Medicinal agent

FIELD: medicine, chemical-pharmaceutical industry, pharmacy.

SUBSTANCE: invention relates to using 4-chloro-2-methylphenoxyacetic acid of the formula (I)

and its pharmacologically acceptable sodium, potassium and lithium salts (mixture of these salts, or mixture of salts and 4-chloro-2-methylphenoxyacetic acid) as a medicinal agent possessing immunomodulating, anti-inflammatory and antitumor properties, and antiviral activity also. 4-Chloro-2-methylphenoxyacetic acid and its mixtures with pharmacologically acceptable alkaline metal salts possess high effectiveness and enhanced bioavailability.

EFFECT: valuable medicinal properties of medicinal agent.

9 cl, 13 ex

 

The present invention relates to medicine, namely to medication a broad spectrum of action.

Known drug "Fu", which is a white or slightly yellowish, slightly soluble in water and in alcohol crystalline powder, which is an antimetabolite, antitumor activity of which is determined by its transformation into cancer cells in a competitive inhibitor involved in nucleic acid synthesis enzyme (see, for example, Medmaravis "Drugs", Moscow, OOO "New Wave", Publisher Sbelow, 2002, Vol.2, s).

This drug by intravenous injection using when inoperable and recurrent stomach cancer, cancer of the colon and rectum, breast, ovary, and pancreas, but the drug is highly toxic and may cause inhibition of blood, diarrhea, loss of appetite, vomiting, ulcerative stomatitis. In addition, this drug is contraindicated General condition of the patient, gastric ulcer and duodenal ulcer, severe functional liver failure.

The closest analogue prototype is the drug "IFN", which is a recombinant α2- interferon produced by a bacterial strain pseud the monad, the genetic machinery which is built leukocyte gene α2interferon - man, released in the form of porous powder, an aqueous solution which prescribe intramuscular or subcutaneous injection (see, for example, Medmaravis "Drugs", Moscow, OOO "New Wave", Publisher Sbelow, 2002, Vol.2, SS-324).

The drug has antiviral, immunomodulatory and antitumor activity, is effective in the treatment of viral hepatitis, is used in the treatment of hairy-cell leukemia, Kaposi's sarcoma (against AIDS), kidney cancer, metastatic melanoma, etc. However, when using reaferona possible fever, malaise, allergic skin reactions, leukopenia and thrombocytopenia. Contraindications the use of this drug in allergic diseases, severe liver disease and kidney failure, pregnancy.

The present invention solves the problem of finding drugs with a wide range of therapeutic effects and does not cause side effects when used in pharmaceutically acceptable amounts.

Known 4-chloro-2-methylphenoxyacetic acid, which are soluble in water and in alcohol colorless crystalline substance used in agriculture as a herbicide under the names of the 2M-4, MSRA, metox is n and the other (see, for example, reference to "Harmful substances in industry", Ed. "Chemistry", L., 1976, p.131).

Experimentally determined that enter the body in the production of and above using 4-chloro-2-methylphenoxyacetic acid is detected in the internal organs, as well as in human blood, and the allocation of this substance from the body occurs primarily in the urine (see, for example, C.A. Bache et al. Daire Sci., 1964, v.47, R-95).

In accordance with the recommendations of VLIEGENTHART for people employed in the production of 4-chloro-2-methylphenoxyacetic acid and its derivatives, set the maximum allowable concentration of these substances in workplaces, which, for example, sodium salt is 1 mg/m3(see, for example, "guidelines for the implementation of sanitary surveillance of working conditions in the production of herbicide 2M-4 (matakana)", Ufa, 1971).

In addition, the results of biochemical studies on the effects of herbicides on the growth factors of plants, they have an impact on the transformation of energy in the cell, increasing the intensity of oxidative processes and oppression fosforilirovanija in mitochondria and accumulation of the herbicide in the membranes causes a disturbance of the complex associated with the membrane protein factor that determines the activity PHiK on Imerese, transcribers specific mRNA, and modify the functional activity of membrane associated enzymes, herbicides with gametocidal properties can cause induction of mRNA synthesis, responsible for the production of a number of enzymes and, as a consequence, the enzymes that convert the carbohydrate components of membranes and cell membranes (see, for example, Hardin J.W., D.J. Morre, C.A. Lembi Enhancement of soybean R NA polymera'se activity by a factor released by auxin from plasma-membrane. - Proc. Naitl. Acad. Sci. US, 1972, v.69, N 11, p.31146-31150).

These data suggest the existence of a similar mechanism of action of some herbicides and on the human body.

The invention consists in the application of 4-chloro-2-methylphenoxyacetic acid having the structural formula:

and its pharmaceutically acceptable derivatives, for example, the corresponding alkali metal salts of this acid or of mixtures of these salts, or mixtures of 4-chloro-2-methylphenoxyacetic acid and these derivatives as a drug with immunomodulatory, anti-inflammatory and anticancer properties, as well as antiviral activity.

When this derivative is 4-chloro-2-methylphenoxyacetic acid represents or potassium, or sodium, or lithium salt of this acid.

In addition, a derivative of 4-chloro-2-methylphenoxyacetic the second acid is a, or a mixture of potassium and sodium salts of this acid in the ratio of the components, wt.%: potassium salt of 4-chloro-2-methylphenoxyacetic acid - 1,0-98,0; sodium salt of this acid - else, or a mixture of potassium and lithium salts of this acid with a ratio of components, wt.%: potassium salt of 4-chloro-2-methylphenoxyacetic acid - 1,0-98,0; the lithium salt of this acid - else, or a mixture of sodium and lithium salts of this acid with a ratio of components, wt.%: sodium salt of 4-chloro-2-methylphenoxyacetic acid - 1,0-98,0; the lithium salt of this acid - else, or a mixture of potassium, sodium and lithium salts of this acid with a ratio of components, wt.%: potassium salt of 4-chloro-2-methylphenoxyacetic acid - 1,0-55,0; sodium salt of 4-chloro-2-methylphenoxyacetic acid - 1,0-85,0; the lithium salt of this acid - rest.

The mixture of 4-chloro-2-methylphenoxyacetic acid and its derivatives executed when the ratio of components, wt.%: 4-chloro-2-methylphenoxyacetic acid - 1,0-98,0; its derivatives - rest.

Studies have shown that the drug is in the form of 4-chloro-2-methylphenoxyacetic acid and its pharmaceutically acceptable derivatives, for example, in the form of corresponding salts of alkali metals and their mixtures stimulates cellular and humoral defense factors of the body, has anti-inflammatory and antitumor effects, which appear the tsya, for example, in the form prescribed by the author dissymmetries therapeutic effect (see, for example, Mevcuttur Cancer. Healing is possible", Ed. "Neva", S.-P., 2003), and has antiviral activity.

This is confirmed by instrumental and laboratory examinations by analysing the blood of patients to test immunological indicators (patients) leukocyte and lymphocyte systems before and after taking the appropriate medication.

The drug, derived from this medicinal product may be administered orally in the form of powder or tablets during or after a meal, and its application in a wide range of dosages from 10 mg to 4 g) does not cause allergic reactions and other side effects, and its effectiveness in the treatment of relevant diseases) not lower than, for example, a drug, selected as a prototype.

4-chloro-2-methylphenoxyacetic acid is obtained by chlorination of o-cresol, followed by reaction with Chloroacetic acid and isolation of the target product from the resulting mixture by, for example, recrystallization.

Alkali metal salts of this acid is manufactured in the form

for example, the interaction of the aqueous solution of this acid with the hydroxide, respectively, or ka is Oia, or sodium, or lithium, and the desired mixture is obtained by selecting the appropriate components in predetermined proportions.

The results of studies of the mechanism of action proposed medicines are given in the examples No. 1 to 6, and the possibility of its application for the treatment of confirmed examples No. 7-12.

