Method of complex treatment of gastroesophageal disease in patients with opisthorchosis

FIELD: medicine.

SUBSTANCE: invention relates to medicine and is intended for treatment of gastroesophageal reflux disease (GERD) in patients with chronic opisthorchosis. PH-monitoring of upper parts of GIT and dehelmintisation are carried out. Type of reflux is determined. Preparations of ursodeoxycholic acid (UDCA) are administered. In case of mixed type of GER with prevalence of acid component dose is 250 mg/day for 2 weeks. In case of mixed type of GER with prevalence of alkali component dose is 500 mg/day before going to bed for 4 weeks. In isolated alkali version dose is 10 mg/kg in two intakes: morning and evening. In case of tgenpH>7 from 16.54 to 27.6%; NpH>7 from 27 to 31, and GER tgenpH>7 from 27.6 to 48.8%; NpH>7 from 31 to 35 - for 4 weeks. In case of tgenpH>7 from 16.54 to 27.6%; NpH>7 from 27 to 31, and GER tgenpH>7 from 27.6 to 48.8%; NpH>7 from 31 to 35 and in case of GER tgenpH>7 from 48.8 to 74.4%, NpH>7 from 36 to 42 - for 8 weeks. In case of tgenpH>7 from 48.8 to 74.4%; NpH>7 from 36 to 42, and GER tgenpH>7 from 16.54 to 74.4%; NpH>7 from 27 to 42 -for 12 weeks.

EFFECT: method makes it possible to reduce motor-tonic disturbances of biliary tract, reduce number of recurrences, enhance treatment efficiency.

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The invention relates to medicine, in particular gastroenterology, and can be used in medical practice in the treatment of gastroesophageal reflux disease (GERD) in patients with chronic opisthorchiasis.

Currently known complex methods of medical treatment of GERD is focused mainly on the severity of endoscopic manifestations of the disease and its "classic" (acid) variant, caused by the overproduction of hydrochloric acid and/or acidic esophageal reflux. The results of numerous studies, based on this medical approach to the treatment of reflux disease esophageal, standardized, unified, recommended and presented in the Protocols for the diagnosis and treatment of patients with diseases of the digestive system" (Grigoriev PA, Yakovenko EP download the film A.I., Agafonova N.A. and others, 2001). This document is modified and supplemented, in some aspects, the variant "of Standards (protocols) for the diagnosis and treatment of patients with diseases of the digestive system", approved by order No. 125 of the Ministry of health of the Russian Federation from 17.04.1998. According to the proposed schemes, as antireflux therapy uses the following classes of drugs: cyclotourisme (inhibitors is Rotondo pump (PPIS), H2-histamine receptors blockers, antacids, prokinetics. The disadvantage of recommended medical approaches and treatments is their lack of effectiveness due to one-way direction of influence - exclusively on acid gastroesophageal reflux (GER), excluding the possibility of the presence of other pH-options esophageal reflux: mixed and alkaline. The presence of sour type GER requires new medical approaches and results in the lack of effectiveness of cyclotourisme therapy and, as a consequence, the disease progression and development of complications. Standard medical therapy based on the use of PPIS, is not effective enough for 5-10% of patients with GERD [2]. Also, there are no standardized treatment recommendations sour GER.

Known methods of treatment of gastroesophageal disease. Some suggest the use as components in the treatment of GERD under alkaline esophagogastric reflux: prokinetic and the combination of these drugs [11, 14]. Under moderate alkaline GER, in addition to IPP, it is recommended the appointment of prokinetics, and in cases of pronounced alkaline GER - antacids. Combined not absorbed antacids containing aluminum or magnesium (Maalox), have a very high level 59-96%, adsorbe the existing capacity in relation to bile acids and lysolecithin. The purpose of prokineticin - eliminates motor-tonic disorders, underlying any type of GER [3]. The purpose of prokinetics reduces the frequency of episodes of duodenogastric reflux (DR), underlying the occurrence of biliary component reluctate, but does not eliminate the damaging effects of bile acids. Taking antacids is symptomatic, and short-term pharmacological effect (3-4 hours), does not eliminate the cause of the development of GERD. Neither class of drugs are not selective in relation to biliary reflux and do not treat the root cause of its occurrence - the dysfunction of the biliary tract.

Biliary reflux esophagitis is in the range of indications for administration of ursodeoxycholic acid (UDCA) [1]. However, the role of drugs of UDCA in the treatment of GERD is poorly understood, and the available studies are not numerous and have character descriptions of individual cases, a series of observations, or simply "a fact" possible use of the drug in this disease, based on its pharmacological effects [12]. There is a method of treatment of reflux esophagitis due to biliary (alkaline) regurgitation, by receiving UDCA (Vidal, 2002) at a dose of 250 mg (1 capsule) per day, once at night, during the month [1]. The known method is not effective enough, because Yes the nye the destination schema drugs does not take into account the intensity of pH-manifestations of the alkaline component of the reflux. The recommended dosage of the drug may be insufficient in patients with severe biliary GER. There is no differentiated approach to prescribing UDCA mixed and alkaline versions GER.

Known methods of treatment of GERD associated with other diseases: upper respiratory tract, cardiovascular and pulmonary pathology. Offer, in these cases, medical approaches do not differ from the standard focus on kislotoobrazovanie option reflux disease of the esophagus and endoscopic manifestations, is not taken into account the possibility of participation in the Genesis of diseases sour esophageal reflux[8, 9, 13].

The presence of concomitant opisthorchosis invasion makes pathomorphosis in pH manifestations of GERD due to the increased frequency of episodes of this resonance, joining components of duodenal contents to the acidic reluctate. For allometrically paintings reflux disease esophageal chronic opisthorchiasis is characteristic: the prevalence of mixed and alkaline variants GER; a tendency to decrease kislotoproduktsiya functions of the stomach, progressive duration of the invasion, more than 5 years from Hypo - to anatsidnyh state. Change allometrically parameters GERD requires new approaches to the treatment of the disease. The underestimation of the features of the pH-manifestations in the appointment of antireflux therapy buslaw is insufficient supports the efficacy of PPIS in patients with mixed pathology - GERD and chronic opisthorchiasis.

There are no schemes for the integrated treatment of GERD on the background of chronic opisthorchosis invasion tailored allometrically paintings reflux disease of the esophagus at this parasitosis: a type of reflux, the condition kislotoproduktsiya functions of the stomach. There is no differentiated approach to the treatment of various pH-types GER. Not designed schemes and criteria for the appointment of UDCA mixed and alkaline versions esophageal reflux.

The closest entity (the prototype) to the claimed method of treatment of GERD is the way offering: in the presence of combinations expressed duodenogastric and gastroesophageal reflux, continuing on treatment cyclotourisme drugs (the bitter taste of the content when the regurgitation) in the complex treatment for 2-4 weeks to include ursodeoxycholic acid (Ursofalk) 200 mg 3 times a day (Siemionow, 2000) [5]. However, the effectiveness of the known method is also insufficient, since its use does not take into account the intensity of pH-manifestations of alkaline and acidic GER.

