Pharmaceutical composition for treating gastroesophageal reflux disease

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to pharmaceutical industry and represents pharmaceutical composition for treating gastroesophageal reflux disease, containing at least one proton pump inhibitor and at least one probiotic, wherein the proton pump inhibitor is taken in the amount of 0.05-25 wt % in the composition; and the probiotic is taken in the amount of 10-95 wt %; additive agents up to 100 wt %.

EFFECT: provided preventing Hpylori translocation, avoiding the necessity of Hpylori detection and antibacterial course of eradication, higher safety of the prolonged therapy with the proton pump inhibitors and avoided gastric mucosa atrophy, and a risk of gastric cancer.

5 cl, 10 tbl

 

The invention relates to medicine and pharmacology, namely to medicines and pharmaceutical compositions (farmcampsite) for the treatment of gastroesophageal reflux disease (GERD).

Gastroesophageal reflux disease is a chronic relapsing disease, characterized by transitions (reflux) into the esophagus gastric or duodenal contents, arising out of violations of motor-evacuation function esophagogastroduodenal zone, which manifest symptoms, disturbing the patient, and/or the development of complications (standards for the diagnosis and treatment of acid associated with Helicobacter pylori disease (fourth Moscow agreement). Experimental and clinical gastroenterology. 2010; 5: 113-118).

The disease is the most frequent lesions of the gastrointestinal tract. Epidemiological studies indicate that the prevalence of GERD (the presence of heartburn and/or regurgitation 1 time per week and more often during the last 12 months) in the countries of Western Europe, North and South America 10%to 20%, Asia 5%, and in Moscow is 23.6%, in Russia (research "with Megre") to 13.3%.

Currently accepted view is that both the presence and eradication of H. pylori are not the cause of GERD. However, it is noted on the negative feedback of the prevalence of N. pylori in the population and the prevalence of GERD, which may indicate a kind of "protective" role of N. pylori. However, due to substantial and long-term drug suppression of acid proton pump inhibitors (PPIS) is the distribution of N. pylori from antral on the body of the stomach (translocation). This may accelerate the processes of loss of specialized glands of the stomach, leading to the development of atrophic gastritis and possibly stomach cancer. So GERD patients who need long-term antisecretory therapy (usually with reflux esophagitis and Barrett's esophagus), it is necessary to make a diagnosis on the presence of N. pylori and identifying the eradication of H. pylori (Consensus "Maastricht-4" (2012), 4-th Moscow agreement on diagnosis and treatment of acid disease (2010)). The relevance of this approach is associated with a high prevalence of N. pylori infection in different populations. It is proved that almost half of the population in the stomach is N. pylori (J.E. Everhart // Gastroenterol. Clin. North Amer. - 2000. - V.29. - P.559-578).

Thus, the need for eradication .pylori is not due to treat GERD, and are intended to prevent translocation of bacteria and, as a consequence, the prevention of the spread of inflammation, and atrophy of the mucous membrane of the stomach, which in turn prevents the development of cancer Gelu the ka.

Now apply the standard scheme of H. pylori eradication therapy, which includes from 2 to 3 antibiotics taken at the same time ("Maastricht-4" (Malfertheiner p, Megraud f, O Morain C.A. et al. Management of Helicobacter pylori infection - the Maastricht IV. / Florence Consensus Report. Gut 2012; 61: 646-664).

This therapy is often accompanied by the development of significant side effects. Because of the wide clinical application of antibiotics that form the basis of eradication schemes around the world is growing resistance to these antibiotics, reduces the effectiveness of the eradication schemes. In this situation, the possibility of exclusion of antibiotic therapy from the treatment of patients with GERD is of great clinical value.

In the prior art it is known the use of PPIS for the treatment of GERD (EN 2361574, publ. 20.07.2009; EN 2207339, publ. 27.06.20036, EN 2184734, publ. 10.07.2002).

Since the introduction of PPIS in the clinical practice of their consumption in the world increases every year. In addition to increasing consumption increases and the number of patients who need long-term acceptance of the IPP. In this regard, particular attention is drawn to the problem of safety treatment. Potential risks from long-term administration of PPIS is largely associated with long-term suppression of acid, and impaired digestion and inactivation of pathogenic microflora, postupayushie is with her. This is why treatment of PPIS is associated increased risk of bacterial intestinal infections and the development of a syndrome of bacterial overgrowth.

The lower protective acid barrier allows the microbes from the oral cavity and upper respiratory tract to colonize the stomach and then the small intestine (Parfenov A.I., 2002). For example, it is known that a daily intake of 20 mg of omeprazole increases in healthy individuals, the number of bacteria in the duodenum and the nearest to it jejunum approximately 2 orders of magnitude (S.J.Lewis et al., 1996).

