Photosensitiser for photodynamic therapy
SUBSTANCE: what is presented is using meso-tetra(3-pyridyl)bacteriochlorin of structural formula (I) as a near-infrared photosensitiser for a photodynamic therapy. Doses 1.0-2.5 mg/kg of the declared photosensitiser have provided 70-100% tumour growth inhibition, 80-131% increase in life expectancy and 25-100% animals' recovery by selective tumour collection and fast clearance.
EFFECT: high photoinduced activity on human tumour cells of various epithelial origin and high dose-dependent anti-tumour effectiveness in the animal with tumours of various origins.
5 dwg, 8 ex
The present invention relates to medicine, namely - to the photosensitizers (PS) for photodynamic therapy (PDT) of malignant tumors and other pathological conditions.
Photodynamic therapy is based on the use of FS that have the ability to selective accumulation (affinity) in tumor tissue and irradiation with light of a specific wavelength pass in the activated state, which initiates the formation of cytotoxic agents, singlet oxygen and free radicals that cause the destruction of the structural elements of the tumor tissue.
The successful application of the method of photodynamic therapy for the treatment of malignant tumors stimulates the search for new FS with improved properties. The most promising for PDT of PS with maximum absorption in the far red and near infrared (700-800 nm), the so-called "therapeutic window" where the self absorption of biological tissues is minimal, allowing deeper penetration of radiation into the tissue and, as a result, high efficiency of therapy (Bonnett R. J. Heterocyclic Chem. 2002. V. 39. P. 455-470).
Promising PS for PDT that absorb in the near-infrared range of the spectrum, are bacteriochlorin (tetrahydropalmatine) (Mironov A. F., green M. A., Zebrowski A. G. et al. / / Bioorganic chemistry. 2003. T. 29. VIP. P. 214-221). So, tokad, palladium derivative bacteriochlorin (Tookad), with maximum absorption at 760 nm is allowed to treat prostate cancer.
However, the vast number of bacteriochlorins is a semi-synthetic drugs, which are used as starting compounds are substances of natural origin. Known same bacteriochlorin purely synthetic origin very difficult to reach - out multi-stage syntheses, as a rule, unstable when stored or photochemically unstable occurring as a result of oxidative processes.
The object of the invention is to find FS, which is characterized by absorption in the near-infrared range of the spectrum, high photoinduced activity, high affinity for tumor tissue, reducing side effects by reducing circulation time in the body, which would significantly increase the effectiveness of treatment.
To solve this problem as PS for PDT, the proposed use very affordable pure synthetic bacteriochlorin - meso-Tetra(3-pyridyl)bacteriochlorin (H2Py4BC) of the following formula:
This compound is described as an intermediate in the synthesis of meso-Tetra[1-(4'-bromobutyl)-3-pyridyl]b�of charikleia of tetrabromide (Patent RF №2479585, C07D 487/22, 2013). H2Py4BC received a two-step synthesis based on pyrrole and 3-pyridinediamine. For its solubilization in aqueous solutions used authorized for medical use non-ionic surfactant Cremophor EL (4% solution).
The invention is illustrated by the following figures:
Fig.1 - absorption Spectrum of a solution of 0.41 mg/ml H2Py4BC 4% Cremophor EL.
Fig.2 - fluorescence Spectra of a solution of H2Py4BC in 0.9% NaCl solution (A) containing 10% FBS medium eagle (MEM) (B) during incubation in dark conditions (1-ex tempore, 2 - a month).
Fig.3 - fluorescence Spectra of H2Py4BC in 0.9% NaCl solution (A) containing 10% FBS medium eagle (MEM) (B) during irradiation (1-ex tempore, 2-5 j/cm2, 3-10 j/cm2).
Fig.4 - Photoinduced activity of H2Py4BC against HEp2 cells (solid line) and EJ (dotted line).
Fig.5 - photo-Induced antitumor activity of H2Py4BC in mice with tumor S37 depending on the dose and the interval between injection and irradiation (1 - 2.5 mg/kg, 30 min; 2 - 2.5 mg/kg, 2 h; 3 - 1.0 mg/kg, 30 min; 4 - 1.0 mg/kg, 2 h; 5 - 0.5 mg/kg, 30 min).
The invention is illustrated by the following examples, but is not limited thereto.
