Immunoglobulin removing sorbent

FIELD: medicine; immunology.

SUBSTANCE: sorbent is offered to remove immunoglobulin from human blood plasma. This sorbent contains agarous matrix covalently combined with ligand. As a ligand at that it contains F(ab)2 fragments of specific affinely-purified polyclonal antibodies blocking human immunoglobulin G. Sorbent is actually biologically inert, biocompatible agarous matrix. Sorbent is characterized with higher sorptive capacity and safety of immunosorbents used practical purposes, specifically for therapeutic aphaeresis in comparison to well-known polyclonal bodies based sorbents.

EFFECT: considerable reduction of prospective immunological response of human body for foreign protein.

1 ex, 1 tbl


The invention relates to medicine, in particular to immunology, and serves to bind immunoglobulins of various subclasses from human blood plasma and other biological fluids, and can also be used in biochemistry and biotechnology to extract specific components from protein solutions.

There are a number of neurological, hematological, systemic autoimmune diseases, the development of which is accompanied by formation and accumulation in the blood of patient antibodies to various antigens of its own body. It is shown that autoantibodies are an important part of the pathological process in such diseases as systemic lupus erythematosus, rheumatoid arthritis, idiopathic thrombocytopenic purpura [1], syndromes Guillena-Barre or?, male, dilated cardiomyopathy [2, 3] the rejection of transplants, immune conflict in pregnancy, etc. In many cases, when drug therapy is not effective or cannot be applied, the removal of immunoglobulins (Ig apheresis) from the bloodstream of the patient can significantly improve the patient's quality of life and prognosis of disease[4, 5, 6, 7].

Any sorption column for medical purposes consists of three main components: a matrix is biologically inert biocompatible material; ligand molecules to the verge covalently attached to the matrix and give the sorbent specificity, and the body of the column, and places the sorbent.

For the columns used in the clinic, the most important parameters are the efficiency and specificity of removal of pathogenic component or components, as well as the safe use of columns in the procedure of therapeutic apheresis. The removal efficiency of pathogenic component is called reduction (%) concentration of this component for the chromatographic cycle or procedure. The efficiency of the sorption column is determined by the sorption capacity of the sorbent, the amount of gel in the column and the reusability of the column within one procedure.

Currently in clinical practice for Ig apheresis most widely used sorbents with immobilized polyclonal antibodies to human immunoglobulins (Ig Adspec"®, NPF "PACKARD, Russia; "Ig-Therasorb"®, "Miltenyi Biotec"®Germany) [7, 8], columns with immobilized protein A ("Immunosorba"® and "Prosorba"®, "Fresenius HemoCare, Germany). Recently created a sorbent from a synthetic Oligopeptide "Globaffin" "Affinna", Germany.

Column "Immunosorba"® contain 62.5 ml of agarose gel with immobilized protein A. the Sorption capacity of this sorbent is approximately 20 mg of IgG /ml of gel sorbent [9]. Speakers designed for repeated use during the procedure. Main weeks the STATCOM sorbent is the selective interaction of a protein And with different IgG subclasses [10], that significantly reduces clinical results in the treatment of several diseases, in particular DC [11]. The sorbent with the immobilized protein And reduced the concentration of IgM and IgA by 20-40%, which is two times less effective than immunosorbents based on antibodies [12].

Similar ligand - protein a used in the columns "Prosorba"®, "Fresenius HemoCare, Germany, containing 300 ml of sorbent is silica-based. The sorption capacity of the sorbent from the column "Prosorba"® is 7.1±1.8 mg IgG/ml gel [13]. In addition to the above disadvantages, defined immobilized protein A, in vitro and in clinical use was marked leakage of the ligand from the medium [14, 15]. The fact that the speakers are "Prosorba"® designed for single use and, therefore, do not regenerate and cannot be re-therapeutic use is another important drawback of such columns [15, 16]because of this fact significantly limits the effectiveness of the columns in the procedure of therapeutic apheresis.

