RU2489157C1 - Method of drug-free therapy of patients with chronic gastrointestinal diseases - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention refers to medicine, and aims at treating chronic gastrointestinal diseases. What is used is a synbiotic water containing bifidus bacteria and immunoactive polysaccharides of brown alga F.evanescens. The dose is 200 ml a day, 2 intakes 30 minutes before meals; the therapeutic course is 6 weeks.

EFFECT: method enables eliminating intestinal dysbiosis, providing higher clinical effectiveness in chronic gastrointestinal diseases.

5 ex, 8 tbl

Description

The invention relates to medicine, namely to methods for the treatment and prevention of diseases of the gastrointestinal tract (GIT).

The main focus of the treatment of patients with chronic gastrointestinal diseases accompanied by dysbiotic disorders is considered to be a targeted effect on certain types of microorganisms, the selective destruction of pathogenic and / or settlement of the missing, or the creation of conditions in the intestine that are unfavorable for the pathogenic flora and contribute to the development of normal microbiota through the use of pro- pre- and synbiotics.

Known methods of treating gastrointestinal diseases by using bacterial biological products based on lyophilized dried strains of probiotic microorganisms. Such preparations are available in the form of powder, tablets, capsules or suppositories. These forms have long shelf life and are not demanding of short-term changes in storage temperature.

Their significant drawback is that the lyophilization process leads to suspended animation (inactive state). To return to an active physiological state, they need 8-10 hours, and during this time, most of the bacteria are removed from the human body. In addition, in the process of lyophilization, bacterial cells lose specific receptors that help them to attach to surfaces, so the possibility of their stay in the intestine is even more reduced.

Liquid “living” probiotics (monocultures or their associations), in which microbial cells remain active and capable of colonizing the gastrointestinal tract after 2 hours, are deprived of the noted drawbacks.

The most widely used probiotics (eubiotics) from representatives of the intestinal normoflora are bifidobacterin, lactobacterin, colibacterin, sporobacterin, bificol, acipol, biosporin, etc.

Regulation of microbiocenosis of the mucous membranes is carried out due to the direct effect of production strains of eubiotics on the microflora by filling the deficit of its corresponding representatives, crowding out pathogenic and excess conditionally pathogenic microorganisms by competing for nutrients, neutralizing pathogen toxins, by changing acidity in the intestines and producing biologically active substances to fight with pathogens, as well as through indirect activation (mobilization or regulation) of their local uniteta and metabolic processes in the body.

The disadvantage of such methods of treatment is the need for prolonged use of these drugs to achieve a stable bacteriological effect and slow correction of local immunity, especially in debilitated patients, including with chronic diseases of the gastrointestinal tract. The disadvantages of treatment are also due to the fact that colonization of the colon with representatives of normoflora in the composition of probiotics is not always effective, since there is a protective acidic environment of the stomach and alkaline environment of the duodenum, the probiotic microorganisms introduced can not withstand the competition with the colon microflora, and under certain conditions they can cause unwanted effects on the body. Thus, isolated cases of generalization of probiotic strains of microorganisms in patients with immunodeficiency states have been reported [Dierick N, Ovyn A, De Smet S. Effect of feeding intact brown seaweed Ascophylum nodosum on some digestive parameters and on iodine content in edible tissues in pigs. J. Sci. Food Agric. 2009. 89. P.584-594].

More effective regulators of the composition and functions of microbiota in the treatment of gastrointestinal diseases are synbiotics - biological products or probiotic products obtained as a result of a rational combination of pro- and prebiotics.

Prebiotics are compounds of non-microbial origin that can stimulate the colonizing ability and reproduction of the intestinal symbiotic flora and influence the host organism and / or microflora through biochemical mechanisms not associated with probiotic action, activating or blocking cell receptors [Gómez-Ordóñez E, Jimenez-Escrig A , Ruperez P. Dietary fiber and physicochemical properties of several edible seaweeds from the northwestern Spanish coast. Food Res Int. 2010. Vol. 43. P.2289-2294; Roberfroid M.B. Prebiotics and probiotics: are they functional foods? // American Journal of Clinical Nutrition. 2000. Vol. 71. N.6. P.1682-1687; Tungland B.C., Meuer D. Nondigestible oligo - and polysaccharides (dietary fiber): their physiology and role in human health and food // Comp. Rev. Food Sci. Food safety. 2002. Vol., No.3. P.73-92]. The use of prebiotics also suppresses toxic metabolites (ammonia, indole, skatol, etc.) and enzymes that are harmful to the body (nitroreductases, azo reductases, β-glucuronidases). The positive side of the action of prebiotics is their ability to decompose under the influence of representatives of normoflora to short chain fatty acids, which lower intestinal pH, stimulate peristalsis, increase fecal volume and moisture, as well as their osmotic pressure [Gardiner, GE, Campbell, AJ, O'Doherty, JV , Pierce, E., Lynch, PB, Leonard, FC, Stanton, C, Ross RP, and Lawlor PG Effect of Ascophyllum nodosum extract on growth performance, digestibility, carcass characteristics and selected intestinal microflora populations of grower-finisher pigs. Animal Feed Science and Technology. 2008. 141. P.259-273].