Example 1. meso-Tetra(3-pyridyl)bacteriochlorin synthesized according to previously described methods (Patent RF №2479585, C07D 487/22, 2013) the restoration of meso-Tetra(3-�iridis)of the porphyrin diimide, generated under the reaction conditions of n-toluensulfonate, in the presence of dry potassium carbonate in dry pyridine. λmaxnm (lgε), chloroform: 747 (5,05), 683 (3,78), 521 (4,71), 491 (3,78), 380 (5,08), 367 (4,95), 357 (5,00).
The source of meso-Tetra(3-pyridyl)porphyrin obtained by condensation of equimolar amounts of pyrrole 3-pyridinylmethyl in boiling propionic acid in the presence of air.
Example 2. Preparation of solution H2Py4BC 4% Cremophor EL
Attachment H2Py4BC (4,1 mg) and non-ionic surfactant Cremophor EL (0.4 g) was dissolved in 20 ml of chloroform. Mixed solution in the round bottom flask of 1 l magnetic stirrer, heating to 40-55°C for the intensification of the process of dissolution. Then the solvent was evaporated on a rotary evaporator in vacuo at the temperature of the water bath 30 to 40°C. the Resulting film was dossible in vacuum, after which he hydrational by adding 10 ml of phosphate buffer solution (PBS) with pH=7,34. Stirring is carried out until complete dissolution of the film; the resulting solution was filtered through a membrane filter (Millipore, Type GS) with a pore size of 0.22 μm. All the stages of preparation of the solution was carried out with minimal external lighting.
The solutions were kept at a temperature of 6-10°C in the dark place. Absorption spectrum of a solution of 0.41 mg/ml H2Py4BC 4% Cremophor EL are shown in Fig.1 (register relative�Uo 4% solution of Cremophor EL in the cell l=0,02 cm).
Example 3. Evaluation of the stability of H2Py4BC.
Assessment of the stability of FS was performed using fluorescence analysis. Solutions for research were prepared ex tempore, reaching the chosen concentration (5 µg/ml) by serial dilutions of the initial solution. The concentration of the feed solution consisted of 0.41 mg/ml) as the solvent used medium eagle containing 10% FBS and 0.9% NaCl solution. Registration of fluorescence of the solutions was carried out in the dynamics of the contact method on laser spectral analyzer for fluorescent diagnosis "Leba-6" (LLP "BIOSPEC", Russia). The fluorescence was excited He-Ne laser at the wavelength of the generation of 632.8 nm, the spectral range from 600 to 950 nm.
Fig.2 shows fluorescence spectra of a solution of H2Py4BC in 0.9% NaCl solution (A) containing 10% FBS medium eagle (MEM) (B) during incubation in dark conditions. No change in the profile of the spectrum and the fluorescence intensity indicates its stability in the selected time range.
Example 4. Evaluation of photostability H2Py4BC in cell-free environment.
Assessment of fotovytsvetaniya was performed in 0.9% solution of sodium chloride in the medium eagle (MEM) containing 10% FBS, upon irradiation with polychromatic light. As a light source used halogen lamp mo�of 500 W with a broadband filter KS-13 (λ≥680 nm) and a water filter of a thickness of 5 cm. The light dose was 5 and 10 j/cm2when power density 32,0±1.0 mW/cm2. The fluorescence measurement was carried out by contact of the laser spectral analyzer "Leba-06" in the spectral range of 600-950 nm. Fluorescence spectra were recorded immediately after preparation of the solution and after exposure to light.
When irradiated with FS (Fig.3) in 0.9% NaCl solution (A) and in the medium eagle (MEM) (B) was observed only a slight decrease (no more than 18-20%) fluorescence intensity (λmax=745±2 nm) without changing the profile of the spectrum, indicating its photostationary.
Example 5. Photoinduced activity and dark cytotoxicity of H2Py4BC in relation to the culture of human cells and HEp2 EJ.
Studies were performed on human tumor cells. Cell culture epidermoid carcinoma of the hypopharynx (HEp2) and carcinoma of the bladder (EJ) obtained from the Institute of Virology. D. I. Ivanovsky RAMS, which were cultivated at 37°C in a humidified atmosphere containing 5% CO2(standard conditions).
