Method of treating pulmonary tuberculosis
SUBSTANCE: invention refers to medicine, namely to phthisiology, and can be used in treating pulmonary tuberculosis accompanied by tuberculosis intoxication. To this effect, administering anti-tuberculosis preparations is combined with the additional intravenous drop-by-drop administration of Reamberin, Heptral and antitoxic polyvalent antigangrenous serum (AGS) preceded by the administration of heparin 50 units/kg; Reamberin is administered in an amount of 400 ml on the first and second day for 2 hours; Heptral is introduced in an amount of 400 ml from the first to the fifth day; AGS is administered on the third day in an amount of 30 thousand International Units, on the fourth day in an amount of 60 thousand International Units, in case of a destructive process - in an amount of 60 thousand International Units on the fifth day; AGS is administered in normal saline NaCl 400 ml, and the first 1 ml of the solution is administered for 5 minutes, the rest amount - for 1.5-2 hours.
EFFECT: method enables increasing the clinical effectiveness of pulmonary tuberculosis as soon as possible by binding and neutralising microbial exo- and endotoxins by serum antibodies with no side effects and reduced financial expenses.
4 tbl, 3 ex
The invention relates to medicine, namely to Phthisiology.
Despite the use of the most effective antibiotics and modern technology, the mortality rate from TB is still high. The growth of genetically mutated bacteria makes us look for a safe strategy for patients fight bacteria. Known method of treatment of pulmonary tuberculosis, representing the use of combinations of antibiotics with Pentaglobin.
Pentaglobin - human immunoglobulin, intravenous, neutralizes endotoxin microbes in bacterial infections. The dosage of 5 ml/kg of body weight, the drug is administered within 3 days.
The disadvantages of the prototype include the fact that it is unstable to the action of bacterial proteases; it cannot be entered when the kidney function, described cases of aseptic meningitis after the introduction of Pentaglobin.
The aim of the invention is to improve the efficiency of treatment of pulmonary tuberculosis.
The essence of the proposed method in the invention is as follows: patients with tuberculosis intoxication, regardless of the stage of infection, intravenous infusion, administered antitoxic, polyvalent, protivomigrenoznoe serum - PGS. Administration scheme: for 400 ml of isotonic NaCl injected antitoxic, polyvalent, protivomigrenoznoe serum - 1 dose (30 thousand. international units). The first 1.0 ml of the resulting solution is injected within 5 minutes as the sample in the reaction, the remaining volume for 1.5 to 2 h (manual approved beg. CH. Ctrl. The USSR Ministry of health, 1988).
The primary mechanism of action of anti-toxic polyvalent protivomigrenoznoe serum (ASG) is binding and neutralization of Exo - and endotoxins microbial antibodies contained in the serum.
Example 1 a specific embodiment of the method.
Ziyavudinov Mr. Murad, 1979, Republic of Dagestan, Makhachkala, PR. Kirova, 59/29. First went to a TB specialist 25.12.09 G. complaints: irritability, insomnia, sweating, long, over 1 month, low-grade fever. In the blood - moderate leukocytosis, lymphocytosis, ESR acceleration. In urine: leukocytes, traces of protein.
R-gram from 25.12.09 - infiltrative lesions of the upper lobe of the right lung. Within 420 days (25.12.09-06.01.12 G.) took anti-TB drugs: isoniazid 900 mg per day, in combination with rifampicin, 750 mg × 2 times a day, for 180 days. Capreomycin 1 g 1 times a day, for 120 days. Ftivazid 1 g × R. 2 a day, for 120 days. In R-gr. lungs No. 1879 from 17.06.10 g, on CT of the lungs from 06.01.10 - infiltrative lesions in the upper lobe of the right lung.
01.05.12 G., simultaneously introduced ME 60 thousand (2 doses) PGS. In R-gr. from 31.05.12, chest - ver�her lobe of the right lung calcified focal shadows. The structural roots. Pulmonary pattern is reinforced. Sinuses available. Heart without features. It is recommended to consult a TB. Removed from the register. Healthy.
Example No. 2.
