhodamine 6G solution is administered rectally, or 1% Rhodamine 6G solution is administered intravenously, or Rhodamine 6G is used rectally as a suppository, or Rhodamine 6G is used as a part of 1-5% ointment .

The prerequisites for the action of Rhodamine 6G on pathologically altered cell structures are associated with its structural formula.

Hydrogen atoms in the cyclic part of Rhodamine 6G are replaced by C ₂ H ₅ groups, which significantly affects the physicochemical properties, in particular, the absorption capacity of the substance and the spectral arrangement of the bands. Dye molecules have a flat skeleton, only some groups of radicals (in this case, C ₂ H ₅ ) go out of the general plane (Journal of Uspekhi Fizicheskikh Nauk. 1968, May, Volume 95, no. 1, pp. 45-50, Stepanov B.I. et al. Optical quantum generators based on dye solutions). The C ₂ H ₅ group, due to the fact that it “sticks out” from the flat Rhodamine 6G molecule, also affects the orientation of the dye molecule oscillators in living tissue, which is an aperiodic liquid crystal or a quasicrystalline (anisotropic) solution. (The journal "Quantum Electronics", No. 6 (2000), p.30, Kulik L.G., Chernyavsky V.A., Mushroom A.F.) The mechanism of action of Rhodamine 6G is based precisely on these properties. At the same time, the C ₂ H ₅ group radically changes the structure of the dye and its physicochemical properties, including fluorescence, absorption, spontaneous emission and photon generation, enhances the suppression of the metabolism and proliferation of melanoma cells, carcinoma, clear cell cancer, adenocarcinoma, etc. . in vitro and ex vivo (i.e. in humans).

In pathologically altered cells and tissues, to one degree or another, light polarization and anisotropy are disturbed. With cancer and amyloidosis, in addition to this, an incorrect (right) spatial folding of proteins occurs, i.e. normal dissymmetry is disturbed and, as a result, spontaneous luminescence of cells is present in a narrow range. The photoactivity of protein structures in the vital functions of cells plays one of the key roles. Many biochemical reactions and mitosis of cells are accompanied by photochemical reactions, which can be described as quantum-mechanical phenomena. The impact on these mechanisms is a prerequisite for the treatment of cancer and other diseases (See the book “Cancer can be cured,” MV Kutushov, ed. V. Sekachev, Moscow, 2005, p. 393). With this effect, fast folding (spatial folding) of proteins occurs due to the quantum mechanism using oscillators (quantum generators). Oscillators can be represented as clusters of certain metals, nanocrystals, protein fragments, or secondary protein structures (see Internet, website: www.kutushov.com.). As is known from physics, the magnitude of the limiting polarization is related to the symmetry of the molecule. With cancerous and amyloid degeneration of cellular structures, the connection of oscillators with protein molecules 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. All this leads to improper folding (spatial packing) of proteins, this in turn leads to the appearance of prion diseases, amyloidosis or cancerous cell degeneration. Thus, if we introduce an acceptable dye into such a system, then, as shown below, it should “equalize” the degree of polarization, restore impaired anisotropy and protein folding. Organic dyes not only perceive photons, but to one extent 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 and amyloidosis, cellular and tissue structures are disturbed due to the right amino acids and proteins. As a result, the resonating properties of tissues and cells change, which leads to the accumulation of amyloid in the cells of the brain, heart, liver, kidneys during amyloidosis, and in cancer - to uncontrolled growth of right proteins and unlimited cell division.