The cells were dispersed into the wells of flat-bottomed 96-well microplate. The test compounds were introduced into the wells 24 hours after seeding, by varying the concentration from 13 to 3200 nm. To assess phototoxicity after 0.5, 2, 4 and 6 hours of incubation with the photosensitizer, cells were irradiated halogen l�the IPA through a broadband filter KS-13 (λ≥680 nm). The power density was 32,0±1.0 mW/cm2, the calculated light dose of 10 j/cm2. Also studies were performed with deletion from FS environment before irradiation, and without removal.
After irradiation the cells were incubated overnight under standard conditions. To assess the cytotoxic activity of the dies were placed in dark conditions for 24 hours. Evaluation of survival rate was determined by visual and colorimetric method using MTT assay. Biologically significant effect is believed inhibition of cell growth in culture by more than 50%. This value was calculated as the average results of three independent tests.
It is revealed that the FS showed maximum photoinduced activity relative to the HEp2 cell cultures and EJ, with 4-hour incubation, IR50was 32±2 nm and 35±3 nm, respectively, with increasing incubation time up to 6 hours value IR50was not changed (Fig.4). Incubation of the cells with the dye at concentrations up to 3200 nm in the absence of light exposure for 24 hours did not affect the growth of cell cultures.
The removal of FCS from the culture medium before exposure to light slightly reduced the effectiveness of photodynamic therapy (15-20%), which indicates the implementation of photoinduced activity mainly due to the activation of intracellular f�.
Thus, the in vitro results showed that H2Py4BC accumulates in the cells and has a high photoinduced activity.
Example 6. The distribution of H2Py4BC in the tumor S37 and fluorescent contrast relative to surrounding tissue.
Assessment of the distribution of FS in tumor and surrounding tissues was performed in mice with sarcoma S37 in the interval from 5 minutes to 48 hours by the method of local fluorescence spectroscopy (LFS). The photosensitizer was injected intravenously at a dose of 2.5 mg/kg. the Fluorescence was recorded by the contact method on laser spectral analyzer for fluorescent diagnosis and monitoring of PDT "Leba-06".
In tumor tissue normalized fluorescence FS reached a maximum of 2.1±0.7 CONV. units) after 5 min and remained at a high level in for 1 hour after administration, and then for 48 hours was reduced by 95% of the maximum value. The highest levels of the normalized fluorescence in the skin (1,8±0,6 CONV. units) was observed 4 hours after the introduction of the FS, in the muscle (3,3±0,3 CONV. units) - after 5 minutes - 2 hours. Maximum fluorescent contrast FS relative to surrounding normal skin tissues were recorded after 5 minutes after injection and was 2.3±0.4 CONV. units, and relatively muscle - 0,9±0,1 CONV. units after 5 minutes and 24 hours after th�.
Example 7. Photo-induced antitumor activity of H2Py4BC in animals with sarcoma S37, vaccinated subcutaneously with the outer side of the right thigh of mice BDF1.
Study of the efficacy of photodynamic therapy was performed on day 7 after tumor inoculation. FS animals were injected once intravenously in doses of 0.5, 1.0 and 2.5 mg/kg. Irradiation was performed using 0.5 and 2 hours after injection of the dye. Was used for irradiation led source (FSUE "SSC "NIOPIK") with a wavelength of 754±14 nm and a power density of 150 mW/cm2(light dose of 150 j/cm2). The control group of animals without effect.
The efficacy of PDT was evaluated using the common in experimental Oncology criteria:
- inhibition of tumor growth SRW=[(VK-Vop)/VK]·100%, where Vopand VK- tumor volume in the experimental and control groups, respectively;
- increased life expectancy, median survival=[(SPop-ALEK)/SPMK]·100%, where the SPMopand ALEK- the average life expectancy in the experimental and control groups, respectively;
- the criterion of cure CI=[PI/No]·100%, where PI and N is the number of cured animals and total number of animals in the experimental group, respectively.
Tumor volume was calculated by the formula: V=d1·d2·d3where d1, d and d3three mutually perpendicular diameter of the tumor.
Measurement of tumor volume was performed for 21 days after irradiation using electronic digital calipers STORMtm 3C301 "Central". The animals were followed for 120 days.
