Complex therapy method for treating duodenal peptic ulcer diseases associated with helicobacter pylori

FIELD: medicine.

SUBSTANCE: method involves introducing Omeprasol at a dose of 20 mg twice a day before taking meals 10 days long, Amoxycillin at a dose of 1000 mg twice a day after breakfast and supper 7 days long, Clarithromycin at a dose of 500 mg twice a day before taking meals and Imudon as local immunomodulating factor at a dose of 8 pills a day making 2-3 h long pauses for resolving drug in oral cavity within 10 days.

EFFECT: enhanced effectiveness of treatment; reduced reinfection risk.

2 tbl

 

The invention relates to medicine, gastroenterology and can be used for treatment of peptic ulcer disease duodenal ulcer associated with Helicobacter pylori (H. pylori).

The known method of complex treatment of peptic ulcer of the duodenum using a solution of bactisporin [patent RU 2187318 C2], where the patient is orally administered a solution of bactisporin 3 doses 3 times a day before meals in the first 3 days, then 2 doses for 7 days. The way you can affect H. pylori and to stimulate regeneration of the mucous membrane of stomach and duodenal ulcers, prevents the development of dysbiosis.

Given the direct connection of peptic ulcer disease duodenal ulcer with Helicobacter pylori infection, in this case, the method of complex treatment of peptic ulcer of the duodenum, allowing you to affect the reservoir of H. pylori in the oral cavity and contribute to the improvement of the immunological properties of saliva. According to research Vdieackua et al. (2001) H. Pylori - positive status of the oral cavity was detected in patients with peptic ulcer of the duodenum in 75% of cases. Proved the presence of H. pylori in dental plaque in patients with peptic ulcer (Desai H.G. et al., 1991): after a course of antibiotic therapy microorganisms disappeared from the stomach, but was detected in dental plaque. Thus plaque is the main reservoir H. pylori infection. There are reports of detection of

H. pylori in dental plaque in the absence of microorganisms in the stomach (Banatvala N. et al., 1993), that allows to consider plaque not only as an important reservoir of H. pylori infection, but also as a place of its colonization in the human body.

Thus, most researchers are inclined to think about the possible existence in the oral cavity of a permanent source of self-experimenting researched and reinfection after successful eradication of H. pylori from the stomach (Nguyen A. N. et al., 1995).

A special place among the risk factors of chronic diseases of the digestive system involves the suppression of immune protection as a failure of adaptation possibilities, against which there is a decrease the body's resistance to Exo - and endogenous factors.

When the ulcers observed a significant decrease of lysozyme, IgA, IgG in saliva, which leads to secondary immunological failure and contributes to the activation of the microbial flora (Egorov E.N. et al., 2003).

According to Nembutal, Schutovae (2004) after standard therapy in patients not occurred restore IgA in saliva to values typical for the group of healthy, testified preserved violation of local immunity.

The problem of studying the efficacy of immunomodulators in the complex is the first treatment of diseases, associated with invasion of N. pylori is currently very topical and provides a basis for rational search for new ways of eradication of H. pylori (Lazebnik LB et al., 2003).

In this regard, the authors assigned the task of eliminating the source of infection (N. pylori infection and reinfection in the oral cavity in patients with peptic ulcer of the duodenum and AIDS in secretory immunity.

Thus, there is an experience of application of immunotropic drugs with the purpose of influence on the indices of cellular and humoral immunity, and in secretory immunity only the authors estimated the effect on activity of saliva.

Therefore, as a prototype of the selected two ways:

- the method of treatment helicobacteraceae chronic duodenal ulcer [patent RU 22252777 C2], where the basic four-part scheme omeprazole - colloidal bismuth subcitrate, amoxicillin - furazolidone advanced applied immunomodulator Likopid. The study revealed the effect of the immunomodulator on strengthening eradication in the gastric mucosa (from 73.7% to 95.5%), reducing the probability of a new flare-up (after treatment in patients not detected coccoid forms of H. pylori), the restoration of the morphological characteristics of the mucous membrane of the gastroduodenal zone, increase clinical efficiency, greater drew is giving lysozyme activity of saliva (95.2 per cent of patients against 78,9%). However, the disadvantage of this method is that it does not reflect the effectiveness of eradication of H. pylori in one of the main tanks - gingival plaque and gives little information about the immunological indicators of saliva.