Some dyes exhibit spontaneous emission (photon generation) in the same narrow range as normal proteins. They are able to temporarily play the role of oscillators (quantum generators) and restore protein folding. At the same time, dyes have a high absorption capacity in the visible region of the spectrum. Therefore, dyes, interacting with such structures, return to them the original narrow absorption spectra or otherwise the so-called equidistant properties. The most important property of Rhodamine 6G is its ability to focus light with the highest efficiency better than other organic dyes. Rhodamine 6G has the highest generation in the visible part of the spectrum, its quantum yield is 98% (see Optical generators based on solutions of organic dyes. B.I. Stepanov and others). Rhodamine 6G, possessing the property of a generator, “pumps” anisotropy into cancer cells. This is because, since the “pump” light is linearly polarized, this leads to forced absorption anisotropy and amplification of the excited region of the solution (in our case, cell protoplasm). As a result of this, the generation condition is satisfied only for one polarization of the radiation generated by the dye, which turns out to be linearly polarized. The degree of polarization is usually close to unity. For Rhodamine 6G, the degree of polarization upon excitation of 374 nm is -0.9, and in the case of a wavelength of 530 nm, it is +1. Rhodamine 6G also has a minimum energy generation threshold (250 J), which is very suitable for biological systems that operate at similar energy levels.

As is known, in symmetric and asymmetric dyes having a symmetry higher than the second order, the limiting polarization practically does not change when the wavelength of the excited light changes within the long-wavelength absorption band. The most important property of dyes is the extremely high cross section for the maximum luminescence amplification, which is five orders of magnitude greater than the R-line of ruby (see the above Optical generators based on solutions of organic dyes. B.I. Stepanov and others).

Aqueous solutions of Rhodamine 6G are characterized by significant fluorescence due to the stiffening of oxygen bridges in the molecule. Rhodamine 6G absorbs quite intensively in the visible and ultraviolet (UV) spectral regions and is characterized by a molecular type of luminescence. Rhodamine 6G possesses the most pronounced property of concentrating photons in a very narrow range, which determined its use in laser technologies. An essential feature is that organic dyes fluoresce in an extremely wide frequency range of the visible spectrum, as opposed to the very narrow fluorescence band of a typical solid-state laser. Light in organic dyes, like dielectric materials, can propagate at a speed much higher than the speed of electrons in a conductor. In addition, photons do not interact as strongly as electrons, thereby reducing energy loss. The use of Rhodamine 6G is typical for many systems; this is due to its high conversion efficiency (approximately 20%) and a wide spectral range of tuning ("Dye Lasers" Internet, www. laserphysics. narod.ru). In normal tissues, spontaneous luminescence in a narrow range is provided due to the photoactivity of protein molecules at the time of phase transitions. With cancer and amyloidosis, the folding of protein molecules occurs, which leads to a violation of the range of absorption and emission spectra, as well as anisotropy and polarization of the molecules. Coherent radiation generated by Rhodamine 6G in a narrow range can restore the anisotropy and polarization of molecules. It is known that in the cellular structures of the substance are in a semi-liquid (suspension, gel, sol) state, i.e. these are essentially liquid smectic, nematic, cholesteric and other crystals. In such systems, all processes occur in waves. The periodic distribution of the refractive index inside the crystal leads to the appearance of a forbidden band — a region of frequencies at which radiation cannot propagate through the crystal. Using a liquid with a high refractive index (in the experiment we used water tinted with the organic dye Rhodamine 6G), it was possible to create an allowed state inside the forbidden zone. Those. a large refractive index affects the structure of cells. When they are in an anisotropic state, this dye does not affect the refraction. T.O. it does not affect healthy cells, as they are anisotropic. In the case of isotropy, it acts as a “lens”, creating forbidden zones or an allowed state inside them, thereby forming refraction, collecting scattered photons and thereby returning anisotropy to cancer cells. Most likely, this mechanism underlies the therapeutic effect of Rhodamine 6G. To implement such a mechanism, the xanthem dye Rhodamine 6G was used, capable of generating and self-generating photons of the desired wavelength. This property, like no other dye, meets all the requirements for dyes used in the treatment of cancer and amyloidosis. Moreover, its LD50 (half lethal dose) is 400 mg / kg, which makes it a substance with low toxicity.