Example No. 1.

In tubes of the experimental group with cancer cells PC-3 (carcinoma of the prostate) in buffer solution (10 ml) is added to the drug in a dilution of 10-5mmol/l, respectively in the form of 4-chloro-2-methylphenoxyacetic acid, its potassium, sodium and lithium salts, mixtures (equal to the ratio of the components) of potassium and sodium, potassium and lithium, sodium and lithium, potassium, sodium and lithium salts of 4-chloro-2-methylphenoxyacetic acid and mixtures of this acid with potassium, sodium and lithium salt (in a ratio of components, wt.%: acid - 25, the corresponding salt of the rest).

In addition, in test tubes with the same pool of cancer cells introduced in the same dilution respectively the drugs adriamycin, IFN, and saline.

Thus was formed the control group of the same number of tubes and with the same components, in addition to cancer cells, which will be replaced by tubes of this group were placed fibroblasts.

After thermostat is work during the day at a temperature of 37° With the analysis of the content of the above tubes.

Examination of the results showed:

In vitro experimental group with drug mitochondrial membrane almost completely destroyed, and the picture is approximately the same for all variants used drugs in tubes of this group with the drug adriamycin marked swelling of the membranes, drug IFN observed swelling of the membranes with partial (60%) their destruction, in the cells in vitro with physiological solution, no changes found.

In tubes of the control group mitochondrial membrane sduty, but their integrity is preserved.

The data obtained indicate that the proposed drug causes the destruction of the membranes of the mitochondria 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 the cells to produce enzymes that cause apoptosis of cancer cells.

Example No. 2.

4 tubes of the experimental group with cancer cells MCF-7 (breast adenocarcinoma) in buffer solution (10 ml) is added to the drug in a dilution of 10-5mmol/l, respectively in the form of 4-chloro-2-methylphenoxyacetic acid and mixtures of this acid with potassium, sodium and lit the eve of salt in the proportions of the components, wt.%: 1. acid - 25, potassium salt - 25, sodium salt - 25, lithium salt - 25; 2. acid - 70, potassium salt - 10, sodium salt - 10, lithium salt - 10; 3. acid - 10, potassium salt - 10, sodium salt - 55, lithium salt - 25.

The control group in test tubes with the same pool of cancer cells entered accordingly in one saline and other drugs adriamycin and IFN.

In test tubes in both groups determined the titers of cytochrome C, which is 1:14000.

After incubation over night at 37 °With the analysis of the content of the above tubes.

Examination of the results showed:

In vitro experimental group entered drug titer of cytochrome C for tubes with 4-chloro-2-methylphenoxyacetic acid was 1:2000, for tubes with the entered medicine in the form of mixtures of this acid with the corresponding salts of the indicated titer determined within the range of 1: (1950-2250).

In test tubes with adriamycin and IFN titer of 1:12000 and 1:9600. In the test tube with saline significant changes in the titer is not marked.

The results suggest that the proposed drug contributes to the release of the membranes of the mitochondria of cancer cells "aggressive" protein cytochrome C, which, starting the mechanism of the ruin is of DNA caspase, causes apoptosis of these cells (see, for example, B.E. Wilson, A. Mochon, Boxer L.M. Induction of bcl-2 expression by phosphorylated CREB proteins during B-cell activation and rescue from apoptosis. Mol.Cell.Biol, 1996, v.16, p.p.5546-5556).

Example No. 3.

In a test tube (10 ml) with transthyretin (protein) in the blood plasma (pH 7,0), the concentration of 0.05 mmol/ml put 4 drops of 0.1% aqueous solution of 4-chloro-2-methylphenoxyacetic acid.

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

After 15 min it was measuring the concentration of transthyretin and measuring the pH of plasma.

Transthyretin is not defined, a pH of 6.0.

It follows that this drug acts on protein denaturation is not like acid, but as a drug that modifies the polymer structure.

This property determines therapeutic effect of this medicinal product in the treatment of, for example, malignant tumors.

Example No. 4.

In a test tube with B-amyloid (protein) in the blood plasma (pH 7,4), a concentration of 0.1 mmol/ml, put 3 drops of 0.1% aqueous solution of sodium salt of 4-chloro-2-methylphenoxyacetic acid (conditional name OF 1).

The tube is placed in an incubator with a temperature of 37°C.

After 15 min produced a measurement of the protein concentration and the pH of blood plasma.

B-amyloid is determined at a concentration of 0.03 mmol/ml, pH 7,2.

From the obtained results it follows that the drug OF 1 prevents the den is urali protein precursor of amyloid a (BPA) and its transition to the b-amyloid.

This property of the drug determines its therapeutic effect in the treatment of amyloidosis and cancer.

Example No. 5.

The blood of a patient with sarcoma (10 ml) and centrifuged.

Part of the obtained plasma dried and photographed in a polarizing microscope. In another part of this same plasma introduced an aqueous solution of the lithium salt of 4-chloro-2-methylphenoxyacetic acid, and the resulting mixture was also photographed in a polarizing microscope.

Results: In the first part is the scattering, in the second observed birefringence.

These data suggest that this drug when cancer returns the modified folding of proteins to normal.

Example No. 6.

The filtrate from melanoma-16 (10 ml) placed in a quartz cuvette, produced by photographing in a polarizing microscope.

Then, the filtrate deposited sodium salt of 4-chloro-2-methylphenoxyacetic acid (OF 1) and re-photographed in polarized light.

Results: In pictures without drug polarization of light is negligible, the shots after drug administration (OF 1) there is a marked polarization passing through the beam composition.

The data obtained indicate that this drug causes structural changes in the proteins of cancer cells.

P the emer No. 7.

In mice breed-5 7 was conducted to check the response of the organism of the animal by the administration of a medicinal product in the form of 4-chloro-2-methylphenoxyacetic acid and its potassium, sodium and lithium salts.

Experimental group consisted of 40 mice and was divided into 4 subgroups based on 10 mice in each test group contained 10 mice, while subgroups are isolated from each other, and mouse each subgroup were numbered respectively from 1 to 10 by applying the respective rooms dye composition, in this case the brilliant greens.

Experimental group of mice within 10 days received the drug, respectively, 1-I subgroup 4-chloro-2-methylphenoxyacetic acid, 2-I subgroup in the form of potassium salt of 4-chloro-2-methylphenoxyacetic acid, 3-I subgroup in the form of the sodium salt of 4-chloro-2-methylphenoxyacetic acid (preparation OF 1), and 4-th subgroup in the form of the lithium salt of 4-chloro-2-methylphenoxyacetic acid, and in each subgroup mouse numbered 1-8 received the appropriate medication in the form of drinking (in aqueous solution), and mouse numbers 9-10 - injection into the peritoneum. In each subgroup mouse numbers 1-2 received the appropriate drug dose of 2 mg, mouse, numbers 3-4 received the drug at a dose of 10 mg, mouse, numbers 5-6 received the drug at a dose of 15 mg, mouse under n the measures 7-8 received the drug at a dose of 20 mg, and mice at 9-10 injection of the corresponding preparation was carried out in a dose of 5 mg per 1 ml of water for injection.

Mice of the control group of the drug is not received.

Results: two weeks after you start taking medicines all mouse experimental and control groups live. Differences in animals from the experimental and control groups is not observed.

Mouse with even numbers in all subgroups scored on day 21.

Traces the introduction of appropriate drugs detected in kidneys of mice with 8 rooms for all subgroups of the experimental group.

Differences in the influence of 4-chloro-2-methylphenoxyacetic acid and its corresponding salt on the body when histology was not found.

Hence, taking into account the weight ratios can be assumed that the human body is a reasonable dosage of up to 4 g single receiving this drug. However, more accurate data can be obtained only by conducting relevant research.