Columns with immobilized peptide capable of binding immunoglobulins G "Globaffin" ("Fresenius, Germany), contains 67 ml agarose gel with immobilized peptide PGAM146. Column "Globaffin" removes a broad range of human immunoglobulins and designed for multiple applications. The sorption capacity when ranta an average of 17 mg IgG/ml gel [17]. Because the use of such columns only begins in the framework of clinical trials, in the literature there are practically no data on the advantages and disadvantages of such a sorbent.

The closest analogue of the invention is a sorbent-based agarose matrix with immobilized polyclonal sheep antibodies against human IgG, which is used in the columns "Ig-Therasorb"®, (Myltenyi Biotec GmbH, Germany)containing 150 ml of agarose gel with immobilized polyclonal sheep antibodies against human IgG. The sorption capacity of the sorbent by an average of 12 mg IgG/ml of gel. Speakers intended for repeated use and regeneration during therapeutic apheresis, bind all subclasses of immunoglobulin G, and partially immunoglobulin classes a and M. the Main disadvantage of this sorbent is the sorption capacity at 30% inferior to the sorbent with immobilized protein A (see table).

The prototype of the present invention is a sorbent used in columns "F Adspec"®, (NPF "PACKARD", Russia), containing 200 ml of agarose gel with immobilized polyclonal sheep antibodies to human IgG. The sorption capacity of 1 ml of gel is 10-12 mg protein antibodies [18]. Column effectively remove IgM and IgA [19], designed for mn is multiple use and can withstand up to 100 cycles of sorption desorption with the loss of sorption capacity, not exceeding 30%. Immunosorbents, containing as a ligand polyclonal sheep antibodies to human IgG, do not have the above disadvantages of the sorbents with immobilized protein A, namely, low binding IgG 3 subclass, weak interaction with IgM and IgA. However, they are inferior to the latter in its sorption capacity.

The objective of the invention is to increase the sorption capacity and safety of the immunosorbents used for practical purposes, in particular in the procedures of therapeutic apheresis. This task is solved by using as a ligand F(ab)2fragments of antibodies immobilized on a matrix in a concentration which provides the desired sorption capacity. In spite of the fame F(ab)2fragments of IgG with the 60-ies of the last century [20], in the literature there are no data on their use as ligands in the synthesis of immunosorbents, found practical application in the field of therapeutic apheresis. This is probably due to the fact that attempts to obtain sorbents with immobilized not modified F(ab)2fragments did not lead to the desired result was not possible to increase the sorption capacity of the sorbent [21]. Thus, the use of F(ab)2fragments of antibodies to receive immunosorbents used for practical purposes, is neo evenin for specialists in this field.

The proposed sorbent is a biologically inert, biocompatible agarose or cellulose matrix, covalently associated with the F(ab)2fragments specific, affinity-purified polyclonal sheep antibodies against immunoglobulin G man. Covalent bond between the ligand and the matrix is formed after activation of the matrix such reagents as brazian or metaperiodate sodium. As a ligand can be used F(ab)2fragments of affinity-purified polyclonal or monoclonal antibodies of different specificity. The main advantage of the proposed sorbent is significantly large compared to the prototype sorption capacity (15,8±1.0 mg IgG/ ml of gel sorbent with immobilized F(ab)2fragments of polyclonal antibodies against immunoglobulin G man and 11.2±0.8 mg of IgG/ml of gel for the prototype), preserving all the above advantages of immunosorbents with antibodies, such as high specificity, interaction with all classes and subclasses of immunoglobulins, the possibility of multiple use. In addition, the absence of ligand constant region of the heavy chains of immunoglobulins, causing interspecific differences immunoglobulins (izotopicheskie antigenic determinant), significantly reduces potentially available is th immunological response of the organism to a foreign protein, thus, increases safety applications immunosorbent assay for the purposes of therapeutic apheresis.

Comparison of the proposed sorbent with literature data for analogs and prototypes are shown in the table, there are private data comparison of sorption capacity of the proposed sorbent with commercially available analogues and the prototype.

The implementation of the invention

Example. Anticigarette sheep to human immunoglobulins were obtained by immunization of animals donor immunoglobulins G man, purified by ion exchange chromatography as described by the authors previously [18]. Specific antibodies sheep to human immunoglobulins were obtained by the method of affinity chromatography sorbent with immobilized antigen immunoglobulin G [18].