Musaev Elmira, 1986 Dagestan, Makhachkala, Ave. Petra-I, house 53, 58 sq (leave to care for a child) 29.11.11 g., due to the severity of the condition, admitted to hospital with DS: Infiltrative Tbc lung in the phase of disintegration. Tuberculosis intoxication. NAM II art.
With 29.11.11 on 18.06.12 during the 215 days treated in hospital. Lung CT from 25.04.12, No. 6854 - in the upper lobes of the lungs and in the lower lobe of the left lung are defined by multiple large pockets, sometimes merging with the formation of infiltrates irregular and rounded shapes, some of which is located subpleural. In part infiltrates seen small cavity decay. Viewed microfocal infiltration in both lungs. Conclusion: CT-signs of hematogenous-disseminated tbc lungs. In R-gr. lungs No. 1836 dated 15.06.12 - left subpleural rounded education: 5×4.5 cm complaints of sleep disturbance, weakness, dry mouth, itchy skin.
15.07.12 G. entered, simultaneously, 2 doses of ASG. 16.07.12 - 2 doses of ASG, on the background of prior administration of heparin.
14.08.12 - tomogram No. 1886. The plot of the cavity is reduced in volume. The deformed contours, perifocal infiltration is difficult to trace, fibrous cord reduced. Consul�targeted by fisierelor. The dynamics is positive. His condition is satisfactory. Conclusion: surgical treatment abstain.
CT 16.05.13, No. to 12,254 in the upper lobe of the right lung, in the upper and lower lobes of the left lung areas are defined tâžistaâ deformation pulmonary stroma, seal the pulmonary interstitium, traction bronchiectasis, multiple dense foci. Amid these changes in the upper lobe, there is a round dense formation with clear contours, with a diameter of 18 mm. the Lumen of a major bronchus is not deformed. Mediastinal lymph nodes are not enlarged. Vascular structures in the mediastinum without features, fluid in the pleural cavity is not revealed. Conclusion: CT-signs of fibrous-focal changes of the lungs.
Example # 3
Musayev Shamil, 1982 Dagestan, Makhachkala, Ave. Petra-I, house of 53 sq 58, the driver of a private enterprise. Spouse Musaeva E. Extremely irritable. From examination and treatment refused.
02.10.12 - entered 1 dose ASG intravenous drip: 03.10.12 G. D. 2 PGS. (the scheme).
CT - 29.10.12 G. comparing (05.09.12) + dynamics. Conclusion infiltrative pattern of spectrins at the level of 1st-2nd segments of the right lung in the phase of resorption.
21.02.13, R-gram of the chest is determined lungs without fresh lesions or infiltrative changes. Single calcined in the upper $ � left lung. Heart without features. 21.02.13 G. removed from the register.
The advantage of the proposed method is as follows:
1. the antibodies contained in the ASG, not broken down under the influence of bacterial proteases;
2. the lack of contraindications for insertion and complications when injected.
In our practice, all patients that were administered anti-toxic protivogangrenoznuyu polyvalent serum, in the next day it was noted positive dynamics: improved health, normal sleep, temperature. Improved indicators and peripheral venous blood (table 1, 2, 3, 4).
The proposed method of treatment of pulmonary tuberculosis allows you to:
1. To achieve positive results, in the shortest possible time, in the absence of side effects and any contraindications for the use of antitoxic serum. ASG.
2. To minimize the risk of developing drug-resistant strains of bacteria.
3. To reduce the time of treatment.
4. To solve the problem of social rehabilitation of the patient.
5. To reduce the financial cost of treatment.
Sources of information
1. Pentaglobin BIOTEST PHARMA Gmbh, Germany - prototype.
2. METHOD of TREATMENT of PNEUMONIA IN extremely premature infants ON mechanical VENTILATION, (RU) patent 2191031.
3. METHOD of TREATMENT of pulmonary TUBERCULOSIS (RU) patent 235745.
4. Pentaglobin (Pentaglobin®): instructions for use, contraindications and composition - Register of medicines - radar.
5. Serum protivomigrenoznae polyvalent equine purified concentrated liquid product form: solution for injection 30 thousand ME, ILA. 1 dose (1) complete with horse serum diluted 1:100, amp. 1 ml (1) Manufacturer: FSUE NPO "Microgen".