The method of complex treatment of erosive and ulcerative lesions with the use of the immunomodulator Gepon, the authors Lazebnik LB et al. "Application of immunomodulatory Gepon in the treatment of erosive or ulcerative gastroduodenal lesions". Experimental and clinical gastroenterology - 2003 - No. 3 - p.17-19.

The use of the drug Gepon in treatment of erosive or ulcerative gastroduodenal lesions leading to improved indicators of cell-mediated immunity, accelerates regeneration processes. The disadvantage of this method that does not take into account the effect of the drug on immunological parameters of saliva.

The present invention is in the treatment of peptic ulcer disease duodenal ulcers associated with H. pylori, including the treatment regimen of local immunomodulator Imudon to eliminate AIDS in the performance of saliva.

The technical result of the invention is:

1) in the expansion of the means for the treatment of peptic ulcer of the duodenum by the drug Imudon in complex therapy;

2) to increase the effectiveness of eradication of H. pylori zubodesneve plaque and accordingly reducing the risk of reinfection in the gastric mucosa;

3) improvement of the immunological parameters of saliva.

This task is achieved by the inventive method of complex treatment of peptic ulcer disease duodenal ulcers associated N. pylori, including the eradication scheme omeprazole 20 mg 2 times a day before meals for 10 days amoxicillin 1000 mg 2 times a day after Breakfast and dinner for 7 days clarithromycin 500 mg 2 times a day before meals and characterized in that, in addition to drug therapy include local immunomodulator Imudon 8 tablets per day with an interval of 2-3 hours for dissolution in the oral cavity within 10 days.

Studies on patent and scientific and technical information sources showed that the proposed method for the treatment of peptic ulcer of the duodenum using local immunomodulator Imudon not known and should not be explicitly studied the prior art, i.e. meets the criteria of "novelty" and "inventive step".

The proposed method is carried out using known techniques:

Fibroesofagogastroduodenoscopia was conducted according to the standard technique of flexible fiber fibroadenoma "OLIMPUS" (Japan) with local anesthesia of the oropharynx lidocaine 10% spray.

Endoscopic control was performed 4 weeks after the end of the complex, the CSO treatment.

During an endoscopy before and after treatment were carried out targeted biopsy of the stomach in 2 points of the antrum.

Biopsy material was fixed in formalin and subjected to histological examination.

Diagnosis Of N. pylori was performed by several methods: histology, urease, respiratory, polymerase chain reaction.

For the detection of N. pylori and other microflora was used coloring 0.1% aqueous solution of methylene blue. The degree of contamination of the mucous membrane of the stomach infection N. pylori was assessed by light microscopy according to the criteria Liewen et al. (1993. Urease breath test (Kornienko E.A., mileyko V.E., 1996, patent RF №2100010).

Estimated increase in ammonia concentrations in the exhaled air. If growth exceeded 0.5 mg/m3the test N. pylori was considered positive. Molecular-biological method of polymerase chain reaction (PCR) was used to identify in a clinical specimen (biopsy of the gastric mucosa) of specific fragments of genomic DNA of N. pylori. The study was performed with kits "HELICOIL" NPF "Licej" (Russia), consisting of a kit for detection of a series 03/39/03 kit for DNA extraction series 07/28 .03.

The analysis was recorded after electrophoretic separation of the amplification products in the direction from the cathode (-) anode (+). Kohn is a role for the electrophoretic separation was carried out visually by the movement of the band of the dye. A final check was performed in the ultraviolet UV-transilluminator with a wavelength of 310 nm. Positive samples contained a strip located on the same level as the positive control lane. Negative samples did not contain stripes.

To study H. pylori status of the oral cavity PCR used the kit for DNA extraction from gingival plaque Helicoper II production NPF Liteh, Russia.

To date, PCR for DNA extraction H. pylori in dental plaque is the most optimal method, as there are restrictions in the use of other diagnostic methods, in particular urease tests is unacceptable due to the neutral environment and the presence of a large number of other freezeprotection in the oral cavity, the application of bacteriological method is limited to technical and economic difficulties, cytological method is considered to be uninformative.

