Composite enterosorbent

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to chemical-pharmaceutical industry and represents a composite enterosorbent of a silicone polymer specified in a group containing methyl monosilane acid xerogel or methyl monosilane acid hydrogel, differing by the fact that contains at least one ingredient specified in a group: lactulose, inulin, lignin, fructooligosaccharide, alginic acid in the form of pharmaceutically acceptable salts, chitosan, pectin, gum resin, beta-glucan in the amount of 0.1 to 10 portions per 1 weight portion of monosilane acid hydrogel or xerogel.

EFFECT: invention provides creating an agent to provide normalising the intestinal microflora and relieving the manifesting intoxication.

3 cl, 6 ex

 

The invention relates to silicon-containing drugs. These drugs are intended to treat diseases involving intoxication syndrome, in particular, diseases of the gastrointestinal tract, especially caused by pathogenic microorganisms and/or toxic substances that cause disruption of the normal microflora of the gastrointestinal tract.

Advanced level of technology

According to modern views intestinal dysbiosis (DK) understand the quantitative and qualitative changes of the normal microflora of the authority in violation of its biological functions, serial excessive reproduction of conditionally pathogenic enterobacteria, due to the influence of various adverse factors.

In English literature, not without reason, uses the term "bacterial overgrowth syndrome is a syndrome of excessive growth of bacteria in German - "bakterielle fehlbesiedlung" - wrong, wrong colonization of bacteria. Naturally, in such a situation is important, not the terminology and meaning, so we are talking about changes in the unnatural penetration flora mentioned in the lumen of the small intestine, as well as a sharp decrease in certain types of normal microflora of the genus Bifidobacterium, Escherichia Coli and simultaneous increase in the colon content of Escherichia coli with weakly expressed enzymatic properties of the mi, lacto-tonegative of entero-bacteria, fungi of the genus Candida and other

Obligate bacteria (bifidobacteria, bacteroids) constantly are part of the normal microflora, for metabolism and function to protect the host organism from infectious agents. They are about 95-97% of the total microflora. Facultative microorganisms (Lactobacillus, E. coli, enterococci), whose share amounts to 4-5%are opportunistic, as they often find in healthy people, but in the case of low immunity of the host, they become aggressive quality and give rise to certain diseases. Residual aerobic saprophytic conditionally pathogenic flora (Klebsiella, Proteus, yeast, Clostridium, Staphylococcus and others) is less than 1% of the total number of microorganisms.

Thus, most of the microorganisms in the colon attached to the intestinal wall, where they form micro-colonies, which are protected from external influences by a biofilm composed of exopolysaccharides of microbial origin and mucin - secret goblet cells (ectoparasite-mutiney matrix that performs for microbial associations the role of a placenta). The number of bacteria in the lumen of the colon (in the "free floating"), much less is to eat a number of localized parietal microorganisms.

Frequency distribution DK among the population of Ukraine on average 20-40%, and in children even 50%.

Among the wide variety of causes leading to the formation of DK in children and adolescents, the highest value (100%) are infections of the gastrointestinal tract, in particular secretory and invasive inflammatory diarrhea, and non-communicable (chronic gastroduodenitis, pathology hepatobiliary system and other) diseases of the digestive system. According to the figurative expression of Professor S.A. Kramarev "... every child undergoing acute intestinal infection, leaves her in a state of dysbiosis of the gut.

The basis of the DC associated with acute and chronic intestinal infections, lies a number of pathogenic mechanisms, among which an important place is occupied by violating the integrity of the mucous membrane, alteration of intestinal motility and development of malabsorption syndrome of malabsorption of nutrients. This syndrome in its development is also largely due to violations of the normal ratio of intestinal flora because she (flora) participates in the so-called parietal digestion. The essence of the process lies in the fact that on the surface of the villi of the mucous membrane of the small intestine, there are numerous microforming on which the adsorbed enzymes and characteristic d the I person microorganisms, which contribute to the reactions of digestion. Moreover, it is established that the share of wall digestion accounts for about 80% of the time required to complete the digestion process. It is clear that the violation of normal microflora can lead to indigestion with all the ensuing consequences, as manifestations of chronic intoxication caused by the accumulation and absorption of oxidized products of metabolism, anemia, vitamin deficiencies, dehydration, cachexia, etc..

