Use of the drug "Pepsan-R" in the treatment of gastroesophageal reflux disease

Use of the drug "Pepsan-R" in the treatment of gastroesophageal reflux disease

O. Minushkin, Doctor of Medical Sciences, Professor, I. Loranskaya, Doctor of Medical Sciences, Professor, I. Zverkov, Doctor of Medical Sciences, Professor, L. Rakitskaya, Candidate of Medical Sciences, L. Mamedova, Candidate of Medical Sciences, V. Vishnevskaya, Candidate of Medical Sciences, L. Maslovsky, Doctor of Medical Sciences,

Department of Gastroenterology, MC UD of the President of the Russian Federation,

The anti-inflammatory effect of the drug “Pepsan-R”, new to the Russian Federation, was assessed, treatment of which was received by 50 patients with gastroesophageal reflux disease (GERD) grades 0–1. Treatment was carried out in monotherapy mode. The drug contains 2 active ingredients: guaiazulene and dimethicone. Its mechanism of action is to suppress the degranulation of mast cells and create a protective layer on the mucous membrane of the esophagus and stomach. The effectiveness of the drug has been clinically demonstrated in 100% of patients (10% of them required an increase in the dose of the drug). Morphoendoscopically positive dynamics over 4 weeks were noted in 50% of patients. No side effects have been reported. Key words : gastroesophageal reflux disease, treatment, Pepsan-R.

* The drug underwent pre-registration studies at 2 centers: the Department of Gastroenterology of the MC UD of the President of the Russian Federation and the Department of Gastroenterology of the Russian Medical Academy of Postgraduate Education.

Reflux is the reflux of contents from the underlying sections of the gastrointestinal tract to the overlying ones in places of physiological narrowings (sphincters) separating physiologically and anatomically different sections of the digestive tract; reflux leads to irritation, inflammation and structural changes in the areas of reflux with the formation of certain clinical manifestations (our definition, 1986).

In clinical practice, they distinguish: gastroesophageal, duodenal-gastric reflux and reflux from the large intestine to the small intestine through the ileocecal valve.

The true incidence of reflux and its clinical significance are unknown. Maximum importance is attached to gastroesophageal reflux, which is most likely due to the most studied clinical manifestations and diagnostic approaches.

The Genval Conference (1999) stated: “The term “gastroesophageal reflux disease” can be used to encompass all individuals who are at risk of physical complications from gastroesophageal reflux or who experience clinically significant impairment of well-being (quality of life) due to reflux-related symptoms after adequate confirmation of the benign nature of these symptoms." Finally, the Montreal Congress of Gastroenterology (2006) defines gastroesophageal reflux disease (GERD) “as a condition that occurs when reflux of stomach contents causes distressing symptoms and/or complications.”

From the definitions it is clear that ideas about GERD are dynamic. This dynamism continues to this day, which is determined by unsatisfactory treatment results.

Thus, until 1995, GERD was associated with erosive reflux esophagitis, the treatment of which was a course of treatment. In 1995, it became clear that the effect of treatment was temporary, and the question arose about prolonged treatment, albeit for certain groups of patients. By 1999, the final point of view had emerged: treatment should be permanent or should begin in the early period of the disease. At the same time, the early stage of GERD was identified - non-erosive reflux disease. Did this solve all the problems? No! But new ones have been born, the solution of which is being addressed by modern gastroenterology.

It has been established that the main mechanism for the development of GERD is a dysfunction of the antireflux barrier, in which the leading role belongs to a decrease in the tone of the lower esophageal sphincter, insufficiency of the obturator mechanism of the cardia, a decrease in esophageal clearance (chemical and peristaltic) and a decrease in the resistance of the esophageal mucosa.

Increased intragastric and intra-abdominal pressure and destruction of the lower esophageal sphincter are considered factors contributing to the development of GERD; consumption of certain foods (coffee, chocolate, citrus fruits, fats) and taking medications (nitrates, antispasmodics, β-blockers, etc.). Under these conditions, reflux of gastric or duodenal contents with damaging agents takes on a decisive role. Gastric juice contains hydrochloric acid and pepsin, which, when they enter the esophageal mucosa, weaken intercellular contacts, widen intercellular spaces, disrupt intercellular interaction, which leads to damage to the esophagus. A protective reaction is the arrival of polymorphonuclear leukocytes to the site of damage, which cannot cope with the protective function, since the aggression factor is not eliminated, lipid peroxidation (LPO) products and free radicals appear, which contribute to aggression [4]. Acid aggression in the esophagus promotes the activation of fat cells, then an increase in their number and degranulation with the release of inflammatory mediators, primarily histamine [2], and, finally, a decrease in the pH of the environment triggers the mechanism of reverse diffusion of hydrogen ions. The consequence of the triggering of the damage mechanism is necrosis of the esophagus with the formation of erosions, and subsequently ulcers of the esophageal mucosa.

