WO2016053142A1

WO2016053142A1 - Composition for body detoxification

Info

Publication number: WO2016053142A1
Application number: PCT/RU2015/000600
Authority: WO
Inventors: Дмитрий Николаевич ПАРХОМЕНКО; Светлана Анатольевна ЗАКИРОВА; Александр Викторович МАТЮШЁНОК
Original assignee: ДИКОВСКИЙ, Алексан Владимирович; Дмитрий Николаевич ПАРХОМЕНКО; Светлана Анатольевна ЗАКИРОВА; Александр Викторович МАТЮШЁНОК
Priority date: 2014-09-30
Filing date: 2015-09-24
Publication date: 2016-04-07
Also published as: EA201650141A1; RU2591791C2; RU2014139542A

Abstract

The invention relates to biotechnology and the food processing and pharmaceutical industry, and specifically to the production of functional food products for normalising the condition of a body, and food supplements and medicinal preparations intended for normalising the condition of the gastrointestinal tract (removing toxic substances from the body). A composition for purifying the body of toxins is in the form of a gel and contains, as active ingredients, an insoluble enterosorbent and a soluble enterosorbent, which forms a matrix-forming base for an insoluble sorbent. The composition effectively binds and holds the bound toxins within the matrix, and has an effective detoxifying effect while requiring an appreciably smaller amount of the product to be used, thus reducing undesirable side effects associated with the use of detoxifying agents.

Description

COMPOSITION FOR DETOXICATION OF THE ORGANISM

The invention relates to biotechnology, the food and pharmaceutical industries, and in particular to the production of functional food products to normalize the state of the body and dietary supplements (BAA) to food and drugs designed to normalize the state of the gastrointestinal tract (removal of toxic substances from the body).

Intoxication of the human and animal organisms is a syndrome that accompanies a wide variety of pathological processes and conditions, such as poisoning by exogenous poisons or infectious diseases, or damage to internal organs and systems, accompanied by either an increased formation or a decrease in the efficiency of elimination and neutralization of endogenous (metabolic) poisons, which are often simplistically referred to as “slags” {Uchaykin V. F. Enterosorption is an effective method of etiopathogenetic therapy of acute intestinal infections / V. F. Uchayk in, A.A. Novokshonov, N.V. Sokolova // Det. infection. - 2005. - N ° 3. - S. 39-43).

Acute intestinal infections (ACI) in the structure of the infectious morbidity of the population take second place after acute respiratory viral infections, are characterized by the absence of seasonality and age-related selectivity of the morbidity, the development of unstable, short-term species-specific immunity, which suggests the re-development of the infectious process caused by another pathogen during a limited time {Pokrovsky V.I., Pozdeev O. (ed.). Medical Microbiology. M .: GOETAR "MEDICINE", 1998. - 1155 s). The creation of new and improvement of existing methods of treatment of acute intestinal infections is formed in parallel with new information obtained in the course of scientific research in the field of pathogenesis of infectious diseases, creating the prerequisites for the development of new dosage forms of drugs and their clinical testing. This application is aimed at creating a tool that allows you to refuse in some cases traditionally used in the treatment of infectious patients with antibacterial agents by enhancing pathogenetic therapy, based on the principle of minimal adverse effects on the patient's body.

Questions of etiopathogenetic therapy of acute intestinal infections remain relevant in connection with their widespread distribution, aggravation of the clinical course of individual nosological forms, and the development of pathogen resistance to traditionally used etiotropic drugs. The widespread and often uncontrolled use of antibacterial agents is often not only ineffective, but also accompanied by undesirable side effects and adverse effects on the patient’s body (A. L. Kostyuchenko Active detoxification // World of Medicine. St. Petersburg, 2000. - M> 9-10) .

Among acute intestinal infections in recent years, much attention has been paid to diarrhea. Diarrhea is a polyetiological clinical syndrome characterized by a relaxation of stool (more than three times a day). The vast majority of cases of acute diarrhea are associated with acute intestinal infections, but non-infectious factors can also be its causes: nutritional errors, dietary overloads, food incompatibility, excess fiber coarse fiber, allergic reactions to certain foods (mushrooms, crustaceans, strawberries), side effects of medicines (Scherbakov P.L., Petukhov V.A. Comparative effectiveness of enterosorbents for diarrhea in children // Questions of modern pediatrics. - 2005. - M 4. - P. 85-89).

