Method for treatment of chronic helicobacter pylori- associated gastritis with preparation "laminolakt"

FIELD: medicine, gastroenterology.

SUBSTANCE: invention relates to methods for treatment of chronic helicobacter pylori-associated gastritis. Method is carried out by monotherapy with the probiotic "Laminolakt" in the dose 3 dragees per 24 h for 1 month. Method provides elimination of Helicobacter pylori cells on the background of activation of the immune response in stomach mucosa by effect on microflora and the colon intestine immune system.

EFFECT: enhanced effectiveness of treatment.

2 tbl, 1 ex

 

The invention relates to medicine, namely to a gastroenterologist. The index of the invention: a 61 f 1/04, a 61 K 35/74.

N. pylori-associated gastritis is the most common gastroenterological pathology. After the discovery of Helicobacter pylori J.Warren and B.Marshall in 1983 became possible etiotropic therapy of diseases such as chronic gastritis, peptic ulcer and MALT-OMA stomach. The main condition of success in the treatment of these diseases is eradication of the organism.

The aim of the invention is the eradication of the microorganism Helicobacter pylori as the main etiological factor in the development of chronic gastritis, by improving the microflora of the colon and enhance the immunoreactivity of the microorganism using the drug Laminolact.

To date this purpose, various schemes, one of the key components of which are antibacterial agents.

The Maastricht agreements-II from 2000. to use the recommended eradication schemes of the first and second line containing antisecretory drug from the group of blockers of the proton pump and two antibacterial agents. Despite the use of powerful antibiotics, eradication efficacy is reduced. One of the reasons is the increase in the number antibioticresistant strains of H pylori,

Table 1.

Dynamics of resistance HP to antimicrobial drugs
Medication199619971998199920002001
Metranidazol.36,1%42%59,6%54,2%56,6%55,5%
Clarithromycin08%14,4%17,7%16,6%13,8%
Amoxicillin8,5%00000
Clarithromycin+amoxicillin5,5%6%6%8,5%10%11,1%

In addition, the use of eradication schemes can lead in some cases to the complications caused by the action of antimicrobial drugs, such as allergic reactions, dyspepsia, diarrhea, dysbiosis.

From these positions interest is the possibility of exposure to a pathogen (Helicobacter pylori) by increasing the immunoreactivity of the microorganism. Most physiological and natural in this regard, we think the reference to the microflora thick the intestine.

During the phylogenetic development of man formed a complex endocrine system that supports dynamic balance between the physiological status of the host and the microbial populations that populate it.

Human microflora consists of approximately 1015microbial cells, which is two orders of magnitude higher than the number of cells of the adult human body. About 60% of the microflora colonizing the different sections of the gastro-intestinal tract. Microbes in the colon and rectum are dominant in quantitative and qualitative terms component of the normal intestinal flora of man and there are about 500 species of bacteria.

The microflora of the colon performs numerous functions, the importance of which can hardly be overestimated.

One of the important components of the obligate microflora of the large intestine is lactic acid bacteria, including Enterococcus. In the digestive tract of humans and animals most often present Enterococcus avium, Enterococcus faecalis and E. faecium. Microorganisms that coliform bacteria are gram-positive cells are spherical or ovoid shape.

In experiments in vitro demonstrated that many strains of enterococci are able to exhibit antimutagenic activity that seems to be of interest in respect of the mutagenic activity of N. pyloi. An important property of enterococci as representatives of lactic acid bacteria is the ability to produce lactic acid and antibiotic like substances (bacteriocins, which leads to their direct antibacterial action.

To ensure postcritical syndrome and other inflammatory diseases of the gastrointestinal tract in Italy used probiotic preparation, made on the basis of live freeze-dried cells of Enterococcus faecium. The purpose of the probiotic on the basis of Streptococcus faecium (strain SF 68) prevented the development of diarrhea associated with the appointment of high doses of antibiotics. Since 1980 in Germany is widely used in the treatment of tonsillitis, upper respiratory infections, nonspecific enteritis and irritable bowel syndrome probiotic preparation, prepared on the basis of a specially selected strain of E. faecalis. Clinical efficacy of this probiotic, assumed to be caused by stimulation of the oral input enterococci immunocompetent cells, which are primarily associated with the local immunity. In addition, live enterococci stimulate the release of interleukin-1β and interleukin-6, and γ-interferon, activate b cells and through a cascade of reactions leading to increased synthesis of IgA.