In the prior art it is known the use of a composition containing a proton pump inhibitor (PPI) and a prebiotic for the treatment of gastric ulcer and 12 duodenal (EN 2410100, publ. 10.10.2010, WO 9403184, publ. 1994-02-17). In this patent does not disclose the possibility of using this composition for the treatment of GERD. Described in the patent the dosage of the drug short course of 2 to 4 weeks, can effectively treat peptic ulcer disease, but does not prevent atrophic processes and stomach cancer with prolonged courses of therapy (at least 8 weeks) in patients with GERD.

Also known pharmaceutical compositions for the treatment of gastroesophageal reflux disease, containing a proton pump inhibitor and the second active substance. At the same time as the second active substance in inalsa sodium bicarbonate, Optima ficus (EP 2201952, publ. 30.10.2010, WO 9959612, publ. On 25.11.1999, EP 2208500, publ. 27.07.2010).

The disadvantages of these compositions is that none of them prevents the development of SIBR and translocation N. pylori, and thus does not prevent the development of gastric cancer. At the same time, these compositions have the ability to weight for GERD. So, for example, neutralization of sodium bicarbonate in the stomach causes the regurgitation of gastric contents, which can lead to deterioration and/or weighting of the condition of patients with GERD. Long-term use of preparations containing sodium bicarbonate, leads to the development of metabolic alkalosis.

The technical purpose of this invention is to provide an effective combination drug for the treatment of GERD, preventing translocation N. pylori and the development of SIBR.

The technical result of the claimed invention is that solved the problem translocation of H. pylori due to colonization of the antrum, lactobacilli and competitive inhibition of H. pylori in the treatment of IPP, which eliminates the need to identify the bacteria H. pylori and antibiotic course of eradication, as well as increased safety of long-term PPI therapy. There is no atrophy of the gastric mucosa, and, consequently, does not increase the risk of developing cancer of the stomach.

The essence of the claimed invention consists in that a pharmaceutical composition for the treatment of gastroesophageal reflux disease consists of at least one proton pump inhibitor and at least one prebiotic in the following components of the composition, wt.%:

the proton pump inhibitorof 0.05-25
prebiotic10-95
excipients100

In private cases, the implementation of the prebiotic composition comprises from the group of aliphatic alcohols include xylitol, sorbitol, lactitol or contains a prebiotic from the group of di - and trisaccharides: lactulose, lactosucrose, melibiose, kilobyte, stachyose, raffinose, or contains the prebiotic group oligosaccharides: fructooligosaccharide, galactooligosaccharide, maltooligosaccharide, xylooligosaccharide, isomaltooligosaccharide, gentilhombre, or contains a prebiotic from the group of polysaccharides: arabinogalactan, pectin, pullulan, inulin.

In private cases, the implementation of the composition may contain a proton pump inhibitor from the group of: omeprazole, pantoprazole, lansoprazole, rabeprazole, esomeprazole and dexlansoprazole.

Preferably HDMI is tion is made in a dosage form for oral administration: suspension for oral administration, solution for oral administration, capsules, tablets, powders, sachets, pellets, granules.

The essence of the claimed invention in the part of the method lies in the fact that the claimed method of treatment of gastroesophageal reflux disease, wherein the presence of N. pylori does not require eradication for the prevention of risks associated with translocation of bacteria from the antrum into the body of the stomach, which is achieved enteral intake of the pharmaceutical composition of the proton pump inhibitor and prebiotic performed according to any of claims 1 to 4, at least once a day during the period determined by the form of the disease, but not less than 4 weeks.

The composition may contain a proton pump inhibitor omeprazole in amounts of 10-40 mg or pantoprazole in amounts of 20-80 mg, or contain lansoprazole in the amount of 30 to 60 mg, or contain rabeprazole in the amount of 10-60 mg, or contain esomeprazole in amounts of 20-80 mg.

Prebiotics - nevereverever ingredients of food that contribute to improved health due to selective stimulation of growth and/or metabolic activity of one or more species of bacteria indigenous microflora that live in the colon (Gibson GR, Roberfroid MB., 1995). Dietary fiber is not digested in the small intestine under the influence of digestive enzymes and get into the thick kick is unchanged. In the lower part of the colon oligosaccharides are fermented by bifidobacteria and lactobacilli. This leads to an increase in the total bacterial mass, stimulate the immune system, increasing intestinal motility and further normalization of functional activity of the digestive tract.

The role of prebiotic (e.g., lactulose, FOS and others) to achieve the stated technical result consists in the active stimulation of the growth of lactobacilli patient in the antral ulcer and 12 duodenal ulcer, which leads to competitive inhibition of growth of Helicobacter pylori, which is the main factor that prevents translocation, and in some cases, and providing for the eradication of the pathogen. After administration of the drug into the stomach and 12 duodenal ulcer begin to actively grow their own lactobacilli patient is their "excess growth"), suppressed the growth and reproduction of Helicobacter pylori, even in the absence of antimicrobial therapy with antibiotics.