The analyzed material using a disposable sterile probes was transferred into 100 µl of saline solution into a test tube of 1.5 ml of type "Eppendorf", mixed. The tube tightly closed. The samples for 2 hours were delivered to the laboratory for PCR analysis.

The study of saliva in patients was conducted in the morning on an empty stomach at the same time before treatment and 4 weeks after comprehensive Ter the FDI.

Prior to the taking of saliva in the patient's mouth washed with deionized water. The collection of saliva for analysis conducted patient is in sitting position, with open eyes, without movements of the facial muscles, slightly bending the head forward (Navaresh M., 1993). The collection of saliva was performed for 5 minutes using the accumulation in the oral cavity without stimulation and emptying it through the funnel into the vessel every 60 seconds.

Immunological investigations included determination of enzyme-linked immunosorbent assay in saliva levels of tumor necrosis factor (TNFα), lactoferrin (LF), interleukin - 6 (IL-6), secretory immunoglobulin A (sIgA) using test systems for TNFα JSC "Vector-best" A - 8756, for IL-6 - test - production systems "Cytokine". The amount of protein and mucin in saliva was determined using the method Achmatova (1980), the activity of complement components was determined by hemolytic method based on molecular titration (Krasilnikov A.P. et al., 1984, Tanaka S. et al., 1986) expression of the reaction in units of effective molecules/mg protein × 108.

Imudon (trade name), International nonproprietary name (INN): active ingredient is a mixture of lysates of bacteria: Lactobacillus acidophilus, Lactobacillus fermentatum, Lactobacillus helveticus, Lactobacilluslactis, Streptococcus faecium, Streptococcus faecalis, Streptococcus sanguis, Staphylococcus aureus, Klebsiella pneumoniae, Corynebacterium pseudodiphthetiticm, Fusiformis fusiformis, candida albicans. Excipients: lactose, D-mannitol, glycine, polyvidone, sodium saccharin, sodium bicarbonate, anhydrous citric acid, mint powder, magnesium stearate.

The drug is registered in the Russian Federation. Registration number: P-8-242-T, dosage form tablets for dissolution in the oral cavity.

Description: Tablets Imudon have a round with beveled edge shape with a diameter of 12.5 mm, smooth shiny surface cream color, have a sour taste with the taste of mint.

Pharmacological properties: an Immunostimulating drug bacterial origin for local use. Imudon activates phagocytosis. Increases the amount of lysozyme in saliva. Increases the number of immune cells, increases the content of secretory immunoglobulin a in saliva.

Properties:

1. Rapid therapeutic effect in inflammatory diseases of the oral cavity and pharynx. therapeutic effect is realized through non-specific immune protective factors, which begin to develop immediately after application of the drug Imudon. The increase in the number of plasma cells in the mucosa and the development of specific sIgA begins 2-4 days, which enhances therapeutic effect and ensures the prophylactic effect of the drug Imudon. Antibacterial and against vospalitelnye properties of the drug Imudon directed equally against the following manifestations, concomitant diseases of the mucous membranes, gums and periodontium: gnetaceae, pain, erythema, fever, difficulty opening the mouth, swelling, bleeding gums, sores, halitosis. This therapeutic effect is determined by the ability of the drug Imudon affect oxidative metabolism of polymorphonuclear neutrophils.

2. Long-term anti-relapse effect.

Immunological properties of the drug Imudon generate immune memory due to generation of specific sIgA, which allows to increase the intensity and duration of the immune response to subsequent infection. Preventive effect lasts for 3-4 months.

Way of application and dose: For adults and adolescents 14 years in acute inflammatory diseases of the oral cavity and the exacerbation of chronic drug taking 8 tablets a day. Tablets resolve in the oral cavity with an interval of 2-3 hours. The average duration of treatment is 10 days.

Study design the effectiveness of the drug IMUDON in the treatment of peptic ulcer disease duodenal ulcer associated with Helicobacter pylori

The study included 53 male patients with peptic ulcer disease duodenal ulcer chronic, associated with N. pylori in active phase. The average is age 39± 4,63 year. The control group consisted of 20 healthy males, matched for age with a group of patients.

