Method for chemotherapy of acute leukosis
FIELD: medicine, oncology.
SUBSTANCE: invention relates to a method for chemotherapy of acute leucosis. Method involves isolation of blast cells and interphase cells from marrow puncture sample leukocyte fraction of blood of a patient subjected for chemotherapy. Then cells are deposited by centrifugation in medium 199 and their concentration is brought about to the level (2-3) x 106 cells/ml. Then isolated cells are incubated with each chemotherapeutic drug chosen from the following group: dexamethasone, cyclophosphanum, vincristine, teniposide, etoposide, citarabinum that are diluted preliminary with isotonic solution to the concentration 1:1000. Then cells treated with chemotherapeutic drugs are centrifuged repeatedly in medium 199 followed by carrying out the annexin test. In the schedule treatment drugs that showed the maximal percent of cells apoptosis are used. Method provides maximal decreasing adverse and toxic effects of chemotherapeutic drugs and to enhance apoptosis of tumor cells based on individual selection of chemotherapeutic drugs for a patient, to prolong remission period and to exclude using additional curative effects.
EFFECT: improved and enhanced method of chemotherapy.
The invention relates to medicine, more specifically to Oncology, and can be used in the treatment of patients with malignant diseases, acute leukemia.
It is known study of the sensitivity of blast cells in the bone marrow for anticancer chemotherapy using the MTT-test and DiSC method in a wide range of lethal concentrations in 4 dilutions (Kuznetsova S., abstract of Diss. Kida. the honey. Sciences, the sensitivity of blast cells to anticancer chemotherapy in children with acute leukemias", Moscow, 2004). The main drawback of this study is repeated breeding lethal doses of anticancer chemotherapy.
There is a method of study the sensitivity of tumor cells with the use of ultra-low doses of anticancer chemotherapy of carcinoma cells of the lung Lewis (Ostrovsky L.A., Buharov NV, Rykov V.A., etc. // Radiat. Biol. Radioecol. - 2003. - 43, No. 3. - S-281). The offered method of determination of sensitivity to anticancer drugs involves the use of two drugs - doxorubicin and nitrosoanatabine that does not always produce a positive effect. It is well known that the combination of several chemotherapy drugs are more effective than monotherapy.
The aim of the invention is the ability of the individual who nogo selection of anticancer chemotherapy.
The goal is to reach that punctate bone marrow in the amount of 7-10 ml is placed in a heparinized medium 199, secrete Mature and blast cells white blood cells and interphase; the latter is twice the gradient ficoll-urografin (ρ 1,077-1,078) besieged by centrifugation in medium 199 and brought to the concentration (2-3)×106/ml. Then treated them divorced isotonic NaCl in concentrations of 1:1 million the following medications: dexamethasone, cyclophosphamide, vincristine, cytoblastema, vinblastine, vamanam, citarabinom, Atsidum and methotrexate (last used at a dilution of 1:1000). Cells with the preparations were incubated at 37°C for 30-60 minutes, after which cells were washed once by centrifugation in medium 199 and once in phosphate-buffered saline (pH 7.3 to 7.4). To assess apoptosis of bone marrow cells were placed anexity test. After evaluation of apoptosis in the treatment of a particular patient included anticancer drugs cause apoptosis in a larger number of blast cells of the patient.
The proposed method for the treatment of acute leukemia is new, as it provides for individual selection of anticancer drugs that cause the most pronounced apoptosis of cells. It is not obvious from the level of medicine in the treatment of patients with acute leukemia who m
In the available open sources information of Russia, CIS and abroad indications similar method was not found.
The developed method is industrially applicable. It can be reproduced and repeated many times in hospitals as a specialized and General profile with immunological laboratory.