6. Serum protivomigrenoznae polyvalent equine purified concentrated liquid (Serum antigangrenosum polyvalentum purificatum concentratum equinum passiflorae): instructions for use, contraindications and composition - radar.
|Table # 1|
|Scheme of the proposed method of treatment, depending on the severity of the process|
|The name of the drug, method of administration, within what time||1st day|
|1. Reamberin of 1.5 in/in drip for 2 hours||400 ml||400 ml|
|2. Heparin IV infusion, at a dose of 50 units/kg simultaneously, before the introduction of PACS||Heparin||Heparin||Heparin|
|3. Antitoxic serum ASG/drip, within 2 hours||1 D. - 30 thousand ME in 400 ml. of physics and R-RA||60 thousand IU - 2D to 400.0 ml of a physical R-RA||60 thousand ME to 400.0 ml of a physical R-RA (destructive process)|
|4. Heptral,/in||400 mg||400 mg||400 mg||400 mg||400 mg|
|Table No. 2|
|A specific example|
|Name Age||DS||The treatment time. On an outpatient basis.||Data R-research and lung CT||Date of introduction and dose of the ATS-PGC||Data R-research and lung CT after modified�CSO treatment||DS Raion|
|Ziyavudinov Mr. Murad, 1979 Dagestan, Makhachkala, PR. Kirova, 59 "a", apt 25||Infiltrative tuberculosis of the upper lobe of the right lung||25.12.09 06.01.12 A/b therapy within 420 days||CT of lungs from 06.01.10, the amount of CT pulmonary tbc upper lobe of the right lung R-gr. lungs No. 1879 from 17.06.10 G. and from 25.12.09 G.: infiltrative lesions of the upper lobe of the right lung||01.05.12 G. D. 2 - ME 60 thousand simultaneous||R-study of the gr. cells from 31.05.12,: in the upper lobe of the right lung calcified focal shadows. The structural roots. Pulmonary pattern is reinforced. Sinuses available. Heart without features||Healthy.|
|Table No. 3|
|A specific example|
|Name age||DS outpatient||Hospital number/days||Data R-research and lung CT||Date of introduction and dose of the ATS-PGC||Data R-research and lung CT after modification�rovannogo treatment||DS of visioforge|
|Musaev Elmira, 1986 RD, M-Kala, Peter D.-I, 53 "in" / 58||Infiltrative-tion tbc lung in a state of collapse. Name article II||29.11.11 -18.06.12. G. Izberg. City hospital 215 K/h.||CT scan-lung from 25.04.12 No. 6854, R-gr. from 15.06.12, No. 1836: in the upper lobes of the lungs and in n/lobe of the left lung, multiple large foci of irregular and rounded, a portion of which is located subpleural. In part infiltrates the cavity decay. Conclusion: signs of hematogenous-dessiminating tbc lungs. In R-gr. lungs from 15.06.12 G. left rounded education 5*4,5, subpleural||15.07.12 G. 2 doses 2 doses 16.07.12 G.||R-research from 14.08.12 G. linear tomogram No. 1886. The plot of the cavity is reduced in diameter, the deformed contours, perifocal infiltration is difficult to trace, fibrous cord reduced. CT No. to 12,254 from 16.05.13 G. + dynamics.|
|Table No. 4|
|A specific example of application of the SGS - in the treatment of tuberculosis, without prior AV-guarantees|
|Name age�t||DS||The treatment time||Data R-research and lung CT||Date of introduction and dose of the ATS-PGC||Data R-research and lung CT after modified treatment||DS ftii-at|
|Musayev Shamil 1982 Dagestan, Makhachkala, Peter-1, 53, 58 sq||Refused therapy.|
Spouse Musaeva Elmira
|3 doses 02.10.12 G. 1 dose 03.10.12 G. 2 doses||R-research from 21.02.13, No. 30. Lungs without focal or infiltrative changes.|
Single calcinate the upper lobe of the left lung. CT-29.10.12. however, the infectious spectrins at 1-2 segments of the right lung in the phase of resorption
A method for the treatment of pulmonary tuberculosis in patients with tuberculosis intoxication, including the introduction of anti-TB drugs, characterized in that it further intravenously administered Reamberin, Heptral and antitoxic protivogangrenoznuyu polyvalent serum (ASG) with the provisional administration of 50 u/kg of heparin, Reamberin injected with 400 ml on the 1st and 2nd day for 2 hours; Heptral �about 400 mg from 1st to 5th day; PGS on day 3 the 30 thousand IU, on the 4th day 60 thousand IU, and in the case of a destructive process - 60 thousand IU for 5 days, and the calibration gas is introduced 400 ml of isotonic NaCl solution and the first 1 ml of the solution was injected for 5 minutes, the remaining volume within 1,5-2 hours.