After signing informed consent, after the patients clinical, instrumental and immunological examination, examination by a dentist (excluded acute inflammation of the mucous membranes of the oral cavity), according to the plan, in three days made the decision to include the patient in the study. The study was characterized by "simple blind, placebo-controlled, in the form of "parallel control".

Depending on the method of treatment were formed two groups of patients, matched for age, anamnesis, clinical and immunological characteristics and basic therapy (eradication of H. pylori), which allowed to consider these groups are homogeneous.

In the first group (n=24) patients received eradication therapy in combination with placebo (glucose tablets), the second group (n=29) - eradication therapy in combination with medication Imudon.

Prerequisites for assignment Imudon were identified immunodeficiency in patients Helicobacter infection, proved the effectiveness of this drug in a number of periodontal diseases and the mucous membranes of the oral cavity in patients with peptic ulcer (Lepikhina E.A., 2004).

Drugs glucose and Imudon was administered topically of peror the flax for dissolution in the oral cavity 8 tablets per day with an interval of 2-3 hours for 10 days.

The research results were expressed as M is an average value, the significance of differences was assessed by the criterion of Mann-Whitney, Wilcoxon signed, Fisher. Reliable considered differences at p<0,05.

Research results and discussion

Infection With N. pylori in biopsy specimens of the gastric mucosa by a combination of three methods detected in 100% of patients.

In 16.9% (9) of patients in periodontal plaque by PCR was determined by DNA N. pylori. In the first group of patients was 4 patients with H. pylori - positive dental status second 5 such patients.

Plaque, apparently, can serve as a natural reservoir of N. pylori in the human body and the source of infection of the gastric mucosa. Accordingly, most cases of unsuccessful eradication in patients with H. pylori - associated gastroduodenal pathology can be explained by the persistence of the pathogen in dental plaque, which can be a source of self-experimenting researched and determinant of recurrent and severe course of the disease. Therefore, one important task at the present stage is the search for pharmacological agents and their combinations, can cause eradication.

The results of the study of the immunological parameters of the saliva of the patients are shown in table 1, 2.

The effectiveness of eradication of H. pylori in slithis the th membrane of the stomach (under the control of three methods of diagnosis) in patients of groups 1 and 2 was 87% and 91%, respectively (p> 0,05).

In the group of patients No. 1 in gingival plaque PCR on DNA N. pylori was positive in all patients in group 2 all patients - negative (p<0,001), despite the fact that in biopsies of the gastric mucosa test N. pylori in all these patients was negative. Thus, some patients were not observed complete eradication of H. pylori in the gastric mucosa in the oral cavity.

Comparison of results of treatment of patients in group # 1 and # 2 on the immunological saliva showed that in the group # 1 after eradication therapy preserved signs of immunodeficiency and increased inflammatory potential in saliva, in terms of the weakening of the complementary activity (SN 30,07 Wed patients against 32,74 uid in the control group), activation of complement by the classical path with the correct level being exceeded its initial proteins (C1, C4, C2), indicating a possible ongoing antigenic stimulation of protein microbial agent. Also remained elevated factors antimicrobial protection (LF, sIgA) and proinflammatory cytokines (TNFα, IL-6).

Patients in group 2 was significantly decreased level of sIgA, increased complementary activity with a predominance of the terminal component (C5), which could indicate the transition of inflammation to the 4th week after complex therapy in final phase. the parallel with these phenomena observed significant reduction of activity of the antimicrobial protection and proinflammatory cytokines. Thus, the complex therapy, including eradication scheme, and local immunomodulator Imudon have a synergistic antimicrobial effect on H. pylori in dental plaque and anti-inflammatory effects on immunological parameters of saliva in patients with peptic ulcer disease duodenal ulcers associated with H. pylori. Appointment only schema eradication is not sufficient to suppress inflammatory factors in the oral cavity in patients with peptic ulcer disease duodenal ulcers associated with H. pylori, and can serve as one of the causes of recurrent disease.

Clinical examples:

1. Patient B., 43, was admitted to the medical ward of the City hospital №4 Chelyabinsk complaining of aching pain in the epigastric area in the evening and at night, loss of appetite, body weight. History of peptic ulcer disease duodenal ulcer within 7 years with annual exacerbations 2-3 times a year. The survey: fibrogastroduodenoscopy: ulcer of the duodenal bulb (6×8 mm), cicatricial deformity of bulbs, signs of obvious gastritis, bullita; histological examination of biopsies of the mucosa of the antrum revealed N. pylori (+++), during the urease breath test resulting increase in the concentration of ammonia is in the exhaled air of 1.2 mg/m 3that gave reason to believe the test is positive. In the dentogingival plaque by PCR revealed the genome DNA of N. pylori.

