Method of treating cervical cancer
SUBSTANCE: invention refers to medicine, namely oncology, and can be used for treating cervical cancer. That is ensured by radiation teletherapy and brachytherapy. Each brachytherapy session is preceded by bringing the Hydrogel Coletex-M Tissue 3-5 ml to the tumour before 12-18 hours. Before gel contact, the Coletex-M Tissue is introduced. Further,1-1,5 hours prior to the brachytherapy session, the textile tissue is removed, and Hydrogel Coletex-ADL Tissue 4-6 ml is brought to the tumour. Preliminary, the Hydrogel Coletex-ADL Tissue is added with lidocaine to achieve the gel concentration 4-6%.
EFFECT: method provides reduced total toxicity and drug load ensured by the required concentration of metronidazole maintained in the tumour before the radiation session, and also analgesia without using narcotic preparations, optimised time and geometry of centring introduction that allows intensifying the damage exposure on the tumour.
The invention relates to medicine, namely to Oncology, and can be used in the treatment of cervical cancer.
There is a method of treatment of recurrent cervical cancer (patent RF №2243766, IPC A61K 31/282, publ. 2005), including the introduction on the first day of platydema, and during the following three days conducting external irradiation with 2.6 Grams. On the fifth day of treatment in the space, introduce a solution of novocaine, suspension hydrocortisone solution, dipyrone, a solution of vitamin B12, gentamicin, cyclophosphamide, methotrexate. These therapeutic effects is repeated in sequence four times.
The disadvantage of this method is the trauma of injection in the space, which can lead to serious complications: injury to major vessels, nerves, abstsedirovanie on the introduction of drugs and other Method is difficult to use and requires additional training of the doctor.
There is a method of treatment of local recurrence of cervical cancer (patent RF №2240114, IPC A61K 31/17, publ. 2004), including the vagina tampons with a therapeutic composition containing ointments Viferon, linseed oil, doxorubicin, methotrexate and hydroxyacetone, within 10 days for 10 hours to conduct daily irradiation session perineal field.
The disadvantage of this method is that the pre is proposed drugs do not provide deep penetration of the medicinal compounds in the tumor tissue, do not have analgesic action, and the irradiation of recurrent cervical cancer in the pelvis with perineal field does not provide the required dose distribution and involves significant radiation dose to the rectum and urethra.
The known method and intratumoral parametreleri the introduction of metronidazole in combined radiotherapy common cancer of the cervix (Mustafin JS Improvement and the implementation of the method of intratumoral and parametrising the introduction of metronidazole in combined radiotherapy common cancer of the cervix. Abstract. Diss. for obtaining the academic degree KMN, M., 1991, p.9), which includes radiation treatment according to the scheme: in the first stage - beam radiation in static mode 4 Grams a day, three or four sessions, then 2 G daily until SOD 16-20 Gy, further holding intracavitary irradiation at 5 Gy twice a week to SOD 50 Gy over five weeks. At the same time, continued exposure zones regional metastasis 2 Gr. Metronidazole was administered before the first 3-4 sessions of exposure in the form of intratumoral injections of the cervix and parametrium.
The disadvantage of this method is its complexity, high invasiveness, high degree of pain with the introduction of metronidazole, a high probability of complications, including wound is their vessels.
The closest is a method of treatment of cancer patients (patent RF №2089247, IPC A61N 5/10, publ. 1997), including radiation therapy in combination with intratumoral the introduction of metronidazole applique on the tumor textile material containing sodium alginate with metronidazole and dimethylsulfoxide.
The disadvantage of this method is that it is necessary to apply a strong analgesic, and sometimes drugs.
The task of the invention is to remedy these disadvantages, the efficiency of the treatment, reducing the overall toxicity and drug load (including drugs) to patients through achieving necessary radiomodification concentrations of metronidazole and maintain this concentration directly into the tumor a significant period of time - before the session of irradiation required for practical work. Also the task of improving the quality of life of the patient when performing brachytherapy by providing antispasmolytic, analgesic, antiseptic and anti-inflammatory effects. This allows you to expand the range of patients who can apply this treatment, including patients with large tumors (more than 80 cm3), as well as those patients who have clinical screening is reported, for example, in heart disease, it is impossible to systematically summarize the high concentration of painkillers.