The main role in protection from infection belongs symbiotic microflora, which provides colonization resistance of the organism. Under colonization resistance understand a set of mechanisms that ensure the stability of the normal microflora and prevent the colonization of the host organism pathogenic or conditionally pathogen is diversified microorganisms.

Research (Castagliuolo I, Riegler MF, et al., 1999; Madsen K, Cornish A, et al., 2001) it was shown that bifidobacteria and lactobacilli inhibit the adhesion of pathogens, neutralize bacterial toxins and increase the barrier function of the mucosal barrier.

Lactobacilli are able to prevent the growth of potentially pathogenic bacteria due to competition for substrates, production of antimicrobial agents, such as bacteriocins, and stimulate the immune system.

It is shown that N. pylori is unable to colonize gnotobiotic mice of BALB/c mice infected with Lactobacillus salivarius, although sterile mice were heavily colonized N. pylori infection and the subsequent development of acute gastritis. The introduction of L. salivarius after infection of H. pylori led to the elimination of colonization.

Most of the studies on the effect of Lactobacillus on H. pylori in vitro and in vivo studies conducted in the conditions of introduction of exogenous Lactobacillus cultures. In vitro conclusively proven competitive inhibition of growth of Helicobacter pylori.

A large number of studies have shown that prebiotics stimulate the growth of bifidobacteria and lactobacilli. For example, in Probert, NM, Gibson, G.R., 2002 was shown stimulation of prebiotics growth of bifidobacteria and lactobacilli. Increased levels of intestinal bifidobacteria and lactobacilli in faeces samples from healthy people taking probiotics.

The increase of bacteria the lactic acid bacteria was also shown in the gastrointestinal mucosa of patients after administration of inulin, enriched with fructooligosaccharide 15 g/day for 2 weeks.

Studies of prebiotic effects of lactulose in a daily dose of 3 g in humans showed a significant increase in the number of Bifidobacterium and Lactobacillus and decrease in the number of Clostridium perfringens, Bacteroides, Enterobacteriaceae and Streptococcus.

Proton pump inhibitors (omeprazole, lansoprazole, pantoprazole, rabeprazole, esomeprazole) is most effective for the treatment of GERD. therapeutic effect of PPIS based on the reduction of the damaging potential of reluctant (volume reduction and modification of the composition by suppressing the acid), which creates conditions for a cessation of symptoms and healing of damaged mucosa of the esophagus. The IPP shall 1-2 times a day for 20-30 minutes before a meal. The duration of the basic course of therapy is at least 8 weeks. In patients with reflux esophagitis its duration increased to 12 weeks. When recurrent erosive or ulcerative reflux esophagitis, Barrett's esophagus is recommended continuous maintenance therapy with PPIS at standard dose; often recurrent endoscopically negative GERD - continuous maintenance therapy with PPIS in the minimum effective dose (individually); the classical reflux syndrome (endoscopically negative GERD) therapy IPP "on demand", under the control of the symptoms of

Use for the treatment of gastroesophageal reflux disease pharmaceutical compositions containing composition, at least one proton pump inhibitor and at least one prebiotic in the content of the components of the composition (wt.%) the proton pump inhibitor of 0.05-25%, prebiotic 10-95%auxiliary substances to 100%, according to the present invention, provides an unexpected synergistic effect of the claimed composition, which consists in the fact that in patients receiving PPIS does not occur translocation of H. pylori from antral into his body, and not the development SYBR on the background of long-term use of PPIS.

As examples of the practical implementation of the claimed invention the results of clinical studies farmkompanii for the treatment of GERD, which included as active components include proton pump inhibitors (PPIS) and a prebiotic.

The study included 100 patients with endoscopically negative form of GERD, men and women aged 19 to 50 years old, infected with HP.

All patients were divided into 10 groups of 10 people, of which 5 groups (I-V) - experimental, and 5 groups (VI-X) - control.

In the experimental group patients received oral claimed dosage forms based on IPP and prebiotic: group I - a composition in which active the mi components were omeprazole and lactulose; Group II - a composition in which the active components were pantoprazole and lactitol; group III - a composition in which the active components have been lansoprazole and inulin; group IV - kompozitsiiu, in which the active components were rabeprazole and fructo-oligosaccharides; group V - esomeprazole and lactulose.

Control group patients received oral monotherapy IPP: group VI - omeprazole; VII group - pantoprazole; VIII group - lansoprazole; (IX group - rabeprazole and X group - esomeprazole.

All patients were treated according to the same scheme: took the composition of the proton pump inhibitor and prebiotic 2 times a day for 56 days.