In addition, the presence of a prebiotic component expands the possibilities of using eubiotics, taking into account their immunoregulatory effect, and opens up broad prospects for use in various clinical situations, including in the treatment of chronic gastrointestinal diseases. So, among the nosological forms in which the administration of drugs of the pro- and prebiotic group is indicated, inflammatory bowel diseases are included, and the effectiveness of probiotic therapy for autoimmune diseases is also discussed.

In clinical conditions, the following synbiotic preparations were used: Dienai dietary supplement containing a complex of enzymes from Bacillus subtillis and fragmented DNA from salmon fish; BAA "Ecoflor" - a consortium of bifidobacteria and lactobacilli immobilized on enterosorbent (SUMS-1); bifidumbacterin forte - B. bifidum adsorbed on activated carbon; lactofiltrum - lactobacilli on enterosorbent, acipol - L. acidophilus and kefir polysaccharide, laminolact - Enterococcus faecium L-3, amino acids, pectins, seaweed, etc.

Currently, the treatment of gastrointestinal diseases, accompanied by intestinal dysbiosis, is carried out in a medication way, which usually includes antibiotics and antispasmodics; histamine H2 receptor blockers; antacids; drugs that eliminate impaired gastrointestinal motility; enzyme preparations; pro and prebiotics.

As part of the complex therapy of chronic gastrointestinal diseases, functional food products (FPP) (including dairy products) containing probiotics based on lactic acid bacteria and / or prebiotics are widely used.

Among FPP, special attention is given to products enriched with pro- and prebiotics. This enrichment gives them the ability to favorably influence various functions of the body, improving not only the state of health, but also preventing various diseases. The therapeutic effect of food enriched with pro- and prebiotics is realized primarily due to the normalization of the microflora of the human gastrointestinal tract. When such products are systematically included in the human diet, they provide the body with energy and plastic material, optimize specific physiological and biochemical functions. Based on the forecasts of the world's leading experts in the field of nutrition and medicine, in the next 15-20 years their share will reach 30% of all products. At the same time, they will displace traditional medicines by 30-50% from the sphere of sale.

A known method of treating functional and inflammatory diseases of the large intestine with fermented milk preparations based on lactobacilli (in particular, Narine) with or without basic antibiotic therapy [Kramar L.V., Goncharova L.V. Prevention of dysbiosis in children suffering from acute intestinal infections with the drug Narine // Materials of the All-Russian Conference of Infectious Diseases. Volgograd. 1995. P.12]. The pronounced effect is achieved due to the fact that in the usual dose of the lactic acid product of microbial bodies is 300 times more than in 10 doses of official bacterial preparations, which are considered the optimal daily dose.

The disadvantage of this method of treatment is that this product is used as a prophylactic for diseases of the gastrointestinal tract along with drug treatment.

The prophylactic use of the lactic acid product "Health" for the treatment of gastrointestinal diseases is known (RF patent No. 2129382, dated 04/27/1999). The composition of this product includes lactic acid bacteria and pectin obtained from the sea grass of the zooster.

The disadvantage of this method of treatment is that this product does not have a high therapeutic and prophylactic effect and is used only as a preventive product.

There is a method of treating the gastrointestinal tract with a fermented milk product prepared using bifidobacteria and Laminal biogel obtained from brown algae — Japanese laminaria (RF patent No. 2383139 dated 08.21.2008 “Method for the preparation of a fermented milk product”).

The disadvantage of this method of treatment is that this product is used as a prophylactic in combination with a standard complex of treatment of the gastrointestinal tract.