The method is as follows. The patient in the treatment room under aseptic conditions to produce a fence 7-10 ml of bone marrow, punctate bone marrow is placed in heparinized medium 199, secrete Mature and blast cells white blood cells and interphase; the latter is twice the gradient ficoll-urografin (ρ 1,077-1,078) besieged by centrifugation in medium 199 and brought to the concentration (2-3)×106/million Then they were processed divorced isotonic NaCl in concentrations of 1:1 million the following medications: dexamethasone, cyclophosphamide, vincristine, cytoblastema, vinblastine, vamanam, citarabinom, Atsidum and methotrexate (last used at a dilution of 1:1000). Cells with the preparations were incubated at 37°C for 30-60 minutes, after which cells were washed once by centrifugation in medium 199 and once in phosphate-buffered saline (pH 7.3 to 7.4). Then put annexinv test and evaluate the apoptosis of cells. In scheme L. the treatment of the patient with acute leukemia include those anticancer drugs, which cause apoptosis in a larger number of cells.
Examples of a specific implementation method can serve as a statement of case histories.
1. Statement of the case history No. 981/f. Patient A., 70 years for the first time has addressed to the Department of chemohormonal Rostov scientific research Institute of 19.01.2005 year. Diagnosis: Acute leukemia, undifferentiated variant. Complaints received at a General weakness. Considers herself a patient since November 2004, when he developed the submandibular lymphoedema, which was treated surgically, in the General analysis of blood were found anemia, blastema. From treatment at the place of residence refused. When entering a state of moderate severity, state of health is satisfactory. Skin, mucous membranes pale, hemorrhagic syndrome is not expressed. Peripheral lymph nodes, liver, spleen not enlarged.
OAK 19.01.2005. hemoglobin 78 g/l, erythrocytes 3,0·1012/l, platelets 192 thousand, leukocytes 3,4·109/l, p/I 6%, C/I 9%, eosinophils 2%, basophils 0%, monocytes 12%, lymphocytes 71%, ESR 67 mm/h. Myelogram 20.01.05 - punctate bone marrow poor cellular elements, there is the oppression of all germ blood. Found blast cells 23%.
In determining the activity of apoptosis blast cells of the bone marrow was detected activation of apoptosis under the influence of ultra-low doses of the following is the courthouse square: dexamethasone in 29% of the cells, teniposide in 28% of the cells, cyclophosphamide 17% of the cells. Focusing on research data in the regimen were included with the above mentioned preparations: 1, 3, and 5 courses of therapy included - cyclophosphamide 600 mg/day 1, cytarabine 100 mg/1 to 5 days, dexamethasone 10 mg/day by mouth 1 to 7 days; 2, 4 and 6 courses - teniposide 100 mg/drip in 1-3 days, cytarabine 100 mg/1 to 5 days, dexamethasone 10 mg/day by mouth in 1-5 days. Treatments were performed without complications, had a positive effect was achieved clinical and hematological remission, which persists until the present time.
2. Statement of the case history No. 571/f. Patient X., 4 years for the first time applied in the pediatric Oncology Department of the Rostov cancer research Institute 17.01.2005 year. Diagnosis: Acute lymphoblastic leukemia. L1, "common" option, the standard risk group.
Complaints when applying for a sore throat when swallowing, frequent "colds". The girl has been sick since August 2004, when the survey about catarrhal phenomena, in General, the analysis of blood lymphocytosis found. In December 2004, there was an increase of body temperature to 38-40°, catarrhal phenomena, sore throat, stomatitis. Received antibacterial therapy. In the blood increased anemia, remained lymphocytosis. When entering a state of moderate severity, health improvement is considerable. It was noted the redness of the throat, hypertrophy of the tonsils. Peripheral lymph nodes, liver, spleen not enlarged. Hemorrhagic syndrome is not defined.
