RU2817151C1 - Enterosorbent composition - Google Patents

Abstract

FIELD: pharmaceutics; biotechnology.

SUBSTANCE: invention relates to pharmacy and biotechnology, is intended for use as enterosorbent with high content of pectin. Proposed enterosorbent composition contains powder of dry apple pomace, starch, kaolin and pectin from sea grass zostera, at following ratio of initial components, wt.%: powder of dry apple pomace – 50–70; starch – 15–25; kaolin – 10–15; zostera sea grass pectin – 5–10.

EFFECT: invention widens the range of enterosorbents and improves therapeutic properties of loose sorbents.

1 cl, 2 tbl

Description

The invention relates to pharmacy and biotechnology, and is intended for use as an enterosorbent with a high pectin content. Allows you to improve the therapeutic and prophylactic properties of bulk sorbents and expand the range of this group of pharmaceuticals.

The sorbing properties of apple pectin are known - a complex of colloidal polysaccharides that can remove radionuclides and heavy metal salts [Panfilova V.N., Taranushenko T.E. The use of enterosorbents in clinical practice // Pediatric pharmacology. - T. 9, No. 6. 2012. - P. 34-39], low-molecular organic substances and metabolites of protein nature. Pectin, by removing harmful bacteria from the body that damage the intestinal epithelium, creates comfortable conditions for the growth and reproduction of beneficial bacteria, i.e. has a prebiotic effect, stimulates the development of local microflora, thereby having a positive effect on local intestinal immunity. An allergy to pectin in fruits and vegetables is extremely rare, but intolerance to synthesized substances E440 - pectins occurs often.

The properties of pectin prepared from the sea grass zostera (zosterol) are known, which consist not only in a mixed sorption mechanism and a large sorption capacity. Zostera contains at least 60% uronic acids, which determines its high sorption quality to heavy metals, viruses and bacteria. The presence of apiose sugar prevents the destruction of pectin from the sea grass zoster by enzymes of the colon bacterium. Pectin from the sea grass zostera does not accumulate in organs and tissues and is completely eliminated from the body within 24-36 hours [RU 2 687831].

However, information about the effect of the drug on the general immunological reactivity of the body is not known.

Additives often used to prepare tablets, powders and jellies, such as kaolin and potato starch, are known to be safe.

Kaolin (white clay, E-559), approved for internal use. Additive E-559 is included in SanPiN 2.3.2.1293-03 as a product that prevents caking and clumping. Kaolin is used in all countries; the permissible limit has not been established. Kaolin is used as a means of etiotropic therapy of intestinal infections [RU 2611356]. Can be taken for a long time, but not more than 1 teaspoon per day, i.e. 5.4 g. With long-term use, it can remove fat-soluble vitamins (A, E, D, K), as it sorbs fats. Therefore, if there is a tendency to deficiency of fat-soluble vitamins, you need to use a minimum dose of kaolin [https://kyrkyma.ru/kaolin].

Native potato starch exhibits enzyme-resistant properties, is able to resist enzymatic hydrolysis in the human small intestine, has a low glycemic index, and leads to a decrease in the postprandial concentration of glucose, cholesterol, triglycerides and insulin response in the blood. Potato starch contains seven amino acids (alanine, glycine, leucine, proline, serine, methionine, aspartic acid) [Litvyak V.V., et al. // 2011. No. 1. P.98-103].

There is a known method [RU 2612011] for producing enterosorbent containing polysorb, apple pectin and sodium alginate in quantities of 50-60 wt.%, 25-20 wt.%, 25-20 wt.%, respectively.

Disadvantages: Polysorb is characterized by a non-selective effect. It removes from the body not only harmful substances, but also useful microelements and vitamins necessary for normal functioning.

There is a known method for producing enterosorbent tablets “Carbopect” [RU 2180231] by mixing activated carbon with microcrystalline cellulose (MCC) and pectin, in the following ratio of components, wt. %: activated carbon - 50-90, MCC - 5-30; pectin - 5-20.

Disadvantages: high content of activated carbon, which has low sorption of protein toxins and high sorption capacity of cyanocobalamin (B12) [Markelov D.A. Comparative study of the adsorption activity of medical sorbents / D.A. Markelov, O.V. Nitsak, I.I. Gerashchenko // Chemical-pharmaceutical journal. - 2008. - T. 42. No. 7. - P. 30-33]. The drug is also characterized by desorption - the reverse release of previously collected harmful substances and their absorption in the gastrointestinal tract (GIT). Oral intake of activated carbon leads to mechanical trauma to the mucous membrane of the digestive tract. When used for more than 7 days, the gastrointestinal tract may experience: heartburn, pain, belching, nausea, flatulence; prolonged use of the sorbent can lead to constipation. Possible malabsorption of calcium, fats, proteins, vitamins, hormones, nutrients; with hemoperfusion through activated carbon, embolism, hemorrhage, hypoglycemia, hypocalcemia, hypothermia, and a decrease in blood pressure may develop [found on the Internet: Carbopect instructions for use]. Activated carbon can cause erosion of the mucous membrane [found on the Internet: Activated carbon. Contraindications https://www.tiensmed.ru/news/post_new5047.html].