Closest to the claimed method is a method of treating the gastrointestinal tract without the use of a standard treatment complex (RF patent No. 2163128 dated 02.02.1999 “A method for producing Bifilact and a method for treating Bifilact of dysbacteriosis.” The essence of the method for treating the gastrointestinal tract is to introduce lacto- and bifidobacteria by taking Bifilact as a drink in a course of 25-45 days daily 400-600 ml in combination with therapeutic enemas.

The disadvantage of this method of treatment is that the method is time consuming for both medical staff and the patient.

The objective of the invention is to increase the effectiveness of non-drug treatment of patients with chronic diseases of the gastrointestinal tract (GIT), through the use of the synbiotic drink "Bifidomarin" in therapeutic doses.

This task is achieved by the fact that the treatment of patients with chronic gastrointestinal diseases is carried out non-pharmacologically by inclusion in the rehabilitation therapy of the synbiotic drink "Bifidomarin" containing bifidobacteria and immuno-and hepatoactive polysaccharides from brown algae F.evanescens in an amount of 200 ml per day in 2 doses for 30 min before meals for 6 weeks.

The Bifidomarin synbiotic drink is a sour-milk bio-product made by fermenting sterilized milk using bifidose sourdough, prepared on the basis of production strains of bifidobacteria B. Iongum B379M, or B. bifidum 791, or LVA-3 (probiotics) with the addition of biologically active additives -C "based on polysaccharides with a prebiotic effect (in the amount of 1 g / l or 0.1 wt.%), Packed in consumer packaging. The drink contains bifidobacteria not less than 10 ⁹ CFU / g (cm ³ ) [TU 9222-008-01898115-2011 "Sour-milk biological product" Bifidomarin "].

The drink was prescribed for 6 weeks (100 g in the morning 30 minutes before meals and 100 g in the evening at night).

The synbiotic drink "Bifidomarin" refers to functional foods. Prescribing before meals is due to the generally accepted method of prescribing probiotic preparations (so that probiotic strains enter the intestines before eating, because their interaction with hydrochloric acid secreted by the stomach during food digestion is undesirable).

The pronounced clinical effect of the Bifidomarin synbiotic drink is due to the fact that it contains two biologically active components - a probiotic strain of bifidobacteria and polysaccharides from brown alga F.evanescens. The synbiotic drink contains live active bifidobacteria in an amount of at least 10 ⁹ CFU / g (cm ³ ) and the biologically active product Fucolam-S.

Bifidobacteria is the leading probiotic in the assortment of probiotic preparations and functional products, since they form the basis of the microecological system of the gastrointestinal tract and are found in the amount of 10 ^8-11 CFU / g of the contents of the human large intestine.

Fucolam-S includes immuno- and hepatoactive polysaccharides from brown alga F.evanescens [Maystrovsky K.V., Zaporozhets TS, Rapovka V.G., Zvyagintseva T.N., Shevchenko N.M. Lipid correction exchange in patients with obliterating atherosclerosis of the vessels of the lower extremities with sulfated polysaccharide from brown alga Fucus evanescens Pacific honey. journal 2010. No4. S.47-51; T.S. Zaporozhets, K.V. Maistrovsky, V.G. Rapovka, L.A. Ivanushko A.K. Gaja, T.P. Smolin. Features of the immune and cytokine status in patients with atherosclerosis of the vessels of the lower extremities // Cytokines and inflammation. 2011. No3. S.68-76]. In addition, "Fucolam-S" provides prebiotic activity [T.A. Kuznetsova, T.S. Zaporozhets, N.N. Besednova, T.N. Zvyagintseva, N.M. Shevchenko, T.N. Imbs, N.V. Mandrakova, V.G. Melnikov Investigation of the prebiotic potential of biologically active substances from marine aquatic organisms and the development of new products of functional nutrition // Vestnik FEB RAS. 2011. No2. S.147-150; T.A. Kuznetsova, T.S. Zaporozhets, I.D. Makarenkova, N.F. Timchenko, N.N. Besednova, T.N. Zvyagintseva, N.M. Shevchenko, N.V. Mandrakova, V.G. Melnikov Prebiotic potential of brown algae polysaccharides F.evanescens and significance for clinical use // Pacific honey. journal 2012. No1. S.37-40].

When choosing the dose of SN "Bifidomarin" we were guided by the calculations of the effective daily dose of the biologically active product "Fucolam-S" and the daily dose of bifidumbacterin.

