RU2755707C1 - Agent for correcting dyspeptic disorders of the gastrointestinal tract - Google Patents

Abstract

FIELD: pharmaceuticals.

SUBSTANCE: invention relates to the field of pharmaceuticals, namely to an agent for correcting dyspeptic disorders of the gastrointestinal tract. The agent contains arabinogalactan from siberian larch in an amount of 20 to 40 wt.% and lecithin from sunflower in an amount of 60 to 80 wt.%

EFFECT: ensures production of a preparation containing arabinogalactan and lecithin, wherefor there are practically no side effects, a convenient form for administration in capsules is created, the frequency of administration is reduced to twice per day, the cost of treatment is reduced compared to analogues, a persistent long-term therapeutic effect is noted - the absence of dyspeptic events for 6 to 12 months after preparation withdrawal.

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Description

The proposed invention relates to medicine, namely to therapy, and can be used to correct intestinal dyspepsia, including after antibiotic and chemotherapy.

The intestinal microbiota has attracted increasing attention of researchers in recent years. Its role for the human body can hardly be overestimated. It performs a protective function, participates in digestion, synthesis of vitamins, detoxification, affects intestinal motility and absorption processes, and has immunomodulatory properties. The balance of the intestinal microflora is easily disturbed by external factors, most often when using antibacterial drugs.

Antimicrobials are among the most commonly prescribed group of drugs in clinical practice. Given that bacterial infections can lead to serious and even life-threatening complications, practitioners, when prescribing antibiotic therapy, strive to achieve maximum effectiveness, often not paying sufficient attention to unwanted drug reactions that occur while taking antibiotics. Among such reactions, in the first place are disorders of the gastrointestinal tract, in particular, antibiotic-associated diarrhea.

Other drugs that aggressively affect the organs of the gastrointestinal tract are chemotherapeutic agents used in oncology. Considering that malignant tumors occupy one of the leading places in terms of prevalence in the world, the issue of leveling the side effects of cytostatic therapy and subsequent rehabilitation is undoubtedly relevant. In the professional environment of oncologists and hematologists, gastrointestinal lesions against the background of chemotherapy are designated by the term "mucositis", the common manifestations of which are pain and dyspeptic syndromes, as well as the development of pathological microflora against the background of immunosuppression. (Ardatskaya M.D. et al. Antibiotic-associated intestinal lesions in the practice of a clinician // Manual for physicians. M .: Prima Print. - 2020; Donush E.K. et al. Diagnostics and treatment of gastroenterological complications of chemotherapy in oncohematological patients in pediatric practice // Attending physician. - 2017. - No. 1. - P. 27 .; Kovaleva Yu.S. et al. Prospects for the creation of combined drugs to correct the composition of the intestinal microflora. - 2017.)

Various drugs are used to correct dyspeptic phenomena associated with antibiotic and chemotherapy. In particular, probiotics are known. Probiotics are potentially beneficial bacteria (rarely yeast) found in normal intestinal microflora. A striking example of a probiotic drug is Linex® Forte (Plotnikova E.Yu., Zakharova Yu.V., Gracheva T.Yu. Possibilities of using Linex® Forte in clinical practice with systemic antibiotic therapy // Medical Council. - 2017. - No. 5. ). The drug normalizes the intestinal microflora. One capsule of Linex Forte contains 2 × 109 colony-forming units of live lyophilized lactic acid bacteria: Lactobacillus acidophilus (LA-5) and Bindobacterium animalis subsp.lactis (BB-12). Live lactic acid bacteria are a normal component of the natural intestinal microflora.

Lactic acid bacteria perform a protective function, synthesizing substances with antibacterial activity, producing enzymes under the influence of which hydrolysis of cellulose, proteins, fats, starch and deconjugation of bile acids occurs, and also participate in the synthesis of vitamins of group B, C, K, amino acids, organic acids.

Lactic acid bacteria LA-5 and BB-12 inhibit the growth of pathogenic bacteria by: shifting the intestinal pH to the acidic side (the result of the ability of LA-5 to synthesize lactic acid and BB-12 to synthesize acetic and succinic acids in addition to lactic acid); the production of metabolites that have a toxic effect on pathogenic bacteria (formation of H2O2); the formation of antimicrobial substances, bacteriocins (LA-5 secretes acidocin, a broad-spectrum bacteriocin that inhibits the growth of bacteria and fungi); competition with pathogenic bacteria for nutrients; interactions with adhesion receptors, thus preventing the colonization of other, potentially pathogenic microorganisms.

Lactic acid bacteria, such as LA-5 and BB-12, act directly in the gastrointestinal tract; when taken orally, the drug does not undergo systemic absorption. Routine pharmacokinetic studies are therefore not applicable. The resistance of LA-5 and BB-12 to the effects of gastric juice and bile allows strains in large quantities to remain viable when passing through the stomach and duodenum. Both strains attach to the intestinal mucosa. Like other microorganisms, they are gradually excreted from the gastrointestinal tract with feces.