In some patients with GERD, it is not the acid that is released, but the alkaline content. In this case, the damaging agents are bile acids and pancreatic enzymes, which are activated in an alkaline environment, and with prolonged exposure lead to the destruction of protective mucus, damage to the epithelium, activation of inflammation, cell damage, the formation of erosive and ulcerative changes, and at later stages - to intestinal metaplasia, dysplasia, neoplasia.

Treatment of GERD primarily involves: avoiding foods that reduce the tone of the lower esophageal sphincter or have an irritating effect (fats, chocolate, mint, spices, onions, coffee, alcohol, orange and tomato juices); a recommendation to avoid a horizontal body position for 3–4 hours after eating; raising the head end of the bed; smoking cessation; loss of body weight if it is excess; refusal to wear tight clothing; if possible, stop taking medications that reduce the tone of the lower esophageal sphincter (antispasmodics, β-blockers, nitrates, anticholinergic drugs, calcium antagonists, theophylline, etc.).

Drug therapy is prescribed in case of ineffectiveness of lifestyle modification measures in the negative form of GERD and immediately in the erosive form of GERD and Barrett's esophagus. Antisecretory drugs are used as basic therapy: H2 receptor blockers or proton pump inhibitors; prokinetics are of auxiliary value. Having achieved a clinical or clinical-endoscopic effect, the patient is transferred to long-term maintenance treatment (minimum effective doses). At the same time, according to the Maastricht III recommendations, in the presence of persistent Helicobacter pylori (Hp) infection, it is necessary to carry out eradication therapy to prevent the migration of Hp, the development of infectious gastritis of the gastric body and the acceleration of mucosal atrophy.

We studied the clinical effectiveness of the drug "Pepsan-R" in the uncomplicated form of GERD (grades 0–1).

The objectives of the study included assessment of clinical and economic indicators during treatment with the drug, drug safety, and development of effective treatment regimens.

The drug "Pepsan-R" contains 2 active ingredients: guaiazulene (an azulene derivative) and dimethicone. Available in gel form or capsules for oral administration. Guiazulen is a chamomile extract. Currently, it is obtained by clinical synthesis. The mechanism of its action is represented by the suppression of degranulation of fat cells, a decrease in the level of histaminase and histamine at the tissue level, which is manifested by its anti-inflammatory effect, and at the level of smooth muscle fibers - by their relaxation. These effects are shown in the works of M. Akagi [1]. According to studies by A. Kouzounakis [3], in vitro, guaiazulene has an antioxidant effect on the membranes of liver microsomes, suppressing lipid peroxidation, which also contributes to the development of inflammation.

The second component of the drug is dimethicone, which is a hydrophobic polymer substance with low surface tension, which reduces gas formation (destroys the shell of gas bubbles and enhances gas removal), i.e. influences bloating and associated clinical manifestations.

All effects of Pepsan-R can be summarized as follows:

• reduces the level of histaminase and histamine;
• suppresses mast cell degranulation;
• has anti-inflammatory and anti-edema effects;
• reduces the aggressive properties of refluxate (reducing the acid-producing function of the stomach);
• shortens the exposure time of refluxate in the esophagus;
• reduces irritation and inflammation of the esophageal mucosa by binding free radicals;
• forms a protective layer on the mucous membrane of the esophagus and stomach;
• eliminates flatulence and reduces the number of gastroesophageal refluxes;
• acts throughout the entire “intestinal tube”.

The study included 50 patients, divided into 2 groups of 25 patients each, with an average age of 46.1±5.2 years.

Concomitant diseases were in remission, without signs of decompensation, and no additional prescriptions were required. Patients of group 1 received the drug in the form of a gel, 1 sachet after each meal; if necessary, they could take an additional sachet if the heartburn did not stop, but not earlier than 15 minutes after the 1st dose.

Patients of the 2nd group received capsules (1 after each meal; they could take an additional capsule if the effect did not occur). In 1 day, no more than 6 capsules or gel packets were allowed. The treatment lasted 28 days.