For inclusion in the pharmaceutical compositions used the following therapeutic doses of PPIS:

Proton pump inhibitors (PPIS)Daily therapeutic dose (mg)
pantoprazole20-80
omeprazole10-40
lansoprazole30-60
rabeprazole10-60
esomeprazole20-80

Diagnostiquer conducted on the basis of objective clinical data (complaints of heartburn and/or regurgitation, disturbing the patient); the inspection of the mucosa of the esophagus method esophagogastroduodenoscopy; accounting of the alginate test (diagnostic test, which assesses the relief of GERD symptoms after a single dose of the drug alginic of Chistota with physical antireflux effect); in some cases the readings were carried out daily pH monitoring and manometry of the esophagus.

In all patients before and after 4 weeks (1 month) after the end of treatment conducted research biopsies of the antrum and body of the stomach for the presence of Helicobacter pylori. For the diagnosis of HP used:

1. Cytological and histological examination of biopsies of the mucosa of antrum and body of stomach, obtained during gastroscopy.

2. Urease test, in which the biopsy of mucous membrane of the antrum and body of the stomach was examined for the presence of urease enzyme, specific for Helicobacter pylori.

In all patients before treatment and on the visits was assessed quality of life visual analogue scale and the GSRS questionnaire.

After signing informed consent and completion of screening procedures patient randomized into one of ten groups therapy for 10 people, of which 5 experimental groups, in which patients received oral claimed medicinal F. RMI based on IPP and prebiotic.

Patients kept a diary, in which daily noted the time of taking the drugs, the severity of the symptoms in the Likert scale, the severity of bloating, stool frequency, etc.

Repeated visits were carried out after 2 and 5 weeks after the start of treatment, when determined its efficacy and safety, and evaluated the possibility of continued therapy. After 56 days (8 weeks) after the start of therapy, the patient came for a visit, during which he evaluated the efficacy and safety of treatment, and it stopped. After 11 weeks after the start of treatment were performed final visit, including the conduct of EGDS with a fence biopsies of the antrum and body of the stomach for the detection of HP.

In all patients before treatment and after its completion (56 day) was evaluated in the presence of SYBR based on hydrogen breath test.

As a result of clinical studies have shown that used to treat the EMBLEM stated farmcampsite has a high therapeutic efficacy against H. pylori, and has a positive effect on the microflora 12 duodenal ulcer, stimulates the growth of lactobacilli, and thus, contributes to the prophylactics SYBR that is one of the determining factors of the effectiveness of the composition. These effects were manifested by the absence of translocation HP from intralingual the body of the stomach, prevention of the development of SIBR and significant decrease in adverse events of therapy. therapeutic efficacy of the claimed composition in respect of the main symptoms of GERD is superior to standard therapy with monotherapy IPP (1-10).

Table 1
The results of the study patients of the first groupn=10
Before the treatmentAfter the treatment
The severity of heartburn on the Likert scale, the score3,6±0,91,0±0,5
The severity of regurgitation on the Likert scale, the score3,4±1,11,1±0,4
Average time relieve heartburn day-7,9±3,3
The average duration of edema regurgitation day-7,0±3,0
The presence of diarrhea, %00
The presence of IU is erisma, %1010
The presence of SYBR, %1010
The selection of Helicobacter pylori in the antrum of the stomach, %10090
The selection of Helicobacter pylori in the body of the stomach, %2020
The quality of life for YOUR mm52,4±22,585,6±18,8
NYA, requiring cessation of therapy, %-0
-0

Table 2
The results of the study patients of group IIn=10
Before the treatmentAfter the treatment
The severity of heartburn on the Likert scale, the score3,5±0,81,1±0,4
The severity of regurgitation on the Likert scale, the score3,4±0,91,1±0,2
Average time relieve heartburn day-7,4±3,6
The average duration of edema regurgitation day-8,0±3,1
The presence of diarrhea, %010
The presence of flatulence, %2020
The presence of SYBR, %1010
The selection of Helicobacter pylori in the antrum of the stomach, %10090
The selection of Helicobacter pylori in the body of the stomach, %3020
The quality of life for YOUR mm55,9±19,6of 83.6±16,4

T the blitz 3
The results of the study patients group IIIn=10
Before the treatmentAfter the treatment
The severity of heartburn on the Likert scale, the score3,7±1,21,0±0,7
The severity of regurgitation on the Likert scale, the score3,5±0,91,0±0,5
Average time relieve heartburn day-7,9±3,5
The average duration of edema regurgitation day-8,0±3,3
The presence of diarrhea, %010
The presence of flatulence, %1020
The presence of SYBR, %1010
The selection of Helicobacter pylori in the antrum of the stomach, %10090
The selection of Helicobacter pylori in the body of the stomach, %2020
The quality of life for YOUR mm58,2±23,1to 88.4±15,9