The incidence of diarrhea, as well as other diseases, depends on the region of residence, duration of stay, and living conditions (water quality and nutrition), as well as the type of activity. In developing countries, diarrhea clearly dominates; 60% or more of those who come ill get sick. It most often occurs in countries of Asia, Africa, Latin America, the Middle East, less often in countries of Southern Europe and the Caribbean (up to 20%), most rarely - in the USA, Canada, countries of Northern Europe, Australia (less than 8%). There is evidence that the disease is detected quite often in residents of developing countries with a low level of sanitary culture when they enter developed countries.

The causative agents of diarrhea are various microorganisms: bacteria, viruses, protozoa. The causes of intestinal dysfunction when entering other countries or another climatic and geographical area can also be changes in diet, diet and lifestyle, salt composition of water, alcohol abuse, unusual food, and a change in the bacterial flora of the intestine against this background.

In all these cases, with pronounced (acute) intoxications, a differentiated approach is provided when choosing means for detoxifying the body, which differ, depending on the nature of the toxic substances that caused the poisoning. In particular, known enterosorbents based on hydrolysis lignin or activated carbon are used.

Various forms of lignin-based enterosorbents for oral administration are known. Lignin-based enterosorbents in the form of granules, powders and tablets are used to prevent and treat acute and chronic diseases of the gastrointestinal tract, liver and kidneys, to treat infectious diseases such as dysentery, viral hepatitis, etc., to treat poisoning, drug and food allergies, asthma, diabetes, impaired fat metabolism. Lignin-based enterosorbents are enterosorbents from hydrolytic lignin, which have been processed to specific quality indicators to produce a product, used for medical purposes, and medical or therapeutic lignin (polyphepan) obtained by special technological processing of hydrolysis lignin (RU2084236 publ. 07/20/1997 A61K35 / 78, RU2125463 publ. 27.01.1999 A61K35 / 78, RU2061488 publ. 10.06.1996 A61K35 / 78, RU2116080 publ. 07.27.1998 A61 35/78, RU2166953 publ. 02.20.2001 A61K35 / 78, RU2167669, publ. 02.20.2001 A61K35 / 78, RU2131260, publ. 10.06.1999 A61K35 / 78, RU2279278, publ. 01.01. .2000 A61K31 / 70).

The disadvantage of solid tablet forms of enterosorbents is their low affinity for the surface of the mucosa in the intestinal lumen, which sharply reduces the contact of enterosorbent with toxins, the irritating effect on the intestinal mucosa and the low ability to bind and excrete uremic toxins. The disadvantage of ionic hypertonic solutions is their inability to bind uremic toxins, the ability to cause diarrhea and hypersecretion of toxins into the intestinal lumen, creating an ionic imbalance in the body

Known compositions for detoxification in the form of hydrogels of methylsilicic acid gels and the method for their preparation according to the patent (RU21 11979, publ. 05.27.1998 C08G77 / 02, GB1079265 publ. 08/16/1967 A61K31 / 42, UA78922 publ. 04/25/2007 S01VZZ / 158).

Also known is a composition for cleansing the body of toxins and normalizing the composition of the microflora of the digestive tract, disrupted due to various diseases, bacterial or chemical intoxication, including during antibiotic therapy. As one of the main components contains cocoa butter (RU 2433751, publ. 10.11.2010, A23L1 / 30).