For this purpose, the method of treatment of cervical cancer, including remote radiation therapy and brachytherapy in combination with the introduction to radiological, metronidazole in the form of application to the tumor textile material containing layer of sodium alginate with metronidazole proposed before each session brachytherapy for 12-18 hours to the tumor to bring hydrogel napkin "Collex-M, volume of 3-5 ml depending on the volume of the tumor. Then before contact with the gel to enter the textile cloth Collex-M", and 1-1 .5 hours before the session brachytherapy delete textile cloth and enter hydrogel napkin "Collex-ADL" in the volume of 4-6 ml, which additionally add lidocaine to achieve 4-6% concentration in the gel, depending on the patient's pain threshold.
This procedure allows, in addition to the effect of radiological, to provide a vaginal cleansing before intrauterine intervention and to achieve good analgesia without the use of strong analgesics and narcotic drugs, to optimize the time and the geometry of the introduction of endostatin.
The implementation of the method is demonstrated on specific clinical examples.
Patient G-VA, 57 years old, is 10-3013, was in the radiotherapy Department of Moscow them. PageRank with 05.05.2010, 28.05.10,
Diagnosis: cervical Cancer IIIB century, T2bN1M0, exophytic form of growth, right parametrium and metastatic variant. Comorbidities: hypertension 2 tbsp., ischemic heart disease, angina, paroxysmal tachycardia.
Histology: particles moderately differentiated adrenoblokatorov cancer with a significant predominance of structures endometrioid adenocarcinoma.
Gynecological status at admission: cervix in mirrors gipertrofirovanie to 6 cm in diameter, the front lip is deformed postpartum breaks. Around the external OS small tumor proliferation. Palpable neck barrel-shaped, gipertrofirovanie in both portions up to 5 cm in diameter, woody density. The body of the uterus is not enlarged. Right parametrium is determined by the cervical tumor infiltration. Left - free.
Given the prevalence of the tumor process, accepted conditionally combined treatment plan: stage 1 - preoperative chemoradiotherapy followed by the decision of the question about the possibility of surgical treatment.
With 04.05 on 25.05.2010, had started remote radiation therapy. Irradiation was performed on the device "ONCOR" (Decel. suc., 18 MeV), using multi-leaf call the matora, dynamic fractionation, GENUS - 4 Gy×3 fractions, then 2.5 G to SOD=29,5 Gr.
Brachytherapy performed on the device "GAMMAMED 12i" by introducing a system of metralleta into the uterine cavity and lateral arches of the vagina, GENUS - 5 Grams in TTA. Number of sessions - 2. Before sessions brachytherapy for 15 hours to the tumor was brought to 3 ml of hydrogel napkins "Collex-M", then the vagina was introduced textile cloth Collex-M" before contact with the gel. 1 hour before the session brachytherapy textile cloth Collex-M was removed and the tumor was summed application hydrogel napkins "Collex-ADL" in the volume of 5 ml dioksidin, which added 4% lidocaine to achieve a 6% concentration in the gel.
After that conducted the session brachytherapy.
Sessions brachytherapy did not require additional injections of analgesics, complications of inflammatory nature. Attacks of paroxysmal tachycardia was not observed.
As a result of the treatment was expressed positive dynamics. At discharge the patient examined in the chair: the cervix is formed sharply shortened, not visually changed. Palpable neck of the uterus is not enlarged, shifting. On the right side is a small cervical infiltration. The body of the uterus is not enlarged. The appendages are not palpable.
The patient is 3.5 weeks was performed radical x is surgical treatment.
The patient was under observation for 10 months with no signs of recurrence.
The patient And society, 37 years old, was in the radiotherapy Department of Moscow them. PageRank with 15.11 on 10.12.2010,
Clinical diagnosis: Cancer of the cervix, IIIB century, T12N1Mo, mixed growth form. Metastatic option.