Fragments specific antibodies were obtained by the method of proteolytic cleavage of the drug polyclonal sheep antibodies to human IgG on a column with immobilized enzyme pepsin ("Pierce, USA). To obtain specific F(ab)2fragments of antibodies affinity-purified polyclonal antibodies sheep in citrate buffer pH 2.5 with a concentration of 10 mg/ml was passed through the column with 2 ml of sorbent with pepsin-agarose. The contact time of the solution of antibodies to the immobilized enzyme was 4 min. Number of antibodies, ispolzuemykh in the reaction of enzymatic degradation, varied from 0.1 to 7.0, the Study of antibody preparations after splitting using vertical electrophoresis in polyacrylamide gel (gradient 4-22%) under denaturing conditions showed the presence of a major band corresponding to F(ab)2(100 kDa)and a minor band with a molecular mass of from 10 to 50 kDa, corresponding to fragments splitting constant region (Fc fragment of the immunoglobulin molecule.

The secretion of immunoactive F(ab)2fragments of antibodies to human immunoglobulins was performed by the method of affinity chromatography on a column with immobilized on agarose matrix antigen immunoglobulin G man. Chromatography was carried out at pH values not below 4.5, the application time of fragmented antibodies on the column was 2 hours. The elution of the active F(ab)2fragments was performed citrate buffer pH of 2.5. The presence of active F(ab)2fragments were determined by ELISA. On the plate the first layer were adsorbed immunoglobulins G man, the second layer rastarivanie F(ab)2fragments of antibodies as detection antibodies used rabbit antibodies to sheep immunoglobulins conjugated to peroxidase.

Received eluate concentrated to 10-15 mg/ml and was immobilized on a pre-activated agarose matrix, for which the solution F(ab)2FR is mentov, cialisovernight against water (pH 4.0 to 4.5) was added 10-fold carbonate buffer pH of 10.0, and incubated for 2 hours with pre-activated with bromine cyan agarose matrix. The concentration of immobilized ligand was assessed by differential method according to the difference in the amount of protein taken for the reaction of immobilization and remaining in solution after incubation with the matrix.


The sorption capacity of the proposed sorbent, prototype and commercial analogues tested by the method of affinity chromatography from plasma of human blood, with the concentration of immunoglobulin G 15 mg/ml Chromatography was performed on 100 μl of the sorbent, the time of contact of the sorbent with the plasma was 1 hour, the volume of plasma 1 ml After incubation sorbents were washed in 5 ml of phosphate buffer, and bound peroxidase protein was suirable 2 ml 0,05 m citrate buffer pH of 2.5. The sorption capacity of the proposed sorbent (the amount of protein in the eluate with 1 ml of gel) ranged from 14,3 to 17.8 mg/ml. the Results of research on the sorption capacity of the proposed sorbent, analogs and prototypes are given in the table.

Specificity, i.e. the ability to specifically bind immunoglobulins G of a mixture of proteins (human blood plasma), confirmed by testing the eluate from the sorbent by electrophoresis in gradient of polyaki the amide gel under denaturing conditions. The eluate from the proposed sorbent contains not less than 90% of immunoglobulins G and contains almost no impurities other plasma proteins. 1 ml of the sorbent with the immobilized F(ab)2fragments of polyclonal antibodies to human immunoglobulins associates 6.9 mg IgM and 3.3 mg of IgA plasma source data level of immunoglobulins 2.6 and 2.8 mg/ml, respectively.

20 chromatographic cycles with the blood plasma of a person lead to the fall of the sorption capacity of the sorbent with the immobilized F(ab)2fragments of antibodies to immunoglobulins G man on 7%, while the fall sorption capacity for 100 cycles does not exceed 30%, which allows efficient use of the proposed sorbent repeatedly.