Disturbance of habitats of microorganisms in the gut may lead to a breach in it abioticheskogo equilibrium that promotes colonization of its exogenous (the body) by microorganisms. As a result, conditionally pathogenic microflora acquires the number of aggressive properties. In such "new", an unusual existence, the conditions of massive death of a large number of microorganisms, accompanied by release of endotoxins, which are soaked in blood, can lead to toxicity or even in extremely severe cases, shock and death.

When these changes violated the metabolism of the cells of the mucous membrane of the small intestine, increased activity of lipid peroxidation, which leads to destabilization of the cell structures. Activation of EN zymes the data proteolytic (destroys proteins) systems involves a destructive effect on the cell membrane of the intestine. The mucous membrane without the protective action of the microvilli of the brush strip is vulnerable to microbial invasion, and the loss of parietal digestion exacerbates the disorder of the secretory and resorptive activity of the small intestine. Consequently, in the cavity of the intestine accumulates a large amount of liquid and gases, which in turn, leads to hyperextension of the gut wall, blocks the normal inflow and outflow of blood, contributes to the development of hypoxia, and is accompanied by disturbances in the activity as of the intestines, with the development of characteristic symptoms, and body in General. Therefore, the treatment of such conditions is an important task of medicine.

A separate question, which is essential in the development of dysbiosis and toxicity is the use of antibiotics. According to statistics, 100% of people in developed countries, ever in my life have been taking antibiotics. But the frequency of occurrence of the state of dysbiosis after a course of antibiotic therapy is not established. It is believed that it reaches 80%. According to Professor Kramarev S.A. (2006) on the background of antibiotic therapy in children there are many complications with the digestive tract: a third of patients on long-term antibiotic therapy diarrhea occurs in one form or another, a 66% abdominal pain, 27% - bloating, 16% - vomiting.

And in terms of operating hospitals or in the other cases, when the course the purpose of broad-spectrum antibiotics, developing the so-called antibiotic-associated diarrhea (AAD) or antibiotic-dissociatively colitis caused by a pathogen Clostridium difficile Clostridium difficile. The incidence of AAD depends on the form prescribed antibiotic and is estimated from 2% to 30%, with almost 30% of the cases ending lethal, especially in young children and elderly patients. Given the number of people taking antibiotics, it is clear that this is a serious scientific problem

It is proved that almost all antibiotics can cause diarrhea, but there are the most "egregious" the perpetrators of this syndrome. From publicly available literature it is known that diarrhea occurs more frequently in patients receiving clindamycin, and the combination of amoxicillin with clavulanic acid.

Be aware that when antibiotics dysbiotic changes are most pronounced, and the state used in the intestine for a long time is not restored.

Therefore, it is clear that the correction status of the intestine is a necessary condition in the first place, in various infectious diseases involving intoxication, and, secondarily, with antibiotic treatment, especially for children and people with whom kablanim health.

The main directions of the correction of the DC, including after acute intestinal infection is the rapid elimination of toxins and restore the population level of the main representatives of the normal anaerobic microflora of the intestine, motility, and increase immune resistance of the organism. In this connection, it should be considered that carrying out correction of dysbacteriosis of the intestine not only will eubios, but also eliminate naturally occurring signs associated secondary immunodeficiency.

Traditionally this purpose avirulent strains of microorganisms, which form the basis of the normal intestinal flora. For this purpose, lactobacilli are used or bifidobacteria respective strains or consortia, E. coli, some yeast.

So, for example in the Eurasian patent №002614 (publ. 27.06.2002)

provides information about the consortium antagonistic among themselves strains of bifidobacteria and new strain B.bifidum No. 791/BUG, which is less sensitive to antibiotics, and effectively restore the intestinal flora.

In the Patent of Ukraine No. 24987 (published 25.12.1998, bull. No. 6) data on food additives, which restores the gut by incubation lacto - and bifidobacteria with polisher DNAME media. This method of getting effective in restoring normal microflora cultures disclosed in the Patent of Russian Federation №2048123, (publ. 20.11.95).