Linex Forte is generally well tolerated. However, when it is used, side effects are still observed (for example, rash, nausea, gas, flatulence, bloating, constipation). Despite the fact that Linex Forte is the leading one in the arsenal of means for correcting disorders of intestinal microbiocenosis, the response of representatives of the intestinal microbiota to the enteral intake of probiotic microorganisms is variable, and in some individuals it may be absent. Scientists still disagree about the need for forced colonization of the normal microbiota in case of intestinal dysbiosis, since the composition of the microbiota normally differs among individuals.

The closest analogue is the method of using prebiotics - physiologically active food ingredients in the form of a substance or a complex of substances that, when systematically consumed by humans, have a beneficial effect on the human body as a result of selective stimulation of growth and / or an increase in the biological activity of normal intestinal microflora.

The main types of prebiotics are: di- and trisaccharides; oligo- and polysaccharides; polyhydric alcohols; amino acids and peptides; enzymes; organic low molecular weight and unsaturated higher fatty acids; antioxidants; plant and microbial extracts useful for humans and others. In particular, Khilak Forte is famous. Hilak Forte regulates the balance of intestinal microflora and normalizes its composition. Due to the content of metabolic products of normal microflora in the preparation, Hilak Forte helps to restore normal intestinal microflora in a biological way and allows you to preserve the physiological and biological functions of the intestinal mucosa. (Aminova A.I. et al. Evolution of the development of science from microbiota and microbiome to metabolome, from probiotics to metabiotics // Questions of practical pediatrics. - 2017. - T. 12. - No. 2. - P. 47-57 .)

The biosynthetic lactic acid and its buffer salts, which are part of the drug, restore the normal value of acidity in the gastrointestinal tract, regardless of whether the patient has increased or decreased acidity.

Against the background of acceleration of the development of normal intestinal symbionts under the action of the drug Khilak Forte, the natural synthesis of vitamins of the B and K groups is normalized. electrolyte balance in the intestinal lumen. There is evidence that Hilak Forte enhances the protective functions of the body by stimulating the immune response.

The disadvantages of this drug are the high cost, inconvenience of taking (liquid form, high frequency - 3 times a day). Side effects include allergic reactions, constipation, or diarrhea.

Tasks:

1.reduction of the cost of treatment of dysbiotic and dyspeptic phenomena;

2. reducing the frequency of side effects arising from the intake of prebiotics;

3. creating a convenient dosage form and reducing the frequency of administration;

4. achieving a stable therapeutic effect.

The essence of the invention is an agent for the correction of intestinal dyspepsia after antibiotic and chemotherapy, which includes in its dry form as a target ingredient arabinogalactan and sunflower lecithin in the following quantitative ratio, wt. %:

Arabinogalactan 20-40 Lecithin 80-60

The technical result of the invention is the inclusion of arabinogalactan and sunflower lecithin in the composition of the agent. The resulting drug has practically no side effects, a convenient form for taking in capsules has been created, the frequency of administration has been reduced to twice a day, a reduction in the cost of treatment has been achieved in comparison with analogues, a persistent, long-term therapeutic effect has been noted (lack of dyspeptic phenomena for 6-12 months after drug withdrawal). These tasks are solved due to the prebiotic properties of arabinogalactan and sunflower lecithin, their positive effect on intestinal motility and improvement of absorption processes, immunomodulatory properties of arabinogalactan.

The combination of arabinogalactan and sunflower lecithin allows you to level the dyspeptic symptoms that occur during antibiotic and chemotherapy within 14-20 days with a minimum amount of side effects from taking the drug.

Arabinogalactan is a dietary fiber from Siberian larch that supports the growth of beneficial microorganisms and increases the production of short-chain fatty acids, which are extremely important for normal intestinal function. In addition, arabinogalactan is an excellent stimulant of the immune system, it is almost 2 times more effective than echinacea in increasing the formation of immune cells.

It is a biologically active polysaccharide. As a source of soluble dietary fiber, arabinogalactan improves nutrition, absorption and maintenance of a healthy gastrointestinal tract.

Arabinogalactan is a dry powder with a slight piney odor and a sweetish taste. Easily soluble in water and forms a low viscosity solution. Stimulates the growth and development of beneficial intestinal microflora, improves intestinal motility, promotes its regular cleansing, adsorbs and removes toxic substances, radionuclides and heavy metals, lowers cholesterol and blood sugar, strengthens the immune system, regulates appetite and affects weight loss, protects against negative consequences of antibiotic therapy, protects the beneficial intestinal microflora from the damaging effect of antibiotics, improves the absorption of drugs in the intestine.

Sunflower Lecithin is a blend of essential phospholipids Lecithin contains a blend of four main phospholipids:

- phosphatidylcholine. The main phospholipid of lecithin, it accounts for about 30% of the total mass of lecithin phospholipids. The molecules of the cell membranes of our body are mainly composed of this lipid;

- phosphatidylethanolamine. This lipid in the mixture is about 20%;

- phosphatidylinositol. Makes 15-18% of the total mass of phospholipids;

- phosphatidylserine. There is the least amount of it in the mixture - 3%. Phospholipids are involved in almost all biochemical processes of the human body, but most of all they are involved in the formation of cell membrane structures - they make the cell membrane mobile, elastic and permeable.