Comparison of commercially available systems for the removal of immunoglobulins in vitro procedure, therapeutic apheresis (literature and own data).
Product nameManufacturerMatrixThe ligandThe volume of gel in the columnThe sorption capacityUse
Qty IgG columnQuantity of IgG per ml of gel
L is teratornis data Own results
Imunosorba®Fresenius AG, Germany (formerly Excorim, Sweden)the agaroseProtein And cell wall of Staphylococcus aureus62,5 ml1.2 g19,2 mg/ml17,2 mg/mlmany times
Prosorba®Fresenius AG, Germany (formerly Imre and Cypress, USA)silica gelProtein And cell wall of Staphylococcus aureus300 ml1.2 g7,0 mg/ml-once the
Globaffin®Fresenius AG, Germany (formerly Affina GmbH, Germany)the agaroseSynthetic Oligopeptide67 ml1.2 g17.9 mg/ml-many times
Ig-TheraSorb®Myltenyi Biotec GmbH, Germany (formerly Baxter and PlasmaSelect, Germany)the agarosePolyclonal sheep antibodies (Pcat) against human IgG150 ml2.0 g13,0 mg/mlof 12.7 mg/mlmany times
Ig Adspec®NPF "PACKARD, Russiathe agarosePcat to human IgG200 ml2.2 g11.0 mg/mlof 11.2 mg/mlm is agarrate
ImmunotecDeveloper - FSE RK NPC, Ministry of Manufacturer - SPF "PACKARD, Russiathe agaroseF(ab)2fragments of polyclonal antibodies100 ml1.5 g-15.8 mg/mlmany times

The list of information sources

1. McMillan R. // autoantibodies are and autoantigens in chronic immune thrombocytopenic purpura. / Semin. Hematol. - 2000. - V.37 (3). - P.239-248.

2. Schulze K., Becker BF., Schauer R., Schultheiss HP. // Antibodies to ADP-ATP carrier - an autoantigen in myocarditis and dilated cardiomyopathy - impair cardiac function. / Circulation. - 1990. - V.81. - P.959-969.

3. Magnusson y, Wallukat G., Waagstein f, Hjalmarson a, Hoebeke J. // Autoimmunity in idiopathic dilated cardiomyopathy. Characterization of antibodies against the β1-adrenoceptor with positive chronotropic effect. / Circulation. - 1994. - V.89. - P.2760-2767.

4. Muller J., Wallukat G., M. Dandel, Bieda H., K. Brandes, Spiegelsberger S., Nissen, E., Kunze R., review : firebreath R. // Immunoglobulin adsorption in patients with idiopathic dilated cardiomyopathy / Circulation. - 2000. - V.101. - P.385-391.

5. Moreso F., R. Poveda, Gil-Vernet s, Carreras L., Garcia-Osuna R., Grino J.M., J. Alsina // Therapeutic immunoadsorption in Goodpasture disease./Med. Clin. (Barc) - 1995 Jun. 10. - V.105 (2). - P.59-61.

6. Robinson J.A. // Apheresis in thoracic organ transplantation. / Ther. Apher. - Feb 1999. - V.3 (1). - P.34-39.

7. Konovalov GA, Belenkov YU.N., Zvezdin PV, Chebyshev A.N., Semin S.N., Kuznetsov, Y., Adam YU, Kipor YEAR, S. Pokrovsky. Apheresis immunoglobulin - a new approach to the treatment of severe forms of dilated cardiomyopathy. // Cardiology. - 2002. - So 6. - Pp.92-96.

8. Koll R.A. // Ig-Therasorb immunoadsorption for selective removal of human immuoglobulins in diseases associated with pathogenic antibodies of all classes and IgG subclasses, immune complexes, and fragments of immunoglobulins. / Ther. Apher. - May 1998. - V.2 (2). - P.147-152.

9. Bygren p, C. Freiburghaus, T. Lindholm, et. al. // Goodpasture''s syndrome treated with gets protein A immunoadsorption. / Lancet. - 1985. - V.2 (8467). - P.1295-1296.

10. Kronvall G., Williams RC., Jr // Differences in anti-protein A activity among IgG subgroups. / J Immunol. - 1969. - V.103 (4), P.828-833.

11. Staudt, A., Bohm, M., Knebel f, Grosse Y., Bischoff, C., Hummel, A., Dahm JB., Borges, A., Jochmann n, Wernecke KD., Wallukat G., Baumann g, Felix SB. Potential role of autoantibodies are belonging to the immunoglobulin G subclass 3 in cardiac dysfunction among patients with dilated cardiomyopathy. / Circulation. - 2002. - V.106 (19). - P.2448-2453.

