RU2564899C2 - Method of treating children suffering from rotavirus infection - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention refers to medicine, more specifically to the hospital treatment of infants with such a common disease as the rotavirus infection. What is presented is a method of treating the children suffering from the rotavirus infection, characterised by the fact that convention therapy is supposed to be added with a food supplement that is Biovestin drink with the therapy conducted at the stage of intestinal dysbacteriosis correction and representing a 10-day therapeutic course according to the schedule: in a dose of 3.0 ml 2 times a day per os between meals in the children aged from 1 to 3 years.

EFFECT: normalising the intestinal microflora enables the body immune system controlling the viral infection with no adverse biological actions of Biovestin.

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Description

The invention relates to medicine, in particular to inpatient treatment of young children with such a common disease as rotavirus infection.

According to WHO experts, almost every child during the first five years of life suffers rotavirus gastroenteritis, regardless of race and socio-economic status. Rotaviruses annually cause more than 137 million cases of acute gastroenteritis in the world, with a significant number of severe forms of the disease with fatal outcomes in both children and adults. Rotavirus infection is accompanied by diarrhea syndrome in 40-60% of cases requiring hospitalization and urgent measures. In Russia, about 1 million patients with acute intestinal infections are registered annually and more than half of them have rotavirus etiology, and the number of unregistered morbidity is generally not accountable.

Viral diarrhea causes lactase deficiency and other forms of fermentopathy that lead to a change in the intestinal microbiota. The etiotropic treatment of rotavirus infection remains to this day an unresolved problem. Conducted antibacterial therapy also leads to disruption of the intestinal microflora and mucous membranes, and in the case of viral diarrhea, it promotes the multiplication of the virus and enhances the clinical symptoms of the disease. Violation of the intestinal microflora leads to a violation of nutrition, energy exchange, and the immune response, which, in turn, exacerbates the course of the underlying disease, increases the risk of bacterial complications, causes psychoemotional disorders, lengthens the treatment time, makes it more costly. Long-term statistics show that rotavirus gastroenteritis is the lot of children mainly of the earliest age group, which confirms the established opinion that the older the person, the less often RVI forms intestinal pathology.

For the formation of intestinal microflora, probiotics are necessary - living microorganisms that live in the intestines of a healthy person, as well as products and medicines that contain bacteria strains grown in a natural way. Probiotics for newborns are used to protect the child's body from pathogenic microbes and establish biological balance in the intestine. Lactobacilli and bifidobacteria are the most common types of microbes used as probiotics, including for young children. Probiotics are usually consumed as part of fermented foods, with specially added active living cultures (as yoghurts, soy yoghurts, and also as food additives (Allen SJ, Martinez EG, Gregorio GV, Dans LF. Probiotics for treating acute infectious diarrhoea (Review ). The Cochrane Library, 2010, Issue 11).

Thus, the urgency of the problem is obvious: effective measures are needed to prevent the development of intestinal dysbiosis, especially in young children.

Ongoing therapy is based mainly on the pathogenetic principle based on pathophysiological ideas about the mechanism of diarrhea, while oral immunoglobulins, enterosorbents and probiotics are used as drugs of non-specific "etiotropic" and pathogenetic therapy.

The main health risk is dehydration, and the main task of doctors is to maintain and improve the status of hydration. However, rehydration solutions used for this purpose not only do not shorten the duration of the course of the disease, but in a significant number of cases do not lead to healing of children.

In recent years, attempts have been made to use pharmacological preparations with antiviral and immunocorrective effects in the etiopathogenetic therapy of rotavirus infection in children. So, the drug for the treatment of rotavirus infection according to US Pat. RF No. 2266742 is 1-methyl-2-phenylthiomethyl-3-carbethoxy-4-dimethylaminomethyl-5-hydroxybromindole or its salts, selected from the group consisting of hydrochloride monohydrate (arbidol), formerly known as immunomodulator, besylate, fumarate, maleate, citrate or hydrates thereof. Foreign preparations and methods of treating infections, including rotavirus nature, are widely represented in the patent literature: United States Patent 5,505,955 Peterson, et al. "Anti-diarrheic product and method of treating rotavirus-associated infection", April 9, 1996; United States Patent 8,501,194 Spector, et al. "Vaccine for viruses that cause persistent or latent infections", August 6, 2013; Pat. Slovenia SI 1660123 (T1) "Rotavirus vaccine", 2013-06-28; Japan Application JP 2011254838 "New glycoprotein having rotavirus infection inhibitory activity", 2011-12-22; United States Patent 8,440,233, Kanamaru, et al. "Compositions against rotavirus infection and processes for producing the same", May 14, 2013; Pat. Ukraine UA 24023 "Method for diagnostics of rotavirus mono- and mixed - infection in children", 2007-06-11).