Studies have shown that Rhodamine 6G as a medicine "OF7" has an antitumor effect, even against extremely malignant metastatic melanoma. This was confirmed in experiments with cells of metastatic human melanoma. Rhodamine 6G inhibits the proliferation and metabolism of cancer cells even at a dose of 10 ^-7 mmol / L. Doxorubicin - one of the most effective anticancer drugs ceases to act at 10 ^-7 mmol / L. It should be noted that its LD 50 (half lethal dose) is 13-15 mg / kg, which corresponds to substances with very high toxicity.

A drug based on Rhodamine 6G can be taken orally in the form of solutions, powder during or after meals, per rectum in the form of solutions, suppositories, externally in the form of suspensions and ointments, intravenous and cavity infusions. Moreover, its use in a wide range of dosages (from 0.01 mg to 20 g) does not cause allergic reactions and other side effects, and its effectiveness (in the treatment of relevant diseases) is higher than, for example, in drugs selected as a prototype.

Rhodamine 6G with the chemical formula C ₂₈ H ₃₁ N ₂ O ₃ .Cl is used as the OF7 medicine for the treatment of malignant neoplasms and amyloidoses with a dosage of 1 mg to 10 g, in the form of a solution in water or in physiological saline or in alcohol . In various applications, Rhodamine 6G solution is taken orally before or after meals, or Rhodamine 6G solution is administered rectally or 1% Rhodamine 6G solution is administered intravenously, or Rhodamine 6G is used rectally as a suppository, or Rhodamine 6G is used as a part of 1-5% ointment.

The results of studies of the mechanism of action of the proposed drug are given in examples No. 1-5, and the effectiveness and possibility of its use for treatment is confirmed by examples No. 6-17.

Example 1

In the test tubes of the experimental group with cancer cells A375 (metastatic human melanoma) in a buffer solution (10 ml), the drug Rhodamine 6G was introduced in a dilution of 10 ^-11 mmol / L in the form of a solution.

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

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 temperature control for 3 days at a temperature of 37 ° C, the analysis of the contents of the above tubes was carried out.

A review of the results showed:

In test tubes of the experimental group with the test drug, the mitochondrial membranes are almost completely destroyed, and the picture is approximately the same for all variants of the used drug, in tubes with the drug Doxorubicin, membranes swell with partial (about 60%) destruction, and in cells in the test tube with saline, no changes detected.

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

The data obtained indicate that the proposed drug causes destruction of the mitochondrial membrane of cancer cells, but does not change the structure of normal cells or, in other words, the drug enhances the ability of the mitochondria of cells to produce enzymes that cause cancer cell apoptosis.

Example 2

In 4 test tubes of the experimental group with cancer cells MCF-7 (breast adenocarcinoma) in a buffer solution (10 ml), the drug Rhodamine 6G was introduced in a dilution of 10 ^-9 mmol / L in the form of a solution.

The control group - in tubes with the same pool of cancer cells, respectively, were introduced into one physiological solution, and Fluorouracil in other drugs.

In test tubes of both groups, titers of cytochrome-C were determined, which amounted to 1: 14000.

After incubation during the day at a temperature of 37 ° C, the analysis of the contents of the above test tubes.

A review of the results showed:

In test tubes of the test group with the drug administered, the titer of cytochrome-C for the tube with Rodamine 6G was 1: 2000.

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

The obtained results suggest that the proposed drug promotes the release of the “aggressive” protein cytochrome-C from the mitochondrial membrane of cancer cells, which, by triggering the mechanism of DNA destruction, causes apoptosis of cancer cells.

Example 3

In a test tube (10 ml) with transthyretin (protein) in blood plasma (pH 7.0), a concentration of 0.05 mmol / ml, 4 drops of a 0.1% aqueous solution of Rhodamine 6G were added.

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

After 15 minutes, the concentration of transthyretin and the measurement of plasma pH were measured.

Transthyretin is not determined, pH 6.0.

It follows that this drug does not act on protein denaturation 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, for example, amyloidosis.

Example 4

The blood of the patient with amyloidosis (10 ml) is centrifuged.