The presence of flatulence, %
Table 4
The results of the study patients of group IVn=10
Before the treatmentAfter the treatment
The severity of heartburn on the Likert scale, the score3,5±1,11,2±0,5
The severity of regurgitation on the Likert scale, the score3,6±0,71,0±0,4
Average time relieve heartburn day-7,5±3,2
The average duration of edema regurgitation day-7,9±3,2
The presence of diarrhea, %010
1010
The presence of SYBR, %1010
The selection of Helicobacter pylori in the antrum of the stomach, %10090
The selection of Helicobacter pylori in the body of the stomach, %2020
The quality of life for YOUR mm56,2±24,187,4±16,9
NYA, requiring cessation of therapy, %0

Table 5
The results of the study patients group-Vn=10
Before the treatmentAfter the treatment
The severity of heartburn on the Likert scale, the score3,6±0,81,0±0,8

The severity of regurgitation on the Likert scale, the score3,7±0,71,1±0,3
Average time relieve heartburn day-7,8±3,3
The average duration of edema regurgitation day-8,0±3,0
The presence of diarrhea, %00
The presence of flatulence, %1010
The presence of SYBR, %1010
The selection of Helicobacter pylori in the antrum of the stomach, %10090
The selection of Helicobacter pylori in the body of the stomach, %3020
The quality of life for YOUR mm55,2±23,185,9±15,7
NYA, requiring cessation of therapy, %0

Table 6The results of the study patients group VIn=10Before the treatmentAfter the treatmentThe severity of heartburn on the Likert scale, the score3,6±0,81,2±0,6The severity of regurgitation on the Likert scale, the score3,5±1,21,1±0,3Average time relieve heartburn day-7,8±3,5The average duration of edema regurgitation day-7,5±3,4The presence of diarrhea, %020The presence of flatulence, %2060The presence of SYBR, %1050The selection of Helicobacter pylori in the antrum of the stomach, %100 100The selection of Helicobacter pylori in the body of the stomach, %2070The quality of life for YOUR mm58,1±18,9of 87.6±21,2NYA, requiring cessation of therapy, %0

Table 7
The results of the study patients group VIIn=10
Before the treatmentAfter the treatment
The severity of heartburn on the Likert scale, the score3.3V±0,51,0±0,4
The severity of regurgitation on the Likert scale, the score3,4±1,11,2±0,3
Average time relieve heartburn day-7,5±3,1
The average duration of edema regurgitation day -7,6±3,4
The presence of diarrhea, %020
The presence of flatulence, %1050
The presence of SYBR, %1040
The selection of Helicobacter pylori in the antrum of the stomach, %100100
The selection of Helicobacter pylori in the body of the stomach, %2080
The quality of life for YOUR mm58,1±18,9of 87.6±21,2
NYA, requiring cessation of therapy, %0

Table 8
The results of the study patients of group VIIIn=10
Before the treatmentAfter the treatment
The severity of heartburn on the Likert scale, the score3,4±0,7was 1.1±0.5
The severity of regurgitation on the Likert scale, the score3,6±1,11,1±0,2
Average time relieve heartburn day-7,8±3,3
The average duration of edema regurgitation day-7,7±3,2
The presence of diarrhea, %020
The presence of flatulence, %1060
The presence of SYBR, %1050
The selection of Helicobacter pylori in the antrum of the stomach, %100100
The selection of Helicobacter pylori in the body of the stomach, %2070
The quality of life for YOUR mm57,4±17,584,2±21,5
NYA, requiring the termination the of therapy, %0

Table 9
The results of the study patients in group IXn=10
Before the treatmentAfter the treatment
The severity of heartburn on the Likert scale, the score3,6±0,71,2±0,6

The severity of regurgitation on the Likert scale, the score3,5±1,11,1±0,3
Average time relieve heartburn day-7,8±3,5
The average duration of edema regurgitation day-7,5±3,4
The presence of diarrhea, %020
The presence of flatulence, %2050
The presence of SYBR, %1040
The selection of Helicobacter pylori in the antrum of the stomach, %100100
The selection of Helicobacter pylori in the body of the stomach, %2080
The quality of life for YOUR mm58,5±20,2of 87.3±19,5
NYA, requiring cessation of therapy, %0

Average time relieve heartburn day
Table 10
The results of the study patients X groupn=10
Before the treatmentAfter the treatment
The severity of heartburn on the Likert scale, the score3,5±0,91,1±0,2
The severity of regurgitation on the Likert scale, the score3,6±1,11,3±0,1
-7,7±3,1
The average duration of edema regurgitation day-7,2±3,1
The presence of diarrhea, %020
The presence of flatulence, %1060
The presence of SYBR, %1050
The selection of Helicobacter pylori in the antrum of the stomach, %100100
The selection of Helicobacter pylori in the body of the stomach, %2080
The quality of life for YOUR mm58,1±18,9of 87.6±21,2
NYA, requiring cessation of therapy, %0

The results of clinical trials to objectively demonstrate the effectiveness of the treatment of GERD by applying the oral administration of the claimed pharmaceutical compositions comprising as active the x components of the IPP and a prebiotic. Increase the quality of life on treatment was comparable in the groups. It is noted that the inclusion in the scheme of prebiotic therapy reduces the frequency of translocation HP from the antrum into the body of the stomach due to the colonization of the antrum, lactobacilli and competitive inhibition of H. pylori. In addition, patients who received the prebiotic marked reduction in the incidence of SYBR due to stimulation of growth of normal microflora in patients.