Example No. 8.

Mice breed-57 experimental and control groups (60 animals in each) vaccinated melanoma-16.

In the experimental and control groups formed by three groups of 20 mice each.

Mouse 1-St, 2-nd and 3-th subgroups of the experimental group in the form of a drink in a dose of 5 mg received the drug in the form of aqueous solutions accordingly is about 4-chloro-2-methylphenoxyacetic acid, its sodium salt (preparation OF 1) and a mixture of 4-chloro-2-methylphenoxyacetic acid and its potassium and lithium salts in the ratio of components, wt.%: 25:25:50, respectively.

Mouse 1-St and 2-nd subgroups of the control group in the form of drinking received aqueous solutions respectively of adriamycin and reaferona in single doses of 5 mg of the drug, mouse 3rd subgroups of the control group of drugs was not received.

Results: Of the 30 mice of the experimental group on day 36 of the experiment survived 22. This 4 mice (2 of 1 and 1 of the 2-nd and 3-th subgroups) died on the 23rd day 3 mouse (1 of 2 and 2 of the 3 subgroups) on day 26 and 1 (2 subgroups) 30 days after the beginning of the experiment. Tumors in 15 (3 1, 8 2 and 4 of the 3rd subgroup) surviving mice - 0.3×0.2 mm, 7 mice (3 out of 1, 1 of the 2-nd and 3 of the 3 subgroups) of the tumor was not determined. Surviving mice were killed at day 36 of the experiment. At the opening of 8 mice (2 of 1, 4 2 and 2 of the 3 subgroups) found isolated lung metastases. The rest of metastases not detected, the internal organs without visible changes.

Mouse 1-St and 2-nd subgroups of the control group. Up to 36 days of the experiment up to 36 days from the start of the experiment survived 2 mouse 1 and 4 mouse 2 subgroups. Tumors on average a 2.0×see 1,0 noted At autopsy the lungs and liver.

Mouse 3-th subgroup of the control group died, all on 12-15-20-25-26 day. When viewed from a bleeding tumor on the back, average of 2.5×2,0 see histology total lysis of both lungs.

Conclusions: the Drug has a pronounced anti-tumor activity, side effects not causes.

Example No. 9.

Patient K. 69 years.

When handling complaints of pain during urination and delay and redness of the urine.

During examination: ultrasound from 08.08.2003, - prostate ≈90 cm3the tumors with indistinct contours 35×48 mm2.

PSA from 8.08.2003, - 27.9 mg/ml

Needle biopsy - adenocarcinoma of the prostate.

Diagnosis: Adenocarcinoma of the prostate.

From surgery and chemotherapy refused.

The treatment drug.

With 09.08.2003, within 10 days, the patient took the drug 4-chloro-2-methylphenoxyacetic acid 300 mg ×2 times a day during meals. During this period, pain during urination decreased urine color is normalized, an ultrasound of the prostate - prostate volume decreased by 30%, the tumor has become clear shapes, sizes 12×24 mm2.

Then continuing treatment by reception within two weeks 400 mg ×2 times a day while eating a mixture of 4-chloro-2-methylphenoxyacetic acid and its potassium and sodium salts in the ratio, wt.%: 50:10:40, respectively, and assigned enema daily at bedtime 2.0 g of sodium is salt of 4-chloro-2-methylphenoxyacetic acid in 50 ml of water.

At the subsequent inspection according to the patient marked the final disappearance of symptoms (sharp during urination, retention of urine and other).

In the control ultrasound prostate ≈42 cm3the tumor decreased to 6×6 mm2.

PSA from 8.10.2003, of 4.1 mg/ml

The patient is recommended to continue taking the drug 4-chloro-2-methylphenoxyacetic acid 200 mg ×2 times a day during meals, and daily at bedtime - enema 2.0 g of a mixture of sodium and potassium salts of 4-chloro-2-methylphenoxyacetic acid (in the ratio, wt.%: 50:50) in 50 ml of water.

Data from laboratory studies of the blood of the patient shown in the table below:

/tr>
Complete blood count.
before the treatmentafter 2 weeksafter 2 months
Hemoglobin, g/l100134145
Erythrocytes, 1×1012/l3,54,34.7
Black. index0,750,850,96
Leukocytes, 1×109/l3,0the 4.76,0
Platelets abs. (thousands)156323354
Eosinophils, %3,03,02,0
Neutrophils:
Stab, %6,06,06,0
Segmented, %697172
Lymphocytes, %212226
Monocytes, %4,56,05,8
ESR, mm/hour301412
Biochemical analysis of blood.
before the treatmentafter 2 weeksafter 2 months
Glucose, mmol/l3,6a 4.94,0
Urea, mg/DLto 43.141,138,7
Uric acid, mg/DL5,26,36,4
Albumin, g/l39,449,650,1
Protein, g/l81,182,988,9
Creatinine, mg/DL0,430,390,35
Aspartate aminotransferase, U/l34,028,03,0
Alanine aminotransferase, U/l77,071,455,9
Gamma-glutamyl-
transferase, U/l129,082,068,6
Lactate dehydrogenase, U/l478,0135,096,8
The results of the study of cellular and humoral immunity.
before the treatmentafter 2 weeksafter 2 months
Immunoglobulin A, g/l2,42,312,59
Immunoglobulin M, g/l1,91,521,65
Immunoglobulin G, g/l11,010,510,6

T-lymphocytes, %54,062,068,0
B - lymphocytes, %14,021,032,0
Phagocytosis of latex %545558
TNFthe 15.623,032
T-helper %24,031,025,0

Example No. 10.

Bol is Naya A., 43 years.

In 2000, in connection with the detection of carcinoma of the right ovary produced extirpation of the uterus and appendages.

After surgery within 2 years of chemotherapy.

At the end of July 2002, there were pains in the rectum and tenesmus.

CT (computer tomography) on August 18, 2002 between the rectum and the bladder a tumor 17,0×15.9 cm2that sprouted through their walls.

The diagnosis of tumor Recurrence.

Due to the inefficiency of continuing chemotherapy treatment drug first, within 14 days by taking potassium salt of 4-chloro-2-methylphenoxyacetic acid 400 mg ×3 times a day and daily therapeutic enemas 2.0 g of a mixture of 4-chloro-2-methylphenoxyacetic acid and its potassium salt (in a ratio, wt.% 90:10, respectively), and then, within 21 days of the mixture of potassium and sodium salts of 4-chloro-2-methylphenoxyacetic acid (in the ratio, wt.% 25:75, respectively) 500 mg ×2 times a day, and the daily therapeutic enemas 2.0 g of a mixture of 4-chloro-2-methylphenoxyacetic acid and its potassium and sodium salts (in the ratio, wt.% 25:25:50, respectively).

On day 3 after the start of treatment pain decreased urge for urination and defecation became less frequent.

Ultrasound: 2 weeks - tumor 7,4×5,7 cm2even after 2 weeks 1,2×2.3 cm2, is determined by clear border between distend the pour and the walls of the rectum and bladder.

In the control ultrasound in 2 months found round 0.6×0.5 cm2with clear boundaries education, which includes thick throbbing artery.

If further examination is satisfactory, the us dated 23.02.2004, we observed formation with a size of 0.2×0.1 cm2with clear contours without visible blood circulation.

Exudate in the pelvis not.