However, by themselves or lacto - no bifidobacteria are not able to fully restore the used condition of the intestine, as well as to show antagonistic activity against other pathogens, such as Staphylococcus aureus. From this point of view, the inclusion in the diet or regimen or to prevent the development of intestinal dysbiosis drugs only culture, or even a consortium of several cultures, as for example, in the drug, known in Ukraine under the brand name "BIFI-form, has a limited antimicrobial effect. This is a consequence of the fact that these cultures are not able to displace all pathogenic or opportunistic microorganisms and fully restore the normal microflora of the human body.

It is impossible not to take into account that the effectiveness of a number of used for the correction of dysbiosis of biological products (probiotics, synonym - eubiotics), which are based on culture representatives of normal microflora of the intestine, is markedly reduced due to a number of objective circumstances. Including technological character. In particular, weakened by drying the bacteria are exposed to the active influence of pH with the food of gastric juice and digestive enzymes when introducing them in the form of capsules or mortar that determines the need for long-term administration of these drugs for full recovery of their biological activity.

A similar effect, as well as technological difficulties in the manufacture, possess and other strains of microorganisms, which are traditionally used for the treatment of dysbacteriosis.

For example, the yeast Saccharomyces boulardii ability to suppress the growth of pathogenic and conditionally pathogenic microorganisms and fungi that violate the biocenosis of the intestine, such as: Clostridium difficile, Clostridium pneumoniae, Staphilococcus aureus, Pseudomonas aeruginosa, Candida krusei, Candida pseudotropical, Candida albicans, Salmonella typhi, Salmonella enteritidis, Ecsherichia coli, Shigella dysenteriae, Shigella flexneri, Klebsiella, Proteus, Vibrio cholerae, and also Enthamoeba histolytica, Lambliae, Enterovirus, Rotavirus, etc..

So in patent # 54103 (published 17.02.2003, bull. No. 2 / 2003) revealed the way of restoration of normal microflora using preparations containing Saccharomyces boulardii in patients with diseases of the pancreas. And in patent No. 62152 (published 15.12.2003, bull. No. 12/2003) disclosed a method to restore the microflora in postoperative patients.

Saccharomyces boulardii have a number of significant advantages over the use of lacto - and bifidobacteria. Genetically Saccharomyces boulardii resistance to the action of antibiotics substantiates the possibility of their ignoreme the nogo use antibiotics to protect normal biocenosis alimentary tract during treatment with antibiotics. In addition, they are able to break down some toxic substances that can accumulate in the intestine when the disruption of the normal microflora.

But the application of the yeast Saccharomyces boulardii in the form of a powder, which is placed in the capsule or tablet may not fully solve the problem of dysbiosis arising from intestinal infections, operations on the bowel, sepsis, various diseases involving intoxication syndrome, such as pancreatitis, irritable bowel syndrome, ulcerative colitis, Crohn's disease, the application of radiation therapy and chemotherapeutic agents in the treatment of cancer, immunodeficiency, for example, acquired immunodeficiency syndrome (AIDS), etc..

This is due to the fact that Saccharomyces boulardii also lose their therapeutic properties when exposed to aggressive factors, such as gastric juice containing hydrochloric acid, and the bile acids that can destroy the membrane of Saccharomyces boulardii.

Therefore, attempts are being made combined use of probiotics to achieve energichnost actions. Known means "Linex" contains bifidobacteria, lactobacilli and enterococci, as well as lactose. It is to some extent possible to speed up the normalization of microflora, because science is data to play biofilms on the mucous membrane per square centimeter of the gastrointestinal mucosa should be not less than 100000 beneficial bacteria. Covering the mucous membranes, the biofilm provides long-lasting protection against various infections and viruses. The biofilm can even be called the Foundation of the immune, hematopoietic, gastrointestinal, enzymatic, hormonal function of the gastrointestinal tract.

However, neither the use of eubiotics apart, neither in the consortium, it is not possible to achieve the desired result, since there is evidence that their use in dry form in the form of tablets or capsules leads to the colonization of just 100 bacterial bodies per square centimeter area of the gastrointestinal mucosa, which is significantly less than needed (op cit.: Levsen M.A. Probiotics in the practice of a General practitioner / M.A. Levsen could BE Kostenko // Gastroenterology (Annex Consilium Medicum). - 2008. No. 1. - P.50-52). In addition, the use of probiotics does not solve the problem of rapid detoxification caused by dysbiosis.

Recent studies have found that the normalization of a microflora of not less than may be useful not only microorganisms (probiotics), but also substances that promote growth and reproduction of the existing normal microflora, i.e. substances as substrates for normal for the body of microorganisms. Such substances are called prebiotics.