12. Matic G., Hofmann D., Winkler R., Tiess M., Michelsen, A., Schneidewind JM., Hebestreit, G., Keysser m, Muller W., Kinze EM., Ramlow W // Removal of immunoglobulins by a protein A versus an antihuman immunoglobulin G-based system: evaluation of 602 sessions of extracorporeal immunoadsorption. / Artif Organs. - 2000. - V.24 (2). - P.103-107.

13. Snyder HW Jr., Henry DH., Messerschmidt GL., et al. // Minimal toxicity during protein A immunoadsorption treatment of malignant disease: an outpatient therapy. / J Clin Apher. - 1991. - V.6 (1). - P.1-10.

14. Ray PK., Besa E., Idiculla, A., Rhoads JE Jr., Bassett JG., Cooper DR., // Efficient removal of abnormal immunoglobulin G from plasma of a multiple myeloma patient. Description of a new method for treatment of the hyperviscosity syndrome. / Cancer. - 1980. - V.45 (10). - 2633-2638.

15. Euler HH., Schwab UM., Schroeder JO., Hasford J. // The Lupus Plasmapheresis Study Group: rationale and updated interim report. /Artif Organs. - 1996. - V.20 (4). - P.356-359.

16. Knobl, P., K. Derfler, Korninger L., Kapiotis, S., Jager, U., Maier-Dobersberger t, Horl W, Lechner K, Pabinger I. // Elimination of acquired factor VIII antibodies by extracorporal antibody-based immunoadsorption (Ig-Therasorb). / Thromb Haemost. - 1995. - V.74 (4). - P.1035-8.

17. Ronspeck W., Brinckmann R., R. Egner, et al. // Peptide based adsorbers for therapeutic immunoadsorption. / Ther Apher Dial. - 2003. - V.7 (1). - P.91-97.

18. Kiseleva E.A., Afanasieva O.I., Kosheleva N.A., Pokrovsky S.N. // Immunosobent for IgG apheresis: an in vitro study. / Transfus. Sci. - 1996. - V.17 (4). - P.519-525.

19. Konovalov GA, Topalov I.N., Histoplasma N.A., Chebyshev A.N., Medicine L.A., V. Shmyrev, Yastrebova N.E., Kiseleva E., I. Afanasyeva, Adam YU, S. Pokrovsky. The first experience of application of course Ig-apheresis in the treatment of patients with multiple sclerosis. // The Kremlin medicine. - 1999. No. 3. - P.48-52.

20. Nisonoff, A., Wissler F.., Lipman L.N. and Woernley D.L. // Separation of univalent fragments from the left-hand drive vehicles rabbit antibody molecule by reduction of disulfide bonds. / Arch. Biodtem. and Biophysics. - 1960. - V.89. - P.230.

21. Yarmush M.L., Lu X., Yarmush D.M. // Coupling of antibody-binding fragments to solid-phase supports: site-directed binding of F(ab)2fragments. / Journal of Biochemical Methods. - 1992. - V.25. - P.285-297.

Sorbent for the removal of immunoglobulins from human blood plasma containing agarose matrix, covalently linked to a ligand, characterized in that, as a ligand, it contains F(ab)2fragments of affinity-purified polyclonal sheep antibodies against immunoglobulin G man.


Same patents:

FIELD: medicine.

SUBSTANCE: method involves applying endolymphatic- and autohemochemotherapy. Stage I of choriocarcinoma involves administering Methotrexate 20 mg/m2 as endolymphatic therapy at 1, 4, 8, 11, 15 and 18-th day; Rubomycin 30 mg/m2 at 1, 4, 8, 11, 15 and 18-th day Vinblastin - 15 mg/m2 at 1, 8 and 16-th day as autohemochemotherapy. Stage II of the disease involves administering Methotrexate 200 mg/m2 at the first day as endolymphatic therapy; Vincristin - 1.5 mg/m2 at 5,11, and 17-th day, Rubomycin 30 mg/m2 at 5, 8, 11, 14, 17 and 20-th day in a 21 days long course with 3 weeks long pause as autohemochemotherapy. The number of courses is 1-3. Stage III of the disease involves administering Methotrexate 200 mg/m2 as endolymphatic therapy, Etoposide -100 mg/m2, Kosmogen - 0.5 mg as autohemochemotherapy at the first day; Kosmogen - 0.5 mg as autohemochemotherapy at the second day; Vincristin - 1.0 mg/m2 Cyclophosphane 600 mg/m2, in 8 days long courses with 3-4 weeks interval and the number of courses is equal to 2-3.