SUBSTANCE: means represents a dry extract of leaves and flowers of Gratiola officinalis, obtained by milling the leaves and flowers of Gratiola officinalis, extraction with 96% alcohol on a water bath to boiling and boiling, evaporation, dilution of the evaporated residue first with distilled water, then by the addition of chloroform, cooling to room temperature and centrifuging with the following separation of a water fraction and drying it under specified conditions.
EFFECT: means is non-toxic, has an expressed anti-tuberculosis action.
2 tbl, 2 ex
SUBSTANCE: agent is presented in the form of a tablet, contains isoniazid and a substance which reduces its toxicity; as the substance which reduces the isoniazid toxicity, it contains thiotriazolin. The isoniazid/thiotriazolin ratio makes 4:1.
EFFECT: combined antituberculous drug ensures reducing toxicity as compared to the known ones and increasing its pharmacological activity.
2 cl, 1 ex, 1 tbl
FIELD: medicine, pharmaceutics.
SUBSTANCE: invention refers to a chemical compound of formula wherein R=benzyl and to an antituberculous therapeutic agent representing a composition of imidazo[1,2-b][1,2,4,5]tetrazine derivative of formula I, wherein R=benzyl, isopropyl or phenyl and the known antituberculous preparation pyrazinamide with the ingredients in mole ratio 1:1.
EFFECT: there are prepared new antituberculous therapeutic agents.
2 cl, 2 tbl, 6 ex
SUBSTANCE: invention relates to organic chemistry and specifically to nitroimidazooxazine derivatives of general formula I, where n equals 1, V and W independently denote H or CH3, and one of X and Y is H and the other is one of the formulae and , where formula IIa includes a single ring labelled at position 3 and position 4 and containing R1 as a substitute, and formula IIb includes a first ring labelled at position 3 and position 4 and containing as substitutes both R2 and a terminal ring, labelled at position 4 and containing R1 as a substitute, where the single ring of formula IIa and the first ring and the terminal ring of formula IIb include C, CH, or N at each ring position, where the single ring of formula IIa and the first ring and the terminal ring of formula IIb independently contain no more than two nitrogen atoms; Z in formulae IIa and IIb is CH2 or a direct bond, R1 is independently any one or two of H, F, C1, CF3, OCF3 or OCH2Ph, and R2 is H. The invention also relates to a pharmaceutical composition based on the compound of formula I, a method of preventing and treating a microbial infection based on use of the compound of formula , and specific nitroimidazooxazine derivatives.
EFFECT: obtaining novel compounds with useful biological activity.
7 cl, 21 dwg, 3 tbl
FIELD: medicine, pharmaceutics.
SUBSTANCE: invention relates to field of genetic engineering, molecular biology and vaccinology. Claimed is polyepitopic anti-tuberculosis vaccine construction for formation of immune response, which provides induction of immune response of CD8+ T-lymphocytes, consisting of universal polyepitopic immunogen, containing CTL-epitopes, selected from immunodominant antigens of M. tuberculosis, fused from N-end with ubiquitin, and having amino acid sequence SEQ ID NO: 1.