Endoscopic monitoring was carried out initially, on the 14th and 28th days of treatment. Clinical symptoms were assessed initially and over time using a 5-point Likert scale with calculation of average scores (on days 1, 14, 28 of the study):

• 1 point – no symptoms;
• 2 points – low intensity (you can’t notice it if you don’t think about it);
• 3 points – moderate severity of symptoms (cannot be ignored, but do not interfere with daytime activity or sleep);
• 4 points – severe intensity (symptoms interfere with daytime activity or sleep);
• 5 points – very strong intensity (daytime activity or sleep is impossible).

Endoscopic pH-metry was performed initially.

Statistical processing of the results included calculating the arithmetic mean and standard deviation, applying the Student's test, and determining the significance of differences between groups.

Patients kept daily diaries with an assessment of the main symptoms: heartburn, burning sensation in the chest, belching.

In the 1st group of patients who took Pepsan-R in the form of a gel, GERD was manifested by heartburn (3.5±0.17 points), belching (2.9±0.18 points), burning sensation in the sternum (2.2± 0.2 points). In group 2 (taking Pepsan-R capsules), the average Likert scale score before treatment was: for heartburn - 3.2±0.21, for belching - 2.4±0.34, for burning sensation in the chest - 1 .7±0.26. There were no significant differences between the groups in these indicators; The pH in the lower third of the esophagus in both groups was >5.

According to endoscopy, the patients were divided approximately equally (negative forms, catarrhal esophagitis; erosive esophagitis was recorded in 6 patients - single erosions).

The average dose of the drug was 3.6 capsules and 3.7 sachets per day; 6 patients received 6 sachets or 6 capsules per day (about 10% of patients).

The dynamics of clinical symptoms during treatment with Pepsan-R are presented in the table.

Assessment of clinical symptoms during treatment with Pepsan-R (M±m)

As can be seen from the table, on the 14th day of treatment in the 1st group of patients receiving the gel, heartburn was assessed at 3.0±0.21 points, belching – at 2.5±0.22 points, burning sensation in the sternum – at 2.0±0.37 points (differences with indicators before treatment are significant only for heartburn; p=0.0149).

In group 2 (Pepsan-R capsules), heartburn was rated at 2.5±0.25 points, belching – at 2.1±0.28 points, burning sensation behind the sternum – at 1.4±0.22 points ( the differences are significant only for heartburn before treatment and on the 14th day of treatment; p = 0.0031).

On the 28th day of treatment in group 1, the average score for heartburn was 2.4±0.22, for belching - 2.1±0.28, for burning sensation in the chest - 1.7±0.30. Only the heartburn indicator was significantly different from that on the 1st day (before treatment) and on the 14th day of treatment (p = 0.0051). For belching, a significant difference was observed only between the 1st and 28th days of treatment (p = 0.02236) and the same for burning behind the sternum (p = 0.0149).

In group 2 (capsules), after completion of treatment, the average score for heartburn was 1.6±0.27, for belching - 1.7±0.21, for burning sensation in the chest - 1.1±0.10. For heartburn, this indicator was significantly different from that on day 1 (p = 0.00075). For belching, there was a significant difference between the initial position and the 14th day of treatment (p = 0.0367), for a burning sensation in the chest - between the initial position and the 28th day of treatment (p = 0.0239).

The assessment of the therapeutic effectiveness of Pepsan-R on a Likert scale is presented in Fig. 1 and 2. The figures show that a significant decrease in the intensity of all clinical symptoms was recorded during treatment with Pepsan-R (gel, capsules).

Rice. 1. Assessment of therapeutic effectiveness on the Likert scale of the drug “Pepsan-R” (gel)

Rice. 2. Assessment of therapeutic effectiveness on the Likert scale of the drug “Pepsan-R” (capsules)

When comparing the effectiveness of treatment in groups 1 and 2 on the 28th day of treatment, a significant difference was found only for heartburn. For other indicators, no significant difference was obtained (p=0.276 and p=0.0738).

Lack of clinical effect was noted in 2 patients; In 1 patient, treatment could not be completed due to the development of urticaria (on the 25th day of treatment).

A control endoscopic study recorded positive dynamics (endoscopic signs of catarrhal esophagitis disappeared in half of the patients).

GERD today is not only the most common gastroenterological pathology, but also the most difficult in therapeutic terms. Due to the instability of the effect of a course of treatment, a permanent treatment option has been adopted as the main one, which is typical for diseases whose nature is not completely clear.