The scope is limited, as there is no information about how to use it in patients with opisthorchiasis. In addition, the prescription of UDCA in 2-4 weeks may be insufficient pronounced the om alkaline GER.

New technical problem - increasing the effectiveness of treatment by obtaining a stable therapeutic effect of a more prolonged remission of disease in relation reflux disease of the esophagus, reducing the number of relapses, prevention of disease progression, development of severe complications and extend the scope of application of the method.

To solve the problem in the method of complex treatment of gastroesophageal reflux disease in patients with chronic opisthorchiasis, by injection of UDCA against the standard for specific endoscopic disease pharmacotherapy, advanced previously conducted pH-monitoring upper GI, defining the parameters: pH type and intensity esophageal reflux condition kislotoproduktsiya functions of the stomach and deworming and mixed variant GER with a predominance of acidic component at tGeneralpH>7from 16,54 to 27.6%; NpH>7from 27 to 31 and the increase in pH in the esophagus from 7 to 8 or from 8 to 8.9; no episodes of massive alkaline GER administered UDCA 250 mg /day for 2 weeks, when mixed variant GER with a predominance of alkaline component tGeneralpH>7from 48,8-74.4 per cent; NpH>736-42, or tGeneralpH>7from 27.6 to 48.8%; NpH>7from 31 to 35, pH 8 to 8.9; single, 1-2 a day, episodes in the conversion of the aqueous alkaline esophageal reflux, enter UDCA at a dose of 500 mg/day at night for 4 weeks. Also, when isolated alkaline variant is administered UDCA at a dose of 10 mg/kg in two doses: morning and evening, and at tGeneralpH>7from 16,54 to 27.6%; NpH>7from 27 to 31 and moderately frequent GER, or tGeneralpH>7from 27.6 to 48.8%; NpH>7from 31 to 35 and the absence of episodes of massive GER; within 4 weeks. Also, when isolated alkaline variant with tGeneralpH>7from 16,54 to 27.6%; NpH>7from 27 to 31, or moderately frequent GER, tGeneralpH>7from 27.6 to 48.8%; NpH>7from 31 to 35; combined with the presence of episodes of massive GER, no more than 5 times per day, with frequent GER tGeneralpH>7from 48,8 to 74.4%, NpH>736 to 42, and the absence of episodes of massive GER, within 8 weeks. Also, when isolated alkaline variant with tGeneralpH>7from 48,8 to 74.4%; NpH>736 to 42, with or without episodes of massive GER; there are episodes of massive GER with tGeneralpH>7from 16,54 to 74.4%; NpH>7from 27 to 42,more than 5 times per day at any frequency alkaline GER for 12 weeks.

The method is as follows after conducting a unified algorithm for evaluation according to the "Standards (protocols) for the diagnosis and treatment of patients with diseases of the digestive system" [7], aimed at verification of diagnoses of GERD and opisthorchiasis, which shall include:

1) endoscopic parameters reflux disease of the esophagus (endoscopy positive or negative form of the disease, the severity of reflux esophagitis assessed by the classification of the Savary-Miller);

2) data opisthorchosis invasion (intensity of infection, as determined by the method of Stoll; anamnestic duration parasitosis; the probability of re-infection; previous deworming);

3) acadametrics characteristics of GERD (pH, type and intensity of esophageal reflux condition kislotoproduktsiya functions of the stomach).

For the treatment offers three comprehensive approach to the treatment of GERD in this category of patients:

1) impact on endoscopic manifestations of the disease and acidic variant GER (kislotoobrazovanie therapy, prokinetic, antacids);

2) elimination of trigger factor for the appearance of the alkaline component in reluctate (deworming);

3) impact on sour variant GER (prescriptions UDCA).

Therapy focused on endoscopic manifestations of the disease, was initially consistent with the recommended standards [7] and included the purpose of the IPP, prokinetics and antacids in the well-known schemes and the dosages.

1. Conduct pH-monitoring upper GI, defining the parameters: pH-type is the intensity of esophageal reflux state kislotoproduktsiya functions of the stomach. pH-monitoring is performed with the use of a specialized device Astroscan-24". Apply three-electrode nasogastric pH-probe (type G3-24). The option to install the probe localization of the measuring electrodes in the GI tract: the esophagus - the cardiac part of stomach body of stomach. Preparation for the study, analysis of the pH-gram and interpretation of the obtained results is carried out according to standard techniques and procedures acidimetry [6]. A prerequisite for patients taking antisecretory drugs is the proper time of their cancellation before pH monitoring, depending on the duration of the pharmacological effect of the drug.

Assessment allometrically data of the stomach is carried out on the basis of the four possible States of its kislotoproduktsiya functions: normaltest, hyperacidity, hypoacidity and antitrust. In cases detected in the basal conditions of the study deviations from physiological norms of acid, conduct specialized diagnostic tests aimed at detecting the truth of the observed changes. Type of test depends on the basal numbers pH: at pH<3 (to identify hyperacidity) - alkaline test (oral administration soda solution), at pH>3 (for vyyavleny the Hypo/antidnase) - stimulated test pentagastrin. According to the results of the daily algometry has identified the following options esophageal reflux: isolated acid, isolated alkaline, mixed-combining the components of the previous two acid and alkaline GER.

To estimate category frequencies alkaline esophageal reflux, the authors have proposed the following gradation:

- rare (total time with pH>7 (tGeneralpH>7from 16,54-27,6%; the number of reflux with pH>7 (NpH>7) - 27-31);

- moderate frequency (tGeneralpH>7from 27.6-48,8%; NpH>731-35);

- frequent (tGeneralpH>7from 48,8-74.4 per cent; NpH>736-42).

2. All patients with chronic opisthorchiasis, with clinical manifestations of reflux disease of the esophagus, it is treated with the aim of eliminating the trigger factor for the occurrence of biliary reflux, which contributes to the success of our proposed method of treatment.

Scheme anthelminthic therapy includes three standard steps: 1 - preparation 2 - proper deworming, 3 - postdetermination. The first and second stages of patient management include activities aimed at desensitization (antihistamines), detoxification (infusion medium), improvement of outflow of bile (blind tyubazhi on Damyanovo). In the choice of anthelmintic (vegetable or FA is mikologicheskie drug), we propose to consider the following criteria:

the intensity of infection (Stoll);

- the severity of clinical manifestations of parasitosis;

the duration of the invasion, the presence of the previously held deworming using pharmacological drugs;

- the risk of re-infestation.

Pharmacological drug biltricid (praziquantel, BAYER) to designate one or a combination of several options:

- high or moderate intensity opisthorchosis invasion;

for the first time held deworming with any degree of intensity of infestation (low, moderate, high) and/or low risk of re-infestation;

- pronounced clinical manifestations of opisthorchosis invasion (including holetsistograficheskih character);

- the duration of parasitise more than 5 years.