EFFECT: vaccine construction provides achievement of effective therapeutic T-cell immune response not only due to antigenspecific cytotoxic CD8+ T-lymphocytes but also intensive response of CD4+ T-lymphocytes.
1 tbl, 11 dwg
SUBSTANCE: invention concerns Mycobacterium tuberculosis growth inhibitors representing (+) and (-)-enantiomers of derivatives of usnic acid containing a furilidene furanone fragment, namely (10R,4Z)-8,13-dihydroxy-7,10-dimethyl-4-(2-furanylmethylidene)-5,16-dioxatetracyclo[7.7.0.02.6.010.15]hexadeca-1,6,8,12,14-pentaen-3,11-dione 4a and (10S,4Z)-8,13-dihydroxy-7,10-dimethyl-4-(2-furanylmethylidene)-5,16-dioxatetracyclo[7.7.0.02.6.010.15]hexadeca-1,6,8,12,14-pentaen-3,11-dione 4b
EFFECT: inhibitors possess the high antimicrobial activity.
2 tbl, 7 ex
SUBSTANCE: invention relates to novel derivatives of 1-(2-chloroquinolin-3-yl)-4-dimethylamino-2-(naphthalen-1-yl)-1-phenylbutan-2-ol of general formula I or their pharmaceutically acceptable salts with acids, where R1 denotes H, R2+R3 denotes -O-(CH2)n-O-, where n=1-2, which forms additional dioxane and 1,3-dioxolane rings. The invention also relates to a method of producing a compound of formula I and to use of the compound of formula I in treating infectious mycobacterial diseases.
EFFECT: obtaining novel compounds with useful biological activity.
4 cl, 2 tbl, 3 ex
SUBSTANCE: for treatment of patients with pulmonary tuberculosis with accompanying non-specific bronchitis at the background of carrying out standard anti-tuberculosis therapy from the first day of treatment additionally daily for 3 months the preparation Wobenzym is introduced in a dose of 1 tablet 2 times per day, 30 minutes before meal, and inhalation with a solution of the preparation Hixozide in a dose of 350 mg in 10 ml of water for injections is performed 2 times per week, the course constitutes 24 procedures.
EFFECT: method makes it possible to increase treatment efficiency by indices of infiltration resorption, closing of the decay cavities and abacillation.
1 tbl, 2 ex
SUBSTANCE: for complex therapy of the first time identified pulmonary tuberculosis traditional anti-tuberculosis therapy is carried out. After two weeks of anti-tuberculosis chemotherapy, complex physiotherapy is performed. In the morning 40-60 minutes after meal ultrasound inhalation with an inhibitor of proteases contrykal in a dose of 5000 UNITS, diluted in 3-4 ml of an isotonic solution of sodium chloride is carried out. Inhalation is carried out at a temperature of the solution of 35°C for 10 minutes on the apparatus "Vulkan-1". 20 minutes after inhalation magnetic infrared laser therapy (MIL-therapy) is performed from the apparatus "Rikta-04/4" on affected zones of the lungs by contact method of the application of the apparatus emitter. Frequency of the laser impact constitutes 5-50 Hz. Average power of infrared light-diode radiation is 60±30 mW, an impact with constant magnetic field is realised with induction 35±10 mT for 1-5 min. The course of treatment constitutes 30-40 daily procedures as well.
EFFECT: enhancement of infiltration resorption, closing decay cavities in the shorter period, arrest of intoxication symptoms by the end of the first month of treatment, reduction of terms of elimination of clinical and laboratory manifestations of tuberculosis.
3 cl, 2 ex
SUBSTANCE: drug preparation for treating tuberculosis contains an active substance isoniaside, and a pharmaceutical carrier tiozol gel with the isoniaside concentration of 5.7-54.5 wt % and the tiozol gel concentration of 45.5-94.3 wt %.
EFFECT: higher clinical effectiveness in tuberculosis and lower toxicity.
2 cl, 2 tbl
SUBSTANCE: invention discloses an immunogen for treating and preventing opiate dependence differing by the fact that the immunogen is presented by polyclonal anti-idiotope (secondary) antibodies to opiates, namely to morphine and its derivatives.