The immunological saliva: sIgA - of 1.27 mg/l, protein 280 mg %, mucin 30 mg %, SN is 27.3, S1 - 0,7, C2 - 1,9, C3 2,9, C4 - 0,9, C5 - 0.8, lactoferrin - 712 ng/ml IL-6 with 12.3 PG/ml, TNFα 4,15 PG/ml.

Diagnosed with peptic ulcer disease duodenal ulcer associated with H. pylori, chronic, moderate severity, in the acute stage.

Patient assigned to eradication therapy with omeprazole 20 mg 2 times a day before meals for 10 days amoxicillin 1000 mg 2 times a day after Breakfast and dinner for 7 days clarithromycin 500 mg 2 times a day before meals, was additionally included local immunomodulator Imudon 8 tablets a day for dissolution in the oral cavity with an interval of 2-3 hours for 10 days.

The condition of the patient after treatment has improved significantly: no pain in the epigastric region, improved appetite.

4 weeks after treatment the survey: control fibrogastroduodenoscopy - scar-ulcer deformity of the duodenal bulb;

test N. pylori in the gastric mucosa histology and urease negative methods;

test N. pylori in dental plaque by PCR is negative, the immunological saliva: sIgA - 0.1 µg/l, protein 204 mg %, mucin 58 mg %, SN - 34,7, C1 - 2,8, C2 - 3,1, C3 3,0, C4 - 3,0, C5 - 2,1, lactoferrin - 125 ng/ml, IL-6 - 11,7 PG/ml, TNFα 1,58 PG/ml.

2. Patient K., 34, admitted to hospital with complaints of sharp pain in the epigastrium, vomiting eaten food. History of peptic ulcer disease duodenal ulcer in the past 12 years with annual exacerbations 2 times a year. Deterioration of health came as a result of violations of the diet is eating hot sauce. The survey: fibrogastroduodenoscopy: ulcer on the upper wall of the duodenal bulb (8×10 mm), cicatricial deformity of bulbs, signs Express gastroduodenitis, multiple erosions in the antrum of the stomach. Histological examination of biopsies of the mucosa of the antrum revealed N. pylori (+++), urease breath test is positive - an increase of ammonia concentration in the exhaled air of 1.7 mg/m3PCR on DNA N. pylori in biopsy samples from the antrum positive.

In the dentogingival plaque by PCR revealed the genome DNA of N. pylori.

The immunological saliva: sIgA - 0,81 g/l, protein 106 mg %, mucin 50 mg %, SN - 26,3, C1 - 0,4, C2 - 0,4, C3 - 0,9, C4 - 0,8, C5 - 0.6 lactoferrin - 553 ng/ml, IL-6 and 36.2 PG/ml, TNFα - 3,54 PG/ml.

Diagnosed with peptic ulcer disease duodenal ulcer associated with H. pylori, chronic the case for the average severity in the acute stage, erosion antrum of the stomach.

Patient assigned to eradication therapy with omeprazole 20 mg 2 times a day before meals for 10 days amoxicillin 1000 mg 2 times a day after Breakfast and dinner for 7 days clarithromycin 500 mg 2 times a day before meals, was additionally included local immunomodulator Imudon 8 tablets a day for dissolution in the oral cavity with an interval of 2-3 hours for 10 days.

The condition of the patient on therapy significantly improved: vomiting stopped on the 2nd day after the start of treatment, pain in the epigastric region were stopped on the 3rd day.

4 weeks after treatment the survey: control fibrogastroduodenoscopy - red scar linear forms 3 mm on the top of the bulb, scar-ulcer deformation duodenal ulcer, erosions in the antrum of the stomach is not detected;

test N. pylori in the gastric mucosa histology and urease and PCR negative;

test N. pylori in dental plaque by PCR is negative, the immunological saliva: sIgA - of 0.58 µg/l, protein 140 mg%, mucin 58 mg %, SN - 35,8, S1 - 0,7, C2 - 0.3, and C3 0,3, C4 - 0,7, C5 - 2,8, lactoferrin - 199 ng/ml, IL-6 - 21,0 PG/ml, TNFα 1,99 PG/ml.