Criteria for the assignment of plant anthelmintic of corsola (LLC Biolit"):

low intensity of opisthorchosis invasion;

- having previously held deworming biltricid;

- high risk of re-infestation;

- latent or subclinical course of parasitosis;

- the duration of opisthorchosis invasion less than 5 years;

- addition to the previously therapy biltricid, with its lack of deworming efficiency.

Regimens deworming drugs used standard: Biltricid: 60 mg/kg per day in three doses with an interval of 4 hours is during the night hours (22 00, 200, 600). Acoral: 3 teaspoons (without top) 3 times a day for 30-40 minutes after meals, course 7 days.

When assigning antireflux therapy take into account pH, type and intensity of GERD. The results of the analysis allometrically data in a comprehensive outline of the treatment of GERD prescribed drugs UDCA (Ursosan firm ABOUT. The HONEY. Cs Praha A.S. - Czech Republic). The selection criteria is the presence of an alkaline component in reluctate as in isolated form or as part of a mixed GER. Drugs UDCA is not appointed at isolated acidic pH-version esophageal reflux. Drugs UDCA began to take already at the preparatory stage of deworming and continued after an anthelminthic therapy.

When mixed variant GER with a predominance of acidic component at tGeneralpH>7from 16,54 to 27.6%; NpH>7from 27 to 31 and the increase in pH in the esophagus from 7 to 8 or from 8 to 8.9; no episodes of massive alkaline GER administered UDCA 250 mg/day for 2 weeks, when mixed variant GER with a predominance of alkaline component tGeneralpH>7from 48,8-74.4 per cent; NpH>736-42, or tGeneralpH>7from 27.6 to 48.8%; NpH>7from 31 to 35, pH 8 to 8.9; single,1-2 a day, episodes of massive alkaline esophageal reflux, administered UDCA at a dose of 500 mg/day at night for 4 weeks. Also, when doing the new alkaline variant is administered UDCA at a dose of 10 mg/kg in two doses: morning and evening, moreover, if tGeneralpH>7from 16,54 to 27.6%; NpH>7from 27 to 31 and moderately frequent GER, or tGeneralpH>7from 27.6 to 48.8%; NpH>7from 31 to 35 and the absence of episodes of massive GER; within 4 weeks. Also, when isolated alkaline variant with tGeneralpH>7from 16,54 to 27.6%; NpH>7from 27 to 31, or moderately frequent GER, tGeneralpH>7from 27.6 to 48.8%; NpH>7from 31 to 35; combined with the presence of episodes of massive GER, no more than 5 times per day, with frequent GER tGeneralpH>7from 48,8 to 74.4%, NpH>736 to 42, and the absence of episodes of massive GER, within 8 weeks. Also, when isolated alkaline variant with tGeneralpH>7from 48,8 to 74.4%; NpH>736 to 42, with or without episodes of massive GER; there are episodes of massive GER with tGeneralpH>7from 16,54 to 74.4%; NpH>7from 27 to 42, more than 5 times per day at any frequency alkaline GER for 12 weeks.

Dose and duration of administration of the drug depended on the following criteria: GER type (mixed or isolated alkaline), the initial pH of the parameters of the alkaline component esophageal reflux, intensity and dynamics of clinical manifestations of biliary regurgitation (feeling of bitterness in the mouth, belching bitter).

The effectiveness of the assignment of UDCA in the treatment of GERD in patients with opisthorchiasis were evaluated: clinically (iened the flax on a background of treatment) and the results of the daily acidimetry, held in the dynamics of three months after completion of treatment.

The method is based on the analysis of literature data and results of studies of patients, which is conducted on the basis of the MUSES Kuibyshev CRH Novosibirsk region in the intensive care unit, a day hospital and hospital for infectious diseases. We offer comprehensive treatment for reflux disease esophageal received 60 patients with verified diagnosis of chronic opisthorchiasis with sour variant GER (1st group). As a comparison group (2nd group), to assess the effectiveness of the appointment of UDCA as a component of antireflux therapy in patients with chronic opisthorchiasis, were equal in number 60 number of patients with similar initial diagnostic data but not receiving this drug in postdetermination period. All patients of the 1st group was held deworming and endoscopically oriented kislotoobrazovanie therapy of GERD. Evaluation of the effectiveness of the assignment in the complex therapy of drugs UDCA has been monitoring the dynamics of clinical and pH-indicators of biliary esophageal regurgitation. All patients depending on the pH and N were divided into groups:

- mixed option GER with a predominance of acidic component 15 people; mixed option with GER transformed what ladanian alkaline component 15 people; isolated alkaline version of the GER - 30 persons; 15 of them are isolated del. option when rare or moderately frequent GER, rare GER, combined with the presence of episodes of massive GER - 10 persons; and frequent GERD with or without episodes of massive GER 5 people

The effectiveness of the assignment of UDCA in the treatment of GERD in patients with opisthorchiasis were evaluated: clinically (weekly on a background of treatment) and the results of the daily acidimetry held in the dynamics of three months after completion of treatment.

1) option 1 mixed GER with a predominance of acidic component. Criteria of this variant mixed reflux are as follows: alkaline component corresponds to the frequency is the total time with pH>7 tGeneralpH>7from 16,54-27,6%; the number of reflux with pH>7 (NpH>7) - 27-31;

- intensity - with increasing pH in the esophagus from 7 to 8 or expressed at a pH of from 8 to 8.9; no episodes of massive alkaline GER. 15 persons;

2) option 2 mixed GER with a predominance of alkaline component. The criteria in this subtype mixed reflux: alkaline component corresponds to the pH of the options - tGeneralpH>7from 27.6-48,8%; NpH>731-35; or when tGeneralpH>7from 48,8-74.4 per cent; NpH>736-42; intensity - expressed pH from 8 to 8.9; may be single (1-2 per day) episodes of massive alkaline the CSOs esophageal reflux 15 persons;

3) isolated alkaline variant GER 30 persons; of these 15 people isolated del. option when rare or moderately frequent GER, rare GER, combined with the presence of episodes of massive GER, 10 people; and frequent GERD with or without episodes of massive GER 5 people

Regimens UDCA mixed and alkaline versions GER:

- Mixed version of the GER with a predominance of acidic component (option 1 mixed GER). Criteria of this variant mixed reflux: alkaline component corresponds to the frequency of "rare"; intensity - weak or distinct; there are no episodes of massive alkaline GER.

UDCA is appointed by 250 mg /day (1 capsule) for 2 weeks.

- Mixed version of the GER with a predominance of alkaline component (option 2 mixed GER). The criteria in this subtype mixed reflux: alkaline component in the frequency of "moderately frequent" or "frequent"; intensity - expressed, can be isolated (1-2 per day) episodes of massive alkaline esophageal reflux.

UDCA is administered in a dose of 500 mg /day (2 capsules at night) for 4 weeks.