EFFECT: immunogen is promising for treating and prevention the addiction in the individuals misusing opiates, such as morphine and its derivatives, particularly heroin and codeine.
6 dwg, 2 ex
FIELD: medicine, pharmaceutics.
SUBSTANCE: invention relates to medicine and deals with histidine-trehalose composition, stable after storage, containing antibody T1h, histidine buffer, trehalose and non-ionic surface-active substance.
EFFECT: invention provides reduction of quantity of highly molecular weight proteins (HMWP) by approximately 20% by weight with respect to initial quantity of HMWP in histidine-trehalose composition within five weeks.
4 cl, 5 ex, 27 dwg
SUBSTANCE: present invention refers to medicine, namely to a method for detecting patients with progressing leukaemia and/or lymphoma and a risk of developing side effects of administering the CD19×CD3 bispecific antibody. A B:T cell ratio is measured in the patients; the ratio of 1:9 or less indicates the risk of possible side effects in the above patient. A dose schedule of the CD19×CD3 bispecific antibody provides: (a) administering the first dose of the CD19×CD3 bispecific antibody for the first time period; and then (b) administering the second dose of the above antibody for the second time period; the above second dose exceeds the above first dose.
EFFECT: using the given method enables facilitating the clinical course or preventing any side effect caused by administering the above bispecific antibody when treating the patients with leukaemia and/or lymphoma.
34 cl, 2 tbl, 9 ex
SUBSTANCE: invention relates to medicine, namely to oncology, and can be applied for the treatment of adenogenous locally advanced cancer of the rectum. For this purpose chemotherapy with 5-fluorouracil, medical therapy, gamma-therapy are realised by a method of dynamic fractioning of a dose. 5-fluorouracil is introduced into the pararectal cellular tissue, adjacent to a tumour, in a volume of 5-15 ml 5-15 min before an irradiation session of before the first three large fractions. As the drug therapy realised is infusion introduction of Mabthera in a dose of 50-70 70 mg/m2 50-60 minutes before radiotherapy on the 1, 7 and 14 days of treatment. From the 1 to 12 days from the treatment beginning radiotherapy is performed on the tumour zone and the zone of regional metastases from 2-4 fields in a mode of dynamic fractioning with SFD=3.6 Gy 3 times and further with SFD=2.2-2.4 Gy 9 times to TFD=32.4-34.8 Gy.
EFFECT: method ensures the reduction of the volume and size of the initial tumour, transfer of non-operable and conditionally operable stages of the disease into the operable state and a possibility of carrying out radical operations with an increase of therapy tolerance as a result of reduction of toxic and cytotoxic effects of the treatment, increase of protective powers of the organism and a possibility of carrying of radiotherapy in the total volume.
FIELD: medicine, pharmaceutics.
SUBSTANCE: invention refers to immunology. What is described is an immunoconjugates targeting CD138-expressing cells containing: IgG4 anti-CD138 antibody containing a heavy chain having CDRs from SEQ ID NO: 1 presented in the description and at least 70% identical to SEQ ID NO: 1, and a light chain having CDRs from SEQ ID NO: 2 presented in the description and at least 70% identical to SEQ ID NO: 2; and an effector molecule presenting a tubulin polymerisation inhibitor, and wherein the effector molecule is attached to the above engineered target antibody through a cleaved linker containing a disulphide bond. Besides, disclosed are a pharmaceutical composition and a kit for inhibition, delaying and/or prevention of tumour growth and/or CD138-expressing tumour cell propagation, wherein the composition contains the above immunoconjugate in an effective amount, and one or more pharmaceutically acceptable excipients; the kit comprises pharmaceutical compositions in independent containers, wherein one container comprises an effective amount of the pharmaceutical composition according to the present invention, while the other container contains a second pharmaceutical composition containing an effective amount of a co-drug, preferentially a cytotoxic agent, and one or more pharmaceutically acceptable excipients. There are presented the following methods implying administering the above immunoconjugate: a) a method of treating multiple myeloma in an individual; b) a method for immunoconjugate-mediated drug delivery; c) a method for inhibition, delaying and/or prevention of CD138-expressing tumour cell growth in a cell culture; d) a method for inhibition, delaying and/or prevention of the growth of a tumour containing CD138 tumour cells, and/or propagation of the tumour cells of this tumour in the patient; e) a method for inhibition, delaying and/or prevention of the tumour growth and/or propagation of CD138-expressing tumour cells in the patient; f) a method of treating the individual suffering a condition expected to be improved by suppressing myeloma cell survival; g) a method for inhibition, delaying and/or prevention of the growth of the tumour containing CD138 tumour cells, and/or propagation of the tumour cells in the individual; h) a method for reducing a cell count in a direct or mediated contact to the CD138-expressing tumour cells in the individual; i) a method for reducing a cell count in a direct or mediated contact to the CD138-expressing tumour cells.