On opredeleniyami - nevereverever substances that contribute to improved health due to selective stimulation of growth and/or metabolic activity of one or more groups of bacteria that inhabit the large intestine, which leads to the normalization of their relations (op cit: PPM Arbatskaya. Clinical use of dietary fiber, Moscow, 2010. 48).

These include substances polysaccharide nature, such as lactulose, inulin, alginates, fructo-oligosaccharides, chitin, pectins, gums, mucilages, lignin.

Indeed, it was established that the use of polysaccharide prebiotics helps to speed up recovery after intestinal infections, accompanied by dysbiosis. In addition, some probiotics, such as lignin, chitosan also possess the ability to absorb toxic substances, which are formed when inadequate digestion, so prebiotics more promising for the treatment of intestinal dysbiosis.

In addition, they have, another very important function - normalize lipid and lipid metabolism. So it is established that the prebiotic based choirboy gums, known in Ukraine under the brand name "Harem", is used for the correction of diabetes and metabolic syndrome, diseases of the cardiovascular system, accompanied by hyperlipidemia.

Some prebiotics, is for example, lactulose, has the ability to reduce the toxic effect of ammonia produced in excessive quantities in diseases of the liver, and has a neurotoxic effect, (op cit: Bengmark S. Colonic food: pre-and probiotics. Am J Gastroenterol 2000; 95 (1) Suppl: S5-

7).

However, the probiotics themselves are also not able to fully solve the problem of violations of the normal microflora and intoxication syndrome that often accompanies such status.

So constantly attempt any impact towards normalization of intestinal flora and detoxification syndrome.

It is known that the use of certain substances based on silicon can improve the condition of microflora when dysbiosis (op cit.: I.A. Zupanets, NV Bezdetko, E.F. the Grintsov, I.E. Bezugly. Pharmaceutical care: symptomatic treatment of impaired function of the gastrointestinal tract. Flatulence. Dysbacteriosis.// The pharmacist. - 2002. No. 16. - P.32, Kharchenko N.V., V.V. Chernenko Modern approaches to the correction of intestinal dysbiosis (methodical recommendations).- M. 2000. -.28 C.). With this purpose, traditionally used polymethylsiloxane: simethicone and Dimethicone, especially when dysbiosis is accompanied by symptoms that disrupts the quality of life, such as colic, flatulence, irregular bowel movements, etc. Associated with the sorbent toxins basically lose their activity and bringing the Xia together with a sorbent in a natural way. This eliminates the intoxication syndrome and decrease the antigenic load on immunocompetent cells, which contributes to the compensation of HIV /secondary/, which occurs due to the development of the pathological process.

Known normalizing effect of the hydrogel metiltselyulozy acid (in other words hydrate polymethylsiloxane) on the microflora of the intestine in many clinical situations (op cit: A. M. Boyarsky, I. Osadchaya, A.A. Millstone, AN. Kovalenko. Application of enterosorbents in treatment of intestinal dysbiosis in children with burn disease // States of emergency Medicine". - 2006 - №1 (2). - P.50-53.), this is what explains the fact that they inhibit the activity of pathogenic microorganisms giving, figuratively speaking, the chance is faster to multiply the growth of beneficial bacteria.

However, as identified by the research, the effectiveness of a minor (op cit: Metcalf TJ, Irons TG, Sher LD, Young PC. Simethicone in the treatment of infant colic: A randomized, placebo-controlled, multicenter trial // Pediatrics, 1994; 94: 29-34.). It is known that other derivatives of silicon have the ability to improve the condition of microflora and health at a dysbacteriosis. For example, the use of enterosorbent, known under the trade name "Enterosgel", which is a hydrogel, metiltselyulozy acid (hydrogel polymethylsiloxane) (op cit.: Black-browed V.N., Paly I.G. Application of p is eparate Enterosgel for the treatment of intestinal dysbiosis // Medical-biological aspects of the use of the enterosorbent Enterosgel for the treatment of various diseases. - M., 2007. - p.76-79). However, these drugs are not able to solve the problem of treating such patients.