In the experimental groups during the day after irradiation the animals were formed intense edema in the impact zone, which was maintained up to 5-15 days. Biologically significant antitumor effect was obtained when using FS in doses of 1.0 and 2.5 mg/kg irradiation after 30 minutes and 2 hours after administration and reached 70-100% TRO (Fig.5), 25-100% cure animals; life expectancy of animals was increased by 80-131%. The highest antitumor effect (100% TRO and 100% KI) with minimal damaging effect obtained by using the FS at the dose of 2.5 mg/kg exposure 2 hours after administration.
Example 8. Pharmacokinetics H2Py4BC in intact mice.
Pharmacokinetics of H2Py4BC was studied by the method of LFS in the organs and tissues of intact mice at a dose of 2.5 mg/kg on normalized fluorescence (FN).
The maximum of the fluorescence spectrum FS in animal tissues was recorded at 744±2 nm. Fluorescent form of the dye quickly (within 5-30 minutes) to be received in the internal organs and tissues of the body, mainly in the liver, then FN is decreased at different rates. M�ximalaya fluorescence in the blood was determined immediately after intravenous administration and within 4 hours was reduced by 95% of the maximum value and through the night was not recorded.
In the internal organs after 24 hours the level of the normalized fluorescence decreased in the liver by 87%, kidneys - 90%, spleen - 92% of the maximum value. Fluorescent form FS at a dose of 2.5 mg/kg was determined in the kidney and spleen up to 2 days in the liver and the residual amount was determined up to 7 days.
In the skin the maximum value of fluorescence was recorded 4 hours after the introduction of the FS, then its normalized fluorescence decreased and after 24 hours was 50% of the maximum value and after 5 days was not determined. This indicates a rapid elimination of the Federal Assembly of the skin. In the muscle after 24 hours the level of the normalized fluorescence also decreased by 82%, and fat 20%. Fluorescent form FS were determined in the muscle up to 5 days, and in the adipose tissue of the residual amount (26%) were registered more than 7 days.
The data indicate a rapid circulation of H2Py4BC in mammals and its excretion is mainly through the liver with the bile.
Thus, Tetra-(3-pyridyl)bacteriochlorin is highly active FS new generation, absorbing in the near infrared region of the spectrum (λmax=745±2 nm); is storage stable and has a high photostability, exhibits a high photo-induced antitumor activity in vitro (4-hour�Oh incubation of cultures HEp2 and EJ IR 50was 32±2 nm and 35±3 nm, respectively) and in vivo (100% TRO and 100% KI in the application of FCS in a dose of 2.5 mg/kg and irradiation after 2 hours). FS has a fast excretion of animals (after 24 hours the contents in the internal organs is reduced by 87-92% of the maximum value, the residual amount is observed up to 7 days).
The application of meso-Tetra(3-pyridyl)bacteriochlorin structural formula
as a photosensitizer, the near-IR region of the spectrum for photodynamic therapy.
FIELD: medicine, pharmaceutics.
SUBSTANCE: presented invention refers to immunology. There are disclosed versions of a dimer compound for forming a multimer capable to reproduce the effector function of aggregated IgG with identical monomers. Each monomer of the dimer comprises: a monomer of IgG2 link region or a monomer of isoleucine zipper, dimerising each of which forms a multimerising region, and at least Fc-domain monomer containing a link region, CH2 domain and CH3 domain of IgG1. What is described is a multimer compound capable to reproduce the effector function of aggregated IgG and containing two or more dimers. There are disclosed a method for changing the immune response using the dimer or multimer, as well as a multimer-based method of treating an inflammatory disease.
EFFECT: using the invention provides the new compounds capable to bind at least one FcR specified in a group consisting of: FcγRI, FcγRII, FcγRIII, FcγRIV, or their non-human version that can find application in medicine for IVIG substitution for treating a wide range of diseases, including the inflammatory and autoimmune diseases.
7 cl, 25 dwg, 5 tbl, 25 ex
FIELD: veterinary medicine.
SUBSTANCE: product comprises Lycopodium clavatum, Acidum arsenicosum, Phosphorus, Podophyllum peltatum, Thuja occidentalis, Echinacea purpurea, Silybum marianum, Selenocysteine, and the components are taken in the dilutions described below in the following ratio, in parts: Lycopodium clavatum ⌀=D1 0.004, Podophyllum peltatum ⌀ 0.003, Acidum arsenicosum ⌀=D2 0.0001, Phosphorus ⌀=D3 0.001, Thuja occidentalis ⌀ 30, Echinacea purpurea ⌀ 30, Silybum marianum ⌀ 60, Selenocysteine 0.2.