The cell membrane is 50% phospholipids. The chemical properties of phospholipids determine the basic properties of membranes.

The effect of lecithin on the gastrointestinal tract is determined by its powerful hepatoprotective and prebiotic properties, a positive effect on intestinal motility and absorption processes. Like arabinogalactan, lecithin can be a "matrix" used to improve the bioavailability of drugs.

Thus, the combined use of arabinogalactan and lecithin is promising, since they are synergistic and can enhance the therapeutic effects of each other.

The tool is prepared as follows: one part of arabinogalactan is placed in the first container and a vacuum is created, an aqueous-alcoholic mixture of ethanol with a temperature of 5 ° C is supplied with active stirring at a speed of 120-150 rpm, the whole process takes place under vacuum conditions. In the second container, one part of sunflower lecithin is placed, poured with ten parts of 96% ethanol with vigorous stirring under vacuum. A vacuum is created in the third container. At the same time, the taps of the first and second containers are opened, the vacuum is released. The contents are fed through a mixing device into a third container. The temperature is raised to 12-15 ° C, evacuated, the water-alcohol mixture is removed. The resulting mixture is crushed, served for packing in capsules.

The agent is used as follows: it is prescribed for oral administration 2 capsules 2 times a day before breakfast and dinner. The course of admission is 1 month.

Examples of receiving funds:

1.arabinogalactan - 200 mg

sunflower lecithin - 800 mg

2.arabinogalactan - 400 mg

sunflower lecithin - 600 mg

Example 1

Patient R., 57 years old, was worried about bloating, heaviness in the epigastric region after eating, diarrhea up to 4 times a day, recurrent pain along the colon. The above phenomena appeared after a 14-day course of antibiotic therapy for pneumonia. The coprogram contains a large number of undigested muscle fibers, starch grains, undigested fiber, and iodophilic flora. The drug is prescribed in a dosage of 2 capsules 2 times a day in a ratio of 200 mg arabinogalactan in one capsule, 800 mg lecithin. After 10 days from the start of taking the drug, a positive trend began to be noted: a decrease in bloating, a decrease in stool frequency, a lack of pain and heaviness in the abdomen. After 3 weeks, dyspeptic symptoms were completely absent, and the stool returned to normal. A month after the start of treatment, the coprogram was without pathological changes. During the next year, no pathological symptoms were observed.

Example 2

Patient A., 35 years old, worried about increased gas production, bloating, aggravated after eating food rich in fiber and sweets, unformed stools 2-3 times a day with particles of undigested food, recurrent pain in the projection of the small intestine. The above phenomena appeared after 2 courses of antibiotic therapy for exacerbation of chronic pyelonephritis. The drug was prescribed in a dosage of 2 capsules 2 times a day in a ratio of 400 mg arabinogalactan, 600 mg lecithin in one capsule. Already after 5 days from the start of taking the drug, positive dynamics began to be observed: a decrease in gas formation and swelling, a more formalized stool. After 2 weeks, dyspeptic symptoms and abdominal pain were completely absent, and the stool returned to normal. During the next year, no pathological symptoms were observed.

Example 3

Patient L., 65 years old, after a course of chemotherapy for breast cancer worried about bloating, loose stools 3-5 times a day, lack of appetite, nausea, heaviness in the epigastrium after eating. The drug is prescribed in a dosage of 2 capsules 2 times a day in a ratio of 200 mg arabinogalactan in one capsule, 800 mg lecithin. The course of treatment is 4 weeks. After 15 days from the start of taking the drug, a positive trend began to be noted: appetite appeared, bloating and stool frequency decreased, pain and heaviness in the abdomen. After 3 weeks, dyspeptic symptoms and pains ceased to bother, stool and appetite returned to normal. Notes that after previous courses of chemotherapy, complaints persisted much longer, usually more than a month.

Example 4

Patient P., 44 years old, was worried about bloating and diarrhea. The above phenomena appeared after 3 courses of chemotherapy. The drug was prescribed in a dosage of 2 capsules 2 times a day in the ratio in one capsule of arabinogalactan 400 mg, lecithin 600 mg, the course of treatment is 4 weeks. After 10 days from the start of taking the drug, positive dynamics began to be observed: a decrease in swelling and a more formalized stool. After 3 weeks, dyspeptic symptoms ceased to bother. During the next 6 months of observation, no pathological symptoms were observed.

Claims (2)

A remedy for the correction of dyspeptic disorders of the gastrointestinal tract, containing arabinogalactan - a prebiotic and lecithin, characterized in that arabinogalactan from Siberian larch and additionally lecithin from sunflower in the following ratio, wt.%: Arabinogalactan 20-40 Lecithin 60-80