Data from laboratory studies of the blood of the patient shown in the table below:

Complete blood count.
before the treatmentafter 2 weeksafter 2 months
Hemoglobin, g/l97123149
Erythrocytes, 1×1012/l2,53,3the 4.7
Black. index0,751,01,0
Leukocytes, 1×109/l3,0the 4.75,5
Platelets abs.(thousands)164223259
Eosinophils, %1,02,01,0
Neutrophils:
Stab, %5,7/td> 5,96,0
Segmented, %716968
Lymphocytes, %222425
Monocytes, %5,55,05,9
ESR, mm/hour331610
Biochemical analysis of blood.
before the treatmentafter 2 weeksafter 2 months
Glucose, mmol/l4,65,95,0
Urea, mg/DL42,544,028,9
Uric acid, mg/DLa 4.96,8of 5.4
Albumin, g/l40,447,850,4
Protein, g/l61,971,681,8
Creatinine, mg/DL0,420,350,34
Aspartate aminotransferase, U/l33,03128,0
Alanine aminotransferase, U/l77,071,455,9
Gamma-glutamyl-
the Shuttle service is for, U/l129,082,068,6
Lactate dehydrogenase, U/l543.5 nm335,0to 126.8

The results of the study of cellular and humoral immunity.
before the treatmentafter 2 weeksafter 2 months
Immunoglobulin A, g/l2,12,30to 2.29
Immunoglobulin M, g/l1,61,51,75
Immunoglobulin G, g/l10,911,010,8
T-lymphocytes ,%56,061,065,0
B - lymphocytes, %to 12.01931,0
Phagocytosis of latex %515556
TNF14,921,034,5
T-helper %23,029,026,0

Example No. 11.

Patient U., 35.

Diagnosis: non-Hodgkin's lymphoma.

Since 1994 he has taken chemotherapy and radiation therapy.

Despite the massive hormonal and anti-inflammatory therapy, the state of whutcha the tsya, lymph nodes have increased dramatically (highest reached 18-20 cm in diameter), have shortness of breath, weakness.

The treatment by taking 4-chloro-2-methylphenoxyacetic acid and its derivatives.

With 12.02.2003, per os took the drug containing a mixture of 4-chloro-2-methylphenoxyacetic acid and its sodium salt (in a ratio, wt.%: 30:70, respectively) 400 mg ×2 times a day during meals. Within 2 weeks the condition has improved, shortness of breath disappeared, appetite, visible lymph nodes decreased in 1,5-2 times.

After 3 weeks was prescribed medication, which includes a mixture of sodium and lithium salts of 4-chloro-2-methylphenoxyacetic acid (in the ratio, wt.%: 75:25, respectively) 300 mg ×2 times a day during meals.

1.5 months from start of treatment lymph nodes disappeared completely (confirmed by ultrasound). The condition is satisfactory, no complaints.

The control of the state through the year - no complaints, recurrence was not observed.

Data from laboratory studies of the blood of the patient shown in the table below:

Complete blood count.
before the treatmentafter 2 weeksafter 2 months
Hemoglobin, g/l130134145
Er is atrocity, 1×1012/l3,54,3the 4.7
Black. index1,051,051,3
Leukocytes, 1×109/l3,0the 4.75,5
Platelets abs. (thousands)140325410
Eosinophils, %3,03,01,0
Neutrophils:
Stab, %5,15,04,5
Segmented, %625654
Lymphocytes, %242125
Monocytes, %0,50,45,0
ESR, mm/hour43329
Biochemical analysis of blood.
before the treatmentafter 2 weeksafter 2 months
Glucose, mmol/l3,1the 4.749
Urea, mg/DL44,144,138,0
Uric acid, mg/DL6,28,37,4
Albumin, g/l37,449,650,1
Protein, g/l80,182,582,9
Creatinine, mg/DL0,450,310,35
Aspartate aminotransferase, U/l36,029,030,0
Alanine aminotransferase, U/l75,065,746,9
Gamma-glutamyl-
transferase, U/l107,098,045,6
Lactate dehydrogenase, U/l459,0230,0217,4
The results of the study of cellular and humoral immunity.
before the treatmentafter 2 weeksafter 2 months
Immunoglobulin A, g/l2,052,32 2,53
Immunoglobulin M, g/l1,9of 1.571,56
Immunoglobulin G, g/l11,011,5the 11.6
T-lymphocytes ,%54,065,069,0

B - lymphocytes, %15,024,042,0
Phagocytosis of latex %438067
TNFthe 15.623,032,3
T-helper %26,030,028,0
T-suppressors, %23,028,031,0

Example No. 12.

Patient N., 27 years.

The diagnosis of Hepatitis C. Liver failure. Ascites.

Infected with hepatitis C virus in 1989 through tools or a blood transfusion, after abdominal surgery about blunt trauma of the abdomen.

The first symptoms appeared after 9 years after infection. Pains in the right hypochondrium, yellowness, deteriorated blood biochemical parameters.

After inpatient treatment - improvement.

In 2001, exacerbation of chronic hepatitis after suffering the CSOs flu.

Appeared ascites and edema of the legs, subfebrile temperature, jaundice.

In November 2002, the patient was offered a liver transplant, which he refused.

In January 2003, we started a therapy with medicines.

In the beginning within 2 weeks, the patient received 4-chloro-2-methylphenoxyacetic acid 250 mg ×2 times a day, and then as the medication is prescribed 400 mg ×3 times while eating a mixture of this acid and its potassium, sodium and lithium salts in equal amounts.

During the month transaminase decreased significantly. Yellowness decreased itching disappeared, complaints of recurrent pain in the right hypochondrium and sweating.

One month single dose of the drug is increased in 2 times.

After 2 months the condition is satisfactory, leg edema and ascites disappeared. Skin with yellowish tint, bright sclera.

Recommended the continuation of the drug in the form of a mixture in equal proportions of potassium and lithium salts of 4-chloro-2-methylphenoxyacetic acid in a dose of 250 mg per month 1-2 times per day.

Data from laboratory studies of the blood of the patient shown in the table below:

Complete blood count.
before the treatmentafter 4 weeks after 3 months
Hemoglobin, g/l100123149
Erythrocytes, 1×1012/l4,54,35,0
Black. index0,851,01,0
Leukocytes, 1×109/l8,0the 4.76,1
Platelets abs.(thousands)104127224
Eosinophils, %3,04,01,0
Neutrophils:
Stab, %4,6a 4.95,0
Segmented, %676865
Lymphocytes, %202323
Monocytes, %4,54,0a 4.9
ESR, mm/hour432412
Biochemical analysis of blood.
before the treatmentafter 4 weeksafter 3 months
Sodium, mmol/l139143143
Potassium, mmol/l3,0 4,24,5
Glucose, mmol/l4,65,95,0
Urea, mg/DL42,544,028,9
Uric acid, mg/DLa 4.96,8of 5.4
Bilirubin, mg/DL2,91,70,8
Albumin, g/DL2,0the 4.7of 5.4
Protein, g/DL6,17,18,4
Creatinine, mg/DL0,420,350,34
Aspartate aminotransferase, U/l73,051,028,0
Alanine aminotransferase, U/l77,071,443,9
Gamma-glutamyl-
transferase, U/l129,082,068,6
Lactate dehydrogenase, U/l543.5 nm335,0247,0

Example 13.

Patient, 32 years old.

Complaints intensive hair loss.

Treatment restorative hair cosmetics and tools recommended by folk medicine (rubbing relevant ointments and trevani the infusions), the desired result is not given.

When handling high frontal receding hairline, sparse hair and piecewise absence (bald spots) hair on the back of the head, cheeks and chin.

After laboratory examination, diagnosed with diffuse alopecia.

Received 2 courses of treatment:

First course - daily for 15 days, the patient took the drug 4-chloro-2-methylphenoxyacetic acid 100 mg ×2 times a day during meals, and 2-3 times a day and cleaned the head and face in an aqueous solution of 50 ml of water, 5.0 g of a mixture of 4-chloro-2-methylphenoxyacetic acid and its potassium, sodium and lithium salts in a ratio by weight of.%: 50:10:30:10 respectively.

After 10-12 days has almost stopped the hair loss.