Thus, clinical examples illustrate the good role of drug Imudon in the treatment of peptic ulcer disease duodenal ulcer, associated with N. pylori.

The proposed method is highly efficient, reflects the positive dynamics of immunological indices of saliva, their role in the eradication of microbial agent in patients with peptic ulcer disease duodenal ulcer associated with Helicobacter pylori, in response to the combined therapy with the inclusion of the drug Imudon, which may play an important role for the prevention of exacerbations of the disease, meets the modern level of examination and treatment of gastroenterological patients. Can be applied in the medical facility with equipment for carrying out morphological, immunological tests and polymerase chain reaction.

Therefore, the claimed invention meets the criterion of "industrial applicability".

to 278.6 >0,05
Table 1

Indicators of immunological indexes of saliva in patients of group 1
IndicatorsControl n=20Group # 1 (before treatment) n=24Group No. 1 (post-treatment) n=24p1p2p3
MMM
sIgA, ug/ml0,951,961,78<0,05<0,05>0,05
Protein, mg %250,1256,3<0,05<0,05>0,05
The mucin, mg %67,348,161,0<0,05>0,05<0,05
SN, Wed32,7428,0330,07>0,05>0,05<0,05
C12,482,48is 3.08>0,05<0,05<0,05
C22,892,053,30<0,05>0,05<0,05
C32,13of 2.212,48>0,05>0,05>0,05
C42,921,832,11>0,05>0,05<0,05
C51,781,611,63>0,05>0,05>0,05
TNFα,0,172,703,32<0,01<0,001>0,05
PG/ml
LF, ng/ml124,3579,7475,3<0,01<0,01
IL-6, PG/ml2,716,617,2<0,001<0,001>0,05
CH 50 complementary activity of saliva

C1-C5 are measured in units of effective molecules in 1 ml

A comparison of the control group and groups of patients before treatment and after treatment were carried out according to the criterion of Mann-Whitney.

A comparison of groups of patients No. 1 before treatment and after treatment were carried out according to the criterion of Wilcoxon signed.

P1 - significance of differences between the control group and the group of patients No. 1 before treatment

P2 - reliability of differences between the control group and the group of patients No. 1 after treatment

P3 - significance of differences between groups of patients No. 1 before treatment and after eradication therapy with placebo

td align="left"> 2,7
Table 2

Indicators of immunological indexes of saliva in patients of group 2
IndicatorsControl n=20Group # 2 (before treatment) n=29Group # 2 (after treatment) n=29p1p2p3
MMM
sIgA, ug/l0,951,550,58 >0,05<0,05<0,01
Protein, mg %to 278.6225,35278,0>0,05>0,05>0,05
The mucin, mg %67,350,1573,5<0,05<0,01<0,01
SN, Wed32,7427,9833,04<0,05>0,05<0,01
C12,482,532,77>0,05>0,05>0,05
C22,89of 2.212,15<0,05<0,05<0,05
C32,132,45to 2.67<0,05<0,01>0,05
C42,921,792,53>0,05>0,05>0,05
C51,781,651,97>0,05>0,05<0,05
TNFα, PG/ml0,176,253,09<0,001<0,01<0,01
LF, ng/ml124,3840,4313,7<0,01<0,05<0,001
IL-6, PG/ml42,6711,0<0,001<0,05<0,001
CH 50 complementary activity of saliva

C1-C5 components of the classical pathway activation of complement, is measured in units of effective molecules in 1 ml

A comparison of the control group and groups of patients before treatment and after treatment were carried out according to the criterion of Mann-Whitney.

A comparison of groups of patients before treatment and after treatment were carried out according to the criterion of Wilcoxon signed.