Part of the obtained plasma is dried and photographed under a polarizing microscope. An aqueous solution of Rhodamine 6G was introduced into another part of the same plasma, and the resulting mixture was also photographed under a polarizing microscope.

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

These data suggest that this drug returns protein folding altered in cancer to normal.

Example 5

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

Then, Rodamine 6G solution was added to this filtrate and repeated spectrophotometry was performed.

Results: in the images without the drug, the absorption spectrum is in the region of 279 nm, and the emission is in the region of 416 nm, in the images after the administration of the drug, the absorption spectrum shifts the far part of the UV radiation to 280 nm and luminescence to 420 nm, respectively. It is known from the literature that a shift of 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 violated in the serum of cancer patients, because normally, the absorption and emission band of protein structures is 280 and 420 nm, respectively. Secondly, the regulatory effect of the drug on structural changes in the proteins of cancer cells is clearly shown.

Treatment examples

Example 6

Patient V., 73 years old. Diagnosis: Amyloidosis. Inhibited, inadequate. On CT of the brain, degenerative changes and foci of the type of amyloidosis are noted. Treatment was prescribed, including the use of a drug based on Rhodamine 6G. The first course of treatment with the drug is 15 drops of 1% solution in a glass of water three times a day by mouth, in the afternoon an additional microclyster of 10 drops of 1% solution in 30 ml of water and at night 1% candle with the drug. Within a week - the condition is basically unchanged, however, the patient noted that after the sessions, a decrease in drowsiness was observed for several hours. In the third week after the start of treatment, the patient's condition improved. According to relatives, it became more adequate. Three months after the start of treatment with the drug on CG, a decrease in amyloid foci in the brain is observed. After a year of treatment, the condition improved significantly, became adequate, amnesia partially disappeared. Blood tests during treatment returned to normal.

Example 7

Patient L., 43 years old.

Three years ago, the left kidney was removed and preventive chemotherapy for clear cell cancer 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. Severe condition: shortness of breath, cyanosis, adynamia. Treatment has been prescribed, including the use of an antitumor drug. The drug Rhodamine 6G was administered through the mouth in the form of a drink, 12 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 injected into the rectum in the form of 1% suppositories and inhaled for 6 months. During therapy, the tumor in the right kidney and metastases in the lungs disappeared. Weight restored.

Example 8

Patient T., 54 years old. Diagnosis: Adenocarcinoma of the right ovary. MTS to the liver. Four years ago, the uterus was extirpated with appendages. A year later, a relapse occurred. Complaints of pain in the pelvis, impaired urination. On a CT scan, between the bladder and the rectum, a tumor formation of 4 × 5 × 4 cm is determined. The condition is moderate, pallor of the skin.

Treatment with the drug has been started according to the scheme of 20 drops of 1% Rhodamine 6G solution in half a glass of water through the mouth and in the form of microclysters. The course lasted 3 months. During treatment, the tumor decreased in size to 1.2 × 0.9 × 0.3 cm. In the second week from the start of treatment, stool returned to normal and pain disappeared. Blood tests during treatment returned to normal within 2 months. Conducted a full course of treatment with the drug for 6 months. During therapy, a tumor in the bladder and rectum disappeared. Weight restored.

Example 9

Patient G., 43 years old. Diagnosis: Multiforme glioblastoma of the brain on the left. Relapse. Two years ago, the tumor was extirpated due to glioblastoma of the brain. Complaints of headaches, nausea, vomiting. On NMR (nuclear magnetic resonance imaging) in the projection of the p / operative scar in the substance of the brain, a tumor with uneven edges of 2.8 × 2.9 cm is determined. The condition is moderate, pallor of the skin. The patient was prescribed Rhodamine 6G at a concentration of 500 mg per 500 ml of physiological saline in sterile form, intravenously, drip. Procedure for 40 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 0.3 × 0.4 cm. After two infusions of the drug, nausea and pain decreased. For 6 months, a single injection of the drug was carried out every two weeks. On CT after 9 months of treatment, the tumor is not detected.