Continuing treatment by admission within 15 days 150 mg ×2 times a day while eating a mixture of potassium and sodium salts of 4-chloro-2-methylphenoxyacetic acid in the ratio, wt.%: 10:90, respectively, and a daily 3-x single proteranii head and face above solution.

On the 20th day after the start of treatment on the back of the head appeared whitish hair "down", and a week later noticed the appearance of dark hair on his head and face.

Recommended for 2 months to continue regularly at least 3 times a day wiping of the head and face water RA is tworoom in 50 ml of water, 5.0 g of a mixture of potassium and sodium salts of 4-chloro-2-methylphenoxyacetic acid in the ratio, wt.%: 40:60, respectively.

Six months after the treatment, the condition of the fur on his head close to the norm, recurrence associated with hair loss, it is not marked.

Example 14. Patient Y., 22 years.

Complaints paroxysmal cough, fever.

When entering tapped moist rales.

Diagnosis: left-sided pneumonia.

From previously assigned treatment (injection kanamycin) refused due to allergies to antibiotics,

A course of drug treatment.

In the first 3 days of the scheduled oral administration of 4-chloro-2-methylphenoxyacetic acid 100 mg ×2 times a day, and then within 7 days of the scheduled oral administration of a mixture of 4-chloro-2-methylphenoxyacetic acid and its potassium and sodium salts of 150 mg when is equal to the ratio of the components 3 times a day, one hour after a meal.

10 days after the start of treatment recommended continuing the above-mentioned mixture of 150 mg once daily for 7 days.

After 2 weeks of treatment when the patient's examination of rales no, the General condition is satisfactory.

Example 15.

Patient I., aged 20.

Complaints about shooting pain in the ears and especially in the left part of the head.

The diagnosis of otitis media.

From antibiotic treatment refused due to allergies.

A course of drug treatment.

In the he 3 day oral administration of a mixture of 4-chloro-2-methylphenoxyacetic acid and its lithium salt in the ratio, wt.%: 95,0:5,0 respectively, 100 mg ×3 times a day, one hour after a meal and in the morning and at night ear swabs soaked in an aqueous solution in 20 ml of water, 2.0 g of a mixture of potassium and lithium salts of 4-chloro-2-methylphenoxyacetic acid in the ratio of components, wt.%: 70,0:30.0 respectively.

On the second day of treatment the pain disappeared.

Over the next 7 days assigned to oral administration of a mixture of 4-chloro-2-methylphenoxyacetic acid and its potassium, sodium and lithium salts, 100 mg at a ratio of components, wt.%: 30:30:30:10 accordingly, on 2 times a day, one hour after meals and at night, ear swabs soaked in an aqueous solution in 20 ml of water, 2.0 g of a mixture of potassium, sodium and lithium salts of 4-chloro-2-methylphenoxyacetic acid in the ratio of components, wt.%: 40,0:40,0:20,0, respectively.

10 days after the start of treatment, the condition is satisfactory.

1. Application of 4-chloro-2-methylphenoxyacetic acid having the structural formula

or its pharmaceutically acceptable derivatives in the form of the corresponding alkali metal salts of this acid, or mixtures of these salts, or mixtures of 4-chloro-2-methylphenoxyacetic acid and these derivatives as a drug with antitumor, immunomodulatory and protiva specialname properties as well as antiviral activity.

2. The use according to claim 1, characterized in that a derivative of 4-chloro-2-methylphenoxyacetic acid is a potassium salt of this acid.

3. The use according to claim 1, characterized in that a derivative of 4-chloro-2-methylphenoxyacetic acid is a sodium salt of this acid.

4. The use according to claim 1, characterized in that a derivative of 4-chloro-2-methylphenoxyacetic acid is a lithium salt of this acid.

5. The use according to claim 1, characterized in that a derivative of 4-chloro-2-methylphenoxyacetic acid is a mixture of potassium and sodium salts of this acid with a ratio of components, wt.%: potassium salt of 4-chloro-2-methylphenoxyacetic acid - 1,0-98,0; sodium salt of this acid - rest.

6. The use according to claim 1, characterized in that a derivative of 4-chloro-2-methylphenoxyacetic acid is a mixture of potassium and lithium salts of this acid with a ratio of components, wt.%: potassium salt of 4-chloro-2-methylphenoxyacetic acid - 1,0-98,0; the lithium salt of this acid - rest.

7. The use according to claim 1, characterized in that a derivative of 4-chloro-2-methylphenoxyacetic acid is a mixture of sodium and lithium salts of this acid with a ratio of components, wt.%: sodium salt of 4-chloro--methylphenoxyacetic acid 1,0-98,0; the lithium salt of this acid - rest.

8. The use according to claim 1, characterized in that a derivative of 4-chloro-2-methylphenoxyacetic acid is a mixture of potassium, sodium and lithium salts of this acid with a ratio of components, wt.%: potassium salt of 4-chloro-2-methylphenoxyacetic acid - 1,0-55,0; sodium salt of 4-chloro-2-methylphenoxyacetic acid - 1,0-85,0; the lithium salt of this acid - rest.

9. The use according to claim 1, characterized in that the mixture of 4-chloro-2-methylphenoxyacetic acid and its derivatives in the form of the corresponding alkali metal salts of this acid or of mixtures of these salts are made with a ratio of components, wt.%: 4-chloro-2-methylphenoxyacetic acid - 1,0-98,0; its derivatives - rest.



 

Same patents:

FIELD: chemistry of peptides, medicine.

SUBSTANCE: invention relates to preparing new peptides possessing immunomodulating, anti-proliferative, anti-tumor and antiviral activity. Invention proposes new peptides comprising up to 30 amino acid residues of the general structural formula: X1-Trp-Gly-Gln-X2 wherein X1 is taken among the following group: -His-Gly-Val-Ser-Gly-, -His-Gly-Gly-Gly-, -His-Val-Gly-Gly-, -His-Gly-Gly-Gly-Gly-, and -Gln-Gly-Gly-Gly-Gly, or absent; X2 is taken among the following group: -His-Gly-Thr-His-Gly, -Gly-Gly-Thr-His-Gly, -Pro-His-Val-Gly-Gly, -Pro-His-Gly-Gly-Gly, -Pro-His-Gly-Gly-Gly-Trp-Gly, -Gly-Gly-Gly-Thr-His-Ser, or absent.

EFFECT: valuable medicinal properties of peptides.

8 cl, 5 tbl, 5 dwg, 6 ex

FIELD: medicine.

SUBSTANCE: method involves administering diacerine influencing DNA synthesis for reducing keratinocytes proliferation without changing their vital activity, inhibiting interleukines IL-1,IL-6 and α-TNF (tumor necrosis factor).

EFFECT: enhanced effectiveness of treatment.

11 cl, 7 dwg, 2 tbl

FIELD: medicine, chemistry of peptides, amino acids.

SUBSTANCE: invention relates to novel biologically active substances. Invention proposes the novel composition comprising peptides of the formula: H-Arg-Gly-Asp-OH and H-Tyr-X-Y-Glu-OH wherein X means Gln and/or Glu; Y means Cys(acm) and/or Cys. The composition shows ability to inhibit proliferative activity of mononuclear cells, to induce suppressive activity and their ability for secretion of cytokines TNF-1β (tumor necrosis factor-1β) and IL-10 (interleukin-10 ).

EFFECT: simplified method for preparing composition, valuable medicinal properties of composition.

4 cl, 16 tbl, 9 ex

FIELD: medicine, phthisiology, pharmacy.