EFFECT: product has an effective stress-protective and growth-stimulating effect, it regulates the metabolism in young farm animals.
3 cl, 10 tbl, 1 ex
SUBSTANCE: method for producing an agent for stimulating body cells involving preparing a mixture of aqueous solution of selenious acid and PEG 400; that is followed by preparing a mixture of hydrazine hydrochloride and PEG 400; the prepared mixtures are combined; the solution is put to dialyse against distilled water; surplus of water is driven off; the produced solution is added with hexamethylene tetramine; pH is reduced to 7.2-7.4; the method is implemented in certain circumstances.
EFFECT: producing high-effective, ecologically safe agent by the synergism of colloidal selenium and hexamethylene tetramine on body cell stimulation.
1 dwg, 2 tbl, 4 ex
SUBSTANCE: invention relates to medicine and can be used for the treatment of radiation-thermal injury of an organism. For this purpose a single subcutaneous introduction of bifidumbacterin, irradiated by gamma-rays in a dose of 14.0 Gy, is carried out. Bifidumbacterin is introduced in a dose of 1.43·106 CFU/kg. After that, 10% hypericum oil is applied on the burnt region. Then a 10% hypericum cream is applied after 3-4 days.
EFFECT: method makes it possible to carry out the treatment of combined radiation-thermal injuries in an effective way with the application of available and cheap pharmacotherapeutic means.
1 tbl, 4 ex
SUBSTANCE: erythrocyte cell medium is added with an aqueous solution of sodium and potassium salts of humic acids prepared on brown coal of leonardite in a dose of 10.0 mg/kg. That is incubated at a temperature of 37°C for 40 minutes before treatment with acidic haemolytic.
EFFECT: invention enables normalising the cell membrane permeability and reducing the damaged cell count under acidic haemolytic.
FIELD: medicine, pharmaceutics.
SUBSTANCE: invention refers to a new intensifier of the antitumour effect, which is a uracil derivative of the general formula (I) or its pharmaceutically acceptable salt. In the general formula (I) X represents a C1-5-alkylene group, and wherein one of methylene groups making an alkylene group is optionally substituted by an oxygen atom; R1 represents a hydrogen atom or a C1-6-alkyl group; R2 represents a hydrogen atom or a halogen atom; and R3 represents a C1-6-alkyl group, C2-6-alkenyl group, C3-6-cycloalkyl group, (C3-6-cycloalkyl)-C1-6-alkyl group, halogen-C1-6-alkyl group or a 5-6-merous saturated heterocyclic group with an oxygen atom as a heteroatom, a uracil derivative presented by the following formula (I). The invention also refers to a method for potentiating the antitumour action or a method of treating tumours, involving administering an effective amount of a combination of the above uracil derivative or its pharmaceutically acceptable salt and an antimetabolite in an effective amount. The antimetabolite represents an agent specified in 5-fluoruracil (5-FU), potassium tegafur/gimeracil/oteracil (TS-1), tegafur/uracil (UFT), capecitabin, 5-fluor-2'-deoxyuridine (FdUrd) and Pemetrexed.
EFFECT: preparing the intensifier of the antitumour effect.