Example 10

Patient L., 64 years old. Diagnosis: Primary liver cancer. 1.5 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, the sterile preparation Rhodamine 6G, 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, the connective tissue scar 0.2 × 0.3 cm remained at the tumor site in the liver. During treatment with the drug, a positive dynamics was observed in the analyzes blood.

General blood test results Main characteristics 11/12/04 01/19/05 02/14/05 04/17/06 Red blood cells 3.22 3.60 4.37 4.67 Hemoglobin 74 80 117 123 Platelets 315 362 286 310 White blood cells 7.2 7.8 5.8 6.7 Basophils 0-1% one - - one Eosinophils 0-5 one 2 2 one Pal. nuclear 1-6% one one - - Segm. nuclear 45-70 21 44 63 65 Lymphocytes 18-40% 9 16 23 37 Monocytes 2-9% fifteen 4.3 four 9 ESR 1-15 mm / h 3,5 8.5 Results of biochemical blood tests Main characteristics Sod. fine 11/10/04 12/20/05 02/04/05 04/07/05 Total protein 65.0-85.0 43,43 49.90 78 64.34 Creatinine hl 98.0 83 79 67 Urea 44-110 7.2 6.4 4.1 2.6 Cholesterol 1.66-8.3 6.21 5.62 5.75 7.03 Common bilirubin 2.90-6.54 11.0 24.2 8.4 8.0 Direct bilirubin 8.5-20.5 3.0 22.3 3.3 2.0 Bilirubin up to 25% 8.0 11.9 5.1 6.0 indirect up to 25% 82 96 84 90 Amylase up to 100 ate 107,2 102 89 78.0 Chlorine 95-110.0 114.0 140 102.8 110.0 Sodium 135.0-147.0 114.20 115.3 114.31 134.2 Potassium 3,5-6,0 3.8 4.9 4.8 4.9 Calcium ionization. 0.98-1.30 2.72 2,32 2.28 2.15 Total calcium 2.1-2.55 19,4 13,4 18.0 17.7 Iron syv. well 8.8-27.0 314.3 395.8 138.0 64,4 ACT 5-40 U / L 190.4 224.7 94.4 43.7 ALT 5-40 U / L 554.5 432.9 103.8 30,4 Phosphatase slit. well up to 104 units / l 665.8 426 154.2 40 LDH 225-450 units / l 5.71 5.48 4,55 6.7 879 556 332 362

No complaints at this time.

Example 11

Patient T., 58 years old. Dz: non-Hodgkin lymphoma. Cachexia. A full course of polychemotherapy was carried out 1.5 years ago. 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, 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 × 3 cm. On the neck on both sides, tumor formation of 2 × 3, 3 × 4 cm. Treatment with malachite green was carried out according to the scheme. 50 drops of a 1% solution of Rhodamine 6G 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 0.3 × 0.4 cm. After 3 months, not a single lymph node was detected. Blood and urine tests were normal. Weight restored. There are no complaints.

Example 12

Patient N., 55 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. 2 years after treatment, pains 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 cyanogical shade, 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, the formation of an irregular shape of 2 × 4 cm with uneven edges is 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 was prescribed Rhodamine 6G in the form of intravenous infusions, microclysters and drinking. The infusion solution is 200 mg. sterilized Rhodamine 6G dissolved in 500 ml of physiological saline. Infusions were carried out weekly for 3 months. Enema is a solution of 20 g of Rhodamine 6G 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% Rhodamine 6G 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 10/09/04 11/24/04 12/09/04 01/09/05 Red blood cells 3.20 3.84 4.44 4.87 Hemoglobin 74 90 115 128 Platelets 120 210 326 440