SUBSTANCE: invention proposes the inhalation preparation in treatment of tuberculosis comprising an antibacterial medicinal agent an aqueous solution. The preparation comprises also a medicinal preparation with the immunomodulating effect as 5-amino-2,3-dihydro-1,4-phthalazinedione potassium salt or 5-amino-2,3-dihydro-1,4-phthalazinedione sodium salt, or 5-amino-2,3-dihydro-1,4-phthalazinedione potassium and sodium salts taken in the equal ratio in the following ratio of components, wt.-%: antibacterial medicinal agent, 1.0-10.0; 5-amino-2,3-dihydro-1,4-phthalazinedione potassium salt or 5-amino-2,3-dihydro-1,4-phthalazinedione sodium salt, or 5-amino-2,3-dihydro-1,4-phthalazinedione potassium and sodium salts taken in the equal ratio, 1.0-10.0; water, the balance. The preparation inhibits activity of macrophages reducing the level of tumor necrosis factor (TNF) and acute-phase proteins that results to weakening intoxication symptoms, activates superoxide-forming function and phagocyte activity of neutrophile granulocytes, enhances the microbiocide system of cells that, in turn, results to arresting the inflammation process. Invention can be used as the inhalation agent in treatment of tuberculosis.

EFFECT: valuable medicinal properties of preparation.

2 cl, 2 ex

FIELD: medicine, rheumatology, pharmacy.

SUBSTANCE: invention proposes ointment as a curative agent that comprises the following components: 5-amino-2,3-dihydro-1,4-phthalazinedione alkaline salt of mixture of alkaline salts, medicinal vaseline, vaseline oil as an ointment base and distilled water taken in the following ratio of components, wt.-%: 5-amino-2,3-dihydro-1,4-phthalazinedione alkaline salt or 5-amino-2,3-dihydro-1,4-phthalazinedione mixture of alkaline salts, 1.0-50.0; medicinal vaseline, 10.0-20.0; vaseline oil, 5.0-10.0, and water, the balance, wherein 5-amino-2,3-dihydro-1,4-phthalazinedione sodium or potassium salt is used as an alkaline salt, and 5-amino-2,3-dihydro-1,4-phthalazinedione sodium and potassium salts mixture is used as mixture of alkaline salts composed of the equal ratio of components, i. e. 5-amino-2,3-dihydro-1,4-phthalazinedione sodium and potassium salts mixture. Indicated ointment normalizes membrane cell to the normal state damaged as result of disease, regulated intra- and intercellular metabolic processes that, in turn, promotes to normalization of metabolism and arresting inflammation for the shortest times. Invention can be used in treatment of autoimmune disease.

EFFECT: improved and valuable medicinal properties of ointment.

3 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to new 6-alkyl-5-(2-isonicotinoylsulfohydrazoyl)uracil hydrochlorides of the general formula (I) wherein R means alkyl comprising 1-4 carbon atom. Compounds possess an anti-mycobacterial and an immunotropic activity and can be used as an immunomodulating agent and an anti-mycobacterial agents. Also, invention relates to a pharmaceutical composition based on thereof.

EFFECT: valuable medicinal properties of compounds.

4 cl, 10 tbl, 2 ex

FIELD: veterinary science.

SUBSTANCE: the present innovation deals with cooling selected fertilized uninfected eggs at 2-4 C up to 7 d followed by homogenization, diluting with physiological solution of egg mass, bactericidal treatment, conservation with phenol solution up to its concentration being 0.3% at subsequent filtration of target product. Moreover, egg mass should be diluted with physiological solution at the ratio of 1:5, then comes thermal treatment upon water bath at 70-80 C for 1 h and before conservation one should cool the target product in bactericidal chamber under the lamp with ultraviolet irradiation for 30-40 min. The method provides increased total and specific body resistance, it enables to obtain cheaper and more acceptable biostimulant and simplified way for preparing.

EFFECT: higher efficiency.

4 ex, 3 tbl

FIELD: medicine, biopharmacology, immunology.

SUBSTANCE: invention relates to manufacturing curative-prophylactic preparations based on leukocyte interferon and natural cytokines. The preparation based on complex of natural cytokines is prepared by induction of human leukocytes with Newcastle disease virus of strain "H". Indicated complex of natural cytokines is prepared by at least two treatments of leukocytes before induction stage with virus with the same natural complex of cytokines prepared in previous stage of induction. Complex is purified from foreign proteins of inductor and comprises 104 IU of antiviral activity of human interferon-alpha in one ampoule, not less, and cellular cytokines, phosphate buffer for maintaining pH 6.9-7.5, sodium chloride and mannitol. The end product is lyophilized for preparing the injection preparation. Invention provides increasing activity of the preparation and to retain the natural complex of cytokines.

EFFECT: improved preparing method, valuable medicinal properties of preparation.

3 cl, 2 ex

FIELD: medicine, gastroenterology, pharmacy.

SUBSTANCE: invention relates to agents used in treatment of ulcerous-erosion injures in gastroduodenal region. Method involves diluting 100 mcg of dry lyophilized powder of immunomodulating agent "Superlimf" in 3-5 ml of 0.9% isotonic solution and irrigation of ulcer or erosion with this solution 1 time per a day by the endoscopy method. The treatment course is 3-4 procedures with break for 4-5 days. Method provides alteration of cytokine pattern of tissues, induction of influx of mononuclear phagocytes to the injure focus that results to localization of inflammation and the complete epithelization of ulcers and erosions.

EFFECT: improved and effective method for treatment.

1 ex

FIELD: medicine, pharmaceutical industry, pharmacy.

SUBSTANCE: invention relates to a method for preparing an anti-inflammatory, wound-healing, capillary-strengthening, immunomodulating agent. Method for preparing an anti-inflammatory, wound-healing, capillary-strengthening, immunomodulating agent is carried out for four stages. At the first stage violet tricolor and/or field milled herb is extracted with fluidized carbon dioxide under the definite condition followed by separation of grist from lipophilic fraction of extract; at the second stage defatted grist is subjected for three-fold extraction by remaceration method under the definite condition followed by treatment and purification of combined extract, treatment, condensation and preparing liquid alcoholic extract; at the third stage liquid alcoholic extract is used for preparing polysaccharide and flavonoid complexes by precipitation of polysaccharide with three-fold volume of 96% ethyl alcohol and the following drying at the definite temperature; at the forth stage grist after isolation of polysaccharide and flavonoid complexes is used for preparing pectins by treatment with three-fold volume of ammonium oxalate solution at the definite temperature, evaporation and drying. Liquid alcoholic is evaporated to 1/5 of the parent volume, dried by spraying drying or lyophilic drying at definite temperatures. Each end product prepared at each stage can be used as both independent medicinal formulation and can be used for preparing other medicinal formulations (tablets, capsules, suppositories, films). Also, invention relates to a method for preparing an anti-inflammatory, wound-healing, capillary-strengthening, immunomodulating agent that involves extraction of violet tricolor and/or field milled herb with 70% ethyl alcohol by infusion for a definite time followed by purification of the end product, settling at the definite temperature and filtration. Method provides preparing agent with broad pharmacological pattern of action and provides the maximal using the medicinal vegetable raw.

EFFECT: improved preparing method, valuable medicinal properties of agent.

5 cl, 5 tbl, 17 ex

FIELD: chemistry of peptides, medicine.

SUBSTANCE: invention relates to preparing new peptides possessing immunomodulating, anti-proliferative, anti-tumor and antiviral activity. Invention proposes new peptides comprising up to 30 amino acid residues of the general structural formula: X1-Trp-Gly-Gln-X2 wherein X1 is taken among the following group: -His-Gly-Val-Ser-Gly-, -His-Gly-Gly-Gly-, -His-Val-Gly-Gly-, -His-Gly-Gly-Gly-Gly-, and -Gln-Gly-Gly-Gly-Gly, or absent; X2 is taken among the following group: -His-Gly-Thr-His-Gly, -Gly-Gly-Thr-His-Gly, -Pro-His-Val-Gly-Gly, -Pro-His-Gly-Gly-Gly, -Pro-His-Gly-Gly-Gly-Trp-Gly, -Gly-Gly-Gly-Thr-His-Ser, or absent.

