Method for lymphostimulation and immunomodulation in cerebrospinal sclerosis

FIELD: medicine, neurology.

SUBSTANCE: method involves intravenous administration of autolymphocytes treated with an immunomodulating agent by extracorporal method using cycloferon (250 mg) as an immunomodulating agent. Simultaneously, the following medicinal mixture comprising lidocaine, 100 mg; lidazum, 32 U; dexamethasone, 4 mg; leukinferon, 10 000 U; 40% glucose solution, 4 ml is administrated into interspinal ligaments of spinal column at levels corresponding to thoracal and lumbar enlargements of the spinal cord. The procedure is repeated three times with interval for 48-72 h. Method provides enhancing the effectiveness of lymphostimulation and immunomodulation in cerebrospinal sclerosis. Invention can be used for lymphostimulation and immunomodulation in cerebrospinal sclerosis.

EFFECT: improved method for treatment.

1 tbl, 1 ex

 

The invention relates to medicine, namely, neurology, and can be used as a treatment for multiple sclerosis (PC).

There is a method of treating PC using steroids - prednisolone, methylprednisolone, dexamethasone, betamethasone (D.S. Goodin, 1991, Zavalishin I.A., 1991, 1996).

There is a method of treating PC using drugs - azathioprine, cyclophosphamide, cyclosporine A (Yudkin P.L. et al., 1991, Mackin G.A.etal., 1993).

There is a method of therapy PC using cytokine - Roferon, reaferona (prototype No. 1), Betaferon (Femandez O. et al., 1995).

There is a method of treating PC using Copaxone (Kenneth Johnson, 1998, the Congress of ECTRIMS 98, Stockholm).

The disadvantages of the method prototype No. 1 - side effects of injection of cytokine - flu-like reactions, hyperthermic syndrome, and intramuscular injection is the possibility of necrosis of the muscles. High probability of generation of blocking antibodies in intravenous or intramuscular injection of cytokines and subsequent decrease the effectiveness of therapy, the lack of effect of the elimination products of autoimmune reactions (including circulating immune complexes).

A known method of immunotherapy and infotemplate when PC (prototype No. 2) using the endolymphatic injection of natural cytokines (Khabarov D.V. 1999). The disadvantage of this method is technically the complexity: the need for surgery - selection and catheterization lymphatic vessel, the possibility of migration of the catheter and rupture of lymphatic vessels, thrombosis, the need to use the dispenser, the administration of drugs (infusion pump, lineament), the possibility of developing infectious complications.

We propose a method, which consists in the introduction to megastate ligaments of the spine at the levels corresponding to the thoracic and lumbar thickening of the spinal cord, medicinal mixture: lidocaine 100 mg, lydasum 32%, dexamethasone 4 mg, lacapere 10000 IU, glucose 40%-4 ml with simultaneous intravenous in vitro treated with the immunomodulator cycloferon (250 mg) at a temperature of 24-26°C for one hour autolymphocyte in the number of 400-1000 cells/ml Procedure was repeated three times with an interval of 48-72 hours.

The technical result of the proposed method is infostealers and immunomodulating effect by indirect infostealers injections comprehensive medicinal mixture, including infostealer and cytokines in combination with effects on the immune system in vitro, namely autolymphocyte drugs class of immunomodulators.

This goal is achieved by performing indirect infostealers injection in megastate ligaments of the spine. The level of injection is s corresponds to the thoracic and lumbar thickening of the spinal cord, depending on neurological symptoms. The composition of a medicinal mixture includes: hyaluronidase (32%), dexamethasone (4 mg), lidocaine (100 mg), 40% p-p glucose (4 ml) and lacapere (10000 IU). This injection is repeated 3-5 times with an interval of 48-72 hours. Lymphocytapheresis is held on the separator blood cells AS-TEC 204 firms “Fresenius”. The resulting autolymphocyte at a concentration of 400-1000 cells/ml exhibited within 1 hour with an immunomodulator (cycloferon 250 mg) at a temperature of 24-26°C, after which autolymphocyte returned to the patient by intravenous infusion. This procedure is repeated three times with an interval of 48-72 hours.