The recommended daily dose of fucoidan for an adult was established experimentally, which is 100-200 mg [TI and TU 9284-065-02698170-2005; instructions for the use of dietary supplements "Fukolam"; conclusion of the Research Institute of Nutrition RAMS No. 72 / Э-6736 / 6-05 dated 10.20.05); sanitary and epidemiological conclusion No. 77.99.13.003.T.000155.01.06 of 01.30.06; certificate of the Federal Service for Supervision of Consumer Rights Protection and Human Well-Being on state registration (No. 77.99.23.3.U.739.1.06 of January 30, 2006)].

The daily dose of fermented milk bifidumbacterin is 200 ml, calculated on the average human weight of 70 kg [TU 9222-001-01898115-94 and TI 1-27033654-94 for the production of fermented milk bifidumbacterin]. The recommended adequate level of consumption of bacteria of the genus Bifidobacterium with proven probiotic properties in fermented milk products for an adult is 5 × 10 ⁸ CFU / day. The upper allowable level of consumption is 5 × 10 ¹⁰ CFU / day (MP 2.3.1.19150-04 “Recommended levels of consumption of food and biologically active substances”)

The Bifidomarin synbiotic drink was taken by patients with chronic gastrointestinal diseases. Table 1 presents the characteristics of patients.

Table 1 Characterization of patients with chronic diseases of the gastrointestinal tract who took HF "Bifidomarin" Patient Characterization Indicator Age 47.2 ± 7.2 Gender m / f 20% / 80% Diagnosis Chr. gastroduodenitis 26.2% History of CJD 21% History of duodenal ulcer 42.1% Chr. cholecystitis 15.8% Chr. pancreatitis 21% Irritable Bowel Syndrome (IBS) one hundred%

The effectiveness of the use of a synbiotic drink in the non-drug treatment of patients was evaluated by clinical symptoms and laboratory indicators of the state of intestinal microbiocenosis, immune status, and lipid metabolism.

Most patients revealed dyspeptic (loss of appetite, belching, nausea) and intestinal syndromes (bloating, rumbling of the intestines, tendency to constipation or loose stools with undigested food residues), as well as malabsorption syndrome (table 2). Under the influence of the course of therapy with the inclusion of HF, a reduction of these syndromes was revealed in patients (table 2).

Table 2. The dynamics of clinical symptoms as a result of treatment with the use of HF "Bifidomarin"

Complaints Indicator (%) Before treatment After treatment Diarrhea (loose stool 4-6 times a day.) 42 - Unstable chair 32 5 Flatulence 47 16 Abdominal pain (avg intensity) 53 - Bloating 74 10.5

Table 3 presents the indicators of the effectiveness of treatment with the use of HF "Bifidomarin".

Table 3 The effectiveness of treatment with the use of HF "Bifidomarin" Treatment effectiveness % Great 70 Good 25 Satisfied 5 Lack of effect -

During bacteriological examination, all examined patients showed dysbiotic changes, which in 53.3% of patients were regarded as violations of the I degree and in 46.7% as II degree of dysbiosis.

The diagnosis of dysbacteriosis was made clinically with confirmation by the data of microbiological examination of feces. The examination and treatment of patients was carried out in accordance with the industry standard "Protocol for the management of patients. Intestinal dysbiosis" OST 91500.11.0004-2003, approved by Order of the Ministry of Health of the Russian Federation No. 231 of 09.06.03.

Dysbiotic disorders in the examined patients were characterized by a decrease in the quantitative content of bifidobacteria and lactobacilli, quantitative and qualitative changes in Escherichia coli, namely an increase in the content of Escherichia with altered properties - lactose-negative, as well as hemolytic E. coli, compared with those in conditionally healthy donors (Table 4 )

When conducting a re-examination (2-3 weeks after the end of taking HF "Bifidomarin"), restoration of microbiocenosis was revealed in 85% of patients. This was expressed in the normalization of the content of bifidobacteria (p = 0.001), an increase in the level of lactobacilli (p = 0.014). In addition, after treatment, a decrease in the titer of hemolytic Escherichia coli was detected (p = 0,000).