Morphological conclusion: no 4121/10 - infiltrative growth of undifferentiated squamous cell cancer with the presence of tumor emboli in the lymph and blood vessels.
Cytological examination punctate iliac lymph node on the right No. 11864-65/10: metastasis of squamous cell carcinoma.
Comorbidities: Nephroangiosclerosis, initial CRF. Inguinal hernia on the right. Posthemorrhagic anemia I class.
When the examination of Moscow:
St.genitalis: cervix deformed, total tumor changed. The exophytic tumor, occupies the entire upper third of the vagina, goes to the vaginal vault, with areas of necrosis, contact bleeding. Palpation supracervical portion of the neck enlarged, hardened. The body of the uterus is not enlarged, shifting, painlessly. The appendages are not enlarged. In parametric freely. Recto-vaginal septum free.
Ultrasound (from 25.10.10 g): the liver is not enlarged, the conventional structure, without focal zones. Gall bladder, kidneys, pancreas, paraaortal region - OS without the features. In supraclavicular and inguinal areas focal areas are not identified. The mammary glands are normal echo patterns. In the right iliac region - l/node 35×13×13 mm, between the external and internal iliac vessels, the group merged nodes total size 37×15×11 mm In the left iliac nodes 25×17×13 mm, 16×8×8 mm Uterus is not enlarged (68×43×65 mm), conventional structure, the endometrium is not thickened (7 mm). The neck is increased (48×40×50 mm), almost completely occupied by the hypoechoic education with increased blood flow, the upper pole of education is slightly above the internal OS. The ovaries are not enlarged (right 26×20×17 mm, left 39×27×18 mm), normal patterns.
Conclusion: the echo picture of the disease cervical cancer, signs of infestation, the entire thickness of the neck, engagement of the inner throat. Secondary lesions of the iliac lymph nodes on both sides.
Given the stage of the disease, extent of the tumor process, the morphological structure of the tumor, the young age of the patient, with the aim of preserving ovarian function in the first stage of the combined treatment was planned execution of preoperative radiotherapy with further discussion on the appropriateness of surgical intervention in the volume of extended removing the uterus with appendages.
Taking into account the presence of a large exophytic component of the tumor, metastatic time is placed in the pelvic lymph nodes, it was decided to hold preoperative radiation therapy with radiologicaly 5-fluorouracil by well-known methods. From platinum drugs to refrain from nephroangiosclerosis. With 15.11 on 06.12.2010 a course of preoperative chemotherapy: type 5-fluorouracil 2,0,
Then started remote radiation therapy LINAC "ONCOR" (Decel. suc., 18 MeV), using a multi-leaf collimator, on the pelvic area with 6 fields, dynamic fractionation, GENUS - 4 Gy×3 fractions, then 2.5 G to SOD=29,5 Gr.
Brachytherapy performed on the device "MULTISOURSE" by introducing a system of metralleta into the uterine cavity and lateral arches of the vagina, GENUS - 5 Grams in TTA. Number of sessions - 2. 18 hours before the session brachytherapy for cervical tumors summed hydrogel napkin "Collex-M with a volume of 5 ml and then, before contact with the gel, textile cloth Collex-M" with metronidazole. 1 hour before the session was extracted textile cloth Collex-M" and the cervix was brought to 5 ml of hydrogel napkins "Kreteks ADL" dioksidin and lidocaine, which added 3% lidocaine to achieve a 5% concentration in the gel.
Despite the technical complexity of the introduction of metralleta in the uterus for more pain during the session, brachytherapy was not required, inflammatory jawline is not marked. Managed to enter undostat to the bottom of the uterus and make endostatin in the lateral arches of the vagina about 2 cm (optimal length).
When the statement is viewed on the chair: the cervix is formed is not increased mucous with granular surface, but not bleeding, appeared plots epithelialization. Palpation the neck is a little thick, even woody density. The body of the uterus is not enlarged, rejected the right. The appendages are not enlarged. In parametric freely.