The advantages of the proposed solution:

the combination lampotiloissa and immunomodulatory therapy allows to mutually improve the efficiency of each method and contribute to the overall effect;

- increased lymphatic drainage from the limb and liver;

- lymphotropic complex cytokine - lacenterra determines infostealers and immunomodulatory effect on the lymphatic region of the spine and spinal cord;

- allocation of the exact number of autolymphocyte, cells, occupying a Central place in the pathogenesis of the disease;

- an impact immunomodulator cold-inducer of endogenous interferons on autolymphocyte in vitro conditions;

- the possibility of elimination from the body is ZMA a certain number of autolymphocyte;

- ability to conduct simultaneously extracorporeal detoxification is the elimination of the plasma, and with it part of the products of autoimmune reactions (including circulating immune complexes). Evaluation of the treatment results was performed according to the following algorithm:

- registration of neurological symptoms;

- immunological examination of patients;

- rheovasography liver.

Following studies were conducted:

- determination of the dynamics of neurological status on a scale assessing the severity of patients on Kurtzke J. (1981, 1983): Disability Status Scale (DSS), Expanded Disability Status Scale (EDSS) in connection with scale functional systems (Functional System, FS). Taken into account additions and modifications made H.I.Weiner and G.W.Ellison (1983) and the authors of the guidance M.R.D. (Minimal Record of Disability for Multiply Sclerosis, 1985).

- General research of the immune status, which showed the state of cellular and humoral immunity and included the determination of total and relative number of lymphocytes and their subpopulations: T-lymphocytes, T-helpers, T-suppressors, T-killer cells, b-lymphocytes, immunoglobulins G, M, A, circulating immune complexes, aggregates - immunoregulatory index (IRI), the determination of the total number of leukocytes and leukocyte;

- determining the expression of proinflammatory and anti-inflammatory cytokines - interleukin (IL) 1 IL 6, IL 4, IL-10, tumor necrosis factor - α (TNFα);

- conducting regulatoryinformation examination of the liver in patients with PC.

These surveys were conducted upon admission to a hospital and before discharge.

Results

When using the proposed method of treatment has a positive dynamics in neurological symptoms in 75% of patients receiving infotemplate in combination with in vitro immunomodulation of autolymphocyte obtained at the cage of blood cells. Neurological dynamics on the scale of Kurtzke J. was 1-4 points 2-3 indicators (symptoms pyramid way, coordination disturbances, disorders of pelvic organs, visual impairment, dysfunction of the cranial nerves). In the comparison group, where he held only lymphocytapheresis with extrakorporale processing autolymphocyte also mentioned the positive neurological dynamics, but in 70% of cases and 1-2 points on the same indicators, but less often when improvement occurred simultaneously on the three symptoms. Positive neurological improvement in patients with endolymphatic introduction of natural cytokines were detected in 53% of cases. Immunological examination conducted before and after the implementation of the proposed method showed that there is an increase in total T-lymphocytes (L is -3) to normal values or to values close to the lower limit of the norm, at the expense of the oppressed link - T-suppressors (LT-8). Thus, normalizes immunoregulatory index. There is a decrease in CEC in cases where this indicator increased. The frequency of expression of proinflammatory cytokines before treatment were: IL-1 - 5,26%, IL-6 - 33,3%, name α and after completion of therapy with the use of the proposed method - IL-1 AND 3.3%, IL-6 - 16,5%, TNF α -. The frequency of expression of anti-inflammatory cytokines before treatment were: IL-4 - 13.3%, and the IL-10 - 33,3%, and after completion of therapy with the use of the proposed method - YL-4 - 20%, IL-10 - 40%. Positive immunological changes were correlated with improvement of neurological symptoms.

Rheovasography the liver of patients with PC showed that in 80% of cases after treatment is the increased speed of the outflow of lymph and venous blood, and the volume of lymphatic and venous outflow, which indicates a rising tone lympho-venous system of the liver and increase detoxification of the body.

Clinical example. The patient And society, 26 years. Diagnosis: Multiple sclerosis. Cerebral form. Cerebellar ataxia, mild lower prepares, dysarthria. Moderate cochleovestibular syndrome. Zerebrasteniceski, neurasthenic syndromes.