18 cl, 10 dwg, 10 tbl, 67 ex
SUBSTANCE: invention relates to medicine, namely to methods of purification and health improvement of an organism. For this purpose therapeutic starvation for not fewer than 5 days in case of a 7-day programme and for not fewer than 7 days in case of a 9-day programme is carried out. The duration of a recovery period constitutes two days. Food intake is realised nine times per day each day both in the process of therapeutic starvation and in the recovery period. In the period of therapeutic starvation the first food intake includes bee products "APIGRANULES 2" in a dose of one teaspoon, "KHINAZI balm" in a dose of one teaspoon, "A-P-V" in a dose of one teaspoon, "APITOK" in a dose of one teaspoon, "Antihelm phyto" - one capsule and still mineral water - one glass. The second food intake includes a drink with ginger, lemon juice, garlic and mint, honey - one teaspoon and one glass of apple-carrot juice. The third food intake supposes an intake of bee products "APIGRANULES 2" in a dose of one teaspoon, "KHINAZI balm" in a dose of one teaspoon, "A-P-V" in a dose of one teaspoon, "Antihelm phyto" - one capsule and still mineral water - one glass. The fourth food intake includes a drink with ginger, lemon juice, garlic and mint, honey - one teaspoon and one glass of apple-carrot juice. The fifth food intake consists of tea black or green with ginger, one teaspoon of honey and one glass of apple-carrot juice. The sixth food intake consists of bee products "APIGRANULES 2" in a dose of one teaspoon, "A-P-V" in a dose of one teaspoon, "Antihelm phyto" - one capsule and one glass of still mineral water. The seventh food intake includes tea black or green with ginger, one teaspoon of honey and one glass of apple-carrot juice. The eighth food intake supposes an intake of tea black or green with ginger, one teaspoon of honey and one glass of apple-carrot juice. The ninth intake of food includes depressant tea, including mint grass, valerian root, fennel seeds, cumin seeds, epilobium or strawberry leaves and one glass of apple-carrot juice. In the recovery period in 1-st, 2-nd, 3-rd, 4-th and 6-th intakes of food the composition of products remains the same as in the process of starvation. For the fifth intake of food the patients take tea black or green with ginger, one teaspoon of honey and vegetable soup. For the seventh intake of food the patients take tea black or green with ginger, "MILK COCKTAIL WITH CHITOSAN". The eighth intake of food includes tea black or green with ginger, one teaspoon of honey, "APICAMPA" cereal. The ninth intake of food for the recovery period includes a baked apple, depressant tea. In addition, a number of procedures are carried out after each food intake during the period of therapeutic starvation and the recovery period. After the first food intake gymnastics "5 Tibetan pearls" is realised. After the second food intake exercises on training apparatuses, procedures of press-therapy, electrolypolysis and myostimulation are realised. After the third food intake exercises of therapeutic physical training or aerobics are performed. After the fourth food intake a rest in form of a walk, a halotherapy session, combined with a session of relaxation therapy are realised. After the fifth food intake a course of strip-plastic is carried out. After the sixth food intake massage by manual application with a peloid-based mixture or manual massage with honey is carried out. After the seventh food intake an infra-red sauna, shower, phytobath with medicinal herbs, honey, ginger, lemon juice is taken. After the eighth food intake a shower is taken.
EFFECT: method ensures effective health improvement of the organism with the preservation of the full value life style and a sense of a comfortable state in the starvation period, reduction of recovery period term after starvation, purification of the organism without loading on the gastrointestinal tract, weight loss, and improvement of the general state and workability of the patients.
3 tbl, 7 ex
FIELD: medicine, pharmaceutics.
SUBSTANCE: invention refers to biotechnology, specifically to a fused protein containing a variant of rodostomin, and can be used in medicine. An ανβ3 integrin selective polypeptide consisting of an amino acid sequence SEQ ID NO:1 conjugated on the N terminal by a linker amino acid sequence containing a combination of the amino acids glycine and serine with a variant of a human serum albumin (HSA) with SEQ ID NO:4.
EFFECT: invention enables the higher therapeutic effectiveness in the diseases related to ανβ3 integrin.
12 cl, 14 dwg, 2 tbl, 7 ex
SUBSTANCE: invention refers to medicine and can be used for the correction of the individual's functional state and performance. That is ensured by administering Semax neuroactive peptide in a dose of two drops in each nasal passage. That is followed by the electric current exposure covering a frontal-mastoid region at pulse length 0.2ms, current intensity 0.8mA and pulse train 800Hz for 40 min. The exposure is combined with at least 10 sessions of hyperbaric oxygenation at pressure 1.6 atm.
EFFECT: method provides the rapid and effective increase of performance in sportsmen, military men and individuals involved in the other professions related to significant physical and mental stress by improving the functions of various regions of brain cortex as a result of the selected complex exposure enabling the substantial vasodilatation and maximum tissue oxygenation.
SUBSTANCE: using a compound representing a bicyclic pyrimidine derivative as Hrf2 transcription factor activators.
EFFECT: compounds of general formula can be used preventively to increase body defences before operations with toxic chemicals and high radiation doses.