White blood cells 9.2 12.0 5.2 5.3 Basophils 0-1% one - - one Eosinophils 0-5 one 2 2 one Pal. nuclear 1-6% 0 one - 2 Segm. nuclear 45-70 2 6 6 5 Lymphocytes 18-40% 35 49 58 69 Monocytes 2-9% 13 four 7 9 ESR 1-15 mm / h 36 12 10 12

Results of biochemical blood tests DOS indicators Sod. fine 10/09/04 11/24/04 12/09/04 01/09/05 Total protein 65.0-80 g / 51.23 62.26 65 82.53 Creatinine 85.0 g / l 118.0 89 74 69 Urea 44-110 8.2 7.4 3,1 2.9 Cholesterol 1.66-8.3 6.21 5.62 5.75 7.03 Common bilirubin 2.90-6.54 11.0 24.2 8.4 8.0 Direct bilirubin 8.5-20.5 3.0 22.3 3.3 2.0 Bilirubin up to 25% 8.0 11.9 5.1 6.0 indirect up to 25% 82 96 84 90 Amylase up to 100 units / l 107,2 102 89 78.0 Chlorine 95-110.0 114.0 140 102.8 110.0 Sodium 135.0-147.0 114.20 115.3 114.31 134.2 Potassium 3,5-6,0 3.8 4.9 4.8 4.9 Calcium ionization. 0.98-1.30 2.72 2,32 2.28 2.15 Total calcium 2.1-2.55 19,4 13,4 18.0 17.7 Iron syv. w 8.8-27.0 314.3 395.8 138.0 64,4 ACT 5-40 U / L 190.4 104.7 54.8 42.9 ALT 5-40 U / L 265.7 125.8 45.7 29.5 w up to 104 units / l 465.8 326 69.2 79 225-450 units / l 623 332 242 228

Weight restored. There are no complaints for 2 years.

Example 13

Patient Sh., 55 years old.

When handling complaints of pain during urination and retention and redness of urine. During the examination: ultrasound - prostate ≈85 cm ³ , a tumor with fuzzy contours 34 × 40 mm ² . PSA - 49.9 mg / ml.

Puncture biopsy - prostate adenocarcinoma.

Diagnosis: Prostate adenocarcinoma.

He refused surgery and chemotherapy.

The treatment with the drug Rhodamine 6G.

For 40 days, the patient took the drug - Rhodamine 6G powder 300 mg × 2 times a day with meals and 30 minutes after administration - Rhodamine 6ZH 200 mg. At night, a candle was administered with 2% of the drug. During this period, pain during urination decreased, the color of the urine returned to normal, with ultrasound, the prostate volume decreased by 40%, the tumor acquired a clear outline, dimensions 13 × 14 mm ² . Then, therapy was continued by taking 300 mg × 2 times a day during meals for 300 mg, respectively. Rhodamine 6G, and also prescribed medical enemas daily before bedtime, 2.0 g of Rhodamine 6ZH in 50 ml of boiled water.

Upon subsequent examination, according to the patient's words, the final disappearance of the symptoms of the disease (pain during urination, urinary retention, etc.) was noted. On the control ultrasound, the prostate ≈35 cm ³ , the tumor decreased to 3 × 4 mm ² , PSA - 1.0 mg / ml.

No relapse is observed within 2 years.

Example 14

Patient T., 52 years old.

In 2001, in connection with the detection of carcinoma of the left ovary, the uterus and appendages were extirpated.

After surgery for 2 years, chemotherapy courses.

At the end of July 2002, pain in the rectum and tenesmus appeared.

On CT between the rectum and the bladder, a tumor of 13.0 × 12.5 cm ^{2 was} detected, which grew through their walls.

There were pains in the rectum and tenesmus.

On CT between the rectum and the bladder, a tumor of 13.0 × 12.5 cm ^{2 was} detected, which grew through their walls.

Diagnosis: Recurrent carcinoma of the right ovary.

Due to the ineffectiveness of continuing chemotherapy, the drug was administered in the form of enemas. At the beginning, within 21 days by taking Rhodamine 6G, 5 g per day.