EFFECT: eliminated metastases in the region of sexual organs and lungs; repaired menstrual cycle.

FIELD: medicine, oncology.

SUBSTANCE: the present innovation deals with surgical therapy and chemoradiation therapy. Moreover, in pre-surgical period a patient's blood plasma should be incubated with the following chemopreparations: cisplatin 10 mg, methotrexate 25 mg, cyclophosphan 600 mg in a thermostat at 37°C for 30 min. Then it is important to inject the incubated plasma into a patient's subcutaneous fatty fiber due to paracentesis from 4 sides through the points marked under US control being beyond vascular system just under the focus of malignant growth. During the same day it is necessary to start gamma-therapy at the dosage of 2.4 Gy daily for 15 d, 2 d later one should carry out operation in the volume of wide dissection of the primary focus. The innovation enables to prolong the life period in patients, prevent tumor dissemination in the course of operation, decrease the risk for the development of disease relapses after surgical dissection of the primary tumor, creates the chance for direct supply of chemopreparations towards tumor focus and, also, develops conditions for their prolonged local impact.

EFFECT: higher efficiency of therapy.

4 dwg, 1 ex

FIELD: medicine, phthisiology.

SUBSTANCE: invention relates to medicinal therapy of tuberculosis. Method involves carrying out autohemochemotherapy to patients suffering from tuberculosis: 100 mf cisplatin is mixed with 200.0 ml of autoblood taken preliminary from elbow vein and incubated at temperature 37°C for 30 min followed by its reinfusion to a patient at 1st and 5th days of treatment by intravenous drop route. Except for, 50 mg of doxorubicin and 1 g of cyclophosphan are mixed with 200.0 ml of autoblood taken preliminary from elbow vein and incubated at temperature 37°C for 30 min followed by its administration to a patient at 9-th and 13-th days of treatment by intravenous drop route. Method provides regression of disease in above 50% and even in case of drug resistance of tuberculosis mycobacteria, and decreasing numbers of adverse effects.

EFFECT: improved method of treatment.

5 dwg, 1 ex

FIELD: medicine, oncology.

SUBSTANCE: the present innovation deals with surgical therapy and chemotherapy. Moreover, in pre-surgical period it is necessary to sample 200 ml blood in such patients, due to centrifuging blood should be divided into plasma, leukomass and thromboerythromass. One should add leukovorin into the vial with leukomass at the dosage of 500 mg/sq. m to incubate in a CO2-incubator for 24 h and fluorouracil into the vial with thromboerythromass at the dosage of 1000 mg/sq. m to incubate for 30 min. Plasma should be frozen. In the course of the operation it is important to introduce intravenously by drops the content of the vial with thromboerythromass. On the next day the incubated leukomass with leukovorin should be injected for a patient intravenously by drops. Then, in post-surgical period on the 12th-14th d defrosted plasma should be incubated with fluorouracil at the dosage of 1000 mg/sq. m and metotrexate at the dosage of 25 mg/sq. m to be intravenously injected by drops. The innovation enables to decrease the frequency of relapses and metastases, decrease toxicity of anti-tumor preparations and prolong life period and improve quality of life in such patients.

EFFECT: higher efficiency of therapy.

1 ex

FIELD: medicine.

SUBSTANCE: method involves taken patient blood in preoperative period in the amount of 200 ml. Plasma is separated from the blood by centrifuging. 40 ml of autoplasma and chemopreparation are introduced into the first flask. The remaining blood corpuscles, plasma and chemopreparation are enclosed in the second flask. The flasks are separately incubated for 40 min at 37°C. Then, operation is executed by subserously introducing autoplasma incubated with chemopreparation from the first flask along the tumor periphery before mobilizing large intestine. Intravenous drip-feed infusion of autoblood incubated with chemopreparation from the second

flask is concurrently carried out into peripheral vein.