P1 - significance of differences between the control group and the group of patients No. 2 before treatment

p2 - reliability of differences between the control group and the group of patients No. 2 after treatment

P3 - significance of differences between groups of patients No. 2 before treatment and after eradication therapy in complex with Imudon

The method of complex treatment of peptic ulcer disease duodenal ulcer associated with Helicobacter pylori, including the introduction of omeprazole at a dose of 20 mg 2 times a day amoxicillin 1000 mg 2 times a day for 7 days clarithromycin 500 mg 2 times a day and immunomodulator, characterized in that the quality of local immunomodulator is administered Imudon 8 tablets a day for dissolution in the oral cavity after 2-3 hours for 10 days omeprazole enter the t before meals for 10 days, amoxicillin - after Breakfast and dinner, and clarithromycin - before a meal.



 

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7 cl, 4 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to derivatives of [1,4]diazepino[6,7,1-IJ]-quinoline of the general formula (I): wherein R1 represents hydrogen atom, (C1-C6)-alkyl, (C2-C6)-alkanoyl or (C7-C11)-carboarylalkoxy-group; each R2 and R3 represents independently hydrogen atom, hydroxy-group, (C1-C6)-alkyl, (C1-C6)-alkoxy-group, halogen atom, (C2-C6)-carboalkyloxy-group, (C1-C6)-perfluoroalkyl, (C2-C6)-alkanoyloxy-group, (C2-C6)-alkanoyl, (C6-C8)-aroyl, (C5-C7)-aryl, (C6-C13)-alkylaryl having 5-7 carbon atoms in aryl moiety; R4 and R5 represents independently hydrogen atom or (C1-C6)-alkyl, or R4 and R5 taken in common with carbon atoms with which they are bound form cyclic group chosen from (C4-C8)-cycloalkane, (C4-C8)-cycloalkene; each R6 and R7 represents independently hydrogen atom or (C1-C6)-alkyl; n = 1 or 2; a dotted line means a double bond optionally. Also, invention describes using compounds of the formula (I) in preparing a drug used in treatment of different psychotic disorders. Also, invention relates to a pharmaceutical composition possessing activity as 5-HT2C antagonist based on proposed compounds, and a method for synthesis of compounds of the formula (I). Invention provides synthesis of novel compounds, preparing a pharmaceutical composition and a drug based on thereof.

EFFECT: improved method of synthesis, valuable medicinal properties of compounds and pharmaceutical composition.

53 cl, 1 tbl, 34 ex

FIELD: medicine.

SUBSTANCE: claimed composition contains core including Rabeprasol or pharmaceutically acceptable salt thereof as acid secretion inhibitor in stomach and basic compound, intermediate coat coating the core, and overcoat applied on intermediate layer and containing water insoluble polymer and enterosoluble polymer. Also described is method for production of composition containing said preparation.

EFFECT: composition of prolonged storage time providing effective concentration of Rabeprasol in blood for long period of time.

16 cl, 5 dwg, 14 ex

FIELD: medicine, pharmacology.

SUBSTANCE: invention relates to using of lactic acid bacteria for target delivery of substances being useful for recipient to specific regions of gastrointestinal tract thereof. Present invention makes it possible to increase effectiveness of treatment of gastrointestinal tract diseases due to carrier application such as lactic acid bacteria.

EFFECT: new effective method for treatment and/or prophylaxis of gastrointestinal tract diseases.

9 cl, 1 ex, 3 tbl

FIELD: veterinary.

SUBSTANCE: claimed additive contains 99.97-99.94 of "Sporovit" (metabolism stimulator) and 0.03-0.06 % of levamisol. Method includes application of biologically active additive in amount of 50-100 ml per 1 kg of formulated feed from 2 weeks to 2 months.

EFFECT: decreasing of invective diseases.

3 ex, 2 tbl

FIELD: veterinary.

SUBSTANCE: claimed method includes preparation of yeast slurry 1:2 in physiological saline and 2 % glucose solution in distilled water. 1 ml of tissue preparation, 1 ml of yeast slurry, and 28 ml of glucose solution are sampled in test tube. The same component wherein tissue preparation is replaced with 1 ml of sterile physiological saline are sampled in control tube. Tubes are sealed with closure with glass tubes ends of which are dropped down in bulb. 1 drop of liquid is sampled from each tube, placed into chamber, and yeast cell amount is calculated. Further chamber is placed into thermostat at temperature of 33-35°C and held for 60-90 min. After agitation 1 drop of solution is simultaneously sampled from control and test tubes and yeast cell amount is calculated. Activity of tissue preparation is evaluated based on volume of released carbon dioxide and amount of yeast cells in test and control tubes (before and after experiment).