Scientific works are known, including those protected by patents of different countries, proposing to use fermented lactic acid products (lactase, whey, etc.) for the prevention and treatment of rotavirus infection (International application WO 2004057981 “Lactic-acid fermented materials able to restrain rotavirus infection and its producting method ", 2004-07-15; Korean Pat. KR 20060002886" Compositions containing lactulose for treating rotavirus infections ", 2006-01-09; Chinese Pat. CN 101130079" Application of lactoferrin in preparing medicament for preventing and controlling disease caused by human rotavirus ". 2008-02-27; Korean Pat. KR 20060002886" Compositions containing lactulose for treating rotavirus infections ", 2006-01-09; Yapo's application ii JP 2007055979 "Recovery promoter from diarrhea by rotavirus infection", 2007-03-08).

Known drugs for the prevention and suppression of rotavirus infection, especially in children, based on the collection of herbs, plant rhizomes and having an antiviral, antibacterial effect, allowing to achieve quick relief of symptoms of chronic diarrhea, taking into account the difficulty of taking pharmacological drugs in young children. A number of proprietary products are used as food additives (United States Patent 2010034909 "Pharmaceutical composition for treating rotavirus and / or respiratory syncitial virus infection and method for preparing the same", 2010-02-11; Chinese Patent CN 103 007145 "Traditional Chinese medicine composition for treating children rotavirus enteritis and preparation method of composition ", 2013-04-03; Pat. China CN 102198262 Chinese medicine preparation for treating infant rotavirus enteritis and preparation method thereof. 2011-09-28; Pat. Korea KR 20110010144" A pharmaceutical composition comprising a polysaccharide having anti-rotavirus activity ", 2011-01-31; Chinese Pat. CN 102475731" Miao ethnic medicine raw mate ", 2012-05-30; Chinese Pat. CN 101716237 Traditional Chinese medicine composition for treating infantile diarrhea caused by rotavirus. 2010-06-02).

However, with all the variety of drugs used to suppress infections, including rotavirus infection, the most effective are probiotic preparations based on bifidobacteria and lactobacilli. Bifidobacterin is the leading probiotic in the assortment of probiotic preparations and functional products, since it forms the basis of the microecological system of the gastrointestinal tract and is found in the amount of 10 8-11 CFU / g of the contents of the human large intestine. Bifidobacteria for newborns are used in all cases in which there is initially a violation of the intestinal microflora. Since bifidobacteria are the main inhabitants of the intestines of a child of the first year of life, mainly bifid preparations are used to normalize the intestines: bifidumbacterin, bificol, bifilong and others (Japanese Application JP 2005102696 "New bacterial strain bifidobacterium longum enabling inhibition of rotavirus and active proteins separated therefrom", 2005- 04-21; United States Patent 8,492,124 Ritter, et al. "Prebiotic formulations and methods of use", July 23, 2013; Mexico Application MX2011006701 "Prevention and treatment ofrotavirus diarrhoea using Bifidobacterium breve CNCM 1-3865", 2011-07-28 .)

Known bifidumbacterin forte - a drug that was previously used to correct the intestinal microflora of a child with acute intestinal infections and intestinal dysbiosis (intestinal dysbiocenosis in children. A manual for doctors. Edited by Kushnir S.M., M., 2002, p. 49).

Known methods for treating young children suffering from acute intestinal infections of various etiologies using compositions of live bifidobacteria and lactobacilli, or separately bifidobacteria in the form of biologically active additives that contribute to the normalization and maintenance of normal intestinal microflora. In most cases, treatment methods exclude antibiotic therapy (Pat. RF 2441399 “Protein-free baby food”; Pat. RF 2258524 “Composition for the treatment of acute respiratory diseases of hib etiology in children and method of treatment”; Pat. RF 2218927 “Method for the treatment of acute intestinal infections "; Pat. RF 2489157" A method for non-drug treatment of patients with chronic diseases of the gastrointestinal tract ").