EFFECT: enhanced effectiveness in preventing local relapses and metastases occurrence in remote period.

FIELD: medicine.

SUBSTANCE: method involves setting ventricle drainage. Intracranial pressure growing 10-15 mm of mercury column higher, 100 ml of cerebrospinal fluid discharged by spontaneous flow is to be collected. Next, it is cleansed by centrifuging at a rate of 2400 rpm during 20 min. Supernatant cerebrospinal fluid portion is pumped off and thermostatted at +56°C during 60 min followed by repeated centrifuging in the same mode. Then, the Supernatant cerebrospinal fluid portion is pumped off and extracorporal system is filled with it to perform.

EFFECT: high liquor filtration safety; prevented dislocation syndrome occurrence; higher degree of protein removal from autoliquor.

1 tbl

FIELD: medicine, oncology.

SUBSTANCE: the present innovation deals with treating patients at not small cell nonoperable pulmonary carcinoma. It is necessary to introduce chemopreparations incubated with a patient's body automedium and carry out radiation therapy. Moreover, medullary iliac suspension should be incubated with chemopreparations in a thermostat at 37°C for 30 min and reinfused for a patient intravenously by drop technique. In 2 wk one should carry out radiation therapy at the mode of accelerated hyperfractioning per 1.3 Gy per 2 fractions daily at a 4-h-long interval between fractions during 2 wk daily. It is important to carry out 3 such cycles that combine the introduction of chemopreparations upon medullary suspension and radiation therapy, at a 2-wk-long interval, the difference being in the mode of radiation therapy only. So, in the course of the second cycle a single dosage of irradiation corresponds to 1.2 Gy twice daily at a 4-h-long interval during 2 wk. During the third cycle - per 1.1 Gy daily at a 4-h-long interval for 2 wk. The innovation enables to improve final results and quality of life in such patients; decrease side manifestations of anti-tumor therapy at inspecific stimulation of immune status with the elements of medullary suspension.

EFFECT: higher efficiency of therapy.

1 ex

FIELD: medicine, neurooncology.

SUBSTANCE: the present innovation deals with treating patients at low-differentiated cerebral gliomas. The method deals with introduction of anti-tumor chemopreparations. So, at first, one should catheterize common carotid artery (CCA) through a surface temporal artery at the side of the tumor, moreover, the catheter should be guided 1 cm below CCA bifurcation. Out of catheterized CCA one should sample 30 ml arterial autoblood into a syringe that contains 1 ml citrate conservant; then it should be supplemented with anti-tumor chemopreparations in therapeutic dosages. The mixture obtained should be incubated in a thermostat at 37°C for 1 h and introduce under the pressure and through the catheter into a patient's CCA once for 2 h. If necessary, this procedure should be repeated in 2 mo. The innovation provides decreased sizes or the absence of further tumor growth due to creating high concentration of chemopreparations directly in the tumor while they pass hematoencephalic barrier at their introduction upon autoblood and it considerably prolongs life duration in such patients.

EFFECT: higher efficiency of therapy.

1 ex

FIELD: medicine, gynecology.

SUBSTANCE: it is necessary to carry out reinfusion of a patient's autoerythrocytes incubated with 1 g cefamisine and 1.0 ATP 1 h before operation. Then, 3 d after operation it is important to introduce oral contraceptive "Belara" in contraceptive mode. Since the 5th d after operation it is necessary to introduce Polyoxidonium as vaginal suppositories during 10 d. The innovation provides complex normalization of body immunoreactivity and female menstrual function and, thus, shortens the quantity of post-abortion complications.

EFFECT: higher accuracy and efficiency of prophylaxis.

2 ex

FIELD: medicine, biology, veterinary.

SUBSTANCE: claimed method includes ozonotherapy of patient by ozonation of 100-150 ml patient blood in sterile glass bottle with ozone/oxygen mixture at ozone concentration of 5000 mug/l.

EFFECT: new method for stimulating of prostaglandin secretion.

4 dwg

FIELD: medicine, oncology.