Thus, a positive dynamics, tumor process recognized resectable.
The patient was operated after 1 month, made an extended hysterectomy with appendages.
The proposed method of treatment of 15 patients. All has been good analgesic and anti-inflammatory, as well as a pronounced antitumor effect. The patient is observed in the period from 1 to 13 months.
The proposed method of treatment is simple and easy to use, requires no special training, helps to enhance the damaging effects of radiation on the tumor and at the same time to reduce the possibility of inflammatory complications in the vagina and the uterus, as well as to reduce and sometimes completely eliminate the use of strong analgesics and narcotic drugs for maintenance sessions brachytherapy.
The method of treatment of cervical cancer, comprising the administration is giving remote radiation therapy and brachytherapy in combination with the introduction of metronidazole applique on the tumor textile material, containing a layer of sodium alginate with metronidazole, characterized in that before each session brachytherapy for 12-18 h, the tumor down hydrogel napkin "Collex-M with a volume of 3-5 ml depending on the volume of the tumor, then before contact with the gel is injected textile cloth Collex-M", and 1-1 .5 h before the session brachytherapy remove textile cloth and injected hydrogel napkin "Collex-ADL" in the volume of 4-6 ml, which additionally add lidocaine to achieve 4-6%concentration in the gel, depending on the patient's pain threshold.
SUBSTANCE: invention relates to humanised anti-beta 7 antibodies; a composition containing said antibody; a method of inhibiting interaction of human integrin beta 7 subunits with a second integrin subunit using said antibody; as well as a version of use of the listed antibodies.
EFFECT: invention can be used to treat chronic inflammatory diseases such as asthma, Crohn's disease, ulcerative colitis, diabetes, complications during organ transplantation and diseases associated with allotransplantation.
47 cl, 22 dwg, 10 tbl, 3 ex
SUBSTANCE: invention relates to an amine compound of formula (I), pharmaceutically acceptable addition salts, hydrates or solvates thereof, having immunodepressive effect , where R - H or P(=O)(OH)2; X - O or S; Y denotes -CH2CH2- or -CH=CH-; Z denotes C1-5-alkylene, C2-5-alkenylene or C2-5-alkynylene; R1 denotes CF3, R2 denotes C1-4-alkyl, substituted with OH or halogen; R3 and R4 independently denotes H < or C1-4-alkyl; A denotes optionally substituted C6-10-aryl, heteroaryl containing 5-10 ring atoms, where 1 or 2 atoms are selected from N, O and S, C3-7-cycloalkyl optionally condensed with optionally substituted benzene, or heterocycloalkyl containing 5-7 ring atoms, where 1 or 2 atoms are selected from N and O, where said substitutes are selected from C1-4-alkylthio, C1-4-alkylsulphanyl, C1-4-alkylsulphonyl, C2-5-alkylcarbonyl, halogen, cyano, nitro, C3-7-cycloalkyl, C6-10-aryl, C7-14-aralkyloxy, C6-10-aryloxy, optionally substituted with oxo or halogen, C2-3-alkyleneoxy, C3-4-alkylene or C1-2-alkylenedioxy, optionally substituted with halogen C1-4-alkyl or C1-4-alkoxy.
EFFECT: novel compound which is effective in reducing the level of lymphocytes in peripheral blood, suppresses tissue breakdown and exhibiting less side effects, such as bradycardia, is disclosed.
20 cl, 237 ex, 2 tbl
SUBSTANCE: invention refers to medicine, namely reflex therapy. A method involves biologically active zone exposure to a flame generated by burning of a wet cotton tincture. It is preceded by steaming the cotton in a herbal infusion, rolling it and used to massage. Then the cotton is smoothed down and placed on an exposure area. It is covered with bands impregnated with an alcoholate and set fire. A burning time is 7 to 30 seconds. The burning time and a number of setting fire is specified on the basis of individual tolerance.
EFFECT: method provides reduced length of body exposure required in various pathological conditions and ensured by improved skin penetration of biologically active substances contained in the herbal infusions.