High clinical efficacy and safety, due to the synergistic action of the proton pump inhibitor and prebiotic in the upper GI and no side effects indicate that the claimed composition is a new promising tool for the treatment of GERD, not previously known from the previous level of technology.

The claimed composition may be made on farmaceutica.com production using standard equipment.

1. Pharmaceutical composition for the treatment of gastroesophageal reflux disease containing composition, at least one proton pump inhibitor (PPI) and at least one prebiotic in the following components of the composition, wt.%:

the proton pump inhibitorof 0.05-25
prebiotic10-95
excipients100

2. The pharmaceutical composition according to claim 1, characterized in that the composition contains a prebiotic from the group of aliphatic alcohols include xylitol, sorbitol, lactitol or contains a prebiotic from the group of di - and trisaccharides: lactulose, lactosucrose, melibiose, kilobyte, stachyose, raffinose, or contains the prebiotic group oligosaccharides: fructooligosaccharide, galactooligosaccharide, maltooligosaccharide, xylooligosaccharide, isomaltooligosaccharide, gentilhombre, or contains a prebiotic from the group of polysaccharides: arabinogalactan, pectin, pullulan, inulin.

3. The pharmaceutical composition according to claim 1, characterized in that it contains a proton pump inhibitor from the group of: omeprazole, pantoprazole, lansoprazole, rabeprazole, esomeprazole and dexlansoprazole.

4. The pharmaceutical composition according to claim 1, characterized in that the composition is made in a dosage form for oral administration: suspension for oral administration, solution for oral administration, capsules, tablets, powders, sachets, pellets, granules.

5. A method of treating gastroesophageal reflux disease in which the presence of N. pylori does not require eradication for the prevention of risks associated with translocation of bacteria from the antrum in the what about the stomach, what is achieved enteral intake of the pharmaceutical composition of the proton pump inhibitor and prebiotic performed according to any of claims 1 to 4, at least once a day during the period determined by the form of the disease, but not less than 4 weeks.



 

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FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention refers to a pharmaceutical composition of such an active agent, as sucralfate for treating disorders, e.g. gastric ulcers, duodenal ulcers, acute gastritis, symptomatic chronic gastritis, gastropathy caused by the intake of anti-inflammatory agents, gastroesophageal reflux disease characterised by the fact that is contains one or more phospholipids.

EFFECT: invention refers to using phospholipids in a combination with the above active agents when administered orally for the purpose of improving the taste of the preparation, and to using phospholipids in a combination with the above active agents when administered orally for the purpose of treating disorders, including gastrointestinal irritation, for the synergetic enhancement of the anti-ulcer effect.

19 cl, 15 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to pharmaceutical industry, and represents a nice to taste solid composition for treating or preventing gastric distresses or such diseases, as acid indigestion, epigastric burning, or gastritis, containing at least one de-acidifier and neutral salivation stimulator, with the neutral salivation stimulator specified in hydrotalcite, calcium carbonate, magnesium hydroxide, magnesium oxide, magnesium carbonate, sodium bicarbonate or mixtures thereof, and the neutral salivation stimulator is specified in Pellitorine.

EFFECT: invention provides nice taste, no taste of chalk in the mouth or teeth.

8 cl, 6 ex

FIELD: medicine.

SUBSTANCE: invention refers to medicine, namely to surgery, and may be used for prevention of acute postoperative pancreatitis. For this purpose, the underlying background therapy is combined with intravenous bolus administration of dalargin 0.002 g and the antioxidant thioctic acid depending on a risk level of the complication measured in terms of the area of intervention in abdominal operations. A high risk level requires thioctic acid to be administered in a dose of 600 mg intravenously drop-by-drop 1 hour before the operation and on the following day, and thioctic acid in a dose of 300 mg on the third day intravenously drop-by-drop. In a moderate risk level thioctic acid is administered intravenously drop-by-drop in a dose of 600 mg 1 hour before the operation and in a dose of 300 mg on the following day. And in a low risk level, thioctic acid is administered intravenously drop-by-drop in a dose of 300 mg 1 hour before the operation.

EFFECT: method enables the more effective prevention of acute postoperative pancreatitis ensured by the combined use of drugs with antisecretory and antioxidant activity.