In addition, it is known that the hydrogel metiltselyulozy acid can link and microorganisms, so the question is not whether there will be "connected" on the surface of the sorbent probiotics remains open. In addition, the use of sorbent with eubiotics hardly possible in the form of a hydrogel, unlike xerogel, i.e. digidratirovannogo polymer, metiltselyulozy acid. However, even in this case there is no information about the sorption characteristics of the xerogel metiltselyulozy acid with the introduction of probiotics, and experts are well aware that the introduction of additives in the composition of different chelators provides end products with new properties. However, such introduction may have an important drawback, namely substantially impair the sorption activity of sorbents that will significantly limit their scope.

Known methods combined use of pre - and probiotics, and prebiotics with other drugs.

So in patent # 82774 (published 12.05.2008, bull. No. 9) disclosed is a method of obtaining and applying eubiotics (probiotics) with enterosorbent-based hydrogel, metiltselyulozy acid (in other words hydrate of polymethylsiloxane). But in patent # 82774 almost no data about how Pro who goes interaction of the sorbent with eubiotics, which are the microorganisms. From the point of view of the technical implementation of such a solution is not obvious, because the hydrogel of metiltselyulozy acid contains water molecules, in the presence of which probiotics are activated and begin to proliferate, which, of course, creates technological difficulties in the manufacture, standardization on microbial number, storage and use of this product. It is therefore important that means for the normalization of the intestinal microflora could solve two key tasks:

1) to normalize the composition and characteristics of the intestinal microflora, and

2) reduce the appearance of intoxication, the development of which is caused by many factors.

The invention

The basis of the invention is the task of creating a composite enterosorbent that provides restoration of normal microflora of the intestine and reducing the symptoms of intoxication".

The problem is solved by the fact that composite enterosorbent based on silicon polymer selected from the group containing xerogel, metiltselyulozy acid or a hydrogel of metiltselyulozy acid, according to the inventive concept further comprises at least one component selected from the group: lactulose, inulin, lignin, fructo-oligosaccharides, alginic acid and its salts, chitosan, too, is h, gum, beta-glucan in an amount of from 0.1 to 10 parts per 1 mass. part of the hydrogel or xerogel of metiltselyulozy acid.

Thus, the composition containing one of these enterosorbents and one of the listed components, capable of the complex restoration of normal microflora of the intestine and reduce the appearance of intoxication syndrome.

This composition suitable for the treatment of patients with dysbiosis has a pronounced intoxication syndrome, especially against the background of acute intestinal infections.

An additional difference is that the product contains from 10% to 90% water. This composition is most suitable for long-term treatment of patients, especially children and elderly, and patients receiving antibiotic therapy.

One additional difference is that the drug can be used in powder form for the manufacture of capsules or tablets or in the form of an aqueous solution (suspension).

It is clear that polymethylsiloxane can be included in the proposed product in the form of pharmaceutically acceptable carriers, and that the polysaccharide can also be applied in the form of ether (ethyl, methyl, acetyl derivative, which provides water-solubility, as well as in the form of salts of alkali and alkaline earth metals.

Detailed description of the invention

D. the more the essence of the invention is explained how to obtain the drug and, in particular, experimental dosage forms; a description of experiments on laboratory models and the obtained results compared with the results of the action of common drugs and methodological recommendations on the use of the proposed drug.

(1) the Means of obtaining the drug (in particular, experimental dosage forms).

Raw material in all cases were pharmacopoeial drugs and chemicals substances these substances, which had the quality of "chemically pure" (chemically pure).

The hydrogel of metiltselyulozy acid get on well-known techniques, and then add water or obtained in the environment of an organic solvent, a solution of polysaccharide respective concentrations. After dispersion and subsequent homogenization of the mixture get a suspension or a paste-like or powdery (after drying of the product to constant weight) form of the product.

Expert it is clear that the calculation of the respective concentrations is carried out in accordance with known methods.

Experimental dosage forms in the form of a paste prepared by mixing a hydrogel of metiltselyulozy acid and an aqueous solution of the polysaccharide. The most effective ratio of the components to obtain a paste is respectively 70% to 30%. Further, these pasty prep the rata in the intended amounts were injected animals, have induced dysbiosis.

Example 1. Getting pasty product forms with different ratio of the hydrogel metiltselyulozy acid and an aqueous solution of the polysaccharide. To 70 g of the hydrogel metiltselyulozy acids are added 30 g of 3% aqueous solution of lactulose.