Table 4. The state of intestinal microbiocenosis in the dynamics of non-drug treatment of patients with the use of HF "Bifidomarin". Types of microorganisms The number of microbial cells in 1 g of feces (CFU / g) Conditionally healthy donors Before treatment After treatment R Bifidobacteria 2.35 ± 0.74 × 10 ⁹ 4.18 ± 1.27 × 10 ⁸ * 1.40 ± 0.16 × 10 ⁹ 0.001 Lactobacilli 5.77 ± 4.98 × 10 ⁷ 0.88 ± 0.08 × 10 ⁶ * 0.92 ± 0.12 × 10 ⁷ 0.014 E. coli typical 3.45 ± 0.43 × 10 ⁷ 1.48 ± 0.44 × 10 ⁷ 1.91 ± 0.48 × 10 ⁷ 0.428 E. coli lactose-negative 2.21 ± 0.55 × 10 ⁴ 5.69 ± 2.88 × 10 ⁶ * 0.2 ± 0.19 × 10 ⁶ 0.08 E. coli hemolytic 0 2666.67 ± 1505.4 × 10 ⁴ * 0.20 ± 0.11 × 10 ⁴ 0,000 Enterococci 2.68 ± 0.77 × 10 ⁶ 4.87 ± 0.97 × 10 ⁶ 5.33 ± 0.99 × 10 ⁶ 0.679 Staphylococcus saprophytic 10 ⁵ not upd. 10 ⁵ not upd. 10 ⁵ not upd. Staphylococcus aureus 0 10 ² not obn. 10 ² not obn. Representatives of the genus Clostridium or clostridia 2.88 ± 0.95 × 10 ⁴ 2.28 ± γ1.03 × 10 ⁴ 2.79 ± 1.16 × 10 ⁴ 0.741 Candida yeast 10 ³ not upd. 10 ³ not upd. 10 ³ not upd. Representatives of the genus Proteus Proteus 10 ³ not upd. 10 ³ not upd. 10 ³ not upd. Note: indicators M ± m; not upd. - not found in a given amount; * - p <0.05 - the significance of differences in relation to indicators in conditionally healthy donors (student criterion was used for independent samples); p - the significance of differences when comparing indicators before and after treatment (paired student criterion was used).

The data obtained indicate that after a course of treatment of HF "Bifidomarin" in patients with chronic diseases of the gastrointestinal tract, accompanied by intestinal dysbiosis, was observed

restoration of intestinal microbiocenosis in 85% of patients, expressed in the normalization of the content of bifidobacteria, an increase in the level of lactobacilli, and a decrease in the titer of hemolytic E. coli.

Immunogram indices characterizing the structure of the main subpopulations of peripheral blood lymphocytes in patients prior to treatment were within the limits of values indicating a satisfactory function of the immune system. However, 50-65% of patients before treatment showed signs of activation of the immune system, coupled with an increase in the number of lymphocytes expressing early and late activation antigens - IL-2 receptor (CD25), antigens of the main histocompatibility complex class II (HLA-DR), apoptotic marker CD95 / Fas, which is evidence of the chronic irritating effect of infectious agents. This is evidenced by both an analysis of the expression of activation antigens taking into account average values (for the sample as a whole), and taking into account patients with initially high values of activated lymphocytes (Table 5).

So, for the sample as a whole, the level of CD25 was 18.5 ± 3.5% compared with 10.6 ± 2.4% in healthy donors; p = 0.022; HLA-DR - 17.6 ± 3.2% compared with 16.0 ± 3.5% in healthy donors; p = 0.142; CD95 / Fas - 26.9 ± 2.7% compared with 19.8 ± 3.2% in healthy donors; p = 0.048.

In the sample, taking into account patients with initially high values of activated lymphocytes, increased expression of CD25 was detected in 65% of patients and amounted to 19.5 ± 2.9% at p = 0,000 compared with healthy donors; increased expression of HLA-DR was detected in 50% of patients and amounted to 19.9 ± 1.5 at p = 0.002 compared with healthy donors; increased expression of CD95 / Fas was detected in 65% of patients and amounted to 28.3 ± 6.4 at p = 0,000 compared with healthy donors) (Table 5).

Table 5. Characterization of the level of expression of activation antigens on peripheral blood lymphocytes of patients with chronic gastrointestinal diseases in the dynamics of treatment of HF "Bifidomarin" Indicators of expression of activation antigens All patients Patients with increased expression of activation antigen

$$\frac{D\mathrm{about}lehen\mathrm{and}\mathrm{I\; am}}{P\mathrm{about}\mathrm{from}lelehen\mathrm{and}\mathrm{I\; am}}$$

Conditionally healthy donors Before treatment After treatment M ± σ p ₁ M ± σ p ₂ M ± σ p ₁ M ± σ p ₂ CD25 ⁺ (%) $$\frac{18.5\pm \mathrm{3,5}}{14.6\pm 3.9}$$