The specified composition also has the following disadvantages. Since a lipid-containing agent is present in this composition, the sorption of this composition will be associated mainly with substances of a lipid nature as well. Since the main the mass of food enters the body with water, a substantial part of the toxins that will be present in the digestive tract are also contained predominantly in the aqueous-organic phase. Thus, the sorption of a significant part of the toxins will be hindered by the fatty phase contained around the enterosorbent, which significantly reduces its sorption effect. On the other hand, in the prevention and treatment of disorders of the gastrointestinal tract, it is often necessary to pay attention to the prevention and treatment of the liver, as the main detoxification organ. In the prevention and treatment of the liver, it is often necessary to take drugs of an essential or lipid nature, for example, such as essential phospholipids and fat-soluble vitamins of groups A and D. Due to their lipophilicity, in combination therapy with an enterosorbent of lipid nature, their administration will not be effective due to their binding and transit evacuation from intestinal lumen together with the bulk of enterosorbent.

Closest to the claimed technical solution is a pharmaceutical composition, in the form of an aqueous suspension of finely divided hydrolytic lignin, used as a treatment for acute and chronic intestinal infections, including exogenous and endogenous intoxications, disorders of fat and other types of metabolism (RU 2026078, publ. 09.01. 1995, A61K35 / 78).

However, this composition has significant disadvantages. Since there is no matrix forming agent in this composition, after the composition enters the digestive tract, water is rapidly sorbed and the particles of insoluble sorbent are concentrated on the surface of the mucosa in the form of a dense layer, thereby significantly reducing its sorption potential. In addition, insoluble particles of the sorbent, due to their small size, tend to penetrate into deeper layers of the epithelium, thereby causing an irritating effect. Finally, all the described compositions based on insoluble dietary fiber or organosilicon compounds have unsatisfactory taste properties, are retained on the mucous membrane of the oral cavity, causing a long unpleasant aftertaste, require drinking plenty of water. All this makes such compositions uncomfortable and often unacceptable for their use in young children.

The technical task of the claimed invention is the creation of an effective composition that provides complete healing of the body due to the rapid removal of toxins from all parts of the digestive tract, reducing unwanted side effects associated with the use of certain categories of detoxification agents, as well as expanding the arsenal of compositions suitable for cleansing the body of toxins due to the use in a more convenient form, including for children.

The technical result of the claimed solution lies in the effective binding and retention of bound toxins in the matrix. It has an effective detoxification effect when using a significantly smaller amount of product, reducing undesirable side effects associated with the use of detoxification agents.

In a composition that includes a matrix-forming base, the irritating effect is eliminated as much as possible due to the protective properties of the matrix.

The technical result of the claimed invention is achieved in that the composition for cleansing the body of toxins in the form of a gel contains, as an active component, an insoluble enterosorbent and a second active component in the form of a soluble enterosorbent. In this case, the soluble enterosorbent forms a matrix-forming base for the insoluble sorbent, the insoluble sorbent and the soluble sorbent

b have a particle size of not more than 150 microns, with the following content of components, in mass%:

- insoluble enterosorbent 3 - 70%;

- soluble enterosorbent 0.1 - 70%.

The composition may contain insoluble enterosorbents from the group: plant fiber, hydrolytic lignin, bran, cellulose and its esters, microcrystalline cellulose, highly esterified insoluble pectin, or a mineral from the group: zeolite, smectite, silica (silicon dioxide), activated carbon.

The composition may contain soluble enterosorbent from the group of dietary fiber: gums, pectins, hemicelluloses, soluble cellulose ethers, starch and its derivatives, polyvidones, polyethylene glycols, polydextrose, dextrins, cyclodextrins, agars, carrageenans,

The composition may contain soluble enterosorbent from the group of dietary fiber: alginates and their derivatives, gums, pectins, hemicelluloses, soluble cellulose ethers, starch and its derivatives, polyvidones, polyethylene glycols, polydextrose, dextrins, cyclodextrins, agars, carrageenans.

The composition may further comprise at least one flavoring, preferably a natural food

flavoring in an amount of not more than 3 mass%.

The composition further comprises at least one flavoring agent, a sweetener in an amount of not more than 20 mass%.

The composition may contain a preservative in an amount of not more than 1 mass%.

The composition can be made in the form of granules for the preparation of an aqueous suspension.

The composition can be made homogeneous in a paste form. The composition may, in embodiments, contain an additional sorbent of up to 49% by mass as an increase in the efficiency of sorption of toxic substances.