Example 2. Getting pasty product forms with different ratio of the hydrogel metiltselyulozy acid and an aqueous solution of the polysaccharide. To 70 g of the hydrogel metiltselyulozy acids are added 30 g of 3% aqueous solution of sodium alginate.

Example 3. Getting pasty product forms with different ratio of the hydrogel metiltselyulozy acid and an aqueous solution of the polysaccharide. To 70 g of the hydrogel metiltselyulozy acids are added 30 g of a 5% aqueous solution of inulin.

Example 4. Getting pasty product forms with different ratio of the hydrogel metiltselyulozy acid and an aqueous solution of the polysaccharide. To 70 g of the hydrogel metiltselyulozy acids are added 30 g of a 5% aqueous solution of beta-glucan.

Example 5. Getting pasty product forms with different ratio of the hydrogel metiltselyulozy acid and an aqueous solution of the polysaccharide. To 70 g of the hydrogel metiltselyulozy acids are added 30 g of a 5% aqueous solution of gum.

Example 6. Getting pasty product forms with different ratio of the hydrogel metiltselyulozy to the slots and an aqueous solution of the polysaccharide. To 70 g of the hydrogel metiltselyulozy acids are added 30 g of a 5% aqueous suspension of lignin.

Professionals it is clear that the production of conventional solid dosage forms (tablets, capsules or suppositories) with the specified content of drug substances and, if necessary, a well-known auxiliary substances, based on standard technological principles.

(2) Examples of carrying out the invention

The effectiveness of the drug experimentally verified by officially recommended methods (see guidelines. Preclinical study of enterosorbents. Kiev: 2010. 62 C.) on experimental models of diarrhea in kriscrash intragastrically injected culture Salmonella tiphimurium with the content of 109cells/ml at the rate of 2 ml/100 g weight of the animal. Composite enterosorbent obtained in example 1, was administered 24 h after infection at a dose of 100 mg of paste to one animal. After 24 h was assessed by the coprogram animals. Similarly were performed series of other experiments, the results of which are presented in table 1.

Also according to these guidelines studied the adsorption properties of the composition of the enteric by spectrophotometry by detecting changes in the concentration of the adsorbate (macromolecular substances) after keeping the mixture (adsorption complex) to establish and the sorption equilibrium. The results are shown in table 2.

The data obtained were processed statistically. In the table, the mark (*) after the numbers indicate statistical differences p<0,05 compared to control (using only polymethylsiloxane in paste form).

105-106 1010-1012 20-60% Hemolytica E.coli
Table 1
Comparative data on therapeutic efficacy of drugs
MicrofloraBefore the treatmentAfter the treatmentP1-2
The hydrogel of metiltselyulozy acid (Enterosgel) (1)The hydrogel of metiltselyulozy acid 70%/30% 1% water R-RA lactulose (2)
Total E. coli102-106108-109109-1010*
Hemolytica E.coli20-60%00*
Salmonella1010-1012103-104*
Lactobacillus105-107107-108108-109*
Bifidobakterii104-105105-107107-108
MicrofloraBefore the treatmentAfter cookiesP1-2
The hydrogel of metiltselyulozy acid (Enterosgel) (1)The hydrogel of metiltselyulozy acid 70%/30% 1% water R-RA inulin (2)
Total E. coli102-106108-109109-1010*
Hemolytica E.coli20-60%00*
Salmonella105-108103-104*
Lactobacillus105-107107-108108-109*
Bifidobakterii104-105105-107109-1010
MicrofloraBefore the treatmentAfter the treatmentP1-2
The hydrogel of metiltselyulozy acid (Enterosgel) (1)The hydrogel of metiltselyulozy acid 70%/30% 1% water R-RA beta-glucan (2)
Total E. coli102-105108-109109-1010*
Hemolytica E.coli20-60%00 *
Salmonella1010-1012105-106103-104*
Langebartel105-107107-108108-109*
Bifidobakterii104-105105-107108-109
MicrofloraBefore the treatmentAfter the treatmentP1-2
The hydrogel of metiltselyulozy acid (Enterosgel) (1)The hydrogel of metiltselyulozy acid 70%/30% 1% water R-RA lignin (2)
Total E. coli102-106108-109109-1010*
Hemolytica E.coli20-60% 00*
Salmonella1010-1012105-1060*
Lactobacillus105-107107-108109-1010*
Bifidobakterii104-105105-107107-108
MicrofloraBefore the treatmentAfter the treatmentP1-2
The hydrogel of metiltselyulozy acid (Enterosgel) (1)The hydrogel of metiltselyulozy acid 70%/30% 1% water R-RA chitosan (2)
Total E. coli102-106108-109109-1010*
Hemolytica E.coli00*
Salmonella1010-1012105-106103-104*
Lactobacillus105-107107-108108-109*
Bifidobakterii104-105105-107107-108
MicrofloraBefore the treatmentAfter the treatmentP1-2
The hydrogel of metiltselyulozy acid (Enterosgel) (1)The hydrogel of metiltselyulozy acid 70%/30% 1% water R-RA gum (2)
Total E. coli102-106108-109109-1010*
20-60%00*
Salmonella1010-1012105-108104-105*
Lactobacillus105-107107-108108-109*
Bifidobakterii104-105105-107108-109
MicrofloraBefore the treatmentAfter the treatment
The hydrogel of metiltselyulozy acid (Enterosgel) (1)The hydrogel of metiltselyulozy acid 70%/30% 1% water R-RA pectin (2)
Total E. coli102-106108-109109-1010/td>
Hemolytica E.coli20-60%00
Salmonella1010-1012105-106104-105
Lactobacillus105-107107-108109-1011
Bifidobakterii104-105105-107108-109