After 2 months of angina noted speech disorders. Turned to never the log. MRI brain data obtained for demyelinizing disease. Diagnosed with multiple sclerosis.

At admission the patient on a scale of damage of functional systems by J. Kurtzke score was 9, after carrying out the proposed method of infotemplate and immunomodulation this indicator was equal to 1 point (see table).

Scale the damage of functional systems by Kurtzke J. (patient a-VA, the only pathological symptoms)

GroupWhen receivingClassification depending on the dysfunctionAt discharge
Symptoms pyramid path31 - pathological pyramid reflexes without compromising strength1
2 - a slight decrease power 
3 - slight or moderate Hemi - or prepares, heavy monopoles 
4 - clear Hemi - or prepares mild tetraparesis 
5 - paraplegia, hemiplegia or distinct tetraparesis 
6 - quadriplegia 
The lack of coordination20
2 - slight ataxia 
3 - moderate ataxia of the trunk or limbs 
4 - severe ataxia in all limbs 
5 - cannot perform directional movements due to ataxia 
Disorders of cranial nerves (except 2 pairs)41 - the symptoms without dysfunction0
2 - moderate nystagmus or other minor 
symptoms of other cranial nerves 
3 - pronounced nystagmus, distinct symptoms involving the eye or facial nerves, moderate symptoms of other cranial nerves 
4 - severe dysarthria or other significant disturbances 
5 - inability to swallow or speak 
 9 1

Immunological examination conducted before treatment, showed absolute T-lymphopenia mainly due to T-suppressor (CD-8) and the violation of Iran. After the l of the treatment, the patient noted an increase in the total number of T-lymphocytes due to CD-8, and the normalization of Iran. Before treatment was revealed the expression prospaltella cytokines - IL-6, TNF αand anti - IL-10. After treatment, the expression of provospalitelna cytokines was not determined, and the expression of IL-10 remained.

Reovazograficheskie study of the liver before and after treatment showed an increase in the speed of outflow of lymph and venous blood, and the volume of the venous outflow.

The use of this method allows to effectively work on the pathological immunological reactivity of the organism, stimulate limfadenektomii mechanisms. Improves and stimulates the interaction of the immune and lymphatic systems. Thus, it is possible to change the course of the disease, resulting in improvement of neurological symptoms and overall immune status, expression of inflammatory cytokines, reovazograficheskie characteristics.

References

1. Zavalishin I.A., Neva O.M. Clinical criteria for the diagnosis and treatment of multiple sclerosis: guidelines //Moscow, 1991.

2. Zhuchenko SO, Zavalishin I.A. the Treatment of multiple sclerosis //Neurology journal, M: Medicine, 1996. No. 1 - P.37-43.

3. Khabarov D.V. Influence of efferent and endolymphatic therapy on the course of the pathological process in patients with multiple sclerosis //AV-tore. Diss. Kida. the unit of Sciences, Novosibirsk, 1999

4. Kurizke J.F. Epidemiology of multiple sclerosis in US veterans; V. Ancestry and the risk of multiple sclerosis //Ann. Neurol, 1993. - N 33. - P.632-639.

5. Fernandez 0., Antiquetful A., Aribisu T. et al. Treatment of relapsing-remitting multiple sclerosis with natural interferon-beta: a multicenter, randomized clinical trial //Multiple Sclerosis, 1995. - N 1 (Suppl.). - Page 67-69.

6. D.S. Goodin The use of immunosupressive agents in the treatment of multiple sclerosis //A critical review. Neurology, 1991. No. 41. - P.980-985.

The way immunomodulation and infotemplate multiple sclerosis, which consists in injecting in vitro treated with immunomodulator of autolymphocyte, wherein the immunomodulator use cycloferon (250 mg) and simultaneously in megastate ligaments of the spine at the levels corresponding to the thoracic and lumbar thickening of the spinal cord, administering a mixture of lidocaine 100 mg, lydasum 32%, dexamethasone 4 mg, lacapere 10000 IU, glucose 40%4 ml, the procedure was repeated three times with an interval of 48-72 hours



 

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FIELD: organic chemistry, medicine.