3 cl, 7 tbl, 11 ex, 9 dwg
SUBSTANCE: cryoprotector is opened in a laminar flow unit; a special syringe of asyringe pump is filled with a cryoprotector; that is followed by introducing a filter solution of the cryoprotector - 55% dimethylsulphoxide with 5% dextran 40 at temperature +4°C in a nucleated cell suspension with haemopoietic stem cells in a cryopackage with the concentrate and mixing mechanically in a mixing apparatus, transferring the system together with the cryoprotector flask into the laminar flow unit; the air is released from the cryopackage and portion of the suspension; the package is sealed and placed into a shrink bag; that is followed by programmed multi-stage freezing, the first stage of which keeping the mixture of the suspension with the stem cells and cryoprotector - a freezing sample - for 10 min at temperature +4°C; the second stage is cooled at a rate of 1°C/min to temperature -12°C; the thirst stage provides cooling at a rate of 20°C/min to temperature -60°C; at the fourth stage, the sample is heated at a rate of 10°C/min to temperature -18°C; at the fifth stage, the sample is cooled at a rate of 1°C/min to -60°C; at the end of the freezing program, the sample is cooled at a rate of 3°C/min to temperature -100°C; after freezing, the sample is placed into a quarantine dewar with liquid nitrogen until infection and bacteriological fungal contamination test results are obtained. After termination of the quarantine shelf life, the sample with haemopoietic stem cells are placed for long-term storage at temperature not exceeding -150°C, into the dewar with liquid nitrogen if observing negative test results. If the infection and bacterial and/or fungal contamination test results are positive, the sample with haemopoietic stem cells are transferred into the dewar with liquid nitrogen for infectious material for long-term storage.
EFFECT: invention enables increasing cell viability in the sample.
3 cl, 4 dwg
SUBSTANCE: invention refers to medicine, particularly to oncourology, and can be used in the non-surgical treatment of the patients suffering early stages of prostate malignant tumour. A method of treating prostate cancer with using prolonged prodrug of octreotide accompanying surgical or drug-induced castration involves a) measuring pre-therapeutic prostate-specific antigen; b) measuring pre-therapeutic blood plasma chromogranin A; c) selecting the patients having high blood chromogranin A of more than 3 nmol/l; d) conducting a therapy with prolonged prodrug of octreotide in a combination with dexamethasone in the selected patients; e) controlling the prostate-specific antigen variation every month and monitoring a decrease thereof in the patients by measuring it intra-therapeutically according to the stage d); the therapeutic efficacy according to the stage d) is evaluated by a therapeutic response, which is accompanied by maximum decrease of the prostate-specific antigen.
EFFECT: invention enables providing the higher therapeutic efficacy in the patients suffering prostate cancer at the different stages.
3 cl, 1 tbl, 5 ex
SUBSTANCE: invention refers to medicine, namely to balneology. A balneological agent for treating and preventing various diseases is prepared by the gradual and sequential mixing at room temperature of yellow clay, natural brine of Bolshoy Tambukan Lake, sage essence, dimethyl sulphoxide in certain relations.
EFFECT: agent possesses the more prominent therapeutic effect.
5 tbl, 2 ex
SUBSTANCE: tissue-specific matrix is obtained by performing a perfusion washing and a decellularisation of a parenchymal organ. Herewith 60-120 minutes before the perfusion washing of the donor organ, measures to prevent intravascular blood cell aggregation and microcirculation disturbances are taken and involve the intramuscular or intravenous administration of a disaggregant or disaggregants (heparin and trental) into a donor. That is followed by an organ perfusion by administering into its vascular bed phosphate-buffered normal saline of the following composition: 138 mM NaCl, 2.67 mM KCl, 1.47 mM KH2PO4, 8.1 mM Na2HPO4, distilled water up to 1l and containing 1% serum albumin and 10-15% glycerol or 10-15% dimethyl sulphoxide with pH 7.4 in an amount equal to a double amount of the vascular bed of the organ at a perfusion pressure of 100-120 mm Hg in its arterial system. Thereafter, the decellularised organ is ground to a particle size of 0.5mm to 4mm; the ground fragments are portioned in an amount of 5-10g, and each portion is frozen by immersing into liquid nitrogen gas for 5-10 minutes. The frozen portions are re-ground to a particle size of no more than 600 mcm; then each portion is de-frozen by re-suspending in phosphate-buffered normal saline 30-70ml of the following composition containing 138 mM NaCl, 2.67 mM KCl, 1.47 mM KH2PO4, 8.1 mM Na2HPO4, distilled water up to 1l , with pH 7.4, at a room temperature. The prepared suspension is cleaned from the particles of less than 200mcm; the prepared fraction is lyophilised and sterilised to prepare the target matrix samples.