EFFECT: valuable medicinal properties of peptides.

8 cl, 5 tbl, 5 dwg, 6 ex

FIELD: organic chemistry, medicine, oncology, pharmacy.

SUBSTANCE: invention relates to new derivatives of quinazoline of the formula (I):

wherein m = 0, 1, 2 or 3; each group R1 that can be similar or different is taken among halogen atom, trifluoromethyl, hydroxy-, amino-group, (C1-C6)-alkyl, (C2-C8)-alkenyl, (C2-C8)-alkynyl, (C1-C6)-alkoxy-, (C2-C6)-alkenyloxy-, (C2-C6)-alkynyloxy-, (C1-C6)-alkylamino-, di-[(C1-C6)-alkyl]amino- and (C2-C6)-alkanoylamino-group, or among the group of the formula: Q1-X1- wherein X1 represents oxygen atom (O); Q1 represents aryl-(C1-C6)-alkyl, heteroaryl, heteroaryl-(C1-C6)-alkyl, heterocyclyl or heterocyclyl-(C1-C6)-alkyl and wherein neighboring carbon atoms in any (C2-C6)-alkylene chain in substitute at R1 are separated optionally by insertion to the chain the group taken among oxygen atom (O) and N(R5) wherein R5 represents hydrogen atom or (C1-C6)-alkyl, or when the inserted group represents N(R5); R5 can represent also (C2-C6)-alkanoyl and wherein any group -CH2 or -CH3 in substitute R1 carries one or more substitutes in each indicated group -CH2 or -CH3 and wherein these substitutes are taken among halogen atom or (C1-C6)-alkyl, or substitute taken among hydroxy-, amino-group, (C1-C6)-alkoxy-, (C1-C6)-alkylthio-group, (C1-C6)-alkylsulfinyl, (C1-C6)-alkylsulfonyl, (C1-C6)-alkylamino-, di-[(C1-C6)-alkyl]amino-, (C2-C6)-alkanoyloxy, (C2-C6)-alkanoylamino- and N-(C1-C6)-alktyl-(C2-C6)-alkanoylamino-group, or among the group of the formula: -X3-Q3wherein X3 represents oxygen atom (O) and Q3 represents heteroaryl, and wherein any aryl, heteroaryl or heterocyclyl group in substitute at R1 carries optionally 1, 2 or 3 substitutes that can be similar or different and taken among halogen atom, trifluoromethyl, cyano-, hydroxy-, amino-group, carbamoyl, (C1-C6)-alkyl, (C2-C8)-alkenyl, (C2-C8)-alkynyl, (C1-C6)-alkoxy-, (C2-C6)-alkenyloxy, (C2-C6)-alkynyloxy,(C1-C6)-alkylthio-group, (C1-C)-alkylsulfinyl, (C1-C6)-alkylsulfonyl, (C1-C6)-alkylamino-, di-[(C1-C6)-alkyl]amino-group, (C1-C6)-alkoxycarbonyl, N-(C1-C6)-alkylcarbamoyl, N,N-di-[(C1-C6)-alkyl]carbamoyl, (C2-C6)-alkanoyl, (C2-C6)-alkanoyloxy-, (C2-C)-alkanoylamino- and N-(C1-C6)-alkyl-(C2-C6)-alkanoylamino-group, or among the group of the formula: -X4-R8 wherein X4 represents a simple bond and R8 represents hydroxy-(C1-C6)-alkyl, (C1-C6)-alkoxy-(C1-C6)-alkyl, cyano-(C1-C6)-alkyl, amino-(C1-C6)-alkyl, (C1-C6)-alkylamino-(C1-C6)-alkyl or di-[(C1-C6)-alkyl]amino-(C1-C6)-alkyl, or among the group of the formula: -X5-Q4 wherein X5 represents a simple bond or -CO, and Q4 represents heterocyclyl or heterocyclyl-(C1-C6)-alkyl that carries optionally 1 or 2 substitutes that can be similar or different and taken among halogen atom, (C1-C6)-alkyl, (C2-C8)-alkenyl, (C2-C8)-alkynyl and (C1-C6)-alkoxy-group and wherein any heterocyclyl group in substitute at R1 carries optionally 1 or 2 oxo-substitutes, and wherein any aryl group in the group R1 represents phenyl; any heteroaryl group in the group R1 is taken among pyrrolyl, imidazolyl, triazolyl and pyridyl, and any heterocyclyl group in the group R1 is taken among oxyranyl, tetrahydrofuranyl, tetrahydropyranyl, pyrrolidinyl, morpholinyl, 1,1-dioxotetrahydro-1,4-thiazinyl, piperidinyl, homopiperidinyl, piperazinyl and homopiperazinyl; R2 represents hydrogen atom; n = 0, 1, 2 or 3; R3 represents halogen atom, trifluoromethyl, cyano-, hydroxy-group, (C1-C6)-alkyl, (C2-C8)-alkenyl, (C2-C8)-alkynyl or (C1-C6)-alkoxy-group, or its pharmaceutically acceptable salt. Also, invention relates to methods for preparing compounds of the formula (1) and to pharmaceutical composition based on thereof for using as an anti-tumor agent. Invention provides preparing new derivatives of quinazoline possessing an anti-tumor activity.

EFFECT: improved preparing method, valuable medicinal properties of compounds and pharmaceutical composition.

17 cl, 7 tbl, 7 ex

FIELD: organic chemistry, medicine, oncology, pharmacy.

SUBSTANCE: invention relates to new derivatives of acridine of the formula (1):

wherein R, R1, R2 and R3 mean hydrogen atom; Z means oxygen or sulfur atom; X means nitrogen atom or C-R5 wherein R5 means hydrogen atom; n = 2; m = 0; R4 means (C1-C3)-alkyl residue that can be substituted with aryl, (C4-C10)-heteroaryl and other substitutes, (C6-C10)-aryl and others, and to their pharmaceutically acceptable salts. Compounds of the formula (1) possess an anti-tumor activity and can be used as an active component of the medicinal agent.

EFFECT: improved preparing method, valuable medicinal properties of compounds and composition.

9 cl, 1 tbl, 20 ex

FIELD: medicine.

SUBSTANCE: method involves combining vaccine prepared from 107 cells of autologic tumor lysate with 60 mg of betaleukine and introducing it strictly in intracutaneous paravertebral mode in three points arranged 3 cm far from each other. The introduction takes place every 3 weeks so that the first two vaccinations are combined with 470 mg of betaleukine introduced into anterior abdominal wall. Vaccination treatment is continued on receiving positive retarded type hypersensitivity response to injection after every vaccination with tumor lysate without betaleukine.

EFFECT: enhanced effectiveness in inducing and supporting antitumor immune response.

FIELD: organic chemistry, biochemistry, pharmacy.

SUBSTANCE: invention relates to new anellated carbamoyl azaheterocycles of the general formula (1)

or (2) possessing the inhibitory effect on protein kinase activity, a focused library comprising these compounds, and pharmaceutical composition based on thereof. In the general formula (1) or (2) R1 represents hydrogen atom or optionally substituted (C1-C6)-alkyl; R2 and R3 represent independently of one another hydrogen atom, inert substitute, optionally substituted (C1-C6)-alkyl, optionally substituted (C3-C8)-cycloalkyl, optionally substituted phenyl, optionally substituted aryl, optionally substituted heterocyclyl; R4 represents optionally substituted (C1-C6)-alkyl, optionally substituted (C3-C8)-cycloalkyl, optionally substituted phenyl, optionally substituted aryl, optionally substituted heterocyclyl; A and B in common with carbon and nitrogen atoms joined to the form an optionally substituted and optionally condensed azaheterocycle; D and F in common with carbon atoms joined form an optionally substituted and optionally condensed phenyl or aryl, optionally substituted and optionally condensed azaheterocycle. K and L in common with carbon and nitrogen atoms joined to them form an optionally substituted azaheterocycle. Also, invention related to methods for preparing compounds of the general formulae (1) or (2).