SUBSTANCE: invention relates to applying compounds of the formula (I) for preparing an antibacterial composition and veterinary composition eliciting with the enhanced activity.

EFFECT: valuable properties of agents.

4 cl, 3 tbl, 78 ex

FIELD: medicine.

SUBSTANCE: method involves taking lavage fluid samples from injured bronchi in preoperative period in making fiber-optic bronchoscopy examination. Microflora colonizing bronchial mucous membrane and its sensitivity to antibiotics is determined. Therapeutic dose of appropriate antibiotic and therapeutic dose of immunomodulator agent like leykinferon is introduced in endolymphatic way 40-60 min before operation. Smears are taken from outlying bronchi in doing operation. Sputum or fluid in retained pleural cavity are taken in 1-2 days after the operation. Prophylaxis effectiveness is determined on basis of bacteriological study data. Therapeutic dose of antibiotics and leykinferon are introduced in 6-8 and 20-24 h after the operation in endolymphatic way. The preparations are introduced at the same doses in endolymphatic way making pauses depending on selected antibiotic elimination half-time once or twice a day until the drains are removed mostly during 48-72 h after operation.

EFFECT: enhanced effectiveness of antibacterial protection; high reliability of antibiotic prophylaxis.

FIELD: organic chemistry, medicine.

SUBSTANCE: invention represents ligands MC-4 and/or MC-3 of the formula (I): , wherein X means hydrogen atom, -OR1, -NR1R1' and -CHR1R1' wherein R1 and R1' are taken among the group: hydrogen atom, (C1-C6)-alkyl and acyl; (1) each R2 is taken independently among the group: hydrogen atom, (C1-C6)-alkyl; or (2) (a) R2 bound with carbon atom that is bound with X and Z1 and substitute R5 can be optionally bound to form carbocyclic or heterocyclic ring that is condensed with phenyl ring J; or (b) R2 bound with carbon atom that is bound with ring Ar can be bound with R7 to form ring condensed with ring Ar; each among Z1, Z2 and Z3 is taken independently from the following groups: -N(R3e)C(R3)(R3a)-, -C(R3)(R3a)N(R3e)-, -C(O)N(R3d)-, -N(R3d)C(O)-, -C(R3)(R3a)C(R3b)(R3c)-, -SO2N(R3d)- and -N(R3d)SO2- wherein each among R3, R3a, R3b and R3c, R3d, R3e when presents is taken independently among hydrogen atom and (C1-C6)-alkyl; p is a whole number from 0 to 5 wherein when p above 0 then R4 and R4' are taken among hydrogen atom, (C1-C6)-alkyl and aryl; R5 represents 5 substitutes in phenyl ring J wherein each R5 is taken among hydrogen atom, hydroxy-, halogen atom, thiol, -OR12, -N(R12)(R12'), (C1-C6)-alkyl, nitro-, aryl wherein R12 and R12' are taken among hydrogen atom and (C1-C6)-alkyl; or two substitutes R5 can be bound optionally to form carbocyclic or heterocyclic ring that is condensed with phenyl ring J; q = 0, 1, 2, 3, 4 or 5 wherein when q above 0 then R6 and R6' are taken among hydrogen atom and (C1-C6)-alkyl; Ar is taken among the group consisting of phenyl, thiophene, furan, oxazole, thiazole, pyrrole and pyridine; R7 are substitutes at ring Ar wherein each R7 is taken among hydrogen, halogen atom, -NR13R13', (C1-C6)-alkyl and nitro- wherein R13 and R13' are taken among hydrogen atom and (C1-C6)-alkyl; r is a whole number from 0 to 7 wherein when r is above 0 then R8 and R8' are taken among hydrogen atom and (C1-C6)-alkyl; B is taken among -N(R14)C(=NR15)NR16R17, -NR20R21, heteroaryl ring and heterocycloalkyl ring wherein R14-R17, R20 and R21 are taken independently among hydrogen atom and (C1-C6)-alkyl; s = 0, 1, 2, 3, 4 or 5 wherein when s is above 0 then R and R9' are taken among hydrogen atom and (C1-C6)-alkyl; R10 is taken among the group consisting of optionally substituted bicyclic aryl ring and optionally substituted bicyclic heteroaryl ring; D is taken among hydrogen atom, amino- and -C(O)R11 wherein R11 is taken among the following group: hydroxy-, alkoxy-, amino-, alkylamino-, -N(R19)CH2C(O)NH2 wherein R19 represents (C1-C6)-alkyl, -NHCH2CH2OH and -N(CH3)CH2CH2OH, or its isomers, salts, hydrates or biohydrolysable ester, amide or imide.