EFFECT: using the invention enables providing the more complete decellularisation procedure ensured by preventing the disturbed microcirculation in the donor organ, providing higher density and uniformity of the re-cellularisation of the entire matrix and easier control thereof by increasing the matrix adhesive surface areas for the contact to inoculating cells as prepared in the form of powder.
4 cl, 5 ex, 9 dwg
SUBSTANCE: invention relates to new heterogeneous ring compounds containing a pentatomic rings, condensed with other nuclei, only with one atom of oxygen as a heteroatom, namely to derivants of acetamid N-((1S)-1',2',3'-trimethoxy-6,7-dihydro-1H-benzo[5',6':5,4]cyclohepta-[3,2-f]benzofuran-1-il) with the general formula 1 , where R - substituent, R=Ph, pyridine-2-il, CH2OH, CH(CH3)OH, CH2CH2OH, CH2OAc, (CH2)8CO2Me or CH2N(CH2CH3)2, and also to their application as an active component of antitumoral medicinal preparation.
EFFECT: increase of activity with inhibition of proliferation of the tumour cells.
10 cl, 3 dwg, 8 ex
SUBSTANCE: set task is solved by application of final slag, formed in production of ferrovanadium by alumino-silicothermic method as bactericidal material.
EFFECT: extension of raw material resources for bactericidal materials.
SUBSTANCE: invention provides benzylidene furanone derivatives of (+)-usnic acid of formula 6-13 as anti-tumour agents. The compounds exhibit cytotoxic activity with respect to tumour cell lines CEM-13, U-937, MT-4.
EFFECT: high activity.
2 dwg, 3 tbl, 8 ex
SUBSTANCE: invention enables creating complex formulations of functional sports supplements of single foods with the specified concentrations of vitamins and mineral substances for sportsmen of various sports.
EFFECT: recovered physiological body saturation with vitamins and mineral substances on the basis of an algorithm for determining sportsmen's body saturation with these nutrients.
SUBSTANCE: agent for stimulating substantia Nissl synthesis in spinal cord motor neurons and spinal cord motor neuronal process growth, and a method for stimulating substantia Nissl synthesis in spinal cord motor neurons and spinal cord motor neuronal process growth. The agent represents a swine or foetal adrenal cortical alcohol extract which contains natural corticosteroids in the minor concentrations. The adrenal cortical alcohol extract of swine or foetal animal cells is prepared on the basis of organ preparations.
EFFECT: agent and method using the presented agent enable providing more effective stimulation of substantia Nissl synthesis in the spinal cord motor neurons which possesses an ability to neutralise toxic products and free radicals formed in process of acting, as well as ensuring higher growth of the processes of forming cell-to-cell communications, activating intracellular granular endoplasmic reticulum, increasing an energy level and antioxidant protection against aggressive radicals.
2 cl, 1 tbl, 4 dwg
FIELD: medicine, pharmaceutics.
SUBSTANCE: group of inventions refers to medicine, namely to psychiatry, and may be used for treating and preventing disorders specified in a group consisting of depressive, affective and anxious disorders, particularly a major depressive disorder. For this purpose, a patient's therapy is added with a stage of administering a therapeutically effective amount of embryonated egg isolate.
EFFECT: group of inventions provides treating the above pathology, including by inhibiting glutamate and neurokinin 2 (NK2) receptors.
15 cl, 12 dwg, 11 tbl, 8 ex
SUBSTANCE: 15-methyl ether 13,17-bis(N,N-diethylaminoethylamide)chlorine photosensitiser e6 selectively accumulates in tumour tissue.
EFFECT: photosensitiser has absorption in the red spectral region and high photo-induced anti-tumour activity, full retardation of tumour growth and animal cure.
5 dwg, 1 tbl, 6 ex