Given the generality of the immune system of the gastric mucosa and Ki is ecnica, the entire gastro-intestinal tract, the important role of the intestinal microflora in maintaining immune homeostasis, as well as direct antihelicobacter activity of lactic acid bacteria, in our study an attempt was made to use with the aim of eradication monotherapy synbiotic “Laminolact”. The composition of the bean laminaat: Enterococcus faecium, purified soy protein, pectin, trace elements.

Was observed in 18 patients (male 8, female 10, ranging in age from 18 to 64 years, with an average age of 31.6) with chronic HP-associated gastritis.

The diagnosis of chronic gastritis was established endoscopic and morphological methods. The presence .pylori infection was determined by histological and molecular (polymerase chain reaction with primers to genes ureB and cagA) methods, the results of which can reliably talk about the presence or absence of infection. All patients underwent inoculation of feces for the study of aerobic and anaerobic spectra of the microflora of the colon was determined by the presence and severity of dysbiosis. The main changes in the microbial spectrum of the colon have been identified as reducing the number of bifidobacteria, lactic acid bacteria, bacteroids, enterococci and increasing the number of representatives of conditionally pathogenic microflora (table 2). The revealed changes consistent with di is the BIOS I-II degree.

All patients received therapy laminolact at a dose of 3 pills 3 times a day for 30 days. Control tests were carried out after 2 months of perechislennye above methods.

At follow-up in 14 patients showed improvement of endoscopic picture (regression of edema, hyperemia of the gastric mucosa), and 9 patients were observed endoscopic remission of chronic gastritis. These 9 patients at follow-up was proven by the absence of N. pylori all assays. In the microbial spectrum considerable improvements have been expressed in the rise and normalization of the number of representatives of normal microflora in most patients. There was observed a decrease in the number of conditionally pathogenic microorganisms.

Eradication efficacy was 50% when available, according to literature data, the frequency of spontaneous eradication 3% (difference is statistically significant).

Monotherapy laminolact has a lower efficiency of eradication compared with the standard eradication schemes, however, it is more physiological, facilitates the mobilization of protective forces of an organism and has no side effects, available antibacterial drugs.

Invented a method of treating hronicheskoj is N. pylori-associated gastritis using laminaat as monotherapy can be applied in clinics and gastroenterology wards with the aim of eradication etiological factor in cases where the use of antibacterial drugs is impossible or undesirable for any reason. Moreover, monotherapy Laminolact may be recommended in some cases as first-line therapy for reducing the frequency of use of antibacterial agents.

Sources of information

1. Shenderov B.A. Medical microbial ecology and functional nutrition. Volume III, Moscow, 2001, pp. 98-99.

2. Lykova E.A., Bondarenko V.M., Isacc Y.A. and other Correction probiotics microbiological and immune disorders in gastroduodenal pathology in children. Microbiology, 1996, No. 2, pp. 88-91.

3. Kabir A.M., Y. Aiba, Tacagi A. et al. Prevention of Helicobacter pylori infection by lactobacilli in a gnotobiotic murine model // Gut, 1997, V.41,49-55.

4. Rusch V., K. Ziommerman Microbial therapy with Enterococcus faecalis and Escherichia coli: Experimental and clinical data // In: Probiotics: prospects of the use in opportunistic infections. Old Herbom University Seminar Monograpg (Eds. Fuller R. Et al). Inst. Environ. Biochem, Herborn-Dill, Germany, 1995, 158-172.

A method for the treatment of chronic Helicobacter pylori-associated gastritis, characterized in that the drug use “Laminolact as monotherapy at a dose of 3 pills 3 times a day for 1 month.



 

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FIELD: medicine.

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5 cl,4 tbl

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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

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

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.

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EFFECT: valuable medicinal properties of compounds.

18 cl, 107 ex

FIELD: organic chemistry, medicine.

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EFFECT: valuable medicinal properties of compounds.

18 cl, 107 ex

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EFFECT: improved preparing method, valuable properties of conjugates.

22 cl, 17 dwg, 12 ex

FIELD: medicine, pharmacology, pharmacy.

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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: biotechnology, microbiology.

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EFFECT: valuable medicinal properties of strain and agent.

3 cl, 5 dwg, 7 ex

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