Data analysis table 1 shows that the hydrogel of metiltselyulozy acid has the ability to reduce the expression of dysbiotic changes of the intestine caused by experimental salmonellosis. However, in combination with prebiotics its activity is significantly higher, as evidenced by the more pronounced breeding colonies lacto - and bifidumbakterin, as well as the reduction of colonies of Salmonella. Depending on the type of prebiotic increases the severity of the growth of certain colonies of probiotic microorganisms, for example, in combination with inulin has a greater positive in the effect on the growth bifidogenic strains of microorganisms, combination with lignin and pectin - lactobacilli, and with lactulose, gum and beta-glucan uniform effect.

Despite the presence of the probiotic effect, it is important that the composition of the sorbent was reduced adsorption properties. Studies have found that the adsorption properties not only not diminished, but rather increased, depending on the ratio of components in the composition, making the composition enterosorbent even more attractive for clinical use (table 2.).

Table 2
The adsorption properties of drugs
The sorption capacity for Congo red, mg/g (p<0,01)The sorption capacity for Methyl orange, mg/g (p<0,01)
Hydrate metiltselyulozy acid 70%/30% water (control)3,22,6
Hydrate metiltselyulozy acid 70%/30% 1% aqueous solution of lactulose3,63,7
Hydrate metiltselyulozy acid 70%/30% 10% aqueous solution of lactulose3,2 3,7
Hydrate metiltselyulozy acid 70%/30% 1% aqueous solution of inulin3,43,1
Hydrate metiltselyulozy acid 70%/30% 10% aqueous solution of inulin3,03,6
Hydrate metiltselyulozy acid 70%/30% 1% aqueous solution of sodium alginate3,64,6
Hydrate metiltselyulozy acid 70%/30% 10% aqueous solution of sodium alginatethe 3.84,8
Hydrate metiltselyulozy acid 70%/30%the 3.84,4
1% aqueous solution of chitosan
Hydrate metiltselyulozy acid 70%/30% 10% aqueous solution of chitosan4,84,4
Hydrate metiltselyulozy acid 70%/30% 1% aqueous solution of gum3,53,2
Hydrate metiltselyulozy acid 70%/30% 10% aqueous solution of gum 4,03,4
Hydrate metiltselyulozy acid 70%/30% 1% aqueous solution of pectinthe 3.8a 4.9
Hydrate metiltselyulozy acid 70%/30% 10% aqueous solution of pectin4,25,6
Hydrate metiltselyulozy acid 70%/30% 1% aqueous solution of beta-glucan3,44,0
Hydrate metiltselyulozy acid 70%/30% 10% aqueous solution of beta-glucan3,34,0
Hydrate metiltselyulozy acid 70%/30% 1% aqueous solution of lignin4,25,1
Hydrate metiltselyulozy acid 70%/30% 10% aqueous solution of lignin4,55,8
Hydrate metiltselyulozy acid 70%/30% 0,9% aqueous solution of lactulose3,22,6
Hydrate metiltselyulozy acid 70%/30% 10,1% aqueous solution of lactulose3,02,4
Hydrate methylchromone the second acid 70%/30% 0,9% aqueous solution of inulin 3,22,4
Hydrate metiltselyulozy acid 70%/30% 10,1% aqueous solution of inulin3,22,6
Hydrate metiltselyulozy acid 70%/30% 0,9% aqueous solution of sodium alginate3,22,7
Hydrate metiltselyulozy acid 70%/30% 10,1% aqueous solution of sodium alginate3,22,6
Hydrate metiltselyulozy acid 70%/30% 0,9% aqueous solution of chitosan3,22,5
Hydrate metiltselyulozy acid 70%/30% 10,1% aqueous solution of chitosan3,22,6
Hydrate metiltselyulozy acid 70%/30% 0,9% aqueous solution of gum3,22,6
Hydrate metiltselyulozy acid 70%/30% 10,1% aqueous solution of gum3,22,6
Hydrate metiltselyulozy acid 70%/30% 0,9% aqueous solution of pectin3,22,6
Hydrate metiltselyulozy acid 70%/30% 10,1% aqueous solution of pectin2,82,8
Hydrate metiltselyulozy acid 70%/30%3,02,5
a 0.9% aqueous solution of beta-glucan
Hydrate metiltselyulozy acid 70%/30% 10,1% aqueous beta-glucan3,22,2
Hydrate metiltselyulozy acid 70%/30% 0,9% aqueous solution of lignin3,22,5
Hydrate metiltselyulozy acid 70%/30% 10,1% aqueous solution of lignin2,83,2