0,000 10.6 ± 2.4 $$\frac{\mathrm{0,022}}{0.115}$$

19.5 ± 9 0,000 15.6 ± 1.7 0,000 HLA-DR ⁺ (%) $$\frac{17.6\pm 3.2}{\mathrm{14,4}\pm \mathrm{3,5}}$$

0,025 16.0 ± 3.5 $$\frac{0.142}{0.240}$$

19.9 ± 1.5 0.937 19.2 ± 1.5 0.002 CD95 ⁺ (%) $$\frac{26.9\pm 2.7}{22.4\pm 5.3}$$

0.001 19.8 ± 3.2 $$\frac{\mathrm{0,048}}{0.652}$$

28.3 ± 6.4 0,055 24.6 ± 4.7 0,000 Note: in the numerator - indicators before treatment, in the denominator - after treatment; p ₁ - significance of differences when comparing indicators before and after treatment (paired student criterion was used); p ₂ - the significance of differences in relation to healthy donors (student criterion was used for the independent option).

After treatment, the sample generally showed a decrease in the expression of activation antigens CD25 ⁺ , CD95 ⁺ and HLA-DR ⁺ . In the subgroup with initially high values of activated lymphocytes after treatment, the expression indices of these antigens also decreased to the normal level (Table 5).

A decrease in the number of activated lymphocytes under the influence of CH Bifidomarin reflecting the chronic irritating effect of infectious agents may indicate a decrease in the antigenic load in patients with dysbiotic disorders.

The phagocytic activity of peripheral blood neutrophils (AF and PS), calculated in the entire sample, was reduced before treatment. After treatment, the average values of the phagocytic activity of neutrophils in the entire sample did not change and remained reduced compared to those in the group of healthy donors. At the same time, 70% of patients responded positively to treatment with the inclusion of Bifidomarin HF: AF and PS increased and did not significantly differ from those in healthy donors (p = 0.823, p = 0.342, respectively) (Table 6).

Analysis of the indicators of the humoral immune response without taking into account antigenic specificity showed that before the start of therapy, the concentration of IgG and IgM immunoglobulins in the blood serum of patients was reduced to borderline low values relative to that of healthy donors, the IgA concentration was within the reference values (Table 6) . After taking Bifidomarin HF, the concentration of IgG and IgM in blood serum increased (p = 0.051 and p = 0.029), although it did not reach the average values in healthy donors. The concentration of IgA, which is a substrate for the formation of secretory IgA, the main protective element of the mucous membranes, increased in patients (p = 0.023) (Table 6).

Table 6. Characterization of the phagocytic activity of blood neutrophils and humoral immunity in patients with chronic gastrointestinal diseases in the dynamics of treatment of HF "Bifidomarin" Indicator Conditionally healthy Sick p ₁ p ₂

M ± σ donors FP% 58.5 ± 8.5

$$\frac{46.8\pm 8.0}{59.0\pm 5.1}$$

$$\frac{\mathrm{0,000}}{0.823}$$

0.010 Ff 4.0 ± 1.5 $$\frac{\mathrm{2,8}\pm \mathrm{1,5}}{3.6\pm \mathrm{1,1}}$$

$$\frac{\mathrm{0,000}}{0.342}$$

0,033 IgG (g / l) 9.8 ± 1.7 $$\frac{7.9\pm 2.2}{9.1\pm \mathrm{1,5}}$$

$$\frac{0.013}{0.156}$$

0.051 IgM (g / l) 1.6 ± 0.7 $$\frac{0.81\pm 0.1}{0.98\pm 0.3}$$

$$\frac{\mathrm{0,000}}{\mathrm{0,000}}$$

0,029 IgA (g / l) 2.1 ± 0.7 $$\frac{2.2\pm 0.8}{2.7\pm 0.5}$$

$$\frac{0.676}{0.003}$$

0,023 Note: indicators - M ± σ; in the numerator - indicators before treatment, in the denominator - after treatment; p ₁ - the significance of differences when comparing indicators before and after treatment in relation to healthy donors (student criterion was used for the independent option); p ₂ - the significance of differences when comparing indicators before and after treatment (paired student criterion was used).

Thus, non-drug treatment of HF “Bifidomarin” in patients with chronic gastrointestinal diseases accompanied by intestinal dysbiosis leads to normalization of the functions of the cellular and humoral parts of the immune system: modulation of lymphocyte activation and differentiation processes, stimulation of the phagocytic activity of neutrophils, enhancement of the synthesis of immunoglobulins, including IgA , which is a substrate for the formation of secretory IgA - the main protective element of the mucous membranes.