There is a known method for producing tableted enterosorbent “Pectostin” [RU 2180230], consisting of microcrystalline cellulose, dry rosehip extract and pectin, in the following ratio of components, wt.%: MCC - 85-55; dry rosehip extract - 5-15; pectin - 10-30.

Disadvantages: unpleasant taste due to the high content of MCC.

All of the above enterosorbents contain purified pectin. The release of pectin is associated with high costs of material and energy resources.

There is a known method for producing dry jelly [RU 2308853], which contains, by weight. %: sugar - 63.7; potato starch 26; dry grain broth -2.9; powder from the seed chambers of apples - 5; citric acid - 0.78; orange peel powder - 1.6. The introduction of powder from the seed chambers of apples into the recipe allows you to increase the nutritional value of the product due to the content of pectin substances (up to 3%), sugars (up to 9%), vitamins (C, PP, B) and minerals (0.6%), organic acids (up to 2%), essential oils and tannins. Apple seeds also contain fat-soluble vitamins, iodine, and selenium. The invention makes it possible to obtain a product at low cost through the use of recycled materials.

Disadvantages: large amount of sugar.

The technical result is improvement of the therapeutic and prophylactic properties of enterosorbent, prevention of side effects, expansion of the range.

The technical result was achieved by developing an enterosorbent composition, including dry apple pomace in powder form, starch, kaolin, pectin from the sea grass zoster in the following ratio of components, wt. %:

dried apple pomace powder 50-70 starch 15-25 kaolin 10-15 Zostera sea grass pectin 5-10

Dry apple pomace powder was obtained according to the method we developed [RU 2645330]. Dry apple pomace contains: 18% pectin, 28.8% insoluble fiber, as well as nitrogen-free extractives, protein, sugar.

When using the enterosorbent we developed, there are no side effects that occur when taking activated carbon; all components included in the composition are devoid of negative mechanical effects on the mucous membrane of the gastrointestinal tract.

The components of the developed composition contain fiber in soluble and insoluble forms. Soluble fiber is known to reduce fat absorption and help regulate weight; prevents the breakdown and digestion of part of the cholesterol coming from food, helps reduce the level of free cholesterol in the blood; stabilizes blood glucose levels, slowing down the absorption of nutrients, including carbohydrates. This means that foods containing soluble fiber are less likely to cause spikes in blood glucose levels. Soluble fiber is a prebiotic, it is a substrate for the growth of beneficial microorganisms that live in the large intestine.

Insoluble fiber is not absorbed by the body and is not fermented in the large intestine. As insoluble fiber passes through the gastrointestinal tract, it absorbs liquid and absorbs by-products formed during the digestion process. In the presence of insoluble fiber, peristalsis increases and the speed of food movement through the gastrointestinal tract increases, which prevents the development of constipation.

The proposed composition is produced in tablet form or powder form in sachet bags.

The method of preparing the composition is as follows. Mix 50-70 g of dry apple pomace powder with 15-25 g of starch, 10-15 g of kaolin and 5-10 g of pectin from the zoster sea grass until a homogeneous mass is obtained. The finished enterosorbent is packaged in sachets.

The method for preparing the tablet form is as follows. Mix 50-70 g of dry apple pomace powder with 15-25 g of starch, 10-15 g of kaolin and 5-10 g of pectin from the zoster sea grass until a homogeneous mass is obtained. Tablets with a diameter of 13 mm are obtained by stamp pressing, with exposure at a pressing pressure of 10 atmospheres for a minute. One tablet has a mass of 1.00 g.

Thanks to its texture, jelly envelops the gastric mucosa, creates a feeling of fullness, and has a pleasant taste. Therefore, jelly is included in the children's diet and treatment menu for diseases of the gastrointestinal tract: ulcers, gastritis, inflammation. Due to its dietary fiber content, the drink helps improve intestinal function.

The most important characteristics of sorbents are the magnitude of sorption activity in relation to test substances.

Based on the data obtained, the composition under study is capable of sorbing methylene blue, gelatin, albumin and cyanocobalamin, the sorption activity is 201.6±4.2 mg/g, 187.3±3.9 mg/g, 58.4±1.3 mg /g and 0.9±0.2 mg/g, respectively. A comparative analysis of the obtained and literature data on the sorption activity of the studied composition with enterosorbents used in medical practice, for example, Carbosorb based on activated carbon, Polysorb colloidal silicon dioxide, Polyphepan hydrolyzed lignin, Smecta - dioctahedral smectite, showed that it is not inferior in sorption of low molecular weight and high molecular weight substances to registered drugs (see Table 1).