Most of the known drugs for the treatment and prevention of infections, including those caused by rotaviruses, are prescribed to patients in tablet form, in the form of capsules, powders, etc. However, it is known that the liquid form of the drug is the easiest form of taking and assimilating medicines to young children.

Known means of suppressing infections - "Method of non-drug treatment of patients with chronic diseases of the gastrointestinal tract" according to US Pat. RF №2489157, MKI A61K 36/00, 08/10/2013. The product is a Bifidomarin drink, and according to the description of the patent, patients are treated non-pharmacologically by including the Bifidomarin probiotic drink, which is a fermented milk biological product made by fermenting sterilized milk using bifidobacteria prepared on the basis of B. bifidobacteria production strains. B379M, or B. bifidum 791, or LVA-3 (probiotics) with the addition of the Fukolam-S dietary supplement based on polysaccharides with prebiotic Kim action (in an amount of 1 g / l or 0.1 wt.%). As a significant limitation to the use of the Bifidomarin drink as a means of suppressing infections, the drink may be based on a combination of probiotics and prebiotics. It should be borne in mind that any component of a complex drug can cause an allergic reaction. In the product "Bifidomarin", the probiotic strain of bifidobacteria is used as the active component - live active bifidobacteria in an amount of at least 109 CFU / g (cm ³ ). However, the biologically active product Fucolam-S, a raw material for use in the food industry for the production of beverages, meat, confectionery and bakery products, is a polysaccharide from seaweed, fucoidan, which is used as a prebiotic, the second essential active component of the drink. In accordance with TU 9284-067-02698170-2010, the product is intended for industrial processing and is not a medicine. As dietary supplements, "Fucola amber" is used, recommended by manufacturers for use as an immunomodulating agent.

An obvious drawback of the Bifidomarin drink used to suppress infections is that the polysaccharide fucoidan included in the drink, isolated from different types of brown algae in structure, But - according to the developers - has different activity, so far insufficiently studied: some types of activities were studied on cell cultures, therefore, it cannot be said that the substance will exhibit the same activity when administered to animals, including to man. In animal studies and in clinical trials based on the Medical Association of the Far Eastern Branch of the Russian Academy of Sciences, it was shown that the drug FUKOLAM AMBER developed on the basis of fucoidan has not been used in pediatric practice to date and there is no data on its therapeutic and prophylactic effect.

As the closest prototype, the method of treating rotavirus infection according to US patent No. 5,505,955 "Anti-diarrheic product and method of treating rotavirus-associated infection" MKI A23L 1/3056; A61K 35/20; A61K 35/55, publ. 1996.04.09.

The prototype method of treating rotavirus infection according to US patent No. 5,505,955 is presented in the form of a complex of granular skim membranes, breast milk in the macromolecular fraction, milk mucin, glycoprotein, a polypeptide capable of binding rotavirus, or a mixture of these components, or this mixture with skim milk , cottage cheese, and / or whey. The method according to the invention has the ability to suppress rotavirus infection and / or diarrhea in newborns and young children (infantile gastroenteritis). The method of treatment according to the invention consists in administering a therapeutic food product to a newborn or young child susceptible to rotavirus infection.

The disadvantage of the invention according to US patent No. 5,505,955 is the complexity and high cost of preparing the product. In addition, the appointment of young children suffering from rotavirus infection, a product that may include thinners, emulsifiers, preservatives, antioxidants, etc., is not always safe: the occurrence of complications against the background of the underlying disease is not ruled out. In addition, the drug has a consistent - not liquid form, which can complicate the use of the drug by young children.

The aim of the present invention is the suppression of rotavirus infection in children in combination with traditional therapy due to the expansion of the arsenal of therapeutic agents.

The goal is solved by the fact that the authors proposed:

A method of treating children with rotavirus infection, based on the fact that the traditional therapy includes the bioactive drink supplement "Biovestin" containing bifidobacteria Bifidobacterium adolescentis MC-42, and the treatment is carried out at the stage of correction of intestinal dysbiosis with a 10-day course according to the scheme: children from 1 year to 3 years - at a dose of 3.0 ml 2 times a day per os in between meals.