OAK from 18.01.2005. hemoglobin 122 g/l, erythrocytes 4,0·1012/l, platelets 208 thousand, leukocytes 3,8·109/l blasts of 0.5%, plasmic order has been revealed at 0.5%, a p/I of 2.5%, with/I 1%, eosinophils 0%, basophils 0%, monocytes 7%, lymphocytes and 88.5%, ESR 31 mm/h. Myelogram 18.01.05 - punctate monomorphic, blast cells of 82.6%, L1 (FAB) lymphocytic variant of acute leukemia. Immunophenotyping of bone marrow 18.01.05 - Common-ALL. Identified in a high percentage of markers of activated cells and stem cells.
Ultrasound pathological formations in the studied organs of the abdominal cavity, retroperitoneal space, neck and supraclavicular areas are not identified. Chest x-ray 21.01.05 pathology has not revealed.
The study of the activity of apoptosis showed that under the influence of ultra-low doses the activity of apoptosis was increased in 11% of the cells during the incubation methotrexate, 15% platinum.
With 28.01.2005 year started polychemotherapy, with the inclusion of drugs: prednisolone 35 mg by mouth in 1-36 days, vincristine 0.9 mg/in, rubomycin 18 mg/8, 15, 22, 29 days, asparaginase 6000 UNITS/12, 15, 18, 21, 24, 27, 30, 33 days; 6-mercaptopurine 36 mg by mouth in 36-64 days, cytarabin 45 mg/37, 38, 39, 40, 45, 46, 47, 48, 52, 53, 54, 55, 59, 60, 61, 62, days, cyclophosphamide 600 mg/drip 36 64 days of treatment.
Control bone marrow examination on day 15 17.02 - blasts 13,0%, on the 33rd day 09.03 - bone marrow cell, is represented by all shoots blood blasts of 1.6%.
With 25.04.2005 year started prozivajushij remission 2 course of chemotherapy, which included: 6-mercaptopurine 15 mg by mouth in 1-56 days of course, methotrexate 620 mg/drip 8, 22, 36, 50 days. With 13.07.2005, conducted 3 chemotherapy, comprising: dexamethasone 6 mg by mouth daily 1-22 days of course, vincristine 0.9 mg/doxorubicin 18 mg/8, 15, 22, 29 days, asparaginase 6000 IU/drip 8, 11, 15, 18 days, tioguanin 36 mg by mouth in the 30-49 days, cyclophosphamide 600 mg in 30 day, cytarabin 45 mg 32, 33, 34, 35, 45, 46, 47, 48 days. Chemotherapy satisfactorily, without severe side effects. Currently she is in clinical and hematological remission on maintenance therapy. Control tests 20.12.2005 years, 3 months after the end of intensive chemotherapy confirmed clinical and hematological remission.
Technical and economic efficiency "of the Way the chemotherapy of acute leukemia" allows you to:
- Used in the treatment of anticancer drugs that cause the most damaging effect on tumor cells of a particular patient.
- To minimize the adverse toxic manifestations of chemotherapy.
- is velicity remission and eliminate the use of additional therapeutic effects during this period.
- To improve the quality of life of a patient with acute leukemia.
The way the chemotherapy of acute leukemia, characterized in that the first patient to be chemotherapy, isolated blast cells and interphase cells white blood cells in the bone marrow punctate, besieging them by centrifugation in medium 199, bring to the concentration (2-3)·106/ml, followed by incubation of the selected cells with each of the chemotherapeutic agents selected from the group of: dexamethasone, cyclophosphamide, vincristine, teniposide, etoposide, cytarabine, pre-diluted saline to a concentration of 1:1000000, and methotrexate, pre-diluted saline to a concentration of 1:1000, then repeat the centrifugation, treated with chemotherapy cells in medium 199, put annexinv test and include in the regimen those anticancer drugs, which caused the highest percentage of apoptosis cells.
SUBSTANCE: method involves taking sample material from various brain regions during surgical intervention. The material is used for cultivating stable transplantable tumor cells strain. Stable growth pattern being achieved, the culture is reinoculated and exposed to treatment with cytotstatic preparations given in therapeutic concentrations. After having accomplished the treatment, the cells are let grow during 1.5-2 weeks. Then, the number of newly grown and survived cells is estimated relative to the number of inoculated cells. The preparation is selected for use, that, when applied, results in minimum newly grown and survived cells.