On the 3rd day after the start of treatment, the pain decreased, urination and bowel movements became less frequent.

On ultrasound: after 2 weeks - a tumor of 3.2 × 3.4 cm ² , after another 4 weeks - 1.2 × 1.23 cm ² , a clear boundary is determined between the tumor and the walls of the rectum and bladder.

On the control ultrasound after 3 months a round 0.3 × 0.4 cm ² in size with clear boundaries was found.

With an additional examination, the condition is satisfactory, an ultrasound scan showed formation of a size of 0.4 × 0.3 cm ² with clear contours. Currently healthy.

Example 15

Patient B., 54 years old. The operation was a resection of the stomach. The histological conclusion: moderately differentiated tubular adenocarcinoma, infiltrating the wall of the stomach to the muscle layer. After the operation, they were not treated anywhere, they only took herbs (hemlock, wrestler, etc.), they underwent 3 courses of dry hunger for 5, 7, and 7 days. CT result: in the lung tissue, volumetric formations, focal and infiltrative changes were not detected; local site of fibrosis in the basal sections S9 n / l of the left lung. The contours of the bronchi 1-3 order are clear, fluid in the pleural cavities is not detected. Abdominal organs: liver of usual shape and location; the contours are even, clear, the structure of the parenchyma is homogeneous, the density is not changed. In the right lobe of the liver, a formation with fuzzy contours of 4 × 5 cm. The intra- and extrahepatic bile ducts are not expanded; gall bladder of normal sizes. Free fluid in the abdominal cavity. Results: general blood test: hemoglobin - 86, white blood cells - 47, lymphocytes - 48. Other indicators are within normal limits. Immune status studies are as follows:

CD16 26 549 II4L-DR 48 608 Cd54 54 1140 Cd38 54 1140 CD44 95.7 2021

The result of genetic analysis for DNA: a change in the 12-codon of the K-ras gene was detected; no other mutations were detected. The tumor and metastases continued to grow. Proposed treatment with Rhodamine 6G, 10 g each, dissolved in 250 ml of water three times a day 20 minutes before meals. Suppositories 5% in the rectum at night. Treatment according to this scheme lasted for 3 months

On CT after 4 months, the primary tumor is not determined, metastases of small sizes in the right lobe of the liver 1 × 2 cm with signs of calcification. Results A general blood test dated December 23, 2006: hemoglobin - 134, white blood cells - 4 thousand, lymphocytes - 43. The remaining indicators are within normal limits.

The immune status studies of December 23, 2006 are as follows:

CD16 26 649 II4L-DR 48 768 Cd54 54 1320 Cd38 54 1240 CD44 95.7 1024

No complaints at this time. Weight 76 kg.

Example 16

Patient T., 67 years old. Diagnosis: Coronary heart disease: atherosclerotic cardiosclerosis, atrial fibrillation. Amyloidosis? Due to the worsening condition (frequent attacks of suffocation), the patient was hospitalized. Upon receipt of the general condition of moderate severity. The skin and visible mucous membranes of normal color, moderate cyanosis of the lips. Heart sounds are deaf, arrhythmic - atrial fibrillation with a ventricular contraction rate of 110 beats / min (pulse deficit 12), blood pressure 100/60 mm RT. Art. In the lungs on the left, blunting of percussion sound was determined below the middle of the scapula; breathing was not performed above these sections. On the right, in the projection of the lower lobe, single wet rales were heard. The liver is painful, its lower edge protrudes 4 cm below the level of the costal arch. Edema of the legs to the middle third of the thighs and anasarca was determined.