Liquid probiotic product "Biovestin" of microbial origin. It was obtained by culturing the main symbionts of man - bifidobacteria and lactobacilli. Bacteria are cultured in bioreactors in a special environment based on cow's milk. Biovestin is designed and manufactured by the Novosibirsk research and production company Bio-Vesta. Production has been underway since 1995. The course of taking the BIOVESTIN product is prescribed as an additional source of bifidobacteria, physiological for humans and beneficial for the body. Bifidobacteria and lactobacilli enhance intestinal motility, promote complete digestion of food, inactivate nitrates, and improve absorption of iron, calcium, and vitamin D salts in the intestines. They participate in the synthesis of vitamins K, thiamine, riboflavin, and other B vitamins, as well as folic, nicotinic, and pantothenic acids, contribute to the absorption of fat-soluble vitamins. Bifidobacteria have a pronounced antagonistic activity against pathogenic and opportunistic microorganisms, inhibiting the growth and reproduction of toxigenic strains of Escherichia, Klebsiella, Proteus, some types of Salmonella, Shigella, Staphylococcus, Streptococcus. Bifidobacteria and lactobacilli are involved in the formation of the immunological reactivity of the body, stimulating the formation of protective proteins, and enhance immunity.

The healing effect of Biovestin is determined by the bifidobacterium Bifidobacterium adolescentis MC-42 contained in it in the living active form. This strain of bifidobacteria is characterized by a high growth rate, acid-forming ability and high antagonistic activity against a number of conditionally pathogenic and pathogenic microorganisms, such as Staph. aureus 209 r (Staphylococcus aureus), Sh. flexneri 170, Sh. flexneri 337, Sh. sonnei 174 b, Proteus vulgaris F-30, Proteus mirabilis F-196, E. coli 0-147.

To study the effect of the action of "Biovestin", 129 sick children aged 1 to 3 years with moderate forms of acute intestinal infections of rotavirus etiology were selected. The control group consisted of 200 children, comparable by sex, age, duration of illness and concomitant diseases. An etiological diagnosis was established on the basis of clinical and epidemiological data characteristic of rotavirus infection and the mandatory detection of rotavirus antigen in patient's co-filtrates in the ELISA reaction before treatment.

Upon admission to the hospital, all children were prescribed conventional basic therapy, which included: diet, oral rehydration, antiviral, infusion (if indicated), enzyme therapy, symptomatic agents (antipyretic, antiemetic, desensitizing, bronchodilator, mucolytic), antibacterial therapy ( complications). 129 patients (the main group) received Biovestin in age dosages with a 10-day course. The control group (200 children) was not prescribed Biovestin.

The duration of the main clinical symptoms of rotavirus infection in children was significantly shorter in the main group of children (table 1).

Table 1 The average duration of clinical symptoms of rotavirus infection in children, depending on the therapy Clinical symptoms The average duration in days from the start of treatment The main group (basic therapy + Biovestin) n = 129 Control group n = 200 Reliability P Lethargy 2.22 ± 0.20 2.95 ± 0.25 > 0.05 Decreased appetite 2.11 ± 0.13 3.10 ± 0.18 > 0.001 Fever 2.06 ± 0.27 2,50 ± 0,25 > 0.05 Exicosis 2.88 ± 0.13 3.90 ± 0.18 > 0.001 Vomiting 1.98 ± 0.20 2.75 ± 0.25 > 0.05 Diarrhea syndrome 2.72 ± 0.12 4.95 ± 0.25 > 0.001 Stomach ache 2.52 ± 0.12 4.85 ± 0.25 > 0.001 Weight dynamics 1.88 ± 0.13 2.90 ± 0.18 > 0.001 Hepatosplenomegaly 6.2 ± 0.13 8.2 ± 0.18 > 0.001 Catarrhal syndrome 6.0 ± 0.13 8.4 ± 0.18 > 0.001 Bronchial obstructive syndrome 2.5 ± 0.13 4,5 ± 0,18 > 0.001

table 2 The dynamics of the disappearance of gastrointestinal tract (diarrheal syndrome) with rotavirus infection in children, depending on the therapy Group Disease day / number of patients whose symptoms disappeared on the day from the start of treatment 1st day 2nd day 3rd day 4th day 5th day 6th day 7th day 8th day 9th day 10th day The main group (basic therapy + Biovestin) n = 129 10 (7.8%) 45 (34.9%) 45 (34.9%) 29 (22.4%) Control group n = 200 0 (0%) 20 (10.0%) 39 (19.5%) 41 (20.5%) 39 (19.5%) 37 (18.5%) 12 (6.0%) 10 (5.0%) 1 (0.5%) 1 (0.5%)

A decrease in stool frequency in the main group of patients was observed from the first day of Biovestin therapy, and normalization was noted already for 3-4 days of treatment, in contrast to the control group (table 3).