EFFECT: high accuracy and reliability in selecting cytostatic preparation.
1 tbl, 1 ex
FIELD: medicine, medicinal technology, pharmacology, analytical chemistry.
SUBSTANCE: method involves analysis of alkaline solutions of humic acids and qualitative assay is carried out in the region from 310-800 nm (absorption bands with maximum at 350 nm and 390 nm). The quantitative content of humic acid is determined at wavelength 350 nm by calibrating plot. Invention provides the lower cost and labor consumptions, higher precision, sensitivity and reproducibility in analysis of humic acids content in peloids. Invention can be used for qualitative and quantitative determination of humic acids in peloids.
EFFECT: improved method of analysis.
2 tbl, 2 dwg, 1 ex
SUBSTANCE: method involves determining sorting, removing primary packaging, destroying secondary packaging, applying alkaline hydrolysis of drugs in installations for activating chemical processes under saturating alkaline solution with air oxygen to 12-14 mg/l, processing hydrolyzate with in electrolyzers with insoluble and then with soluble electrodes, removing coagulation products by settling alkaline solution and filtering it through inert filtering materials and returning the alkaline solution into the technological process.
EFFECT: enhanced effectiveness of solid and/or liquid drug recovery.
2 cl, 1 dwg
SUBSTANCE: method involves sorting drugs produced from oil refining products, lipids, alcohols and fatty acids, extracting their lipophilic and hydrophilic ingredients with used oil and aqueous alkaline of pH 11-12 taken in 1:0.7-1 proportion, respectively, with hydrophilic ingredients being destructured by applying electrocoagulation and lipophilic ones by burning.
EFFECT: wide range of ecological advantages.
SUBSTANCE: claimed method includes preparation of yeast slurry 1:2 in physiological saline and 2 % glucose solution in distilled water. 1 ml of tissue preparation, 1 ml of yeast slurry, and 28 ml of glucose solution are sampled in test tube. The same component wherein tissue preparation is replaced with 1 ml of sterile physiological saline are sampled in control tube. Tubes are sealed with closure with glass tubes ends of which are dropped down in bulb. 1 drop of liquid is sampled from each tube, placed into chamber, and yeast cell amount is calculated. Further chamber is placed into thermostat at temperature of 33-35°C and held for 60-90 min. After agitation 1 drop of solution is simultaneously sampled from control and test tubes and yeast cell amount is calculated. Activity of tissue preparation is evaluated based on volume of released carbon dioxide and amount of yeast cells in test and control tubes (before and after experiment).
EFFECT: accelerated method of decreased cost and increased accuracy.
3 tbl, 5 ex
FIELD: medicine, clinical pharmacology, forensic medicine.
SUBSTANCE: in the course of testing the quality of solutions for injections they should be injected under the skin of a piglet's abdomen at the volume being sufficient to create "lemon peel" effect, then one should fix the time, detect the dynamics of post-injectional inflammation of skin and subcutaneous-fatty fiber and in case of irreversible character and the onset of necrotic alterations it is possible to conclude upon low safety of preparations under testing and the chance for provoking post-injectional necrosis due to their application. The innovation provides the chance to detect medicinal iatrogeny due to widening the information upon the quality of medicinal preparations in the form of either availability or absence of necrotic action.
EFFECT: higher quality of testing.
SUBSTANCE: the present innovation deals with treating certain neurological and psychic disorders in mammalians including human beings and refers to the introduction of a selective inhibitor PDE10, moreover, the innovation in question deals with the ways to identify chemical compound that possesses he efficiency of a selective inhibitor PDE10. The innovation enables to develop new method for screening the compounds for the presence of the ability to selectively inhibit PDE10.