Analysis of the data from tables 1 and 2 allows us to conclude that the synergistic effect of the composition of the enteric observed when the ratio of the components is 1 mass part of metiltselyulozy acid from 0.1 mass parts to 10 mass parts of the polysaccharide. When the mixing ratio is outside the specified bounds, the decrease of the sorption activity assessed by both marker substances or one of them that the auger is not desirable from a clinical point of view, as marker substances - Congo red and methyl orange are markers on the sorption of substances with different molecular weight, which reflects the ability to simulate the processes of sorption, important in clinical practice. Therefore, if the activity of the sorbent by the same token increases and another decreases, this indicates that the selectivity of sorption. In clinical practice it is important that the sorbent zombiroval toxic substances, the molecular weight of which, most often, is in the range of molecular weight Congo red and methyl orange, for example, urea, creatinine, some toxins and metabolites (saveliyivna acid, formic acid).

Thus, the sorbent activity is not only not reduced, and in some cases increases in both markers have a preference.

Recommendations for use of the proposed drug based on the availability of experimentally determined eurotechnik properties. Therefore it should be used to prevent the development of dysbacteriosis and treatment of various complications, especially intoxication Genesis.

It is clear that doctors may prescribe proposed remedy together with some of the above-described other means for treatment of the gastrointestinal tract, such as blockers of the proton pump, H2-gistaminoblokatory, intestinal antiseptics other sorbents, for example, on the basis of activated charcoal.

Industrial applicability

Ingredients composition of enterosorbent are available on the pharmaceutical market and approved for use. So the drug after the official testing can be used to treat patients with gastrointestinal diseases, including infectious and not infectious Genesis, in any dosage form, namely:

in the form of tablets or capsules for receiving per os,

in the form of suppositories for rectal administration,

in the form of a gel, paste or suspension for receiving per os

1. Composite enterosorbent based on silicon polymer selected from the group containing xerogel, metiltselyulozy acid or a hydrogel of metiltselyulozy acid, characterized in that it contains at least one component selected from the group: lactulose, inulin, lignin, fructo-oligosaccharides, alginic acid in the form of pharmaceutically acceptable salts, chitosan, pectin, gum, beta-glucan in an amount of from 0.1 to 10 parts to 1 parts by weight of the hydrogel or xerogel of metiltselyulozy acid.

2. Composite enterosorbent according to claim 1, characterized in that it contains from 10% to 90% water.

3. Composite enterosorbent according to claim 1, characterized in that it is used in powder form for the manufacture of capsules or tablets, paste or in the form of water, R is the target.



 

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