2 tbl, 3 cl
FIELD: medicine, pharmaceutics.
SUBSTANCE: described is a new polycyclic compound with general formula (I-1) and (1-3) or a pharmaceutically acceptable salt thereof where X1- -CR1 =CR2 - where R1 and R2 independently stand for hydrogen or C1-6 alkyl while Het stands for a radical of the following formulae: that may be substituted 1-3 times additionally described is a pharmaceutical composition containing such compound and intended for prevention or treatment of diseases caused by β-amyloid.
EFFECT: production of a pharmaceutical composition prevention or treatment of diseases caused by β-amyloid.
7 cl, 392 ex, 12 tbl
FIELD: medicine, pharmaceutics.
SUBSTANCE: present invention refers to new compounds of formula
, where X1, X2, Y, R1a, R1b, R2a, R2b, A1, A2, A3 and A4 have the values specified in the description, which are vanilloid receptor subtype 1 (VR1) antagonists.
EFFECT: preparing a pharmaceutical composition on the basis of the compounds of formula 1 and developing methods of managing pain, neurotic pain, allodynia, inflammation or inflammatory disease associated pain, inflammatory hyperalgesia, bladder hyperactivity and urine incontinence.
22 cl, 21 ex
FIELD: medicine, pharmaceutics.
SUBSTANCE: invention concerns applying urea derivatives or their pharmaceutically acceptable salts characterised by formula , wherein RB is specified in: while R3, R4, R'2, R'3, R'4, R'5, and R'6 represent hydrogen as GSK-3 inhibitors, pharmaceutical compositions containing them, and using them for treating and/or preventing disorders the development of which involves GSK-3.
EFFECT: preparing the pharmaceutical compositions containing them, and using them for treating and/or preventing disorders the development of which involves GSK-3.
14 cl, 2 ex, 1 tbl, 4 dwg
FIELD: medicine, pharmaceutics.
SUBSTANCE: there are offered a combination for preventing or treating a proliferative disease, containing a microtubular active agent epothilone B and a pharmaceutically active agent, 1H-pyrazolo[3,4-d]pyrimidine-4-amine 3-(4-chloriophenyl)-1-(1,1-dimethylethyl)-(9CI); the related pharmaceutical composition containing said combination, methods of preventing and treating (versions), a commercial packing including said combination (versions). Particularly, the proliferative disease can represent ovarian cancer, carcinoma of lung and melanoma.
EFFECT: what is shown is synergism of the combination in growth inhibition of non-small cell carcinoma of lung in relation to independent action of its ingredients.
17 cl, 3 dwg, 1 tbl
SUBSTANCE: invention refers to medicine, and may be applied as an agent for prosthetic stomatitis accompanying a denture adaptation period. It involves mouth rinsing with 0.2% aqueous acetylsalicylic acid. The regimen is at least three times a day before meals. The length is at least five days.
EFFECT: method enables decreasing saliva viscosity and surface force, enhancing its wetting properties, providing a shorter denture adaptation period.
SUBSTANCE: invention refers to preparing drugs in the form of a herbal ointment for fibrocystic disease (mastopathy). As active substances, the ointment contains an alcoholic extract of milk-wax green walnut and pericarp, walnut and buckeye leaves in equal proportions of the active substances, an ointment base containing vegetable oil, emulsion wax, interior fat, purified water and parabens.
EFFECT: ointment provides hormone balance control in females.
SUBSTANCE: invention refers to medicine, specifically cardiosurgery, and may be used for treating thromboembolia of pulmonary artery. For this purpose a surgical intervention accompanied by artificial circulation involves mechanical thrombus removal from greater branches of the pulmonary artery. It is followed by exposing a left atrium and conducting a retrograde pulmonary perfusion by sequential perfusion of each of the four pulmonary veins for 4 minutes by a combination solution. The combination solution is prepared by mixing blood from a pump oxygenator and a protective solution in proportions 3:1. The protective solution consists of 0.9% sodium chloride 800 ml, dexamethasone 16 ml, actovegin 400 ml and 15% mannitol 100 ml. The perfusion procedure is conducted at volumetric speed 200-250 ml/min and perfusion pressure 20 mm Hg. Thromboemboles are removed from peripheral parts of the pulmonary artery by aspiration of blood stream from the incised pulmonary artery. The procedure is terminated with hermetically closed wound of the pulmonary artery. A left atrium cavity is closed with recovering cardiac activity, and the incisional wound is closed in layers.