2 tbl, 3 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: controlled release solid preparation contains a combination of (1) an antacid, (2) an immediate release portion containing a proton pump inhibitor, preferentially lansoprazole, and a basic substance, and (3) a delayed release portion comprising a proton pump inhibitor and a pH-independent material.

EFFECT: solid preparation according to the invention shows an increase in gastric pH up to 4 or higher 0,5 h after oral administration into a mammal and a retention time at pH 4 or higher for at least 14 hours a day.

16 cl, 8 ex

FIELD: medicine.

SUBSTANCE: invention refers to medicine, namely to gastroenterology, laser therapy. The method involves administering the drugs: a proton pump inhibitor and a prokinetic accompanied by laser therapy. The proton pump inhibitor is presented by Controloc 20 mg 2 times a day. Gaviscon is administered in a dose of 2 tablets 3 times a day daily. Trimedat 200 mg is administered 3 times a day. The laser therapy is differentiated. That involves taking into account a severity of gastroesophageal reflux disease, a degree of manifestation of endothelial dysfunction and a severity of upper gastrointestinal motor dysfunction. The manifestation of endothelial dysfunction is shown by the contents of nitrogen oxide, pro-inflammatory, namely IL-1β, IL-6, TNF-α and anti-inflammatory, namely IL-4 cytokines. The degree of upper gastrointestinal motor dysfunction is shown by a stomach/duodenum ratio Pi/P(i+1). A mild degree of gastroesophageal reflux disease implying the levels of nitrogen oxide 35.2±2.7 mcmole/l and more, IL-1β 1.5±0.3 pg/ml or more, IL-6 1.8±0.8 pg/ml or more, TNF-α 2.78±0.35 pg/ml or more, IL-4 4.4±0.42 pg/ml or less, the ratio Pi/P(i+1) of 11.2±5.6% or less requires 6-7 daily procedures of the intravenous laser blood irradiation. The exposure length is 15 minutes at wave length 0.405 mcm, end face output density 1-1.5 mWt, pulse frequency 80 Hz, in a continuous mode. The moderate or severe gastroesophageal reflux disease with the levels of nitrogen oxide less than 35.2.2±2.7 mcmole/l, IL-1β 1.83±0.3 pg/ml or less, IL-6 1.98±0.8 pg/ml or less, TNF-α 10.04±2.84 pg/ml or less, IL-4 3.15±0.43 pg/ml or more, the ratio Pi/P(i+1) of 12.3±4.8% or more requires 9-10 daily procedures of the intravenous laser blood irradiation. The exposure length is 15 minutes at wave length 0.405 mcm, end face output density 1-1.5 mWt, pulse frequency 80 Hz, in a continuous mode.

EFFECT: method reduces the drug-induced load, reduces the length of treatment.

3 tbl, 3 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to chemical-pharmaceutical industry, particularly to a composition containing i) fenofibric acid or a physiologically acceptable salt thereof representing a salt formed with a base, ii) a binding ingredient or a combination of binding agents. Also, the invention concerns a capsule containing the above composition.

EFFECT: preparing the new composition.

27 cl, 16 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to medicine, namely to pharmaceutical compositions for treating urination disturbance that is a syndrome manifested by frequent urination, urinary incontinence, urine retention, etc. The pharmaceutical composition contains an anticholinergic preparation that is diphenyl-acetic acid tropine ester, and preparations of the other mode of action, including Tamsulosin hydrochloride or calcium channels or baclofen in the form of prolonged release tablets or capsules or transdermal dosage forms (gels, ointments or plasters).

EFFECT: using the invention enables extending the range of therapeutic agents and improving the clinical effectiveness in urination disturbances accompanying a variety of common urological, neurological and gynaecological conditions alongside with improving the quality of life in patients with the urination disturbance.

4 cl, 24 tbl, 3 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to pharmaceutics, particularly to solid pharmaceutical compositions for the immune system suppression and multiple sclerosis treatment. The pharmaceutical composition exhibiting improved flowability contains a S1P receptor modulator representing 2-amino-2-[2-(4-octylphenyl)ethyl]propane-1,3-diol or a pharmaceutically acceptable salt thereof, lactulose, polyethylene glycol-6000 and polyvinylpyrrolidone. What is also described is a drug preparation containing 2- amino-2-[2-(4-octylphenyl)ethyl]propane-1,3-diol or a pharmaceutically acceptable salt thereof, in the form of a tablet or capsule, placed in pharmaceutically acceptable package, and a method for preparing the drug preparation for oral administration.

EFFECT: invention provides a uniform distribution of the active ingredient in the solid composition, high stability and improved flowability of the solid pharmaceutical composition; the improved flowability of the composition presented in the invention enables using the same on automated equipment.