EFFECT: accelerated method of decreased cost and increased accuracy.

3 tbl, 5 ex

FIELD: veterinary therapy.

SUBSTANCE: it is necessary to carry out general post-surgical therapy and additionally and simultaneously introduce sel-plex at the dosage of 5 mg/kg body weight once daily for 14 d and thymogen intramuscularly at the dosage of 3 mcg/kg body weight once daily for 10 d. The innovation enables to reconstruct supporting function in dogs and cats after osteosynthesis very quickly and decrease the quantity of post-surgical complications.

EFFECT: higher efficiency of stimulation.

3 ex, 1 tbl

FIELD: veterinary microbiology.

SUBSTANCE: claimed method includes application of preparation based on suspension of two bacteria Bacillus subtilis strains in equal ratio.

EFFECT: preparation for prophylaxis of alimentary mycotoxicosis, increasing of immunobiological reactivity and normalizing of intestinal microbiotic community.

FIELD: biotechnology, medicine, veterinary, in particular inhibition of vegetative and spore cell (Bacillus anthracis) vitality and malignant anthrax prophylaxis.

SUBSTANCE: invention relates to agent of bactericide action in relates to vegetative spore cells Bacillus anthracis. Agent contains bacteriolytic complex produced by Lysobacter sp.XL1. In method for malignant anthrax prophylaxis bacteriolytic complex produced by abovementioned bacterium strain is used as active ingredient. Said method includes subdermal injection in one dose not later than 3 hours after contamination, or application of dressing (drape) impregnated with active ingredient on place of possible exciter penetration, or treatment of possible contamination focus with aerosol.

EFFECT: bactericide agent without side effects and decreased prophylaxis time.

6 cl, 8 ex, 8 tbl

FIELD: biotechnological methods.

SUBSTANCE: invention is intended for use in medicinal, food processing, and perfumery industries and provides strain GI 1.1 of suspension culture of cells of plants Serratula coronata L. N 64 is producer of ecdisteroids.

EFFECT: enabled effective preparation of ecdisteroids.

2 dwg

FIELD: biotechnological methods.

SUBSTANCE: invention is intended for use in medicinal, food processing, and perfumery industries and provides strain E IVk of suspension culture of cells of plants Ajuga reptans L. N 63 is producer of ecdisteroids.

EFFECT: enabled preparation of ecdisteroids.

2 dwg

FIELD: biotechnology, veterinary science.

SUBSTANCE: invention relates to technology for preparing bacterial preparations used in prophylaxis diseases in animals. Method involves the separate culturing under conditions of submerged culturing of microorganisms Bacillus subtilis VKPM B-8130, Lactobacillus acidophilus Scav. VKPM B-4625 and Rhuminococcus albus Kr. The grown mother cultures of B. subtilis VKPM B-8130, L. acidophilus Scav. VKPM B-4625 and R. albus Kr in the ratio = 1:1 and autoclaved sunflower grist is inoculated with this mixture in the following ratio of components, wt.-%: autoclaved sunflower grist, 45-55; mother culture of Lactobacillus acidophilus Scav. VKPM B-4625, Rhuminococcus albus Kr, 20-30, and mother culture of Bacillus subtilis VKPM B-8130, 20-30. The prepared mixture is incubated at temperature 30-45°C for 4-8 days to obtain 1 x 108 cells/g of preparation in semi-wet preparation, and prepared preparation is mixed with sunflower grist in the ratio = (1:10)-(1:12) to obtain the preparation with residual moisture 8-10%. Invention provides enhancing effectiveness in preparing the dry probiotic preparation, reducing material consumptions in its production, simplifying technology for its preparing and using inexpensive raw in preparing the preparation based on exclusion the drying step from the technological schedule and preparing the preparation with higher titer value.

EFFECT: improved preparing method.

3 tbl

FIELD: veterinary medicine.

SUBSTANCE: method involves administering Aversect-2 with Cordeon probiotic added at a dose of 50 mg/kg of live weight during 5 days.

EFFECT: enhanced effectiveness of treatment; improved blood biochemical and hematological properties.

3 tbl

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.

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