EFFECT: method provides considerably reduced death rate and risk of postoperative complications in the case patients, as well as provided effective removal of small thromboembols from the peripheral parts of the pulmonary artery and prevented developing air embolism of the pulmonary artery.
1 tbl, 1 ex
SUBSTANCE: invention concerns medicine, oncology, and is applicable for photodynamic therapy of malignant growths. That is ensured by introducing a photosensitiser and conducting light illumination of the new growth at wave length corresponding to a maximum absorption of chlorine derivatives. The photosensitiser is presented by a gelatinous capsule with powder microparticles of chlorine derivatives mixed with lyophilised spirulina platensis. Each powder microparticle is coated with a protective acid-resistant film. The gelatinous capsule is introduced orally. Each gelatinous capsule contains the ingredients in the following proportions (Mg): chlorine derivatives - 1-1.5; spirulina platensis - 100-150; protective acid-resistant film - 50-75; calcium stearate - 0.5-0.75.
EFFECT: method enables providing higher clinical and preventative effectiveness in malignant new growths.
8 cl, 1 dwg, 3 ex
FIELD: medicine, pharmaceutics.
SUBSTANCE: group of inventions refers to medicine, and concerns pharmaceutical compositions able to induce cancer cell apoptosis for diagnosing and treating B-cell chronic lymphocytic leukaemia. Substance of the inventions involves the pharmaceutical compositions for treating B-cell chronic lymphocytic leukaemia containing an active ingredient presented by a humanised monoclonal antibody T1h from a secreting hybridoma IOR-TIA under depositary No. ECACC 96112640, identifying a leukocyte differentiation antigen CD6. A diagnostic reagent also contains said antibody.
EFFECT: advantage of the group of inventions consists in higher specific activity.
11 cl, 4 ex, 4 dwg
FIELD: medicine, pharmaceutics.
SUBSTANCE: invention refers to pharmaceutics and medicine and concerns triindolyl methane derivatives of formula
and as anticancer drugs showing cytotoxic, apoptotic action on tumour cells, and also blocking NFkB transcription factor activity.
EFFECT: compounds exhibit high anticancer activity.
4 dwg, 3 tbl, 4 ex
SUBSTANCE: group of inventions refers to medicine and veterinary science. A method involves sequential intravenous introduction of a binary catalytic system (BCS): an oxidation catalyst - a metal complex and an oxidation substratum - ascorbic acid (AA). The oxidation catalyst is introduced in a maximally tolerable or lower doses, and AA - in doses related to molar ratio of the metal complex: AK=1:10. The method also involves local hyperthermia of the tumour with using near infra-red laser emission. The tumour temperature is maintained within the range of 43-45°C by adjusting laser power density. The emission is terminated after achieving the minimum power density maintaining the tumour temperature within the preset temperature range. The declared device comprises a near infra-red laser with emissive power switch-on, switch-off and adjustment systems, and optical system of laser beam formation, a tumour temperature control system with its output connected both with an input of a laser negative feedback system, a laser power density control system. The device comprises an additionally adjustable power density discriminator. An input of the laser power density discriminator is connected with an output of the laser power density control system. The output of the discriminator is connected to an input of the laser switch-off system.
EFFECT: invention provides higher clinical effectiveness.
5 cl, 1 dwg, 1 ex
FIELD: medicine, pharmaceutics.