- When an isolated alkaline variant GER daily dose UDCA is 10 mg/kg (but not more than 6 capsules per day), divided into two sessions (morning, evening). Consider justified the appointment of the above dose of the drug when in isolation the Christmas version esophageal reflux, taking into account the need to influence not only the fact of biliary GER, but the primary cause of its occurrence, i.e. expressed dyskinesia GIT. The duration of drug postdetermination period is from 4 to 12 weeks and depends on such factors as the severity alkaline esophageal reflux (frequency and intensity) and the dynamics of clinical symptoms of GERD on a background of treatment.

Selection criteria duration of therapy UDCA at isolated alkaline GER. UDCA at isolated alkaline variant GER appointed:

1) - in a rare and moderately frequent GERD and no episodes of massive GER; within 4 weeks;

2) - when rare or moderately frequent GER, combined with the presence of episodes of massive GER, no more than 5 times per day, with frequent GERD and no episodes of massive GER, within 8 weeks;

3) - with frequent GERD with or without episodes of massive; there are episodes of massive GER more than 5 times per day at any frequency alkaline GER for 12 weeks.

The effectiveness of the assignment of UDCA in the treatment of GERD in patients with opisthorchiasis were evaluated: clinically (weekly on a background of treatment) and the results of the daily acidimetry conducted over three months after completion of treatment.

In case of insufficient clinical efficacy after okoncane the planned course of UDCA (save symptoms gall esophageal regurgitation), the treatment extended by 2 weeks at half the daily dose of the drug. Necessarily excluded the possibility of inefficient deworming, as the cause of persistent biliary reflux.

All 60 patients of the first group of clinical and pH-metric remission reflux disease of the esophagus was achieved during the forecast period. In patients receiving UDCA was observed significantly more pronounced (p<0,05) progressive positive dynamics of clinical and pH manifestations of GERD sour Genesis. The purpose of UDCA in postdetermination period, in the presence of alkali and mixed GER, made it possible to achieve remission reflux disease of the esophagus in a significantly shorter time (p<0,05). At the same time, some patients (n=10) of the second group having an isolated alkaline GER and not treated with UDCA, on a background of antireflux treatment using kislotozavisimyh drugs, long-continued (for 1-11/2years postdetermination period) pH-symptoms of biliary regurgitation, in the case of proven effectiveness of deworming. In addition, in 75% of cases, patients with isolated alkaline or mixed variants GER and not receiving medication alone in postdetermination period, for the remission of GERD was required prolongation of course, cyclotourism therapy and/or there was a need for "treatment on demand" after antireflux treatment, achieved remission were incomplete and/or unstable.

Clinical examples of the application of the proposed method of treatment.

1. The use of UDCA in complex therapy of reflux disease of the esophagus in a patient with chronic opisthorchiasis mixed variant GER (with a predominance of alkaline component).

Patient N., 1975 birth, was admitted to the Department of therapy in a planned manner. Diagnosis directions: GERD.

Dyspeptic complaints: heartburn, feeling sour and bitter taste in the mouth; belching sour, bitter; nausea.

Anamnesis. Located on the "D" register reflux disease esophageal within 7 years. Two years ago, newly diagnosed opisthorchiasis, deworming was not conducted. Treatment of GERD in history - gets the courses antisecretory therapy at least two times a year. Against this background remains frequent need for treatment on demand: omeprazole (20 mg at night for three days), Almagel (in severe heartburn and pain in the mouth). A month and a half ago underwent another course of antireflux therapy with PPIS (omeprazole) and prokineticin (motilium). The effectiveness of the treatment is incomplete and short-lived. On the background of therapy, the symptoms of gall esophageal regurgitation decreased, but was not cured completely - remained bitter belching. One week after the end of the ecene clinical manifestations of biliary GER resumed with the same frequency.

Within three weeks prior to hospitalization, cyclotourisme therapy was not accepted, only antacids - with pronounced bitterness in the mouth.

The results of the survey. Data of objective examination: tongue coated whitish-yellow tinge; the size of the liver by karlovu: 9×8×7 cm, the edge of the liver is under the right costal arch, moderately painful to palpation, smooth. Laboratory parameters: ESR - 10 mm/h, no eosinophilia; biochemical manifestations of cytolysis, mesenchymal-cell inflammation and cholestasis was not detected.

Endoscopy: the signs of inflammation of the mucosa of the duodenum, without erosive-ulcerous defects. Esophagitis, with the presence of a single erosion within one of the folds of the mucous membrane of the esophagus.

Duodenal intubation: hypotonic-hypokinetic type of dyskinesia GWP, the intensity of opisthorchosis invasion by the method of the Stele - moderate (1500 in 1 g of feces).

The study according to the proposed method: 24-hour acidimetry upper GI: 1) the true state of kislotoproduktsiya functions of the stomach meets the parameters of normaltest - pH of the gastric body basal - 1.6≤pH≤2.0, the stimulation pentagastrinom - 1.2≤pH≤2.0;

2) pH-type GER is defined as mixed with a predominance of alkaline component (tGeneralpH>7to 27.6%; NpH>7- 37) and the presence of acid GER moderate intense is Vesti (pH in the range from 3.9 to 3.2; tGeneralpH<4to 5.7%; NpH<4- 47).

The final diagnosis of GERD, reflux esophagitis 1 severity (Savary-Miller), is not complicated. Chronic opisthorchiasis, cholecystopathy option, phase of moderate exacerbation. Dyskinesia GIT on hypokinetic type.

Treatment. The standard for this endoscopic forms reflux disease of the esophagus, treatment supplemented by the appointment of UDCA. Conducted deworming biltricid. The destination schema UDCA, taking into account the pH of the parameters GER: 500 mg (2 capsules) in the evening, the drug began to take on a preparatory stage to helminthization and continued for 4 weeks postdetermination period. Positive dynamics of clinical manifestations of biliary esophageal regurgitation was observed already on the second day from the beginning of reception of UDCA. The patient was observed by us in the next 2 years. In patients receiving UDCA and after the course of therapy with this drug, the symptoms of gall GER was not renewed. De-worming is confirmed by the results of the second duodenal intubation. Control pH-monitoring, conducted 3 months after the course of treatment with UDCA did not reveal the presence of pathological reflux. In follow-up - after the complex treatment of GERD: the need for standard antireflux therapy, with the use of the group kislotozavisimyh drugs it was not during the entire period of supervision of the patient.

2. The use of UDCA in complex therapy of reflux disease of the esophagus in a patient with chronic opisthorchiasis mixed variant GER (with a predominance of acidic component).

Patient K., 1981 birth, was admitted to the Department of therapy in a planned manner. Diagnosis directions: GERD.

Dyspeptic complaints: heartburn, feeling sour and bitter taste in the mouth; belching sour, bitter; nausea. Intensity of subjective sensations dominates the symptom of heartburn.

