RU2308270C1 - Pharmaceutical agent - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention relates to pharmaceutical agent suppressing tumor cell growth (cancer, carcinoma). As such agent methylated primuline derivative Thioflavin T (known as agent for amyloidosis diagnosis) is used.

EFFECT: agent causing tumor size decrease (including metastasis tumor) without allergic reactions and side effects.

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Description

The invention relates to medicine, namely to drugs that inhibit the growth of cancer cells and stop (cure) diseases of accumulation (amyloidosis).

Known drug "Adriamycin", which is an antibiotic of the anthracycline group and having pronounced antitumor activity (M.D. Mashkovsky. Medicines. M: Medicine, 1985, v. 2, p. 460-461).

However, when using the drug, nausea, vomiting, leuko- and thrombocytopenia, and cardiovascular disorders may occur.

Known drug "Cyclophosphamide", available in the form of a white crystalline powder, soluble in water, easily soluble in alcohol, it is difficult - in isotonic sodium chloride solution (M.D. Mashkovsky. Medicines. M .: Medicine, 1985, v.2 , p. 433-434).

This drug has a relatively broad antitumor spectrum, and is also an immunosuppressive agent, however, its use can cause side effects, such as dizziness, nausea and vomiting, often after some time after the start of application, hair loss on the head is noted.

For the treatment of amyloidosis, non-steroidal anti-inflammatory drugs, systemic steroid drugs, aminoanthracycline derivatives and colchicine are used.

The well-known drug "Colchicine", used to treat amyloidosis, refers to drugs that affect the metabolism of uric acid (www.kuban.su). The active ingredient in the preparation "Colchicine" is INN-mono. Contraindications for taking the drug are hypersensitivity, gastrointestinal tract, bone marrow, neutropenia, impaired liver and kidney function, cardiovascular disease, purulent infections, alcoholism, pregnancy, old age. When ingestion of high doses, dyspeptic symptoms (nausea, vomiting, anorexia, diarrhea, etc.), myelosuppression (leukopenia, agranulocytosis, aplastic anemia) occur.

A medicament is known containing pharmacologically acceptable derivatives of tri-n-aminotriphenylchloromethane having an antitumor and immunomodulating effect.

However, tri-n-aminotriphenylchloromethane preparations have a rather pronounced toxic effect (Patent No. 2257200 dated 05/12/2004, class A61K 31/14, RF).

The objective of the invention is to provide a drug with antitumor and anti-amyloid effect, and not causing allergic reactions and other undesirable side effects.

The problem is solved in that as a drug having antitumor and anti-amyloid properties, it is proposed to use a derivative of methylated primulin - Thioflavin T. A method for producing Thioflavin T is known. Its full Latin name is: Thioflavin T. Basic Yellowl. Thioflavine T 2- [4 (Dimethylamino) phenl] 3,6dimethylbenzothiazoliumchlorid. Its empirical formula is: C ₁₇ H ₁₉ CIN ₂ S). The molecular weight is 318.86.

Its structural formula:

It is known that thiazole organic dyes (for example, thioflavin) are used for dyeing silk, cotton, leather, etc. (http // www.booksite.ru). This substance is also used for the diagnosis of amyloidosis in vitro preparations (Chapter 16, Sickness Diseases, www.med-lib.ru).

Amyloidosis, amyloid dystrophy, impaired protein metabolism are accompanied by the formation in the tissues of a specific protein-polysaccharide complex - amyloid. The development of amyloidosis is associated with a distortion of the protein-synthetic function of the reticulo-endothelial system, the accumulation of abnormal proteins in the blood plasma, which serve as autoantigens and cause the formation of auto-antibodies. As a result of the interaction of the antigen with the antibody, the coarsely dispersed proteins involved in the formation of amyloid precipitate. Being deposited in tissues (for example, in the walls of blood vessels, glandular tissues, etc.), the amyloid displaces the functionally specialized elements of the organ, which leads to its death. Amyloid in tissues appears either around collagen fibers (pericollagen amyloidosis), or on the basement membranes, or around reticular fibers (perireticular amyloidosis) (Amyloidosis of the kidneys, G.E. Gendlin, MD, professor, Russian State Medical University, Moscow, www.medlincs.ru).

The oligomers of the proteins that make up the amyloid and cancerous structures bind the amyloid dye Thioflavin T and consist of b-layers (Lavrikova MA, Abstract of Cand. Diss., Study of the fibrillation of artificial protein Albertin and its derivatives, Biophysics, 03.00.02, Pushchino, 2005).

According to our theory, cancer is a violation of the folding (self-organization) of proteins (Kutushov MV, “Cancer can be cured,” ed. Sekachev, Moscow, 2005). Thioflavin T, joining oligomers of protein molecules, namely b-layers, changes the strength of ionic interactions, enhances fluorescence, thereby restoring normal fibrillation and protein folding, which normalizes cell mitosis, protein metabolism and reduces the formation of amyloid structures. Studies have shown that the drug Thioflavin T has anabolic activity, restores protein metabolism and has an antitumor effect. This is confirmed by instrumental laboratory examinations of patients by conducting a blood test and histological preparations.

The proposed drug can be taken orally in the form of a powder or tablets during or after meals, in the form of enemas, as well as intravenously and intramuscularly, and their use in a wide dosage range (from 0.5 mg to 20 g) does not cause allergic reactions or other side effects, its effectiveness in the treatment of relevant diseases is higher than that of known drugs.

The possibility of using the proposed drug is confirmed by examples.