The synergistic effect of the insoluble enterosorbent and the soluble enterosorbent is due to the fact that the insoluble enterosorbent interacts with the substance mainly due to dispersion forces, which determine the sorption effect of the “solid” carrier on the one hand, and the soluble enterosorbent interacts with the substance mainly due to the distribution forces between the two liquid phases , as well as causing a spatial configuration with particles of insoluble enterosorbent evenly distributed in it, further enhances the effect of insoluble particles sorption sorbent by forming the maximum potential and optimally distributed "binding sites". The particles of insoluble enterosorbent, in turn, form a framework that enhances the sorption potential of the matrix-forming elements of the soluble enterosorbent, as well as significantly expanding the range in size and sorption mechanism for efficient binding and elimination of toxins from the body. The matrix-forming base may consist of two or more soluble enterosorbents.For example, when using a combination of soluble enterosorbents, such as alginate and pectin, an additional increase in sorption activity occurs due to the unique combination of available sets of functional groups that substantially complement the sorption mechanisms of each component. Alginate in the claimed composition simultaneously performs the function of a gelling agent, as well as the function of a sorbent of water-soluble substances upon entry into the gastrointestinal tract. Thus, pathogenic microbes and their metabolic products are removed, and the effect of irritation of the upper mucosa is reduced. digestive tract (oral cavity, esophagus, stomach) by sorbent particles and the severity of inflammatory processes in the mucous membranes of the gastrointestinal tract decreases due to improved product properties, elimination of a wide range of toxins of various origins from the body, and due to this - for faster healing of the body.

In view of the foregoing, the active components in the presented pharmaceutical composition have a summing effect of the interaction in action significantly superior to the healing properties of each individual component of the composition.

The gel form of the composition used has a positive effect on the organoleptic properties of the product, it eliminates or significantly reduces the unpleasant taste sensations from the effects of many sorbents (the taste of wood sawdust of hydrolysis lignin, an unpleasant sour taste of activated carbon, some mineral sorbents based on alumina, etc.) also significantly reduce the irritating effect of sorbent particles on the mechanical (tactile) receptors of the tongue and oral mucosa, I attach Suspensions and disintegrating tablets in the mouth unpleasant sensations of rough “granularity”. The adhesion (adhesion) of the sorbent particles to the surface of the mucosa is significantly reduced, and therefore, taking the drug does not require washing it with a large amount of water. The latter is especially important if it is necessary to take the drug outdoors.

The technological advantages of the proposed options for compositions are that the proposed approach can significantly expand the possibilities of manufacturing affordable and convenient forms of the product for mass consumption, both its medicinal options and non-drug consumer forms (dietary supplements, functional foods, etc. by A substantial expansion of the field of technological implementation of the composition is achieved.

The composition can be made on the basis of a known sorbent - for example, a mineral enterosorbent such as smectite, zeolite, alumina, silica gel, hydrolysis lignin, microcrystalline cellulose. A composition based on the listed ingredients is made in the form of a suspension, gel, paste and spherical granules of solid jelly. An additional solubilizer (for example, propylene glycol in an amount of not more than 5% by weight), as well as taste correctors (flavoring, sweetener, etc.) in quantities necessary to impart a proper taste sensation can be introduced into the product.

In addition, to obtain the product of the required consistency, the composition may include permitted for use in food products and (or) pharmaceutical acceptable excipients (cellulose derivatives, antioxidants, preservatives.

An important property and feature of the proposed composition is the use of sorbent powders having a particle size of not more than 150 microns in its composition. Particle size affects the basic properties of the composition in a direct way. Firstly, it is widely known that the sorption ability of sorbents strongly depends on the particle size: the larger the total surface area, the higher the total sorption capacity of the sorbent. The total surface area of the particles is the higher, the smaller their geometric mean diameter. At the same time, excessive grinding of the sorbent leads to the manifestation of negative aspects: 1) product losses increase sharply, since the efficiency of obtaining very small (less than 10 microns) particles by known methods and devices quickly decreases; 2) with too small particle sizes, the destruction of the internal porous structure of many sorbents, which leads not to the further expected increase in their sorption capacity, but, on the contrary, to its rapid decline. 3) the manufacturability of the product decreases, which acquires the ability to quickly transition to a suspended state (“volatility” of powders) with an increase in technological losses at the production stages; 4) at the same time, sanitary and hygienic conditions of production are deteriorating (the dustiness of the premises is growing):