Anamnesis. Seeing a gastroenterologist for GERD for 3 years. Once a year undergoing treatment according to the standard scheme, using:

kislotozavisimyh drugs prokinetics, antacids. The patient notes that on the background and on completion of the course of treatment remains is the feeling of bitterness in the mouth, and the necessity to take antacids "on demand" with a view to its elimination. Five years ago diagnosed with opisthorchiasis (according to the results of duodenal intubation), treatment was not conducted due to low intensity of infection and a high risk of re-infestation. Earlier in the survey opisthorchiasis were not found. Four months ago underwent another course of treatment of GERD (omeprazole 20 mg/day for 6 weeks, motilium 10 mg 3 times a day for 10 days), against which achieved a partial wedge is ical remission: symptoms of heartburn cropped, but remained manifestations of biliary esophageal regurgitation (bitter belching, feeling of bitterness in the mouth).

The results of the survey. Objective examination and laboratory tests (General and biochemical blood tests) revealed no deviations in the values of indicators from physiological norms. There are no laboratory syndromes inflammatory changes, cytolysis, cholestasis, mesenchymal cell inflammation. The number of eosinophils in the leukocyte formula was 2%.

EGD: signs of esophagitis and duodenitis without erosive defects.

Duodenal intubation: hypotonic-hypokinetic type of dyskinesia GWP, the intensity of opisthorchosis invasion by the method of the Stele - moderate (1800 in 1 g of feces).

Conducted 24-hour acidimetry upper GI: 1) the state kislotoproduktsiya functions of the stomach in basal conditions match the parameters of normaltest - 1.6≤pH of the gastric body ≤2.0; during stimulation pentagastrinom - found hidden hyperacidity - 1.1≤pH≤1.4;

2) pH-type GER - mixed, with a predominance of acidic component in reluctate. pH-parameters acidic component reflux corresponds to the average severity of this algometrical option - tGeneralpH<4- 6.2%; NpH<4- 58. The alkaline component GER weak intensity (tGeneralpH>722%; NpH&t; 7- 30).

Treatment. The patient is assigned a comprehensive treatment of GERD according to the proposed method. The standard for this endoscopic forms reflux disease of the esophagus, treatment cyclotourisme drugs, prokinetic, antacids: omeprazole 20 mg once in 15 hours (6 weeks), motilium 10 mg 2 times a day (10 days), antacid medication (Almagell) 1 dose (5 ml) in an hour after meal 3 times a day and at bedtime (10 days in the future "on demand"). Conducted deworming biltricid. Assigned UDCA, according to the scheme recommended by us when this type and pH parameters GER: 250 mg/day (1 capsule) in the evening. The drug was administered at the preparatory stage to helminthization, and then within 2 weeks postdetermination period. The duration of taking the drug was sufficient to achieve sustainable clinical and pH-remission of the disease. 24-hour acidimetry conducted over 3 months after completing the course receive UDCA did not reveal the presence of pathological reflux. Thus, by assigning UDCA failed to arrest the symptoms of biliary regurgitation, resistant to previously held standard cyclotourisme the treatment of GERD. The patient was observed by us within 2 years of acute reflux disease of the esophagus was not recorded.

3. Examples of the use of UDCA in whom the integrated therapy of reflux disease of the esophagus in patients with chronic opisthorchiasis at isolated alkaline variant GER depending on the pH of the manifestations of the latter.

3.1. When rare and moderately frequent alkaline GER and no episodes of massive GER.

Patient M., born in 1965.

Has addressed to therapist in the clinic. The diagnosis of GERD.

Complaints: feeling of bitterness in the mouth, nausea. Heartburn no.

In the anamnesis. Duration of disease reflux disease esophageal 6 years. Held annually on the treatment of exacerbation of the disease, with the use of antisecretory drugs: proton pump inhibitors - omeprazole in a dose of 20 mg/day during 6 weeks. Drugs UDCA was not appointed. On a background of treatment remained a feeling of bitterness in the mouth. The last three years of the disease: heartburn no worries - marked feeling of bitterness in the mouth and bitter belching. A year ago held deworming biltricid. Anamnestic duration of opisthorchiasis, until its specific treatment was 7-8 years. De-worming is confirmed by results of duodenal intubation, repeated and not revealed the presence of opisthorchis in bile.

According to the results of previously conducted a comprehensive survey is no different than ismotorola GWP in postresidential period of chronic opisthorchiasis, pathology pancreato-hepato-biliary system (data USI), which could be due to the presence of biliary reflux. The form of the disease is GERD - endoscopically negative. Algometrical research, evaluation of pH-parameters GERD during previous hospitalizations was not conducted.

Therapy reflux disease of the esophagus was administered empirically: using kislotozavisimyh drugs, excluding state kislotoproduktsiya functions of the stomach and the pH-type GER. Two months ago underwent another course of PPIS, on the background of which a feeling of bitterness in the mouth occurred sporadically and resumed with the same frequency (as before treatment) 2 weeks after cessation of therapy.

We performed pH-monitoring of upper GI patient. Results: true hypoacidity environment of the stomach - basal 2.5≤pH of the gastric body ≤5.3, the stimulation pentagastrinom - 2.2≤pH≤3.0; type GER - isolated alkaline, pH-parameters - moderately frequent (tGeneralpH>735%; NpH>733), episodes of massive GER (pH more than 8.9%) were not registered.

UDCA is assigned according to the scheme according to the proposed method in this pH-type and the parameters of the GER - the rate of 10 mg/kg/day that was for our patient 750 mg/day, 1 capsule in the morning and two in the evening for 4 weeks. By the end of the terms of the proposed treatment was achieved complete clinical remission of the disease. Needs to extend the course of treatment with this drug or therapy is on - demand did not arise. pH-monitoring, conducted 6 months after the end of treatment did not reveal the presence of pathologic esophageal reflux, Gioachino the state of the environment of the stomach remained. In the next two years of monitoring the condition of the patient exacerbations reflux disease of the esophagus was not recorded.

3.2. When rare or moderately frequent alkaline GER, combined with the presence of episodes of massive GER (no more than 5 times per day).

Patient A., born in 1956.

The diagnosis of Gastroesophageal reflux disease, endoscopically negative form. After deworming: six months ago, held deworming biltricid.

Complaints: feeling of bitterness in the mouth and a burning sensation behind the breastbone, bitter belching, and nausea. These clinical manifestations of concern for many years prior to three years - more pronounced.

Anamnesis. Is "D." accounting for GERD for 10 years. Two times a year courses receive treatment: omeprazole, antacids, prokinetics. Every month there is a necessity for therapy on demand - antacids and cyclotourisme drugs. On the background of therapy is almost always subjective symptoms is the feeling of bitterness in the mouth. Five years ago - changing symptoms of GERD and reduce the effectiveness of the treatment antisecretory drugs. This is currently the clinical picture is dominated by manifestations of biliary regurgitation (feeling of bitterness in the mouth, belching bitter), formerly predominant was subjective symptoms of acid GERD (heartburn, belching sour). pH-monitoring with evaluation kislotoproduktsiya functions of the stomach and the type of GER was not conducted. Kislotoobrazovanie therapy was administered empirically.