For GERD, secretion blockers are used, which reduce the aggressiveness of reflux, and agents that regulate the tone and motility of the esophagus and sphincters, reducing reflux into the esophagus. These two links are very important for the initiation and formation of the disease, but its inflammatory morphological substrate remains without direct influence.

Clinical and morpho-endoscopic data from the study allow us to hope that the drug "Pepsan-R" can take its rightful place in the complex therapy of GERD, since, thanks to its mechanism of action, it reduces the content of the inflammatory mediator - histamine, blocking the degranulation of mast cells.

The results of the study allow us to draw the following conclusions:

1. Pepsan-R reduces and relieves symptoms in the vast majority of patients with GERD stage 0–I. 10% of patients need to increase the standard dose: 3 capsules (sachets) per day to 6 capsules (sachets).
2. Positive endoscopic dynamics over 28 days of treatment were observed in 50% of patients.
3. The drug was well tolerated; adverse reactions (urticaria) were noted in 1 (2%) patient.
4. The drug can and should be used in complex therapy of GERD and in maintenance treatment.

Literature

1. Akagi M., Matsui N., Mochizuki S. et al. Inhibitory 1. effect of egualen sodium: a new stable derivative of azulen on histamine release from mast cell – like cells in the stomach // Pharmacology. – 2001; 63(4):203–209.
2. Barclay RL, Dinda PK, Morris GP et al. Morphological evidence of mast cell degranulation in an animal model of acid-induced esophageal mucosal injuri // Dig Dis Sci. – 1995; 40(8):1651–1658.
3. Kourounakis AP, Rekka EA, Kourounakis PN Antioxidant activity of guaiazulene and protection against paracetamol hepatoxicity in rats // J. Pharm. Pharmacol. – 1997; 49(9):938–942.
4. Oh TY, Lee JS, Ahn BO et al. Oxidative damages are critical in the pathogenesis of reflux esophagitis: implication of antioxodants in its treatment // Free Radic Biol Med. – 2001; 30(8):905–915.

Pepsan-R

Pepsan-R is a combined drug in the form of a gel or capsules for oral use that reduces the formation of gases in the gastrointestinal tract and promotes their elimination during flatulence. Unfavorable environmental conditions, a large proportion of synthetic products in the diet - all these factors contribute to the more frequent development of dyspeptic disorders, including heartburn, belching, epigastric pain and increased gas formation. These problems can be eliminated by Pepsan-R from the French pharmaceutical company. Dimethicone, which is part of the drug, is the so-called. defoamer. It eliminates heaviness in the stomach, flatulence, bloating, and also forms a protective film on the mucous membrane of the digestive tract. Another component of the drug, a substance of plant origin, guaiazulene, exhibits anti-inflammatory and anti-allergic effects, helps accelerate regeneration processes, and acts as an antioxidant. It prevents the release of histamine from mast cells in the gastric mucosa, thereby suppressing the secretion of hydrochloric acid. Pepsan-R is indicated for the symptomatic treatment of epigastric pain of various natures, incl. with increased acidity of the stomach, heartburn, ulcerative-erosive lesions of the mucous membrane of the digestive tract, inflammation of the esophagus, stomach, duodenum. Pepsan-R is sold from pharmacies without a prescription. The drug can be used both as monotherapy and in complex treatment of diseases of the digestive tract in combination with other drugs.

Another area of ​​application of Pepsan-R is as an adjuvant before diagnostic measures (radiography, ultrasound of the abdominal cavity). The advantages of the drug include the absence of an effect on the transit of intestinal contents and on the absorption of other drugs from the gastrointestinal tract, the absence of sugar in the composition (which allows its use in patients with diabetes), and the possibility of use in elderly patients. The drug is contraindicated in case of individual intolerance to the components. Pregnancy and lactation are not contraindications to taking Pepsan-R. Single dose - 1 sachet (a type of packaging in the form of a small flat bag). Frequency of use: 2-3 times a day. The optimal time to take it is before meals or in case of stomach pain. The medication course is determined on an individual basis. Dosage regimen in preparation for diagnostic instrumental examinations of the abdominal cavity: 1 dose 2-3 times a day preceding the examination and 1 dose in the morning on the day of the examination. A single dose for Pepsan-R in capsule form is 1 capsule. The dosage regimen is the same as for the gel. Possible side effects: allergies (if individual intolerance), bloating.