15 cl, 1 tbl, 4 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: group of inventions refers to capsule suspensions prepared by coacervation, and to methods for reducing leakage of the capsule content in such suspensions during storage. Substance of the method for reducing leakage of the capsule content consists in storage of the capsules prepared by coacervation, in the capsule suspension containing min. 20 wt %, a moisturiser, which is at least a moisturiser specified in sorbitol, glycerol, polyethylene glycol, propylene glycol, xylitol, erythritol or betaine. What is also presented is the above capsule suspension containing at least one capsule prepared by coacervation and at least 20 wt % of the above moisturiser.

EFFECT: using the above moisturiser in the amount of min 20 wt % provides reducing the leakage rate of the capsule content.

21 cl, 4 tbl, 2 ex, 2 dwg

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to medicine and chemical-pharmaceutical industry, namely to using ipidacrine as an agent for treating disturbed potency.

EFFECT: pharmaceutical composition of ipidacrine represents a tablet, including a prolonged action tablet, or a solid gel capsule.

4 cl, 4 ex, 3 dwg

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to a synergetic preparation for treating cardiovascular insufficiency, types I and II diabetes mellitus, hepatobiliary diseases, containing a combination of a pharmaceutically acceptable salt of 2-ethyl-6-methyl-3-pyridin-3-ole and taurin in the amount of 2-75% and pharmaceutically acceptable carriers, excipients and additives with the mass ratio of the active ingredients of the combination making 9:1 to 1:9. The preparation may be presented in the form of a tablet, a capsule or a solution for injections. The invention also refers to a method of treating cardiovascular insufficiency, types I and II diabetes mellitus, hepatobiliary diseases wherein the therapeutically effective amount of the synergetic preparation is administered to the patient.

EFFECT: preparations possess the higher efficacy as compared to the common analogues.

5 cl, 7 tbl, 7 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: per oral pharmaceutical drug form, in composition of which included are at least two medical substances in from of separately preliminarily formed pills. In claimed form medicinal substances from one side are together in hermetically in vivo water-soluble wrapping or coating, and from the other side are separated in such a way, that active agents of combined medicinal substances cannot contact with each other. At least one of medications is selected from the following groups of therapeutic medications: non-steroidal anti-inflammatory preparation (NAIP), inhibitor of proton pump (IPP), beta-blocker, statin, conversion enzyme inhibitor (CEI), biguanide, neuromuscular blocking agent, calcium inhibitor, corticoid, antidepressant, benzodiazepine, inhibitor of intestinal transit of non-atropine-like action, intestinal antibacterial medication, and following therapeutic molecules: spironolactone, propranolol, clarithromycin, amoxicillin, low dose acetylsalicylic acid, potassium, clopidogrel.

EFFECT: pharmaceutical drug form by invention ensures patient with one drug form for several medicinal preparations, which makes it possible to avoid separate introduction of medicinal preparations.

21 cl, 7 dwg

FIELD: medicine, pharmaceutics.

SUBSTANCE: what is disclosed is a pharmaceutical formulation containing an active agent stabilising an amorphous form of imatinib mesylate, and amorphous imatinib mesylate. The active agent is selected from solid dispersions, and dry co-milling products with excipients. The solid dispersion contains an additional excipient selected from cellulose derivatives, polyvinylpyrrolidone, polyethylene glycols of various molecular weight, polyethylene/polypropylene/polyethylene oxide block copolymers, and polymethacrylates. The excipients for dry co-milling selected from polyvinylpyrrolidone, cellulose derivatives, alkaline earth silicates, and silicon dioxide.

EFFECT: active agents stabilise imatinib mesylate in the amorphous form.

3 cl, 4 tbl, 5 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to medicine and chemical-pharmaceutical industry, namely to neurology, and concerns new compositions containing memantine and melatonin. It is possible to implement the invention by preparing a solid dosage form, such as a tablet or capsule.

EFFECT: intensified effect of memantine when combined with melatonin.

10 cl, 5 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to pharmaceutical industry, namely to a solid pharmaceutical composition for oral administration on the basis of taxane. The solid pharmaceutical composition for oral administration contains amorphous taxane, a hydrophilic carrier and a surfactant (sodium dodecylsulphate (SDS)), with specific weight proportions of taxane and the carrier with taxane, the carrier and the surfactant found in a solid dispersion. The use of the composition for preparing a drug for treating a neoplastic disease. A method for preparing the pharmaceutical composition.

EFFECT: pharmaceutical composition is characterised by higher solubility and higher dissolution rate of taxane.

16 cl, 21 dwg, 18 tbl, 5 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to chemical-pharmaceutical industry, particularly to a composition containing i) fenofibric acid or a physiologically acceptable salt thereof representing a salt formed with a base, ii) a binding ingredient or a combination of binding agents. Also, the invention concerns a capsule containing the above composition.

EFFECT: preparing the new composition.

27 cl, 16 ex

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