Six months ago, held deworming biltricid, the success of anti-parasitic treatment is confirmed by the results of the second duodenal intubation, does not produce a opisthorchiasis. Anamnestic duration parasites accounted for more than 15 years. In postdetermination period, with the aim to arrest the existing symptoms of GERD (a feeling of bitterness in the mouth and a burning sensation behind the breastbone, bitter belching, nausea), assigned to the IPP. Taking antireflux therapy completed a month ago. Remain subjective manifestations of biliary GER. When expressed bitterness in the mouth takes Almagell, the effect is only temporary.

The results of the survey.

Ultrasound: concrements in the gallbladder and biliary ductal system not identified; anomalies GIT structural in nature, causing a possible cause of their dysfunction, not detected; there is postresidency signs of chronic cholecystitis, gall traces of bile.

24-hour acidimetry upper GI: state kislotoproduktsiya functions Gelu the ka - true antighost (basal pH of the gastric body >6-stimulated pentagastrin - pH 5.1); type GER - isolated alkaline; parameters tGeneralpH>742%; NpH>735), episodes of massive alkaline GER - 3 times per day. Assigned UDCA in a daily dose of 10 mg/kg of body weight, the scheme of Taxifolin - 3 capsules 2 times a day for 8 weeks. After a week of therapy there was a strong positive dynamics of clinical manifestations of biliary GER. By the end of the treatment UDCA - achieved complete clinical remission of the disease. Re pH-monitoring, conducted three months after receiving UDCA revealed positive dynamics allometrically parameters GERD: pathologic esophageal reflux are not fixed. The patient was observed by us in the next two years: acute reflux disease of the esophagus was not recorded.

3.3. Frequent alkaline GER with episodes of massive GER.

Patient L., born in 1951.

Previously we observed about chronic opisthorchiasis. There are clinical manifestations of GERD (exclusively bile regurgitation): bitter belching, feeling Greci mouth. Heartburn is not worried. Performed endoscopic examination of the upper GI showed no changes in the mucous membrane of the esophagus; there are phenomena of Boden is the without erosive changes. Once a year there is a need in the course of treatment of GERD. Prescribed PPIS are not effective. On a background of reception of these preparations are stored clinical manifestations of biliary GER. During previous hospitalizations pH monitoring, upper GI was not conducted. Antireflux therapy was administered empirically - classic (cyclotourisme) scheme with the use of antisecretory drugs (omeprazole 20 mg 1 time a day for 6 weeks). Achieved remission was incomplete, short-term (up to 2 months). The use of PPIS was not eliminated symptoms of biliary regurgitation. During the month preceding the present treatment of the patient, almost daily there was a need for therapy "on demand" with the use of antacids. Anamnestic duration opisthorchosis invasion 17 years. Previously deworming was not conducted. Occasionally, as the medication, the patient took a decoction of the bark of aspen. A year ago was administered UDCA in a dose of 250 mg once at night for 2 weeks. In patients receiving the drug showed positive dynamics of biliary symptoms of GERD. However, the duration of treatment with UDCA and assigned dosage of the drug was not sufficient for long-term clinical effect, and the presence of retain is of egasa trigger factor biliary regurgitation - in the form of opisthorchosis invasion is not possible to achieve stable remission of the disease. The feeling of bitterness in the mouth resumed after 3 months after discontinuation of the drug, but less intense subjective feelings than before the treatment.

At the stage of this treatment, the patient received pH-monitoring. The results of the 24-hour acidimetry: state kislotoproduktsiya functions of the stomach corresponds to the true antidnase - basal pH of the gastric body ≥6.5, the stimulation pentagastrinom pH changed little and was ≥6.2; type GER - isolated alkaline corresponding to the category of "frequent" (tGeneralpH>760%; NpH>738)recorded two episodes of massive GER (pH more than 8.9%).

Treatment. Conducted deworming biltricid. According to antidnase dosage prescribed kislotozavisimyh drugs reduced by 1/2 of the daily dose recommended in this endoscopic variant of GERD, and amounted to 20 mg famotidine overnight. UDCA scheduled to deworm, then the drug is continued, according to our proposed scheme at this pH variation and parameter esophageal reflux. In recalculation on weight of the patient daily dose was 750 mg/day (3 capsules per day). The destination schema UDCA: 1 capsule (250 m the morning and two in the evening daily for 12 weeks postdetermination period (3 months). One week from start of treatment was observed progressive positive dynamics of clinical manifestations of biliary regurgitation. After completing the course of therapy is completely cropped: a feeling of bitterness in the mouth, belching bitter. Given the severity of the initial pH of the manifestations of alkaline GER, in order to improve the clinical effect of treatment ugh extended for 2 weeks in1/2daily dose (11/2capsules per day, once at night). pH-monitoring conducted in the dynamics - 6 months after completion of the course of drug treatment alone did not reveal the presence of pathological GER, antitrust environment of the stomach remained. De-worming is confirmed by the results of duodenal intubation with microscopy of bile in the presence of opistorhisov. The patient was observed by us in the next 2 years - exacerbation of GERD was not observed

The method consists in the following: In the complex treatment of GERD in patients with chronic opisthorchiasis to maximize the effectiveness of antireflux therapy, prescribed drugs UDCA. Regimens of the drug depend on the state kislotoproduktsiya functions of the stomach. In addition, all patients with chronic opisthorchiasis, with clinical manifestations of reflux disease of the esophagus, an is correctly carried out deworming - to eliminate trigger factors of occurrence of biliary reflux.

You and pathogenetically justified the inclusion of the drugs alone in the complex therapy of GERD in patients with chronic opisthorchiasis with sour esophageal reflux. Range of pharmacological effects of UDCA, you can affect: the root cause of biliary reflux - dysfunction of the biliary tract (normalizes motor-tonic condition of the biliary system); the factors damaging the ability of bile (binds to hydrophobic bile acids, providing deterious effect on the mucosa of the gastrointestinal (GI)tract, including the esophagus); secondary manifestations of opisthorchosis invasion (fixes cholestasis syndrome, normalizes the rheology of bile). UDCA improves the rheological properties of bile and its chemical composition (reduces the level of hydrophobic bile acids with determineusing properties of the mucous membrane of the digestive tract)and can be used for biliary dyskinesia (GWP) and duodeno the reflux [10], i.e. the primary stages of the Genesis of biliary reflux into the esophagus. Bile acids in reluctate capable of directly damaging effect on the mucous membrane of the digestive tract. Role of bile acids as aggressive agents high [11]. It is known that p is fridaywe action on the mucous membrane of the stomach and esophagus hydrochloric acid and the components of bile are competing for the right to be more aggressive agent [4].