EFFECT: higher efficiency.
2 cl, 6 dwg, 7 ex, 4 tbl
FIELD: analytical measurements, pharmacy.
SUBSTANCE: method involves using a substance representing a pharmaceutically active component in a medicinal formulation characterized by sustained releasing preferably. Method involves carrying out the following procedures: (1) contacting a diluted nonaqueous composition containing analyzed substance and nonaqueous base, for example, wax or fat with an aqueous dissolving medium for predetermined time, and (ii) measurement of analyzed substance amount in aqueous dissolving medium. Invention provides enhancing precision and safety in assay of dissolving rate of analyzed substance.
EFFECT: improved assay method.
34 cl, 8 dwg, 3 tbl
FIELD: medicine, pharmacy.
SUBSTANCE: invention relates to a method for treatment of a patient with inflammatory disease or risk for its development. Method involves administration to a patient the following drugs: (i) tricyclic antidepressant, for example, amoxapine and (ii) corticosteroid, for example, prednisolon. Medicinal agents (i) and (ii) are administrated simultaneously or in interval in limits for 14 days in doses sufficient for inhibition of inflammation or reducing risk for its development. Also, invention relates to a pharmaceutical composition and pharmaceutical package containing medicinal agents (i) and (ii). Also, invention relates to a method for identification of combinations of compounds used in treatment of inflammation by assay of decreasing levels of pro-inflammatory cytokine in contact of immune cells with the combination of compound-candidate with (i) or (ii). Invention provides expanding assortment of anti-inflammatory agents and combinations, identification of such combinations and reducing toxicity in carrying out the anti-inflammatory treatment.
EFFECT: valuable medicinal properties of combinations, improved method of treatment.
36 cl, 3 tbl, 3 ex
FIELD: analytical chemistry; medicine.
SUBSTANCE: method involves applying copper (II) salicylate complex with following obtained colored compound extraction and photometric examination of the extract. Copper (II) sulfate and sodium salicylate solutions taken in volume proportion of 0.8-1.8-1.0-2.2 ml per volume of sample under analysis are added to the preparation solution amount equal to 1 ml of 1% lidocaine hydrochloride solution. After having treated the mixture with the reagent, extraction with chloroform is carried out and optical density of the extract is measured at wavelength λ=750 nm. Lidocaine hydrochloride amount is determined from calibration plot.
EFFECT: improved specificity, selectivity of the method.
1 dwg, 7 tbl
FIELD: organic chemistry, medicine, oncology, pharmacy, biochemistry.
SUBSTANCE: invention relates to amide derivative represented by the following formula :
in any of the following cases (A) or (B), or its salt. In the case (A) R1 represents 5-7-membered saturated cyclic group comprising 1-2 nitrogen atoms as atom forming cycle (saturated cyclic amino-group can be substituted with 1-3 similar or different substitutes chosen from group consisting of (C1-C10)-alkyl, (C1-C10)-alkoxycarbonyl), mono-(C1-C10)-alkylamino- or di-(C1-C10)-alkylamino-group; R2 represents (C1-C10)-alkyl, halogen atom, halogen-(C1-C10)-alkyl, (C1-C10)-alkoxy-group, (C1-C10)-alkoxycarbonyl, nitro-group, mono-(C1-C10)-alkylcarbamoyl, di-(C1-C10)-alkylcarbamoyl or cyano-group; R3 represents hydrogen atom, halogen atom or (C1-C10)-alkoxy-group; Het1 represents any of the following formulae:  ,  ,  ,  ,  ,  and  ; Het2 represents pyridyl, pyrimidinyl, pyrazinyl or 1,2-dihydropyridazinyl (wherein Het2 can be substituted with 1-3 similar or different substitutes chosen from halogen atom) but except for compound wherein R1 means (i) pyrrolidinyl, piperidinyl, piperazinyl or morpholinyl and each of them can be substituted with 1-3 similar or different substitutes chosen from group consisting of alkyl, alkoxycarbonyl, halogen atom, halogenalkyl, hydroxyalkyl, amino-, monoalkylamino-, dialkylamino-group, carbamoyl, monoalkylcarbamoyl and dialkylcarbamoyl; (ii) monoalkylamino-group, or (iii) dialkylamino-group; Het1 means group of the formula , and Het2 means pyrazinyl or pyridyl and each of them can mean a substituted alkyl. In case the (B) R1 represents 4-methylpiperazin-1-yl, 1-pyrrolidinyl, piperidino-group, 4-ethylpiperazin-1-yl, 4-n-propylpiperazin-1-yl, cis-3,5-dimethylpiperazin-1-yl, morpholino-, dimethylamino- or diethylamino-group; R2 represents methyl, halogen atom, trifluoromethyl, methoxy-group, methoxycarbonyl, nitro-group, dimethylcarbamoyl or cyano-group; R3 represents hydrogen atom, bromine atom or methoxy-group; Het1 represents compound of the formula ; Het2 represents 3-pyridyl. Invention relates to a pharmaceutical composition possessing inhibitory activity with respect to BCR-ABL tyrosine kinase comprising amide derivative of the formula (I) or its salt as active component and a pharmaceutically acceptable nontoxic and inert carrier. Also, invention relates to BCR-ABL tyrosine kinase inhibitor, therapeutic agents comprising amide derivative of the formula (I) or its salt and, optionally, a pharmaceutically acceptable nontoxic and inert carrier used in treatment of chronic myelogenous leukemia, acute lymphoblast cell leukemia, acute myelogenous leukemia. Invention provides and proposes amide derivative inhibiting activity of BCR-ABL tyrosine kinase.
EFFECT: valuable medicinal properties of compounds and pharmaceutical composition.
8 cl, 2 tbl, 83 ex
FIELD: medicine, oncology, pharmacy.
SUBSTANCE: invention proposes a pharmaceutical composition that contains compounds of chlorogenic acid isolated from Piper betel leaves extract or from any other part of plant Piper betel and a pharmaceutically acceptable excipient. Invention provides enhanced effectiveness of treatment of such diseases as acute and chronic myeloid leucosis and lymphoid leucosis and absence of its effect on normal cells. Invention can be used in treatment of patients suffering from acute and chronic myeloid and lymphoid leucosis.
EFFECT: enhanced and valuable medicinal properties of pharmaceutical composition.
32 cl, 4 tbl, 4 dwg, 11 ex
FIELD: organic chemistry, pharmacy, veterinary science.
SUBSTANCE: invention relates to compound comprising 1-(2-methylpropyl)-1H-imidazo[4,5-c][1,5]naphthyridine-4-amine or pharmaceutically acceptable salt of this compound and pharmaceutical composition used for stimulation of biosynthesis of cytokine based on abovementioned compound Also, invention claims a method for stimulation of biosynthesis of cytokines in animal body involving administration in animal body of above described compound or its salt. Invention provides preparing a novel compound possessing useful biological properties.
EFFECT: valuable biological properties of compound and pharmaceutical composition.
3 cl, 12 tbl, 213 ex
FIELD: medicine, peptides.
SUBSTANCE: invention relates to osteogenic growth oligopeptides used as stimulators of hemopoiesis. Invention proposes using an oligopeptide of molecular mass in the range from 200 to 1000 Da, comprising one of the following sequence: Tyr-Gly-Phe-Gly-Gly, Met-Tyr-Gly-Phe-Gly-Gly used in preparing a pharmaceutical composition and enhancing mobilization of hemopoietic stem cells from many differentiation line into peripheral blood, in particular, CD34-positive hemopoietic stem cells. Advantage of the invention involves expanding field in using oligopeptides used in stimulation of hemopoiesis.
EFFECT: enhanced and valuable properties of oligopeptides.