SUBSTANCE: method includes the consecutive stages: (a) administration of at least one dose of anti-angiogenic cyclo-(arginine-glycine-asparagine acid)-containing pentapeptide (pentapeptide cRGD), such as cyclo-(Arg-Gly-Asp-D-Phe-[N-Me]-Val); (b) administration of anti-tumor effective amount of radio immunotherapeutic agent(RIT) not later than in 1 hour following administration of pentapeptide cRGD at stage (a); and (c) administration of at least two additional doses of pentapeptide cRGD, where the first additional dose is administered within 2 days after RIT and each additional dose of pentapeptide cRGD is administered with intervals between doses not more than 2 days.

EFFECT: invention provides the synergic effect in regard to apoptosis of tumor cells and endothelial cells of tumor vessels.

30 cl, 6 dwg, 2 tbl

FIELD: medicine, molecular biology, antibodies.

SUBSTANCE: invention relates to an antibody raised against CCR5 and comprising: (i) two light chains wherein each light chain comprises product of plasmid expression and designated as pVK:HuPRO140-VK (ATCC - PTA-4097), and (ii) two heavy chains wherein each heavy chain comprises product of plasmid expression and designated as pVg4:HuPRO140 HG2-VH (ATCC - PTA-4098), or plasmid designated as pVg4:HuPRO140 (mut B+D+I)-VH (ATCC - PTA-4099), or fragment of such antibody binding with CCR5 on a human cell surface. Invention relates to nucleic acid encoding light and heavy chains of antibody, expression vector, cell-host transformed with at least one vector, and a method for preparing antibody. Antibody is used as an active component in composition used for inhibition of infection of cells CD4 + HIV-1, and to a pharmaceutical composition used in treatment of a patient with HIV-1 infection. Also, invention relates to antibody conjugate against CCR5 and its using. Use of antibodies provides enhancing effectiveness of prophylaxis and treatment of HIV-1 infection.

EFFECT: valuable medicinal properties of antibody.

31 cl, 23 dwg, 3 ex

FIELD: medicine.

SUBSTANCE: method involves applying effective doses of epidermis growth factor receptors antagonists being active ingredient in drug for inhibiting various types of resistant human tumors. The epidermis growth factor receptor antagonists are combined with other chemotherapeutic agents like Cisplatin, Irinotecan or ionizing radiation.

EFFECT: enhanced effectiveness of treatment.

50 cl, 2 tbl

FIELD: medicine, oncology, immunology, tumor biology.

SUBSTANCE: invention relates, in particular, to methods for enhancing cytotoxicity based on applying anti-CD38-immune toxins. Method involves carrying out the treatment of patient with pathophysiological state taken among the group including myelomas and leukosis and involves the following stages: a) administration to the indicated patient the pharmacologically effective dose of retinoid that enhances expression of antigen CD38; and b) administration to the indicated patient the pharmacologically effective dose of immune toxin acting against effectively expressing antigen CD38. Method provides enhancing the cytotoxicity with respect to above said diseases in their resistance to anti-tumor medicinal agents.

EFFECT: enhanced and valuable method for treatment.

6 cl, 1 tbl, 9 dwg, 10 ex

The invention relates to biotechnology

The invention relates to medicine and relates to antibodies with reduced total positive charge

The invention relates to biotechnology and immunology, and can be used to generate neutralizing antibodies against different strains and clinical isolates of HIV-1

The invention relates to medicine, in particular to the immunological treatment response graft-versus-host (GVHD)

The invention relates to medicine and relates to a method of modifying a protein such as an antibody, methods of securing binding protein antibody pharmaceutical compositions of modified proteins for the treatment of human

FIELD: medicine, oncology, endocrinology, pharmacy.

SUBSTANCE: invention relates to an agent used in prophylaxis or treatment of patients suffering from anorexia and containing antibody raised against protein relates to the human parathyroid hormone (PTHrP) as an active component. Agent can comprise antibody raised against human PTHrP wherein antibody can represent human, humanized or chimeric one and shows the low antigenicity. Using the proposed agent provides improving a patient state suffering from malignant tumor.

EFFECT: valuable medicinal properties of agent.

6 cl, 6 tbl, 10 ex