Thus, the new key approach underlying the proposed method for the treatment of reflux disease of the esophagus, is the consideration of the peculiarities of pH-parameters of GERD in patients with opisthorchiasis with the addition of UDCA preparations, in addition to classic cyclotourisme therapy in non-acidic nature of esophageal reflux. Regimens UDCA depended on the intensity of pH-manifestations of the alkaline component esophageal reflux.

Important are used in the proposed method approaches the tactics of treatment of reflux disease:

1. A comprehensive three-tiered approach in the tactics of treatment of reflux disease of the esophagus in this category of patients, taking into account: endoscopic manifestations of the disease, presence of concurrent opisthorchosis invasion (as a trigger factor for biliary component reluctate), particularly pH manifestations of GERD (type of reflux, the condition of acidity).

2. Consideration of possible pH-features reflux disease esophageal amid opisthorchosis invasion (the predominance of alkaline component GER in isolated or mixed variants, the tendency to reduction of acid in the stomach), requiring dose adjustment kislotozavisimyh drugs and destination more pathogenetically justified therapy drugs UDCA.

3. It is important, also, carrying the s deworming, aimed at eliminating the primary trigger factor motor-tonic disorders of the biliary tract, causing the presence of bile (alkaline component) reluctate.

4. The prescription of UDCA as a component of antireflux therapy in the presence of mixed and isolated alkaline GER.

5. A record of the intensity of pH-manifestations of the alkaline component GER when assigning regimens UDCA.

Thus, the proposed method can improve the efficiency of treatment by obtaining a stable therapeutic effect of a more prolonged remission of disease in relation reflux disease of the esophagus, reducing the number of relapses, prevention of disease progression, development of severe complications and to extend its application scope.

Sources of information

1. Vidal. On The Main Page. Drugs in Russia: a Handbook. - M.: Astroparticles, 2002. - 1488 S.

2. Ivashkin V.T., Noodles TL the Most significant of acid disease in physician practice. - M.: Russian Gastroenterological Association, 2005. - 30 S.

3. Ivashkin V.T., the performance took place AA, Trukhmanov A.S. and other Diagnosis and treatment of gastroesophageal reflux disease / Manual for doctors, executives of health authorities and medical institutions. - M.: Moscow, 2003. - 29 S.

Carolina N.A., Zakharova, I.N., Malova N.E. enzymes with digestive disorders in children / a Guide for physicians (Russian Medical Academy of postgraduate education of the Ministry of health and social development of the Russian Federation). - M.: Moscow. - 2005. - 36 S.

5. The Pimanov SR Esophagitis, gastritis and peptic ulcer disease. - M: Medical book, Nizhny Novgorod: publishing house of the ngma, 2000. - 378 S.

6. Rapoport S.I., Lakshin A.A., Rakitin BV and other pH-metry of the esophagus and stomach diseases of the upper gastrointestinal tract / edited by academician of the Russian Academy of medical Sciences Fionaluv. - M.: publishing house MEDPRAKTIKA - M., 2005. - 208 S.

7. Standards (protocols) for the diagnosis and treatment of patients with diseases of the digestive system / the Ministry of health of the Russian Federation No. 125. - 1998.

8. Belevsky A.S. Bronchoobstructive syndrome and GERD // the Results of the Symposium "Gastroesophagealreflux disease interdisciplinary problem", April 21, 2004 in the framework of the 9th National Congress "Man and medicine". - P.12.

9. Vasilenko US the Diagnosis and treatment of laryngitis associated with gastroesophageal reflux // the Results of the Symposium "Gastroesophagealreflux disease interdisciplinary problem", April 21, 2004 in the framework of the 9th National Congress "Man and medicine". - S.

10. Ivanchenkov R. Treatment of chronic diseases of the biliary bile acid drugs /Doctor/. - 2004. No. 8. - P.52-55.

11. Mayev I.V., Samsonov AA antacid Use of modern tools in therapy of acid diseases of the gastrointestinal tract // Directory of outpatient physician. - 2005. No. 5. - P.3-7.

12. Naginsky M. Study of ursodeoxycholic acid in Hepatology from positions of medicine based on scientific evidence // Consilium medicum. - 2003. - V.5, №6. - S-322.

13. Tkachenko E. Therapy extraesophageal manifestations of GERD // Experimental and clinical medicine. - 2004. No. 5. - P.40.

14. Trukhmanov AS Gastroesophageal reflux disease: clinic, diagnostics, treatment // Library for breast cancer (diseases of the digestive system). - 2001. - Vol. 3, No. 1. - P.19-24.

1. The method of complex treatment of gastroesophageal reflux disease in patients with opisthorchiasis by administration of UDCA against the standard for specific endoscopic disease pharmacotherapy, advanced previously conducted pH-monitoring of upper gastrointestinal (GI) defining the parameters: pH type and intensity esophageal reflux condition kislotoproduktsiya functions of the stomach and deworming and mixed variant GER with a predominance of acidic component at tGeneralpH>7from 16,54 to 27.6%; NpH>7from 27 to 31 and the increase in pH in the esophagus from 7 to 8 or from 8 to 8.9; no episodes of massive alkaline GER, enter the UD IS TO 250 mg/day for 2 weeks, when mixed variant GER with a predominance of alkaline component tGeneralpH>7from 48,8-74.4 per cent; NpH>736-42, or tGeneralpH>7from 27.6 to 48.8%; NpH>7from 31 to 35, pH 8 to 8.9; single, 1-2 day episodes of massive alkaline esophageal reflux, administered UDCA at a dose of 500 mg/day at night for 4 weeks, with isolated alkaline variant is administered UDCA at a dose of 10 mg/kg in two doses: morning and evening.

2. The method according to claim 1, characterized in that at isolated alkaline form, with tGeneralpH>7from 16,54 to 27.6%; NpH>7from 27 to 31 and moderately frequent GER, or tGeneralpH>7from 27.6 to 48.8%; NpH>7from 31 to 35 and the absence of episodes of massive GER; treatment within 4 weeks.

3. The method according to claim 1, characterized in that at isolated alkaline variant with tGeneralpH>7from 16,54 to 27.6%; NpH>7from 27 to 31, or moderately frequent GER, tGeneralpH>7from 27.6 to 48.8%; NpH>7from 31 to 35; combined with the presence of episodes of massive GER, no more than 5 times per day, with frequent GER tGeneralpH>7from 48,8 to 74.4%, NpH>736 to 42, and the absence of episodes of massive GER, treatment for 8 weeks.

4. The method according to claim 1, characterized in that at isolated alkaline variant with tGeneralpH>7from 48,8 to 74.4%; NpH>736 to 42, with or without episodes of massive; there are episodes by weight of the active GER with t GeneralpH>7from 16,54 to 74.4%; NpH>7from 27 to 42, more than 5 times per day at any frequency alkaline GER course of treatment is 12 weeks.



 

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3 cl, 2 dwg, 2 ex

FIELD: medicine.