EFFECT: valuable medicinal properties of compounds.

18 cl, 107 ex

FIELD: organic chemistry, medicine.

SUBSTANCE: invention represents ligands MC-4 and/or MC-3 of the formula (I): , wherein X means hydrogen atom, -OR1, -NR1R1' and -CHR1R1' wherein R1 and R1' are taken among the group: hydrogen atom, (C1-C6)-alkyl and acyl; (1) each R2 is taken independently among the group: hydrogen atom, (C1-C6)-alkyl; or (2) (a) R2 bound with carbon atom that is bound with X and Z1 and substitute R5 can be optionally bound to form carbocyclic or heterocyclic ring that is condensed with phenyl ring J; or (b) R2 bound with carbon atom that is bound with ring Ar can be bound with R7 to form ring condensed with ring Ar; each among Z1, Z2 and Z3 is taken independently from the following groups: -N(R3e)C(R3)(R3a)-, -C(R3)(R3a)N(R3e)-, -C(O)N(R3d)-, -N(R3d)C(O)-, -C(R3)(R3a)C(R3b)(R3c)-, -SO2N(R3d)- and -N(R3d)SO2- wherein each among R3, R3a, R3b and R3c, R3d, R3e when presents is taken independently among hydrogen atom and (C1-C6)-alkyl; p is a whole number from 0 to 5 wherein when p above 0 then R4 and R4' are taken among hydrogen atom, (C1-C6)-alkyl and aryl; R5 represents 5 substitutes in phenyl ring J wherein each R5 is taken among hydrogen atom, hydroxy-, halogen atom, thiol, -OR12, -N(R12)(R12'), (C1-C6)-alkyl, nitro-, aryl wherein R12 and R12' are taken among hydrogen atom and (C1-C6)-alkyl; or two substitutes R5 can be bound optionally to form carbocyclic or heterocyclic ring that is condensed with phenyl ring J; q = 0, 1, 2, 3, 4 or 5 wherein when q above 0 then R6 and R6' are taken among hydrogen atom and (C1-C6)-alkyl; Ar is taken among the group consisting of phenyl, thiophene, furan, oxazole, thiazole, pyrrole and pyridine; R7 are substitutes at ring Ar wherein each R7 is taken among hydrogen, halogen atom, -NR13R13', (C1-C6)-alkyl and nitro- wherein R13 and R13' are taken among hydrogen atom and (C1-C6)-alkyl; r is a whole number from 0 to 7 wherein when r is above 0 then R8 and R8' are taken among hydrogen atom and (C1-C6)-alkyl; B is taken among -N(R14)C(=NR15)NR16R17, -NR20R21, heteroaryl ring and heterocycloalkyl ring wherein R14-R17, R20 and R21 are taken independently among hydrogen atom and (C1-C6)-alkyl; s = 0, 1, 2, 3, 4 or 5 wherein when s is above 0 then R and R9' are taken among hydrogen atom and (C1-C6)-alkyl; R10 is taken among the group consisting of optionally substituted bicyclic aryl ring and optionally substituted bicyclic heteroaryl ring; D is taken among hydrogen atom, amino- and -C(O)R11 wherein R11 is taken among the following group: hydroxy-, alkoxy-, amino-, alkylamino-, -N(R19)CH2C(O)NH2 wherein R19 represents (C1-C6)-alkyl, -NHCH2CH2OH and -N(CH3)CH2CH2OH, or its isomers, salts, hydrates or biohydrolysable ester, amide or imide.

EFFECT: valuable medicinal properties of compounds.

18 cl, 107 ex

FIELD: organic chemistry, medicine.