Together, all of the above effects provide the claimed composition with an increased ability to prevent the effects of chronic poisoning with harmful substances, poisons that enter the body from the outside, or accumulate in the body with various diseases; supplemented and enhanced the healing effect of each of the individual components:

a) the sorption properties of the insoluble enterosorbent in relation to various toxic molecules are significantly enhanced due to the synergistic effect of interaction with a matrix-resolving aqueous organic system;

b) the matrix agent forms a complex polymer system that allows you to maintain the effective sorption potential of the insoluble enterosorbent for a long time after the product enters the body due to the strong moisture-retaining properties of the matrix-forming agent from a number of soluble dietary fibers;

c) due to the inclusion of an insoluble enterosorbent in the composition, unwanted side effects associated with the use of solid sorbents, such as the irritating effect on the gastrointestinal mucosa and constipation, are significantly reduced;

d) alginate, like many other soluble dietary fibers, has an independent cytoprotective effect, protecting the mucous membranes of various parts of the gastrointestinal tract from traumatic chemical and mechanical influences; e) acting together with an insoluble enterosorbent that binds toxic substances, the matrix-forming agent in the composition significantly expands the sorption range of sorbed substances due to the formation of additional binding mechanisms, including due to extrusion sterically determined effects. e) due to the inclusion of an insoluble enterosorbent in the composition, it became possible to significantly change the organoleptic properties of the pharmaceutical composition, since due to the inclusion of an insoluble sorbent in the matrix, it was possible to significantly mask the unpleasant sensations arising from its use in the composition.

g) due to the inclusion of an insoluble enterosorbent in the composition, it was possible to create a platform for creating convenient for use in children and age categories of patients who have difficulty swallowing.

Assessment of sorption activity of the claimed composition.

The main target groups of sorbates are represented by low molecular weight and high molecular weight compounds. Markers were selected that are characterized by a correspondingly low molecular weight and high molecular weight structure, reflecting the sorption of the corresponding group of substances in the body (sorption markers).

Sorption of drug samples at the stage of screening studies was evaluated using three markers as an example: methylene blue, methyl orange and Congo red. Methylene blue is a low molecular weight positively charged marker. It is a generally accepted marker for evaluating the sorption properties of a wide range of sorbents. Congo red - has a large molecule and is negatively charged in total. As an analytical determination technique, spectrophotometry-based techniques were selected. Additionally Initially, the sorption potential was estimated using methyl orange, but the practice of its use showed its lack of information in relation to the selected array of substances.

To assess the sorption activity of the claimed product, the effectiveness of sorption in vitro was evaluated. For this, an exact sample of the preparation was placed in a 100 ml conical flask with a ground stopper, 20.0 ml of methylene blue solution A was added, closed with a stopper and stirred for 1 h on a magnetic stirrer or shaken on a laboratory shaking apparatus with a vibration number of at least 120 min-1. The suspension was centrifuged for 15 minutes at 6,000 rpm. 1.0 ml of the supernatant was placed in a 100 ml volumetric flask, the volume of the solution was adjusted to the mark with water and mixed (test solution). The optical density of solution B of methylene blue and the test solution was measured on a spectrophotometer at the absorption maximum at a wavelength of 665 nm in a cuvette with a layer thickness of 10 mm. As a comparison solution used water. Next, a calculation was made according to the corresponding formula. Almost similarly, sorption with Congo red was evaluated.

An array of primary data was formed using various components, primarily using various gelling bases.

As a comparison, the bases themselves were chosen, without the addition of hydrolytic lignin, an aqueous suspension of hydrolytic lignin, and a silicon-organic sorbent in the form of a gel. Further studies were carried out using high molecular weight compounds, such as proteins. The experimental results are shown in table 1. Table

Sorption Efficiency

Note: * - MS - methylene, ** - KK - Congo red

From the results of the experiment it follows that the combined preparation based on the sorbent of lignin and alginate is able to efficiently bind both low-molecular and medium-molecular molecules and high-molecular substances, while individual components showed lower sorption results.