EFFECT: invention enables preparing a homogenously targeted agent for treating the CD138-related diseases.
45 cl, 13 dwg, 5 tbl, 1 ex
FIELD: medicine, pharmaceutics.
SUBSTANCE: invention refers to immunology. Presented are variants of anti-CD20 modified antibody or its antigen-binding fragment. Each of the variants is characterised by the fact that it contains a variable light and heavy chain domain, and induces a higher apoptosis level as compared to anti-B-Ly1 chimeric antibody. There are presented: a mixture of antibodies, wherein at least 20% of oligosaccharides in Fc domain have a branched chain and are not fucosylated, as well as a pharmaceutical composition for producing a therapeutic agent for a malignant haematological or autoimmune disease by using the antibodies or the mixture of antibodies. Described are: an expression vector, a based host cell, variants of coding polynucleotides, as well as a method for producing the antibody in the cell.
EFFECT: using these inventions provides the new antibodies with the improved therapeutic properties, including with increased binding of Fc receptor, and with the increased effector function that can find application for treating the malignant haematological or autoimmune disease.
32 cl, 3 ex, 9 tbl, 26 dwg
SUBSTANCE: invention relates to field of biochemistry, in particular to method of obtaining bivalent bispecific antibody, which includes transformation of host cell by vectors, containing molecules of nucleic acids, coding first light chain and first heavy chain of bivalent bispecific antibody, and vectors, containing molecules of nucleic acids, coding second light chain and second heavy chain of bivalent bispecific antibody, cultivation of host cell under conditions, providing synthesis of molecule of bivalent bispecific antibody from said culture. Said antibody contains first light chain and first heavy chain of antibody, specifically binding with first antigen, and second light chain and second heavy chain of antibody, specifically binding with second antigen, in which variable domains VL and VH of second light chain and second heavy chain are replaced by each other and constant domains CL and CH1 of second light chain and second heavy chain are replaced by each other.
EFFECT: invention makes it possible to increase output of correct bispecific antibody by increasing the level of correct heterodimerisation of heavy chains of wild type and modification of heavy chains resulting from crossing over.
2 cl, 31 dwg, 3 tbl, 4 ex
SUBSTANCE: present invention refers to immunology. Presented is a molecule of bispecific single-chain antibody containing a first binding domain able to bind to epitope of CD3-epsilon-chain of human and Callithrix jacchus (tamarin), Saguinus oedipus (cotton-top tamarin) and Saimiri sciureus (squirrel monkey), and a second binding domain able to bind to an antigen specified in a group consisting of: PSCA, CD19, C-MET, endosialin, EGF-like domain 1 EpCAM coded by exon 2, FAP-alpha or IGF-IR (or IGF-1R) or a human and/or a primate. The epitope CD3e contains an amino acid sequence disclosed in the description. Disclosed are a nucleic acid coding the above molecule of the bispecific single-chain antibody, an expression vector, a host cell and a method for producing the antibody, as well as the antibody produced by the method. Described is a based pharmaceutical composition containing the molecule of the bispecific single-chain antibody and a method for preventing, treating or relieving cancer or an autoimmune antibody. Presented is using the above molecule of the bispecific single-chain antibody for making the pharmaceutical composition for preventing, treating or relieving cancer or the autoimmune disease.