Table 3 The dynamics of normalization of stool frequency in groups of patients depending on the therapy. Group Disease day / average stool frequency per day on the day of treatment 1st day 2nd day 3rd day 4th day 5th day 6th day 7th day 8th day 9th day 10th day The main group (basic therapy + Biovestin) n = 129 6.6 4,5 1.9 1,1 1,0 1,0 1,0 1,0 1,0 1,0 Control group n = 200 9.5 5.8 4.0 4.0 2.2 1.7 1,5 1,2 1.0 1,0

The dynamics of the disappearance of the clinical symptoms of infectious toxicosis (decreased appetite, fever, lethargy, weakness) was positive, but the terms were shorter in the main group (table 4).

Table 4 The dynamics of the disappearance of clinical symptoms of infectious toxicosis with rotavirus infection in children, depending on the therapy. Group Disease day / number of patients whose symptoms disappeared on the day of treatment start 1st day 2nd day 3rd day 4th day 5th day 6th day 7th day 8th day 9th day 10th day The main group (basic therapy + Biovestin) n = 129 2 (1.6%) 47 (36.4%) 67 (52%) 13 (10%) - - - - - - Control group n = 200 0 1 (0.5%) 26 (13.0%) 75 (37.5%) 68 (34.0%) 19 (4.5%) 9 (9.5%) 1 (0.5%) 1 (0.5%) -

The state of intestinal microbiocenosis in the dynamics of treatment: in almost all patients (in both groups) already in the initial period of the disease there were significant violations in the quantitative and qualitative composition of the intestinal microflora, which were of the same type and were characterized by a decrease in the log index. concentrations below the age norm of bifidobacteria, lactobacilli, to a lesser extent enterococci and an increase in the total number of Escherichia coli, including hemolytic forms. From day 5 from the start of treatment, dysbiotic changes in the intestinal microflora in the main group returned to normal, in the control group they remained, and in some patients they even progressed (table 5).

Table 5 The dynamics of the indicator log. the concentration of intestinal microflora in rotavirus infection in children, depending on the treatment treatment before treatment on day 10 Reliability p Types of microorganisms The main group n = 129 Control group n = 200 The main group (basic therapy + Biovestin) n = 129 Control group n = 200 bifidobacteria 5.0 ± 0.65 5.1 ± 0.66 6.1 ± 0.65 4.1 ± 0.53 > 0.05 lactobacilli 5.6 ± 0.22 5.7 ± 0.23 7.8 ± 0.22 5.8 ± 0.25 > 0.05 Escherichia 8.2 ± 0.65 8.3 ± 0.65 5.6 ± 0.22 8.6 ± 0.24 > 0.05 enterococci 5.8 ± 0.54 5.7 ± 0.55 7.7 ± 0.32 6.7 ± 0.35 > 0.05

The obtained research results indicate that the additional appointment of the probiotic preparation "Biovestin" to the complex therapy of rotavirus infection in children helps to normalize the quantitative composition of individual representatives of the intestinal normoflora.

Assessment of patient satisfaction with treatment results was carried out on the scale of Integrative Medicine Patient Satisfaction Scale - IMPSS and consisted of 5 points:

- completely satisfied

- satisfied

- I am neutral

- not satisfied

- extremely dissatisfied

When analyzing questionnaires completed by 129 mothers - children of the main group, 69 people (53.5%) answered - completely satisfied, 40 people (31.0%) - satisfied, 13 people (10.0%) - neutral, 7 (3 , 5%) - not satisfied and 0% - extremely dissatisfied (Table 6).

Table 6 Satisfaction results in the clinical effectiveness of the therapy Clinical effect and number of patients A great Good Weakly expressed The drug is canceled The main group (basic therapy + Biovestin) n = 129 69 (53.5%) 40 (31.0%) 13 (10.0%) 7 (3.5%)

The doctor evaluated the treatment results according to the Intergrative Medicine Outcome Scale - IMOS scale and consisted of 5 points:

- full recovery

- significant improvement

- moderate or slight improvement

- without changes

- deterioration.