SUBSTANCE: invention relates to medicine, namely to gastroenterology, and can be applied for treatment of duodenum ulcerous disease in children (UDD). For this purpose in complex therapy included is fluconazole (diflucan). Doses and regime of fluconazole introduction are determined depending on the level of circulating candidal antigen in blood serum. At high level of candidal antigenemia (10-4/10-5 mg/ml) medication is administered in form of intravenous injections in dose 5 mg/kg 1 time per day during 3 days, then 7 days inside in dose 3 mg/kg, and after that 1 time per week once during a month in dose 150 mg. At moderate level of candidal antigenemia (10-6 /10-7 mg/ml) flucanazole is administered inside by 5 mg/kg during 7 days, then 1 time per week in dose 150 mg during a month. At low level of candidal antigen in blood serum (10-8 /10-9 mg/ml) medication is taken inside in dose of 3 mg/kg during 7 days, then once in dose 150 mg.

EFFECT: method makes it possible to reduce level of circulating candidal antigen in blood serum of patients with any level of candidal antigenemia.

3 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention refers to compound described by formula where R1 represents a monocyclic nitrogen-containing heterocyclic group optionally condensed with heterocycle with the monocyclic nitrogen-containing heterocyclic group optionally condensed with heterocycle, optionally having 1 to 5 substitutes chosen from a group consisting of (1) halogen atom, (2) cyano, (3) hydroxy, (4) C1-6 alkoxy optionally having 1 to 3 halogen atoms, (5) amino, (6) mono- C1-6 alkylamino, (7) C1-6 alkoxycarbonyl and (8) C1-6 alkyl optionally having 1 to 3 halogen atoms, R2 represents (i) C6-14 aryl group optionally substituted by 1 to 5 substitutes chosen of a group consisting of (1) halogen atom, (2) cyano, (3) C1-6 alkoxy optionally having 1 to 3 halogen atoms, (4) C1-6 alkylthio optionally having 1 to 3 halogen atoms, (5) C1-6alkylcarbonyl, (6) C1-6 alkylsulphonyl, (7) C1-6 alkylthionyl, (8) C3-7 cycloalkyl, (9) C1-6 alkyl group optionally having 1 to 3 halogen atoms, and (10) C1-6 alkyl group substituted by 1 to 3 hydroxy, (ii) a thienyl group optionally substituted by 1 to 4 substitutes chosen from a group consisting of (1) cyano and (2) C1-6 alkyl group optionally having 1 to 3 halogen atoms, (iii) a pyridyl group optionally substituted by 1 to 4 substitutes chosen from a group consisting of (1) halogen atom, (2) 5-10-members aromatic heterocyclic group containing carbon atom, and 1 or 2 presentations of 1-4 heteroatoms chosen from nitrogen atom, sulphur atom and oxygen atom, and (3) C1-6 alkyl group optionally having 1 to 3 halogen atoms, or (iv) a bipyridyl group optionally substituted by 1 to 3 halogen atoms, each R3 and R4 represents hydrogen atom, or one of R3 and R4 represents hydrogen atom, and another represent a lower alkyl group, halogen atom or a cyanogroup, and R5 represents an alkyl group, or to its salt. Also, the invention refers to a pharmaceutical composition showing an acid secretion inhibitory effect enabled by the compound of formula I, to a method for treatment or prevention, besides, to application of the compound of formula I for preparing a pharmaceutical composition for treatment or prevention of a number of diseases presented in the patent claim.

EFFECT: preparation of the new compounds showing the acid secretion inhibitory effect and exhibiting antiulcerant action.

20 cl, 92 ex, 24 tbl

FIELD: medicine.

SUBSTANCE: invention refers to experimental medicine and veterinary science. The invention disclosed unexpected administration of Pro-Gly-Pro peptide as an intranasal agent in prevention and treatment of gastric ulcer in rats.

EFFECT: invention provides higher effectiveness and simplified administration of the agent.

5 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to chemical-pharmaceutical industry and medicine, namely to pharmaceutical composition in form of solid gelatin capsules, which contains rabeprazole for treatment of ulcer of stomach and duodenum, composition contains as additional substances filler (thinners), binding agents, loosening agents, sliding, lubricating, film-formers, inert carriers.

EFFECT: method of obtaining composition in form of gelatin capsules additionally can include sputtering on gelatin capsule of solution, which contains enterosoluble polymer.

15 cl, 1 tbl, 1 dwg, 5 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to novel chemical compounds of formula R1=R2=H, R3=OCH3 (la), R1=H, R2=R3=OCH3 (Ib), R1=NH2, R2=R3=H (Ic) R1=R2=H, R3=F (Id), possessing high anti-ulcer activity.

EFFECT: obtained and described are novel compounds, which can be applied in medicine.

1 cl, 8 ex, 1 tbl

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of formula (I)

or pharmaceutically acceptable salts thereof, in which: R1, R2, R3, R4, A and E are as described in the claim, and to pharmaceutical composition containing said compounds, and a method of treating and application in order to treat conditions mediated by antagonistic activity towards acid pump, such as gastrointestinal diseases, gastrooesophageal diseases, gastrooesophageal reflux disease (GERD), laryngopharyngeal reflux disease, peptic ulcers, gastric ulcers, duodenal ulcers, NSAID- induced ulcers, gastritis, Helicobacter pylori infection, dyspepsia, functional dyspepsia, Zollinger-Ellison syndrome, nonerosive reflux disease (NERD), viscerogenic pain, cancer, heartburn, nausea, oesophagitis, dysphagia, hypersalivation, disorders of the respiratory channel or asthma.

EFFECT: possibility of using compounds to treat different diseases.

9 cl, 1 tbl, 16 ex

FIELD: medicine.

SUBSTANCE: pharmaceutical composition for treating gastric and duodenal ulcers contains a proton pump inhibitor (PPI) in amount 0.05-25 wt %, and a prebiotic in amount 40-95 wt % specified in aliphatic alcohols, di-, tri-, oligo- or polysaccharides. A method of treating gastric and duodenal ulcers implies enteral administration of said pharmaceutical composition once a day for 14 days.

EFFECT: synergetic action of the proton pump inhibitor and prebiotic provides faster repair of gastric mucosal ulcers, effective stable eradication of Hpylori without using antibacterial therapy, the absence of side effects and recurrences.

14 cl, 8 tbl

FIELD: medicine.

SUBSTANCE: invention concerns medicine, namely oncology, and can be used in treatment of unresectable biliary tract cancer complicated by obstructive jaundice. Substance of the invention consist that the patients underwent external biliary tract drainage, for the 10th postoperative day deliver bottled autobile 50 ml and 5-fluorouracil 500 mg. Then bottles are incubated during 40 minutes at 37°C. Further autobile with 5-fluorouracil is introduced into biliary tracts through stoma then to be blocked for 6 hours. Autobile chemotherapy into biliary tracts involves 10 sessions every second day.

EFFECT: application of the invention allows improving clinical effectiveness in the patients ensured by better patency of biliary tracts in direct antineoplastic action of 5-fluorouracil and lower toxicity of the method.

1 ex

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