Moreover, in the case of a combination of insoluble enterosorbent with soluble, not only arithmetic increase due to the total effect of the components included in the composition occurs, but a synergistic increase in the sorption potential.

In addition to studying the sorption properties, acceptable organoleptic properties of the polymers used and their combinations were investigated. Table 2.

The study of organoleptic properties of samples.

Note: 1 - slightly, 2 - medium, 3 - significantly

In terms of organoleptic indicators, the worst indicators in organoleptic are combinations of hydrolytic lignin with povidone K90 and pectin. However, the combination of pectin with other gelling agents significantly improves the quality of the taste indicators of the drug.

A study of the effectiveness of the combination was carried out on an experimental model of acute intestinal infection of rats.

Modeling of acute intestinal infection (ACI) consisted of two stages: modeling of dysbiosis and infection by the introduction of opportunistic bacteria (UPM). As test systems used rats - males of the Wistar line, weighing 200 g.

Dysbacteriosis in rats was caused by oral administration of the doxycycline antibiotic. The administration of doxycycline to animals was carried out daily at a dose of 0.2 mg. The duration of the administration course was 3 days. After that, OKI was induced in rats by oral administration of 1.0 ml of a mixture of UPM cultures every 4 hours for 5 days (E. coli hemolytic 10 ¹⁰ CFU / ml, K. pneumoniae 10 ¹⁰ CFU / ml, St. aureus (hyaluronidase, lecithinase, coagulase, hemagglutinating activity) 10 ^th CFU / ml, Ps. aeruginosae 10 ¹⁰ CFU / ml, Enterobacter cloacae 10 ¹⁰ CFU / ml, Str. faecalis 10 ¹⁰ CFU / ml).

Experimental animals were divided into six groups of 10 animals in each group.

To determine the therapeutic efficacy of the substance and combination, it was administered after infection with per os in doses recommended for the treatment of acute intestinal infections according to the instructions for the medical use of analogues. The term of drug administration was 7 days. Study groups are shown in table 3.

Table 3

Study groups

Efficiency was evaluated based on the percentage of surviving / dead animals after the introduction of cultures, the clinical condition of the animals, the histological picture of the small, large intestines. After the animals were removed from the experiment by decapitation under ether anesthesia, fragments of the colon and small intestine were taken. Histological sections were stained with hematoxylin-eosin according to standard methods. In the small intestine, wall thickness, crypt depth, length and diameter of villi were measured; in the thick one, wall thickness, crypt depth, length and diameter of lunate folds. We studied the macroscopic picture of the mucous membrane for visible damage — edema, hyperemia, hemorrhage.

results

At the first stage, the duration of doxycycline administration was 3 days. Most animals in the experimental group receiving doxycycline at a dose of 0.4 mg had diarrhea, rats gained weight more slowly than animals in the control groups. In 20% of the animals of the experimental group, after the course of the administration of doxycycline, a decrease in body weight by an average of 7% was noted compared with the initial average weight. In animals of the control groups, the weight gain was 3%.

After modeling dysbiosis, a study was conducted of the qualitative and quantitative characteristics of fecal microflora in laboratory animals (table 4).

Table 4.

The composition of the intestinal microflora after modeling dysbiosis

Culture medium group

Animal Staphyl Enterobacterium Lactoba Bifidob Mushrooms

o Kluyver Klebsiella Other cillus a p. Candida coccus a oxytoca spp. cterium

spp. Cryocres spp.

cens

CFU / g

large mucous membranes

Doxycyclic colony, continuous growth in the application zone,

1.6 · 10 ³ 3.5 · 10 ³ 2.5 10 ³ 1Д-10 ⁷ 7.7 · 10 ⁶

> 10 ⁷

large mucous membranes

colonies, 10 ² control 6.5 - 10 ² - - 3.3 - 10 ² 7.4 - 10 ⁶ 6.1 10 ⁵ Small matte colonies, 2.5 10 ⁵ intact small matte

3 10 ³ - 2.5 - 10 ⁷ 3.7 - 10 ⁶ colonies,

10 ²

In the second stage, 1.0 ml of a mixture of UPM cultures was orally administered every 4 hours for 5 days.