The adsorption activity of coal for methylene blue must be at least 225 mg/g (GOST 4453-74 “Active brightening powdered coal”). The adsorption activity of Polysorb MP for gelatin in terms of dry matter should be at least 220 mg/g (FS 42-3731-99 “Polysorb MP”).

Example of concrete execution

60 g of apple pomace powder is mixed with 23 g of starch, 11 g of kaolin and 6 g of zoster pectin. The homogeneous mixture is packaged in 5 g sachets. Before use, a single dose is poured with 100 ml of water heated to 60°C-80°C, mixed and after 2-3 minutes a liquid jelly is obtained.

For the purpose of comparative analysis of the properties of the developed and known sorbent, a series of studies was carried out on the effect on the intestinal microflora. We chose the commonly used Smecta sorbent as a comparison composition.

Since the composition contains approved components, volunteers participating in the study were explained in detail the composition and informed consent to participate in the study was obtained.

Study participants were selected from among those who sought help for complaints of digestive disorders.

A group of ten patients was formed, who were offered, along with the treatment recommended by the standards, a powder of the developed sorbent composition. Ten people with similar complaints and medical history took the drug Smecta in addition to the regimens provided for by the standards. The course of taking sorbents in both groups was seven days, three times a day between meals.

Both groups used a powder form, a single dose of 3 grams.

Patients were monitored for levels of inflammatory markers based on blood tests, erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), as well as the content of intestinal microorganisms based on stool analysis using polymerase chain reaction (PCR). The study was performed twice - when applying for help and ten days after completing the course of taking sorbents.

It was established (see Table 2) that during the initial treatment, inflammatory markers were elevated, and the composition of the microflora was unbalanced. The proportion of representatives of normal flora (bifidobacteria, lactobacilli, bacteroides, prevolella) was reduced, while the proportion of pathogenic flora (klebsiella, clostridia, enterobacteria) was increased [Soldatkin P.K. Intestinal dysbiosis, textbook, Blagoveshchensk, 2015. - 44 p.].

When seeking help, before starting to take sorbents, there were no statistically significant differences in the level of indicators between the groups of patients for the studied indicators. Table 2 shows general data for a contingent of 20 people at the first examination.

From the data in the table it follows that the developed sorbent contributes to a statistically significant increase in the specific ratio of bifidobacteria, lactobacilli, bacteroids and a decrease in clostridia in the general pool of intestinal microflora. No significant changes in the level of prevolella, klebsiella and enterobacteria were detected in comparison with Smecta, although the dynamics of positive changes in the ratio of normal and pathogenic microflora was more pronounced in the group where the developed sorbent was used.

Thus, we have developed a new enterosorbent composition that exhibits properties of influence on the ratio of normal and pathogenic intestinal flora that are not described in known sources.

List of sources cited in Table 2:

1. Veprikova E.V., Shchipko M.L., Chunarev E.N. Properties of powdered and tablet preparations based on enterosorbent from birch bark bast. Chemistry of plant materials. 2010; No. 2: 31-36.

2. Veprikova E.V., Kuznetsova S.A., Skvortsova G.P., Shchipko M.L. Properties and application of sorption materials from birch bark bast. Journal of the Siberian Federal University. Chemistry. 2008. T. 1, No. 3: 286-292.

3. Kelus N.V., Sheikin V.V., Gundareva A.E., Kaydash O.A. Development of a draft pharmacopoeial monograph for the substance of brown sphagnum (Sphagnuma fuscum G.). Bulletin of Siberian Medicine. 2011; No. 5: 121-125.

4. Ovchinnikova M.V., Islyaeva M.N., Nikolaev V.G., Bardakhivskaya K.I., Nikiforov A.K. Assessment of the functional activity of a specific anticholera enterosorbent. 2015. Issue 2: 83-86.

5. Markelov D.A., Nitsak O.V., Gerashchenko I.I. Comparative study of the adsorption activity of medical sorbents. Chemical-Pharmaceutical Journal. 2008; T. 42, No. 7: 30-33.

6. Reshetnikov V.I. Assessment of the adsorption capacity of enterosorbents and their dosage forms. Chemical-Pharmaceutical Journal. 2003. T. 37, No. 5: 28-32.

7. Kovekhova A.V., Arefieva O.D., Zemnukhova L.A., Tolmacheva M.A., Polyakova N.V. Comparative characteristics of the sorption properties of sodium aluminosilicate from rice straw and commercial enterosorbents. International scientific and practical conference October 06-08, 2021, Sevastopol: 289-293.

Claims (3)

1. The composition of the enterosorbent containing dry apple pomace powder, starch, kaolin and pectin from the sea grass zoster, with the following ratio of initial components, wt.%: Dry apple pomace powder 50-70 Starch 15-25 Kaolin 10-15 Zostera sea grass pectin 5-10 2. The composition according to claim 1, characterized in that it is stamped to obtain a tablet form of enterosorbent or packaged in sachets.