SUBSTANCE: invention represents ligands MC-4 and/or MC-3 of the formula (I): , wherein X means hydrogen atom, -OR1, -NR1R1' and -CHR1R1' wherein R1 and R1' are taken among the group: hydrogen atom, (C1-C6)-alkyl and acyl; (1) each R2 is taken independently among the group: hydrogen atom, (C1-C6)-alkyl; or (2) (a) R2 bound with carbon atom that is bound with X and Z1 and substitute R5 can be optionally bound to form carbocyclic or heterocyclic ring that is condensed with phenyl ring J; or (b) R2 bound with carbon atom that is bound with ring Ar can be bound with R7 to form ring condensed with ring Ar; each among Z1, Z2 and Z3 is taken independently from the following groups: -N(R3e)C(R3)(R3a)-, -C(R3)(R3a)N(R3e)-, -C(O)N(R3d)-, -N(R3d)C(O)-, -C(R3)(R3a)C(R3b)(R3c)-, -SO2N(R3d)- and -N(R3d)SO2- wherein each among R3, R3a, R3b and R3c, R3d, R3e when presents is taken independently among hydrogen atom and (C1-C6)-alkyl; p is a whole number from 0 to 5 wherein when p above 0 then R4 and R4' are taken among hydrogen atom, (C1-C6)-alkyl and aryl; R5 represents 5 substitutes in phenyl ring J wherein each R5 is taken among hydrogen atom, hydroxy-, halogen atom, thiol, -OR12, -N(R12)(R12'), (C1-C6)-alkyl, nitro-, aryl wherein R12 and R12' are taken among hydrogen atom and (C1-C6)-alkyl; or two substitutes R5 can be bound optionally to form carbocyclic or heterocyclic ring that is condensed with phenyl ring J; q = 0, 1, 2, 3, 4 or 5 wherein when q above 0 then R6 and R6' are taken among hydrogen atom and (C1-C6)-alkyl; Ar is taken among the group consisting of phenyl, thiophene, furan, oxazole, thiazole, pyrrole and pyridine; R7 are substitutes at ring Ar wherein each R7 is taken among hydrogen, halogen atom, -NR13R13', (C1-C6)-alkyl and nitro- wherein R13 and R13' are taken among hydrogen atom and (C1-C6)-alkyl; r is a whole number from 0 to 7 wherein when r is above 0 then R8 and R8' are taken among hydrogen atom and (C1-C6)-alkyl; B is taken among -N(R14)C(=NR15)NR16R17, -NR20R21, heteroaryl ring and heterocycloalkyl ring wherein R14-R17, R20 and R21 are taken independently among hydrogen atom and (C1-C6)-alkyl; s = 0, 1, 2, 3, 4 or 5 wherein when s is above 0 then R and R9' are taken among hydrogen atom and (C1-C6)-alkyl; R10 is taken among the group consisting of optionally substituted bicyclic aryl ring and optionally substituted bicyclic heteroaryl ring; D is taken among hydrogen atom, amino- and -C(O)R11 wherein R11 is taken among the following group: hydroxy-, alkoxy-, amino-, alkylamino-, -N(R19)CH2C(O)NH2 wherein R19 represents (C1-C6)-alkyl, -NHCH2CH2OH and -N(CH3)CH2CH2OH, or its isomers, salts, hydrates or biohydrolysable ester, amide or imide.

EFFECT: valuable medicinal properties of compounds.

18 cl, 107 ex

FIELD: biochemistry, pharmaceutical chemistry.

SUBSTANCE: invention relates to preparing conjugate of naturally occurring or recombinant urate oxidase (uricase) bound covalently with poly-(ethylene glycol) or poly-(ethylene oxide) (both are designated as PEG) wherein in average from 4 to 10 PEG strands are conjugated with each subunit of uricase and molecular mass of PEG is about between 20 and 40 kDa. Prepared PEG-uricase conjugates are nonimmunogenic practically and retain at least 75% of uricolytic activity of nonmodified enzyme.

EFFECT: improved preparing method, valuable properties of conjugates.

22 cl, 17 dwg, 12 ex

FIELD: medicine, pharmacology, pharmacy.