34 cl, 2 tbl, 7 dwg, 4 ex
SUBSTANCE: invention characterizes compositions, their employment, and embodiments of a method of treatment of B-cellular lymphomas, leucosis, and other malignant tumors CD40+. Principal active therapeutical agent is anti-CD40L antibody or another CD40L antagonist inhibiting CD40-CD40L intermediate. In combination or composition with indicated CD40L antagonist any one or several of the following components can be additionally used: anti-CD20 antibody, a chemotherapeutical agent or a combination thereof, and radiotherapy.
EFFECT: enhanced mechanisms of apoptosis of tumor CD40+ cells due to sensitization of these earlier destruction-resistant cells.
88 cl, 4 dwg, 6 tbl, 8 ex
FIELD: organic chemistry, chemical technology, medicine, pharmacy.
SUBSTANCE: invention relates to compounds of the formula (I)
or their pharmaceutically acceptable salts or esters hydrolyzing in vivo and possessing activity inhibiting the cellular cycle and selective with respect to CDK-2, CDK-4 and CDK-6. Compounds can be used in cancer treatment. In the formula (I) R1 represents halogen atom, amino-group, (C1-C)-alkyl, (C1-C6)-alkoxy-group; p = 0-4 wherein values R1 can be similar or different; R2 represents sulfamoyl or group Ra-Rb-; q = 0-2 wherein values R2 can be similar or different and wherein p + q = 0-5; R3 represents halogen atom or cyano-group; n = 0-2 wherein values R3 can be similar or different; R4 represents hydrogen atom, (C1-C6)-alkyl, (C2-C6)-alkenyl, (C2-C6)-alkynyl, (C3-C8)-cycloalkyl, phenyl or heterocyclic group bound with carbon atom wherein R4 can be optionally substituted at carbon atom with one or some groups Rd; R5 and R6 are chosen independently from hydrogen, halogen atom, (C1-C)-alkyl, (C2-C6)-alkenyl or (C3-C8)-cycloalkyl wherein R5 and R6 can be substituted at carbon atom independently of one another with one or some groups Re; Ra is chosen from (C1-C6)-alkyl, (C2-C6)-alkenyl, (C2-C6)-alkynyl, (C3-C8)-cycloalkyl, (C3-C8)-cycloalkyl-(C1-C6)-alkyl, phenyl, heterocyclic group, phenyl-(C1-C)-alkyl or (heterocyclic group)-(C1-C6)-alkyl wherein Ra can be substituted optionally at carbon atom with one or some groups Rg and wherein if indicated heterocyclic group comprises residue -NH- then its nitrogen atom can be optionally substituted with group chosen from the group Rh; Rb represents -N(Rm)C(O)-, -C(O)N(Rm)-, -S(O)r-, -OC(O)N(Rm)SO2-, -SO2N(Rm)- or -N(Rm)SO2- wherein Rm represents hydrogen atom or (C1-C6)-alkyl, and r = 1-2. Also, invention relates to methods for synthesis of these compounds, a pharmaceutical composition, method for inhibition and using these compounds.
EFFECT: improved preparing method, valuable medicinal properties of compounds and pharmaceutical compositions.
24 cl, 3 sch, 166 ex
FIELD: organic chemistry, vitamins, medicine, pharmacy.
SUBSTANCE: invention relates to a new compound of the formula (I): wherein X means hydrogen atom or hydroxy group; R1 and R2 that can be similar or different mean hydrogen atom, (C1-C4)-alkyl; R3 means hydrogen atom, methyl group, fluorine or chlorine atom. Also, invention relates to its esters able to hydrolysis in vivo in combination with pharmaceutically acceptable acids. Also, invention relates to a pharmaceutical composition eliciting the inhibitory activity with respect to proliferation and promoting differentiation of cells and comprising the effective dose of compound of the formula (I) in common with pharmaceutically acceptable carriers and/or excipients. Also, invention relates to applying compound of the formula (I) for preparing a medicine used in treatment and prophylaxis of disease characterizing by abnormal differentiation of cells and/or proliferation of cells.