EFFECT: improved preparing methods.

10 cl, 2 sch, 25 tbl, 7 ex

FIELD: medicine, oncology.

SUBSTANCE: invention relates to method for malignant tumor treatment (including cancer, sarcoma, melanocytoma) in human by ectasceine ET743 intravenous infusion in dose of 500-1650 mug/m2 of surface are; to similar treatment by combination of ET743 with antiemetic agent; as well as to relative composite preparation. Method of present invention provides clinical amelioration in subject suffering from progressive or metastasing cancer and improves treatment effectiveness of diseases being progressed after known chemotherapy.

EFFECT: new effective method for cancer treatment; drug with good acceptability.

31 cl, 3 ex, 1 tbl

FIELD: medicine, oncology, gastroenterology, immunobiotechnology.

SUBSTANCE: invention describes an antibody or its derivative, or its fragment showing the structure able to bind the target structure. Antibody is located inside and on surface of human gastroenteric tract epithelial tumor cells and in subpopulation of normal gastroenteric tract epithelial cells. Indicated binding structures comprise sequences determining the complementarity of the region (CDR) in light chain comprising in main amino acids at number 23-33 (CDR 1), 49-55 (CDR 2), 88-98 (CDR 3) of amino acid sequence represented in SEQ ID NO:2, and CDR sequence in heavy chains comprising in main amino acids at number 158-162 (CDR 1), 177-193 (CDR 2), 226-238 (CDR 3) of amino acid sequence represented in SEQ ID NO:2, or other binding structures with similar unique binding properties. Also, invention describes the target-structure located inside or on surface of tumor cells: vaccine composition designated for treatment of malignant disease in human and comprising abovementioned antibody. Also, invention describes methods for treatment and diagnosis of malignant disease. Using this invention provides preparing antibodies that relieve identification of new phenotype-specific tumor-associated antigens, to predict and treat metastatic human diseases. Invention can be used in medicinal practice.

EFFECT: valuable medicinal properties of antibodies.

37 cl, 21 dwg, 4 tbl, 8 ex

Chalcone coumarins // 2266291

FIELD: organic chemistry, medicine, oncology, pharmacy.

SUBSTANCE: invention relates to compounds of the formula (I): or their pharmaceutically acceptable salts or solvates wherein Ar represents a substituted or unsubstituted (preferably aromatic one) carbocyclic or heterocyclic group wherein abovementioned carbocyclic or heterocyclic group comprises 5 or 6 atoms in cyclic structure wherein a heteroatom is taken among the group consisting of nitrogen (N) and sulfur (S) atom and any substitutes at Ar group are taken independently of one another of the group consisting of Cl, Br, F atoms and OR10 wherein R10 represents saturated or unsaturated lower hydrocarbon (C1-C6)-radical of normal or branched structure; R represents OR10 wherein R10 corresponds to above given value; R1 represents lower hydrocarbon (C1-C6)-radical of normal or branched structure under condition that if R1 represents -CH3 and R means -OCH3 or -OH then Ar group can't represent 4-methoxyphenyl or 3,4-dimethoxyphenyl. Also, invention proposes a component of medicinal agent used in treatment or prophylaxis of neoplasms. Also, invention proposes a pharmaceutical composition possessing with an anti-proliferative activity and comprising the effective amount of one or some compounds of the formula (I) in combination with one or some pharmaceutically acceptable additives. Invention provides the development of chalcone coumarins possessing with the enhanced anti-proliferative effect with respect to sensitive tumor cells, cells with resistance to conventional chemotherapeutic agents, among them, to anti-tumor medicinal agents of the last generation represented by paclitaxel and docetaxel.

EFFECT: valuable medicinal properties of compounds and compositions.

1 tbl, 21 ex

FIELD: organic chemistry, medicine, oncology, pharmacy.

SUBSTANCE: invention relates to substituted derivatives of N-benzylindol-3-yl-glyoxylic acid of the formula (1): wherein groups R, R1, R2, R3, R4 and Z have the following values: R means -NO2, -NH2, (C1-C6)-acylamino-, aroylamino-, nicotinoyl or isonicotinoyl, arylsulfonylamino-, succinimido- wherein this residue R can be substituted with (C1-C6)-group by choosing by carbon atom at positions 2, 3 and 4 of phenyl ring; R1 means hydrogen atom (H), (C1-C6)-alkyl that can be replaced with at least one phenyl group; R2 means pyridyl; R3 and R4 mean H; Z means oxygen (O), sulfur (S) atom. Compounds of the formula (1) possess an antitumor effect that allows their using in pharmaceutical compositions.

EFFECT: valuable medicinal properties of compounds and compositions.

6 cl, 2 dwg, 3 tbl, 9 ex

FIELD: pharmaceutical and cosmetic industries, biological aromatic vitamin D analogs.

SUBSTANCE: invention relates to compounds selected from group containing (E)-6-[3-(3,4-bis-hydroxymethylbenzyloxy)phenyl]-1,1,1-trifluoro-2-trifluoromethyloct-5-en-3-in-2-ol, (3E,5E)-6-[3-(3,4-bis-hydroxymethylbenzyloxy)phenyl]-1,1,1-trifluoro-2-trifluoromethylocta-3,5-dien-2-ol, (E)-6-{3-[2-(3,4-bis-hydroxymethylphenyl)ethyl]phenyl}-1,1,1-trifluoro-2-trifluoromethyloct-5-en-3-in-2-ol; and (3E,5E)-6-{3-[2-(3,4-bis-hydroxymethylphenyl)ethyl]phenyl}-1,1,1-trifluoro-2-trifluoromethylocta-3,5-dien-2-ol, as well as from abovementioned compounds wherein one or more hydroxyl groups have protective group of formula -(C=O)-R, wherein R represents linear or branched C1-C6-alkyl, or C6-C10-aryl, or C7-C11-aralkyl; and aryl and aralkyl radicals may be substituted with one or two hydroxyl groups, C1-C3-alkoxy groups, halogen atoms, nitro or amino groups. Also disclosed are methods for application of said analogs in pharmaceutical composition with cell proliferation and differentiation activity useful in therapy and veterinary (i.e. dermatology, oncology, autoimmune diseases, organ and tissue transplantation), as well as in cosmetic composition.

EFFECT: vitamin D analogs with value pharmaceutical and cosmetic properties.

12 cl, 5 tbl, 6 dwg, 10 ex

FIELD: chemistry of peptides, medicine.

SUBSTANCE: invention relates to preparing new peptides possessing immunomodulating, anti-proliferative, anti-tumor and antiviral activity. Invention proposes new peptides comprising up to 30 amino acid residues of the general structural formula: X1-Trp-Gly-Gln-X2 wherein X1 is taken among the following group: -His-Gly-Val-Ser-Gly-, -His-Gly-Gly-Gly-, -His-Val-Gly-Gly-, -His-Gly-Gly-Gly-Gly-, and -Gln-Gly-Gly-Gly-Gly, or absent; X2 is taken among the following group: -His-Gly-Thr-His-Gly, -Gly-Gly-Thr-His-Gly, -Pro-His-Val-Gly-Gly, -Pro-His-Gly-Gly-Gly, -Pro-His-Gly-Gly-Gly-Trp-Gly, -Gly-Gly-Gly-Thr-His-Ser, or absent.

EFFECT: valuable medicinal properties of peptides.

8 cl, 5 tbl, 5 dwg, 6 ex

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