SUBSTANCE: group of inventions refers to medicine and is applicable in the form of liposome-containing compounds for cancer therapy. A liposome contains one or more phosphatidylcholines, a first derivative of N-(ω)-dicarboxylic acid and phosphatidylethanolamine, an orientation modified derivative of N-(ω)-dicarboxylic acid and phosphatidylethanolamine, an encapsulated therapeutic agent and at least one additional lipid which represents cholesterol or a cholesterol derivative. The orientation modified derivative of N-(ω)-dicarboxylic acid and phosphatidylethanolamine contains an orientation ligand attached to a second derivative of N-(ω)-dicarboxylic acid and phosphatidylethanolamine. The first derivative of N-(ω)-dicarboxylic acid and phosphatidylethanolamine is presented by formula 1,
and the second derivative of N-(ω)-dicarboxylic acid and phosphatidylethanolamine is presented by formula 3, . The orientation ligand preferentially represents transferring, while the encapsulated therapeutic agent is oxalyplatine. The liposome is free from non-modified phosphatidylethanolamine, egg phosphatidylcholine or hydrophilic polymer used to prolong a half lifetime of the liposome in a circulatory channel, and the orientation ligand is other than an intact antibody. What is also described is a method of producing the liposome and a method of treating cancer with using it.
EFFECT: group of inventions provides better target delivery of the therapeutic substance in the tumour cells.
113 cl, 25 dwg, 4 tbl, 30 ex
SUBSTANCE: invention relates to peptide-based compounds containing three-member rings containing a heteroatom, which efficiently and selectively inhibit specific activity of N-terminal nucleophilic (Ntn) hydrolase, bonded with a proteasome. The peptide-based compounds contain epoxide and are functionalised at the N-end.
EFFECT: peptide-based compounds exhibit anti-inflammatory properties and cell proliferation inhibition, oral administration of said peptide-based proteasome inhibitors is possible owing to bioavailability thereof.
23 cl, 14 ex
SUBSTANCE: invention relates to novel derivatives of the anti-tumour antibiotic of the aureolic acid olivomycin A group, having anti-tumour activity and low toxicity, and synthesis method thereof. The invention also relates to a method of producing derivatives of the antibiotic of the aureolic acid olivomycin A group, involving selective oxidation of the side chain of olivomycin A aglycone through reaction with sodium periodate, followed by amidation of the obtained key intermediate 1'-des-(2,3-dihydroxy-n-butyroyl)-1'-carboxyolivomycin A with corresponding amines in the presence of a condensing agent.
EFFECT: disclosed compounds have marked anti-tumour activity and low toxicity compared with the original olivomycin A.
2 cl, 9 ex, 1 dwg, 6 tbl
SUBSTANCE: invention relates to compounds of formula (I), having histone deacetylase (HDAC) enzyme inhibiting action, stereoisomers, hydrates, solvates and pharmaceutically acceptable salts thereof, compounds of formula (II), compounds selected from a list, a method of producing compounds of formula (I), a pharmaceutical composition, an inhibition method and methods of treating using compounds of formula (I). In formulae
R denotes substituted or unsubstituted groups selected from (C6-C10)aryl, (C3-C12)cycloalkyl, heteroaryl, (C6-C10)aryl (C1-C6)alkyl and heterocyclyl; where the heterocyclyl hereinafter is a 5-10-member ring radical which consists of carbon atoms and 1-5 heteroatoms selected from nitrogen, oxygen and sulphur, and heteroaryl hereinafter is an aromatic heterocyclyl, and each aryl, cycloalkyl, heteroaryl, arylalkyl and heterocyclyl can be substituted with one or more substitutes selected from halogens, including fluorine, chlorine, bromine, iodine, (C1-C6)alkyl, (C1-C6)alkoxy, (C6-C10)aryl, halogen(C1-C6)alkyl, (C6-C10)aryl(C1-C6)alkoxy, -O-(C3-C12)cycloalkyl, -O-CH2-(C3-C12)cycloalkyl, hydroxyl, NRaRb and ORa, where Ra and Rb independently denote (C1-C6)alkyl