EFFECT: using the invention provides the clinical improvement in relation to T-cell redistribution, reducing it, and the improved safety profile.
23 cl, 74 dwg, 17 tbl, 33 ex
SUBSTANCE: invention refers to biotechnology, more specifically to biospecific antibodies, and can be used in medicine. Constructed is an antibody containing one of the following groups of six hypervariable region (HVR) sequences: (a) HVR-L1 containing the sequence NIAKTISGY; (b) HVR-L2, containing the sequence WGSFLY; (c) HVR-L3 containing the sequence HYSSPP; (d) HVR-H1 containing the sequence NIKDTY; (e) HVR-H2 containing the sequence RIYPTNGYTR; and (f) HVR-H3 containing the sequence WGGDGFYAMD; or (a) HVR-L1 containing the sequence NIAKTISGY; (b) HVR-L2 containing the sequence WGSFLY; (c) HVR-L3 containing the sequence HYSSPP; (d) HVR-H1 containing the sequence NISGTY; (e) HVR-H2 containing the sequence RIYPSEGYTR; and (f) HVR-H3 containing the sequence WVGVGFYAMD. The produced antibody specifically binds human epidermal growth factor receptor 2 (HER2) and vascular endothelial growth factor (VEGF) The invention also refers to a recovered Fab fragment of the above antibody, a polynucleotide coding it, to an expression vector, a host cell, a method for producing it, as well as to using it for treating HER2-mediated diseases.
EFFECT: present invention enables producing the bispecific high-affinity antibody able to bind VEGF and HER2 simultaneously.
14 cl, 65 dwg, 16 tbl, 8 ex
FIELD: medicine, pharmaceutics.
SUBSTANCE: present invention refers to antibodies including human antibodies and their antigen-binding portions, which specifically bind to CCR2, in particular to human CCR2, and can act as CCR2 inhibitors. Anti-CCR2 antibodies are those binding to first and/or second extra-cellular CCR2 loops. The present invention also refers to human anti-CCR2 antibodies and to their antigen-binding portions. The present invention refers to the recovered heavy and light chains of immunoglobulin initiated from human anti-CCR2 antibodies, and to nucleic acid molecules coding such immunoglobulins. The present invention also refers to methods for preparing human anti-CCR2 antibodies and their antigen-binding portions, to compositions containing such antibodies or their antigen-binding portions, and to methods for using antibodies and their antigen-binding portions, and compositions for diagnosing and treating.
EFFECT: invention refers to methods for gene therapy with the use of nucleic acid molecules coding molecules of heavy and light chains of immunoglobulin, wherein the above molecules contain anti-CCR2 antibodies and their antigen-binding portions.
25 cl, 24 dwg, 8 tbl, 17 ex
FIELD: medicine, pharmaceutics.
SUBSTANCE: group of inventions relates to medicine and deals with a crystalloid cardioplegic solution, which contains salt solution, including sodium chloride, potassium chloride, magnesium chloride, calcium chloride, sodium hydrogen carbonate, water for injections and a structural analogue of natural apelin X-Arg(NGY)-Pro-Arg-Leu-Ser-His-Lys-Cly-Pro-Nle-Pro-Phe-Z, where X=CH3, Y=H, Z=OH. The group of inventions also deals with the crystalloid cardioplegic solution, containing salt solution, including sodium chloride, potassium chloride, magnesium chloride, calcium chloride, sodium hydrogen carbonate, water for injections and structural analogue of natural apelin X-Arg(NGY)-Pro-Arg-Leu-Ser-His-Lys-Cly-Pro-Nle-Pro-Phe-Z, where X=H, Y=NO2, Z=NH2.
EFFECT: group of inventions provides the recovery of the coronary flow, cardiac contractile and pump function in case of the reperfusion and the reduction of injury to membranes of cardiomyocytes.
2 cl, 2 dwg, 8 tbl, 4 ex