Example 1. Patient Z., 45 years old. Diagnosis: Low-grade cancer of the right lung. Sick for 3 years. Conducted several chemotherapy courses. In the past 2 years, the condition has noticeably worsened, shortness of breath and pain in the lungs, hemoptysis. When handling: serious condition, pale skin with a cyanotic hue. Stridor respiration is noted. In the neck area on the left, a dense formation of 3 × 2 cm, painfully fused with adjacent tissues. On the x-ray from 06/20/2002, in the right lung a tumor-like formation of 14 × 13 cm with uneven contours. Paroxysmal cough and suffocation. A blood test from 06/20/2002: leukocytes up to 24 thousand, red blood cells - 2.5 million, platelets - 69 thousand.

The drug was treated with Thioflavin T 350 mg 2 times a day with meals. A sharp improvement was noted after the first 14 days of taking the drug. The attacks of suffocation ceased. After a 2-month course of treatment, the tumor on the neck almost disappeared, with palpation, this area is painless. On the roentgenogram, the tumor decreased to 2 × 3 cm. Blood analysis from 09/22/2002: leukocytes - 5.5 thousand, red blood cells - 6.5 million, platelets - 350 thousand units. Currently, the condition is good, there is no relapse of the disease.

Example 2. Patient P., 53 years old. Diagnosis: stage 3-4 prostate carcinoma with liver metastases. When handling a state of extreme severity. On ultrasound in the prostate, formation with fuzzy contours of 3 × 5 cm is determined. The volume of the prostate is 40% more. Ultrasound of the liver 3 metastases of medium size. Thioflavin T was treated for 2 months. The first 7 days of 250 mg 3 times a day microclysters, then for 3 weeks 300 mg 3 times a day, then for a month 300 mg 2 times a day. On the fifth day after the start of treatment, an improvement in the general condition was noted, painkillers were canceled. In the course of further treatment, positive dynamics were observed. After 2 months, the patient's condition returned to normal, on CT and ultrasound, the primary tumor and metastases were not determined.

Example 3. Patient N., 53 years old. Diagnosis: amyloidosis, cirrhosis, ascites. Several years prior to treatment, the patient was treated with drug complexes: steroids, colchicine according to the scheme. There was no effect. A liver transplant is proposed, which the patient refused. Thioflavin T was treated - 600 mg powder 2 times a day 30 minutes before meals. On the 15th day, the pain in the liver disappeared. The treatment was continued at 500 mg 2 times a day. By the end of the 4th week after the start of treatment, ascites phenomena decreased. Swelling in the lower third of the legs and lower back decreased. After 3 months, the condition is satisfactory. Complaints of periodic weakness. Hepatic tests showed an improvement in the metabolic and synthetic function of the liver. Blood counts returned to normal at week 4 of treatment. Periodically, once every six months, preventive treatment is carried out. Observation over the past 5 years indicate an almost complete cure. No complaints at this time.

Complete blood count before treatment after 4 weeks after 3 months Hemoglobin g / l one hundred 125 139 Red blood cells × 10 ¹² / L 3,5 4.3 5,0 Col. indicator 0.85 1,0 1.4 White blood cells × 10 ⁹ / L 2.2 4.7 5.9 Platelets Abs. 104 127 384 Eosinophils% 1,0 4.0 3.0 Neutrophils: Stab% 1,6 4.9 5,0 Segmented% 57 68 65 Lymphocytes% 10 twenty 23 Monocytes% 1,5 4.0 4.6 ESR mm / hour 43 24 12 Blood chemistry Before treatment After 4 weeks Sodium mmol / L 139 143 Potassium mmol / L 3.0 4.2 Glucose mmol / L 3.6 5.9 Urea mg / dl 42.5 44.0 Uric acid mg / dl 4.9 6.8 Bilirubin mg / dl 2.9 1.7

Before treatment After 4 weeks Albumin g / dl 2.0 4.7 Protein g / dl 3,1 7.1 Creatinine mg / dl 0.42 0.35 Aspartate aminotransferase u / l 473.0 51.0 Alanine aminotransferase u / l 377.0 45.4 Gamma-glutamyltransferase u / l 529.0 82.0 Lactate dehydrogenase u / l 243.5 135.0 The results of the study of cellular and humoral immunity Before treatment In 3 months Immunoglobulin A g / l 1.4 2,31 Immunoglobulin M g / l 1.9 1,52 Immunoglobulin g / l 3.0 10.5 T lymphocytes% 23.0 62.0 B-lymphocytes% 7.0 21.0 Phagocytosis latex% 34 55 TNF 11.6 23.0

Example 4. Patient S., 49 years old. Diagnosis: amyloidosis.

Sick for 2 years, asthenia, swollen fingers and toes, high fever, previous treatment with known agents did not work. Treated with Thioflavin T 500 mg 2 times a day 30 minutes before meals for 4 months. According to the examination, the patient already within 3 weeks from the start of treatment with this drug, the symptoms of amyloidosis smoothed out. After another 4 weeks, the general condition improved, the temperature is normal. Blood counts returned to normal. Currently, 2 years after treatment, no complaints.

Example 5. Patient K., 20 years old. Diagnosis: amyloidosis, nephrotic syndrome. Complaints of weakness, shortness of breath, swelling.

Objectively: pallor of the skin, swelling of the lower legs and waist. In the analyzes, the increase in creatinine and urea is higher than normal. Several hemodialysis sessions were performed.

Thioflavin T was treated with 150 mg once a week intravenously in 500 ml of sterile saline for 3 months, and then for another 2 months 300 mg 3 times a week. After 3 months of treatment, creatinine and urea returned to normal, hemodialysis is canceled. Over the next 4 months, the condition returned to normal. According to the results of blood tests, the number of neutrophils in%: stab - 6.0 (at the beginning of treatment - 5.3), segmented - 79.0 (at the beginning of treatment - 47.6). After 2 years no complaints.

Claims (1)

The use of Thioflavin T as a drug with antitumor and anti-amyloid properties.