EFFECT: valuable medicinal properties of compounds.
13 cl, 3 sch, 3 tbl, 6 ex
FIELD: organic chemistry, biochemistry, medicine, pharmacy.
SUBSTANCE: invention relates to new inhibitors of farnesyltransferase of the formula (I):
wherein R1 means hydrogen atom (H), group of the formula R5C(O)- wherein R5 means phenyl, pyridyl or N-methylpiperidine; R2 means hydrogen atom (H), isopropyl, cyclopentyl or N-methyltetrahydropyridyl; R3 means hydrogen atom (H), halogen atom; R4 means hydrogen atom (H), halogen atom; L means -CH2-Z- wherein Z means NH; Y means sulfur atom (S), S(O) or S(O)2; or its salt. Compounds of the formula (I) inhibit activity of enzyme, farnesyl(protein)transferase, that allows their using in pharmaceutical composition in cancer treatment.
EFFECT: valuable medicinal properties of inhibitors.
18 cl, 3 tbl, 3 sch, 6 ex
FIELD: medicine, oncohematology.
SUBSTANCE: the present innovation deals with treating elderly patients with chronic lympholeukosis accompanied with cardiovascular failure. The method deals with applying chemopreparations and cytoprotector. Moreover, 1 wk before the onset of chemotherapeutic therapy one should prescribe preductal at the dosage of 105 mg daily. At this background one should sample blood out of elbow vein at the volume of 200 ml into a vial with glugicir to centrifuge it, isolate plasma, divide into two portions, add into the 1st vial - cyclophosphan 600-800 mg/sq. m, vincristin 1.4 mg/sq. m, into the 2nd vial - adriamycin 50 mg/sq. m to be incubated for 30 min at 37 C and intravenously injected by drops for patients. Simultaneously, the intake of prednisolone should be prescribed at the dosage of 60 mg/sq. m since the 1st d and during the next 5 d and preductal at the dosage of 105 mg daily during a week, and then 2 wk more at the dosage of 60 mg daily. All the procedures should be repeated in above-mentioned sequence 4-6 times. The method enables to decrease toxic manifestations of chemotherapy while applying adequate dosages of cytostatics, anthracycline antibiotics, among them, at no great manifestations of their toxicity due to preductal's cardioprotective action.
EFFECT: higher efficiency of therapy.
1 ex, 5 tbl
FIELD: medicine, oncology.
SUBSTANCE: invention relates to a method for treatment of chronic lympholeukosis. Method involves intravenous drop and jet administration of antitumor chemopreparations and carrying out the autochemotherapy. At the 1-st and 8-th day of treatment cyclophosphan in the dose 750 mg/m2, vincristine in the dose 1.4 mg/m2 and doxorubicin in the dose 30 mg/m2 incubated with 200 ml of autoblood are administrated to patients. From the 1-st to 14-th day of treatment prednisolone is used every day in the therapeutic dose. The treatment course is repeated in 30-35 days depending on blood indices and patient state. The total treatment of courses is 4-5. Method provides reducing cardiotoxicity of doxorubicin and cumulative toxicity of chemopreparations that allows carrying out administration of antitumor chemopreparations in the full volume to patients of elderly age groups.
EFFECT: improved method for treatment.
FIELD: medicine, pharmacology, bioorganic chemistry, pharmacy.
SUBSTANCE: invention relates to the effective using amount of β-L-2'-deoxynucleoside of the formula (I) or (II) used in manufacturing a medicinal agent used in treatment of hepatitis B, pharmaceutical compositions containing thereof, and methods for treatment of hepatitis B. Proposed agent shows the enhanced effectiveness in treatment of hepatitis B.
EFFECT: enhanced and valuable medicinal properties of agent.
83 cl, 6 tbl, 11 ex