On the ECG recorded a low voltage of the teeth, a tachystolic form of atrial fibrillation. QS in leads V1-V4. On the echocardiography were determined: dilatation of the left (anteroposterior size 50 mm) and the right atrium (56 × 52 mm); pseudo-hypertrophy of the myocardium of the interventricular septum (17 mm thick in diastole) and the posterior wall of the left ventricle (15 mm thick in diastole); normal sizes of the left and right ventricles (end-diastolic sizes 49 mm and 24 mm, respectively). There was a violation of diastolic relaxation of the left ventricular myocardium. In the general analysis of blood revealed: hypochromic anemia (er. 2.66-2.77-10 ¹² / l, hemoglobin - 95 g / l); moderate leukocytosis (10.3), leukocyte formula unchanged and accelerated ESR (43 mm / h). In a biochemical blood test, the level of total protein decreased (up to 50 g / l) and the levels of urea (up to 9.66 mmol / l) and creatinine (up to 149 mmol / l) increased. Proteinuria (0.05 g / l) was noted in the urine. Ultrasound of the abdominal organs: the liver is enlarged (the right lobe is 16.9 cm), its echogenicity is reduced and the structure is heterogeneous; portal vein - 15 mm. Gall bladder: 52 × 22 mm, wall up to 4 mm, clearance is free. Pancreas: homogeneous, increased echogenicity, foci of diffuse changes. The right kidney is 102 × 51 mm, the left kidney is 1023 × 54 mm, the cortical layer of both kidneys is 1.8 mm. The pyelocaliceal system of both kidneys is not expanded. On a direct chest x-ray, the fuzziness of the pulmonary pattern and diffuse changes were determined. To exclude amyloidosis, a liver biopsy was performed. Signs of primary amyloidosis have been identified. Based on these data, the diagnosis was made: Primary generalized amyloidosis with predominant damage to the heart, kidneys and liver. Standard treatment did not give any effect and the patient's condition progressively worsened. It was decided to conduct therapy with the help of Rhodamine 6G, 5 g each, dissolved in 250 ml of water three times a day for 20 minutes. before meals. Suppositories 5% in the rectum at night. Treatment according to this scheme lasted for 2 months. The patient's condition gradually improved, but to accelerate the elimination of amyloids, an intravenous administration of 2 g was prescribed. Intravenously 2 times a week. The course lasted 2 months. As a result of treatment on an echocardiogram, the size of the heart decreased. On the ECG, the voltage of the teeth is normal, there is no fibrillation. On echocardiography: dilatation of the left and right atria decreased significantly. Ultrasound of the liver and kidneys of normal size. Blood and urine tests are normal. There are no complaints.

Example 17

Patient Sh., 75 years old. Dz: Melanoma of the left leg, metastasis to the inguinal lymph node. In the region of the left tibia, a swelling neoplasm of dark brown color 5 × 7 × 9 cm with perifocal edema. In the left inguinal region, an enlarged lymph node, fused to surrounding tissues. The histological diagnosis is melanoma. 5% ointment based on Rhodamine 6G was treated. Within 2 months, the size of the tumor decreased by 70%. The lymph node is not determined. After 3 months, hyperpigmentation and a primary tumor of 2 × 3 × 2 cm are determined at the site of the tumor. There are no complaints. No relapse for 3 years.

Thus, the examples confirm that an affordable and inexpensive drug has been found that has a wide range of therapeutic effects.

Moreover, the created drug is characterized by a wide range of applications for cancer and amyloidosis, low toxicity and side effects when used in pharmaceutically acceptable doses, the treatment time is shortened, and the treatment efficiency is increased.

Claims (5)

1. The use of Rhodamine 6G in the form of 9- (2-ethoxycarbonyl) phenyl) -3,6-bis (ethylamino) 2,7-dimethylxanthyl chloride with the chemical formula C ₂₈ H ₃₁ N ₂ O ₃ Cl as an agent for the treatment of amyloidosis. 2. The use according to claim 1. characterized in that Rhodamine 6G is used as a solution. 3. The use according to claim 2, characterized in that the aqueous solution of Rhodamine 6G is taken orally before or after a meal. 4. The use according to any one of claims 1 and 2, characterized in that the Rodamine 6G solution is administered rectally. 5. The use according to claim 4, characterized in that Rhodamine 6G is used rectally as a suppository.