According to the doctor’s assessment, out of 129 children of the main group, 129 people (100%) showed a complete recovery from rotavirus infection in a shorter time and with normalization of intestinal microflora compared with children of the control group.

Example

Vanya S., 2 years old

He was admitted to a children's hospital with a diagnosis of ARVI (rhinopharyngitis). An acute onset of the disease was noted, which had a sudden and rapid course. Complaints: double vomiting, fever up to 39.5 ° C, nasal congestion, sore throat, dry cough, once loose stool.

Upon admission - a moderate state (severe symptoms of intoxication - fever up to 39 ° C, chills, weakness, lethargy, decreased appetite), cramping pains with localization in mesogastrium, palpation of the abdomen is soft, painful in the umbilical region, diarrhea (10 times per day, bowel movements were pronounced enteric in nature (liquid, watery, fetid, foamy, flatulence, rumbling in the abdomen, urges to defecate were sudden, frequent, imperative), catarrhal syndrome (nasal congestion, nasal mucous discharge, hyperemia of the pharynx, granularity of the posterior pharyngeal wall, dry cough), degree 1 dehydration symptoms (thirst, dry mouth, hoarseness, weakness, pallor). Auscultation causes puerile breathing, muffled heart sounds, tachycardia up to 136 beats per minute. admission: rotavirus infection (rhinopharyngitis, gastroenteritis), moderate to severe Hemogram: leukocytosis with neutrophilia and increased ESR (due to hemoconcentration), later, against the background of rehydration - a tendency to leukopenia with lymphocytosis. Urinalysis - without pathology. Caprogram: steatorrhea, amylorrhea, creatorrhea. Positive test of Benedict. Feces for dysbiosis: a decrease in the concentration below the age norm of bifidobacteria, lactobacilli, enterococci and an increase in the total number of Escherichia coli, including hemolytic forms. On the 10th day from the start of treatment, dysbiotic changes in the intestinal microflora returned to normal. The results of bacteriological and serological studies on bacteria - pathogens of acute intestinal infections are negative. The diagnosis of rotavirus gastroenteritis is confirmed by the detection of rotavirus in feces on the second day of the disease by ELISA.

Treatment: regimen - bed rest, diet (taking into account disturbances in the activity of a number of digestive enzymes, in particular lactase, excluded milk and dairy products, foods rich in carbohydrates), antiviral therapy (arbidol), oral rehydration therapy (rehydron), antipyretic drugs (paracetamol), enteroserptons (smecta), enzyme preparations (pancreatin), nasal drops (nasol). From the first day - Biovestin in a dose of 3.0 ml 2 times a day per os between meals for 10 days. The course of the disease without complications. On the second day of the disease - low-grade fever, abdominal pain ceased, stool mushy up to 3 times a day. On the third day - a temperature of 36.6 ° C, stool 1 time per day. Full recovery came on the seventh day of illness.

All of the above allows us to conclude that the biologically active additive-drink "Biovestin" has a positive effect on the dynamics of the underlying disease, while the tolerance of the product can be considered good, which is confirmed by the data given in the tables.

An analysis of the results of clinical and laboratory studies in children who received course treatment using the Biovestin dietary supplement, made it possible to draw the following conclusions:

1. The drink "Biovestin" does not have side biological effects.

2. Treatment with Biovestin drink leads to a clear clinical improvement and improvement of patients' well-being.

3. It is advisable to use the Biovestin drink in the treatment of rotavirus infection in young children at the stage of correction of intestinal dysbiosis in order to suppress pathogenic and conditionally pathogenic flora and reduce the duration of the disease.

4. Drink "Biovestin" is an effective tool that restores the internal ecology of the macroorganism, which allows the body's immune system to quickly cope with a viral infection.

The obtained results of clinical and laboratory studies allow us to consider the biologically active supplement-drink "Biovestin" for the initial correction of dysbiosis in sick young children with rotavirus infection.

Claims (1)

A method of treating children with rotavirus infection, characterized in that the traditional therapy includes a biologically active additive - drink "Biovestin" containing bifidobacteria Bifidobacterium adolescentis МС-42, while the treatment is carried out at the stage of correction of intestinal dysbiosis with a 10-day course according to the scheme: children from 1 year to 3 years - at a dose of 3.0 ml 2 times a day per os in between meals.