When assessing the biochemical parameters of the lipid profile in patients before treatment (throughout the sample), an increased level of total cholesterol and low density lipoproteins (LDL) in the blood serum was revealed, which indicates a violation of lipid metabolism (Table 7). When analyzing lipid metabolism after treatment, significant changes in the concentration of total cholesterol and LDL were not detected. However, there was a positive dynamics in the level of anti-atherogenic fractions of cholesterol - HDL, ARO-A1, a decrease in the ratio of APO-B / ARO-A1, which indicates a normalization of the distribution of cholesterol between fractions of lipoproteins, and a decrease in the atherogenic coefficient (CA) (Table 7).

Table 7. The dynamics of changes in the blood lipid spectrum in patients with chronic diseases of the gastrointestinal tract in the dynamics of treatment of HF "Bifidomarin" Group Cholesterol, mmol / L LDL, mmol / l HDL, mmol / l Triglycerides, mmol / L VLDL mmol / L ARO-A1, g / l ARO-B, g / l ARO-V / ARO-A1 Coeff. atherogenicity Experienced group

$$\frac{4.49\pm 0.83}{4.45\pm 0.71}$$

$$\frac{2.83\pm 0.8}{\mathrm{2,51}\pm 0.5}$$

$$\frac{1.43\pm 0.3}{1.83\pm 0.5}$$

$$\frac{\mathrm{1,0}\pm 0.6}{\mathrm{1,1}\pm 0.6}$$

$$\frac{0.54\pm 0.3}{0.51\pm 0.3}$$

$$\frac{1.46\pm 0.31}{1.76\pm 23}$$

$$\frac{1.26\pm 0.3}{1.35\pm 0.3}$$

$$\frac{0.86}{0.76}$$

$$\frac{\mathrm{2,4}\pm \mathrm{1,0}}{1.7\pm \mathrm{1,1}}$$

P = 0.200 P = 0.113 P = 0,000 P = 0.333 P = 0.509 P = 0.001 P = 0.177 P = 0.042 Conditionally healthy donors 3.8 ± 0.8 2.4 ± 0.4 1.5 ± 0.2 0.96 ± 0.2 8 0.5 ± 0.1 1.55 ± 0.3 1.03 ± 0.28 0.76 2.1 ± 0.2 Note: indicators - M ± σ; p - significance of differences when comparing indicators before and after treatment in relation to healthy donors (student criterion was used for the independent option)

The analysis of lipid metabolism in patients depending on the effectiveness of treatment (with a positive effect of therapy or with no effect of therapy) showed that 70% of patients responded positively to treatment with the use of HF Bifidomarin. In particular, in these patients a decrease in the concentration of total cholesterol, LDL and ARO-B was revealed, an increase in the concentration of the antiatherogenic fraction of cholesterol ARO-A1, which is evidence of normalization of lipid metabolism (Table 8).

Table 8. Dynamics of the level of atherogenic and antiatherogenic fractions of cholesterol in patients with a positive effect of therapy and lack of effect of therapy

Indicator Patients with a positive effect of therapy (70%) Patients with no treatment effect (30%)

$$\frac{D\mathrm{about}lehen\mathrm{and}\mathrm{I\; am}}{P\mathrm{about}\mathrm{from}lelehen\mathrm{and}\mathrm{I\; am}}$$

$$\frac{D\mathrm{about}lehen\mathrm{and}\mathrm{I\; am}}{P\mathrm{about}\mathrm{from}lelehen\mathrm{and}\mathrm{I\; am}}$$

M ± σ R M ± σ R Cholesterol, mmol / L $$\frac{4.60\pm 0.90}{4.04\pm 0.78}$$

0.002 $$\frac{4.12\pm 0.55}{4.66\pm 0.30}$$

0.015 LDL, mmol / l $$\frac{2.6\pm 0.7}{2.0\pm 0.6}$$

0.007 $$\frac{1.9\pm \mathrm{1,0}}{2.6\pm \mathrm{1,0}}$$

0.002 Triglycerides, mmol / L $$\frac{0.8\pm 0.4}{0.6\pm 0.2}$$

0.011 $$\frac{1.4\pm 0.5}{\mathrm{1,6}\pm 0.6}$$

0.322 ARO-B, g / l $$\frac{141.9\pm 26}{\mathrm{110,4}\pm 36}$$

0.015 $$\frac{124.5\pm \mathrm{thirty}}{142.3\pm 27}$$

0,000 HDL, mmol / L $$\frac{1.4\pm 0.3}{1.8\pm 0.4}$$

0,000 $$\frac{\mathrm{1,5}\pm 0.3}{1.7\pm 0.6}$$

0.537 ARO-A1, g / l $$\frac{134.8\pm 26}{180\pm 45}$$

0,000 $$\frac{177.7\pm \mathrm{twenty}}{164.9\pm \mathrm{eighteen}}$$

0.130 Note: indicators - M ± σ; p - significance of differences when comparing providers before and after treatment (paired student criterion was used).