In the control group, on 2.38 ± 0.18 days of the introduction of a mixture of UPM cultures in experimental animals of all groups, cognitive and motor activity was inhibited, and appetite decreased. Thirst joined 4.63 ± 0.13 days, loose stools of green-brown color without impurities of mucus, blood, and body weight decreased on average by (9.81 ± 0.3). The peak mortality rate (up to 80%) was on the 4th day after infection.

According to the experiment, as a result of therapeutic administration of protective drugs, it was possible to reduce the mortality of animals with simulated OKI (Table 5).

Table 5

Survival of animals in the treatment of AKI

Suspension Smectite 128 1 2 2 2 - - 5/5 50 dioctahedral - 45 mg / kg

%

Control - 1 1 1 3 3 1 10/0 0

Intact animals 0/10 100

For the entire period of observation of animal death in the study group N ° l was not observed. The lowest survival rate (about 50%) was revealed in the N2N2 2,4,6 group, which indicated a relatively low contribution of components from the toxic effect of pathogenic strains. The survival rate was higher in animal groups N2 3, 5 - 60% and 70%, respectively.

In group 1 rats, a restoration of appetite, behavioral and motor reactions, and a decrease in diarrhea syndrome were observed on 2.23 ± 0.53 days from the start of therapy. There was a faster, in comparison with other groups, normalization of bowel movements on the (4.38 ± 0.18) day from the start of treatment, respectively, p <0.001.

A histological examination of samples of the small intestine of rats of the control group showed no deviations from the norm, and enteritis, more pronounced in groups 2, 4, was observed in animals with a simulated OKI. Destructed villi occupied a significant amount, inflammatory infiltration of the entire intestine was observed with the formation of crypt abscesses.

Under the conditions of administering the pharmaceutical composition, hydrolysis Lignin gel - 8% + Sodium alginate - 2% in the N ° l group revealed an optimization of the histological structure of the small intestine. The destruction of the villi, tissue edema were less pronounced, and lymphohistiocytic infiltration was localized mainly in the submucosal layer.

There was a decrease in wall thickness compared to the control by 18.99% (p <0.001) in rats of group 1, and in animals of groups 2-6, by an average of 25.99% (p <0.001). These changes are due to dystrophic and destructive changes in the mucous membrane of the small intestine due to active desquamation of the epithelium of the villi, destruction of their tops and inflammatory infiltration. So, in comparison with rats of group 1, in experimental animals treated with other components, the length of the villi decreased by an average of 60.60% (p <0.001), and under the conditions of administration of the test composition, hydrolysis lignin gel - 8% + sodium alginate - The 2% decrease was only 6.70% (p <0.05) (Table 6).

There was also a deepening of the intestinal crypts in rats of group 2.4 by 70.06% of the values of the intact group (p <0.001), and compared with group 1 by 21.01% (p <0.05).

Colon microscopy data were characterized by unidirectional histological changes, indicating the manifestation of colitis in rats with acute intestinal infections caused by UPM, which was more pronounced in animals of 3.4.6 groups. Due to endotoxemia, desquamation of the intestinal epithelium, tissue edema with plethora and destruction of the vessels of the submucosal layer occurred, and the lymph nodes contained bright proliferation centers, which indicates a pronounced activity of the inflammatory response to the pathogen.

In the group N-> 1 OCI, the phenomena of colitis had a minimal degree of severity, as indicated by a partial destruction of the semilunar folds, less pronounced phenomena of discirculatory changes and edema.

Morphometry of the wall of the large intestine revealed an increase in its thickness, most pronounced in group 4, by 195.62%, least pronounced in the conditions of therapy, hydrolytic lignin gel - 8% + sodium alginate - 2% in the Ni group? 1 by 125.87%, respectively (p <0.05).