SUBSTANCE: invention relates to a new growth/differentiation factor of TGF-β-family representing the amino acid sequence SEQ ID NO.2 or, if necessary, its functionally active moieties and to pharmaceutical composition based on thereof that can be used for inducing angiogenesis. Invention provides the enhancement of biological activity of preparation.

EFFECT: valuable biological properties of factor.

4 cl, 3 tbl, 4 dwg, 3 ex

FIELD: biotechnology, molecular biology, medicine, genetic engineering, pharmacy.

SUBSTANCE: the hemopoietic protein comprises the amino acid sequence of the formula: R1-L1-R1, R2-L1-R1, R1-R2 or R2-R1 wherein R1 represents the modified ligand flt-3; R2 represents the modified human IL-3, the modified or unmodified colony-stimulating factor. Modification of R1 is carried out by addition of N-end with C-end directly or through linker (L2) that is able to join N-end with C-end to form new C- and N-ends. The modified human IL-3 is prepared by replacing amino acids at positions 17-123. The human G-CSF is modified by exchange of amino acids. The hemopoietic protein is prepared by culturing cells transformed with vector comprising DNA that encodes the hemopoietic protein. The hemopoietic protein stimulates producing hemopoietic cells and this protein is used as a component of pharmaceutical composition used in treatment of humans suffering with tumor, infectious or autoimmune disease. Invention provides preparing multifunctional hemopoietic proteins eliciting the enhanced activity with respect to stimulation of hemopoietic cells and eliciting the improved physical indices. Invention can be used for preparing chimeric multifunctional hemopoietic proteins.

EFFECT: improved preparing and producing method, valuable medicinal properties of protein.

22 cl, 19 dwg, 18 tbl, 117 ex

FIELD: medicine, phthisiology, anesthesiology.

SUBSTANCE: during the day of operation one should perform autohemotransfusion, then introduce epocrine intravenously by drops at the dosage of 50-200 U/kg patient's body weight; next day after interference one should inject epocrine subcutaneously at the dosage of 25-100 U/kg; at hematocrit level being below 35% 48 h after operation it is necessary to repeat subcutaneous injection of the above-mentioned preparation at the dosage not exceeding 50 U/kg. The present innovation favors hemopoiesis stimulation in postoperational period, that, in its turn, accelerates postoperational rehabilitation in patients of this group and enables, also, to avoid allotransfusions being dangerous because of immunoconflicting reactions.

EFFECT: higher efficiency of compensation.

1 ex, 1 tbl

Thrombopoietin // 2245365

FIELD: medicine, molecular biology, polypeptides.

SUBSTANCE: invention describes homogenous polypeptide ligand mpI representing polypeptide fragment of the formula: X-hTPO-Y wherein hTPO has amino acid sequence of human fragments TPO (hML); X means a amino-terminal amino-group or amino acid(s) residue(s); Y means carboxy-terminal carboxy-group or amino acid(s) residue(s), or chimeric polypeptide, or polypeptide fragment comprising N-terminal residues of amino acid sequence hML. Also, invention relates to nucleic acid encoding polypeptide and expressing vector comprising nucleic acid. Invention describes methods for preparing the polypeptide using cell-host transformed with vector, and antibodies raised against to polypeptide. Invention describes methods and agents using active agents of this invention. The polypeptide ligand mpI effects on replication, differentiation or maturation of blood cells being especially on megacaryocytes and progenitor megacaryocyte cells that allows using polypeptides for treatment of thrombocytopenia.

EFFECT: valuable medicinal properties of polypeptide.

21 cl, 92 dwg, 14 tbl, 24 ex

FIELD: medicine, surgery.

SUBSTANCE: at the background of basic therapy in complex therapy of acute pancreatitis one should introduce ceruloplasmin to be applied at the dosage of 600-1000 mg/d for 5 d. If necessary, the course of ceruloplasmin introduction should be repeated. This method provides pancreatic tissues viability in case of pancreonecrosis by increasing efficiency of correction the endogenous intoxication and decreasing the number of complications in the course of therapy conducted.

EFFECT: higher efficiency of pharmacological correction.

3 ex

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