and aryl; R1 denotes (C6-C10)aryl; R2 and R3 independently denote hydrogen, (C1-C6)alkyl, -COOR5, -CONR5R6, -CH2NR5R6, -CH2CH2NR5R6, -CH2CH2OH or -CH2OH; provided that one of R5 or R6 is hydrogen or unsubstituted alkyl, the other is neither hydrogen nor unsubstituted alkyl; R5 and R6 independently denote hydrogen, (C1-C6)alkyl, (C3-C12)cycloalkyl, (C6-C10)aryl, (C6-C10)aryl(C1-C6)alkyl, heteroaryl or heteroaryl(C1-C6)alkyl, which can be unsubstituted or substituted; or R5 and R6 can be combined to form a saturated or unsaturated 3-8-member ring having 0-2 heteroatoms, including N, O or S; where the heteroaryl hereinafter is a 5-10-member ring radical consisting of carbon atoms and 1-5 heteroatoms selected from nitrogen, oxygen and sulphur, and each alkyl, cycloalkyl, aryl, arylalkyl, heteroaryl or heteroarylalkyl can be substituted with one or more substitutes selected from halogen, including chlorine, fluorine, bromine or iodine,(C1-C6)alkoxy and NRaRb; R4 denotes OH, (C6-C10)aryl, ortho-substituted aniline or amino (C6-C10) aryl, which can be optionally substituted with one or more groups selected from halogens, including fluorine, chlorine, bromine, iodine, hydroxyl, amino groups or (C6-C10)aryl; X denotes -NR7-, -CONR7- or -N R7CO; R7 denotes hydrogen or (C1-C6)alkyl; Y denotes (C6-C10)aryl or (C6-C10)aryl(C2-C6)alkenyl; m is an integer from 0 to 1; n is an integer from 0 to 1; o is an integer from 0 to 7; and p is an integer from 0 to 1.
EFFECT: improved method.
SUBSTANCE: invention refers to medicine, namely oncology, and is applicable for treating rectal cancer with synchronous remote metastases. That is ensured by radiation therapy together with radio modifiers and combined with chemotherapy followed by radical resection of a primary tumour and remote metastases. The radio modifiers are presented by the intrarectal introduction of metronidazole as a part of a composite mixture containing sodium alginate and 2% dimethylsulphoxide, and also local microwave hyperthermia. The chemotherapy is presented by a two-day intensive course of chemotherapy FOLFOX6 involving high doses of platinum and 5-fluorouracil in the form of the 48-hour infusion.
EFFECT: method allows reducing total length of treatment, enabling a complete course of effective preoperative radiation chemotherapy with minimum toxicity in a relatively short time, performing earlier sphincter-preserving operations with well-timed resection of the primary tumour, regional and remote metastases ensured by implementing mechanisms, chemosensitisation and synergic effect of said radio sensitising agents.
SUBSTANCE: invention refers to cell biology. Dopamine and/or its synthetic analogues, particularly substituted 3,4-dihydro-2(1H)-pyrimidinthione is applied as a cytotoxic agent having an effect on human cancer cells in culture.
EFFECT: presented substances can find application in medicine as a base for developing dosage forms used for therapy of malignant growths.
5 dwg, 3 ex
SUBSTANCE: invention refers to medical equipment, namely to radiation therapeutic apparatuses. An apparatus comprises an X-ray source with an electronic gun, a target and a electrode potential source of an electronic gun cathode, a resonator arranged along an electron ray and connected to a microwave signal source allowing frequency tuning, a detector of passed pathological radiation material, a frequency recorder. A conductor is introduced to couple a resonator and said target. The resonator is toroidal and has a gap to pass the electron ray, while a distance of the resonator gap and the target is specified provided 1.3>UINπfd/v0|Up|>1.1 wherein UIN is a microwave signal amplitude in the resonator gap, f is a microwave signal frequency, d is a distance of the gap and the target, v0 is an electron flow, Up is a cathode potential of the electronic gun cathode with respect to the resonator.
EFFECT: use of the apparatus provides more complete elimination of pathology of the radiated biological material.
2 cl, 4 dwg, 1 tbl