In groups 6 and 4 of the experimental animals, an increase in the length of the lunate folds was noted with a decrease in their diameter and a deepening of the crypts. So, the length of the lunate folds was 23.77% longer (p <0.01), and crypt depth - by 99.47% (p <0.001) (Table 7). Such changes in the structure of the colon can be explained by the greater intensity of inflammatory wall infiltration, hyperplasia of lymphoid elements and tissue edema. The difference in morphometric indices in the compared groups shows the effectiveness of the use of the composition Lignin hydrolysis - 8% + Sodium alginate - 2% in the treatment of acute intestinal infections compared with other sorbenates.

It was shown that when modeling OKI in rats during the period of early convalescence in the small and large intestines, both destructive and compensatory-adaptive processes are observed in the form of desquamation of the intestinal epithelium, destruction of the villi, inflammatory cell infiltration, and severe tissue edema. The least pronounced destructive phenomena were observed in the group N ° l.

The hydrolysis Lignin gel composition - 8% Sodium alginate - 2% provided the highest protection of animals against UPM toxins - protection was observed in 100% with the “therapeutic” introduction of such a composition.

Table 6

Morphometric indicators of the wall of the small intestine of rats (M ± t)

note: a significant difference in the indicators of groups of animals (p <0.05-0.001)

* significant difference in the indicators of groups of animals (p <0, 05-0, 001) with control

1 significant difference in the performance of animal groups (p <0.05-0.001) with the group N ° l

Table 7

Morphometric indicators of the wall of the colon of rats (M ± t)

note:

^ significant difference in indicators of groups of animals (p <0.05-0.001) with control

The obtained research results objectively demonstrate the effectiveness of the claimed composition by oral administration of the pharmaceutical composition in gel form, which includes insoluble and soluble enterosorbents as active components. High efficiency and safety of the composition is achieved due to the effective binding and retention of toxins.

The claimed composition can be manufactured in pharmaceutical production using standard equipment.

Claims

Claim

1. A composition for cleansing the body of toxins in the form of a gel, containing, as an active component, an insoluble enterosorbent characterized in that it contains a second active component in the form of a soluble enterosorbent, wherein the soluble enterosorbent forms a matrix-forming base for the insoluble sorbent, the insoluble sorbent and the soluble sorbent particle size not more than 150 microns, with the following content of components, in mass%:

- insoluble enterosorbent 3 - 70%;

- soluble enterosorbent 0.1 - 70%.

2. The composition according to claim 1, characterized in that it contains components from the group as an insoluble enterosorbent: plant fiber, hydrolysis lignin, bran, cellulose and its esters, microcrystalline cellulose, highly esterified insoluble pectin, or mineral from the group: zeolite, smectite , silica (silicon dioxide), activated carbon.

3. The composition according to claim 1, characterized in that it contains dietary fiber from the group of gums, pectins, hemicelluloses, soluble cellulose ethers, starch and its derivatives, polyvidones, polyethylene glycols, polydextrose, dextrins, cyclodextrins, agar, carrageenans .

4. The composition according to claim 1, characterized in that it further comprises a composition of soluble dietary fiber from the group: alginates and their derivatives, gums, pectins, hemicelluloses, soluble cellulose ethers, starch and its derivatives, polyvidones, polyethylene glycols, polydextrose, dextrins, cyclodextrins, agars, carrageenans.

5. The composition according to claim 1, characterized in that it further comprises at least one flavoring additive, preferably a natural food flavoring in an amount of not more than 3% by weight.

6. The composition according to claim 1, characterized in that it further comprises at least one flavoring agent, a sweetener in an amount of not more than 20 mass%.

7. The composition according to claim 1, characterized in that it contains a preservative in an amount of not more than 1 mass%.

8. The composition according to claim 1, characterized in that it can be made in the form of granules for the preparation of an aqueous suspension.

9. The composition according to claim 1, characterized in that it can be made of a homogeneous consistency in a paste form.

10. The composition according to claim 1, characterized in that in the variants of its execution contains an additional sorbent up to 49 wt% as an agent that increases the efficiency of sorption of toxic substances.