The data obtained indicate that non-drug therapy with the use of HF "Bifidomarin" in patients with chronic diseases of the gastrointestinal tract, accompanied by intestinal dysbiosis, leads to a normalization of the distribution of cholesterol between fractions of lipoproteins and a decrease in the coefficient of atherogenicity.

Examples of specific application.

Example 1. Petrova EP

Patient P., 70 years old. Diagnosis: hr. gastroduodenitis, chronic cholecystitis, intestinal dysbiosis of the 2nd degree. Complaints before taking Bifidomarin: decreased appetite, belching, pain and bloating, rumbling in the abdomen, tendency to constipation. After a 6-week course of taking Bifidomarin in an amount of 200 mg, twice a day: there are no complaints of pain and bloating, and flatulence, belching decreased significantly, the stool became regular. He feels great.

Example 2. Pestryakova Y. F.

Patient Peninsula, 35 years old. Diagnosis: chronic cholecystitis, intestinal dysbiosis of 1 degree. Complaints before taking Bifidomarin: fatigue, weakness, lack of appetite, bitterness in the mouth, heaviness in the right hypochondrium, spastic pain along the large intestine, a feeling of incomplete bowel movement, tendency to constipation. After a 6-week course of taking Bifidomarin: an improvement in appetite, a decrease in weakness, a decrease in severity in the right hypochondrium, there were spastic pain along the intestines, the feeling of incomplete bowel movement rarely began to disturb, the stool became regular. She feels well.

Example 3. Dobryakov E.Yu.

Patient D., 45 years old. Diagnosis: hr. parenchymal pancreatitis, intestinal dysbiosis 2 degrees. Complaints before taking Bifidomarin: decreased appetite, nausea when eating fatty foods, bloating, spastic pain along the intestines, a tendency to diarrhea. After a 6-week course of taking Bifidomarin: there were no complaints of pain and bloating, nausea, and stool became regular. The general state of health is good.

Example 4. Kozyavina VA Patient K., 66 years old. Diagnosis: hr. colitis with impaired motor-evacuation function, biliary dyskinesia, intestinal dysbiosis of the 2nd degree. Complaints before taking Bifidomarin: belching, metallic taste in the mouth, feeling of heaviness in the epigastrium, bloating, cramping pain along the intestines, unstable stool, weakness, fatigue, headaches. After a 6-week course of taking Bifidomarin: a significant reduction in weakness and fatigue, the metallic taste in the mouth disappeared, complaints of bloating disappeared, the stool became regular and regular.

Example 5. Ignatenko N.N.

Patient I., 48 years old. Diagnosis: hr. gastroduodenitis, hr. enterocolitis, intestinal dysbiosis of 1 degree. Complaints before taking Bifidomarin: decreased appetite, belching, rumbling of the intestines, bloating, tendency to constipation, dry skin, brittle nails. After a 6-week course of taking Bifidomarin: complaints of bloating and rumbling of the abdomen, and no burping, the stool returned to normal, general health, skin and nails improved.

Thus, the studies showed that in patients with chronic gastrointestinal diseases accompanied by intestinal dysbiosis, taking the Bifidomarin synbiotic drink containing bifidobacteria and immunoactive polysaccharides from brown alga F. Evanescens, relief of clinical symptoms and improvement in general condition, restoration of microbiocenosis were observed normalization of the immune and metabolic status (lipid spectrum). "Bifidomarin" is an effective means of correcting dysbiotic and associated immune and metabolic disorders in patients with chronic gastrointestinal diseases, accompanied by intestinal dysbiosis.

Claims (1)

A method of non-drug treatment of patients with chronic diseases of the gastrointestinal tract (GIT), characterized in that the rehabilitation therapy includes a synbiotic drink containing bifidobacteria and immunoactive polysaccharides from brown alga F.evanescens in an amount of 200 ml per day in 2 doses 30 minutes before food for 6 weeks.