RU2279278C2 - Enterosorbent - Google Patents

Abstract

FIELD: medicine, food processing industry.

SUBSTANCE: invention relates to lignin-base disintoxicating agents, in particular, to biologically active supplements to food and medicinal agents prepared as a tableted formulation and suitable for using. Enterosorbent shows the additional probiotic properties and represents biologically active supplement to food or medicinal agent in tableted formulation of the following components, wt.-%: hydrolyzed lignin or medicinal lignin polyphepan), 50-99; lactose, 1-50. Except for the abovementioned components the enterosorbent can comprise the following accessory substances, for example: starch, polyvinylpyrrolidone, calcium state, lauryl sulfate, magnesium stearate, derivatives of carbohydrates, microcrystalline cellulose, calcium phosphate, calcium carbonate, calcium sulfate, magnesium carbonate, magnesium oxide, natural gums, alginates, alginic acid, pectin, amylose, dextrose, polyethylene oxide-400, polyglycol, sodium chloride, sweetening agents, Tween-80, talc, hydroxypropylmethylcellulose, carboxymethylcellulose, stearyl alcohol, stearic acid, glycol, polyethylene glycol, aerosil, titanium dioxide, ethylcellulose.

EFFECT: valuable properties of enterosorbent.

5 cl, 5 ex

Description

The invention relates to the field of lignin-based detoxification agents: biologically active food additives (BAA) and medicines in tablet form suitable for use.

Various forms of lignin-based enterosorbents for oral administration are widely 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 has been processed to specific quality parameters to produce a product used for medical purposes, and medical or therapeutic lignin (polyphepan), obtained by special technological processing of hydrolyzed lignin. Methods of such processing and the properties of such enterosorbents are known, for example, from patents RU No. 2084236, RU No. 2124463, RU No. 2061488, RU No. 2026078, RU No. 21166080, RU No. 2166953, RU No. 2167669, RU No. 2131260, etc. However, not all known enterosorbents have complex health-improving and enhanced therapeutic and prophylactic properties.

So, the well-known technical solution according to patent RU No. 2131260, which can conditionally be considered the closest analogue, is an enterosorbent drug for the treatment of gastrointestinal diseases, for example dysbiosis, as well as disorders of fat metabolism, viral and chronic hepatitis, general intoxications of any nature. The composition of the enterosorbent includes alkaline hydrolysis lignin in an amount of 60-90 wt.% And lactulose in an amount of 10-40 wt.%. The drug is used in liquid form. It is believed that lactulose has an additional effect on maintaining the level of normal intestinal microflora. However, lactulose is not the best nutrient substrate for probiotic microorganisms, and not everyone has such an enterosorbent, precisely because of problems with the absorption of lactulose, is indicated.

The present application for a invention is a partial development of the invention described in the known patent RU No. 2084236. The use of lactose as a special case of sugar according to patent RU No. 2084236, and the identification of additional prebiotic properties of the known enterosorbent as a result, is an object of the present invention.

The problem is solved in that the enterosorbent with prebiotic properties is a biologically active food supplement or medicine in tablet form with the following composition of components, wt.%:

hydrolysis lignin or medical lignin (polyphepan) 50-99 non-indifferent auxiliary lactose component (milk sugar) 1-50

In the particular case of the present enterosorbent, as an additional auxiliary component, it can also contain a substance from the following series of standard fillers and binders: starch, polyvinylpyrrolidone, calcium stearate, magnesium stearate, lauryl sulfate, sugars, carbohydrate derivatives, microcrystalline cellulose, calcium phosphate, calcium carbonate , calcium sulfate, magnesium carbonate, magnesium oxide, natural gums, alginates, alginic acid, pectin, amylose, dextrose, polyethylene oxide-400, polyglycol, chloride n Trier, sweeteners, glycol, Tween-80, stearic acid, aerosil, ethylcellulose, talc, hydroxypropylmethylcellulose, titanium dioxide, carboxymethylcellulose, stearyl alcohol, polyethylene glycol. Moreover, as a sugar and carbohydrate derivatives, the enterosorbent may contain a substance from the following series: sucrose, mannitol, glucose, fructose, sorbitol, saccharin.

Usually, these excipients are used when tabletting enterosorbents, since they potentiate and stabilize the specific activity of enterosorbents, correct the side effects of enterosorbents (often constipation and irritation of the gastrointestinal tract), ensure the manufacturability of tableted masses (binders, dusting, baking powder, antifriction, etc. .) (V.I.Reshetnikov, A.V.Suldin, "Methodology of tableting of enterosorbents", Pharmaceutical science in resolving drug supply issues. Scientific Works, Volume XXXVII, Part 1, Moscow, 1998, s.200-204). Therefore, they are used in the particular case of the embodiment of the present invention.

The natural enterosorbent, consisting of the hydrolysis products of the lignin polymer wood components, the structural elements of which are phenylpropane and hydrocellulose derivatives, has a high enterosorbing ability, nonspecific detoxification effect and prebiotic activity. It binds and eliminates pathogenic bacteria and bacterial toxins, drugs, poisons, heavy metal salts, alcohol, allergens, as well as an excess of certain metabolic products, including bilirubin, cholesterol, urea, metabolites responsible for the development of endogenous toxicosis. Unlike antibacterial agents, it does not lead to the development of dysbiosis. Non-toxic, non-absorbable, completely excreted from the intestine within 24 hours.

As a detoxification agent in adults, this enterosorbent is indicated for exogenous and endogenous intoxications of various origins:

- acute poisoning with drugs, alkaloids, salts of heavy metals, alcohol and other poisons;

- complex treatment of foodborne toxicoinfections, salmonellosis, dysentery, dysbiosis, dyspepsia, as well as purulent-inflammatory diseases accompanied by severe intoxication;

- hyperbilirubinemia and hyperazotemia (hepatic and renal failure);

- food and drug allergies;

- Prevention of chronic intoxication among workers in hazardous industries.

In addition, the claimed enterosorbent has practically no side effects when used.

Depending on the purpose, dosage and severity of deviations or diseases, enterosorbent is produced in the form of dietary supplement or in the form of a medicinal product. The weight of the tablet can be from 0.1 g to 2.0 g.

The technical result of the claimed invention is as follows.

Obtaining a drug with new properties when sharing hydrolysis lignin or medical lignin (polyphepan) with lactose. Moreover, lactose is not only an indifferent standard filler, and the authors of the present invention revealed that it, when interacting with lignin inside the human body, also provides the manifestation of prebiotic properties in enterosorbent.

Milk sugar - lactose - a disaccharide whose molecule consists of galactose and glucose. Lactose is a reducing sugar in which the linkage of sugar residues is due to the interaction of the glycosidic hydroxyl and the secondary alcohol group.

When passing through the esophagus and gastrointestinal tract, lactose reacts with the amino groups of proteins and free amino acids and a number of other functional groups in the human body, hydrolyzing under the action of acids and enzymes, it eventually splits into the components of monosaccharide: glucose and galactose, therefore, its delivery to the intestines as a whole is not an easy task. In the present invention, this is ensured by the immobilization of lactose on hydrolytic or medical lignin (polyphepan) and the metered delivery of lactose on such a carrier onto mucus tissue purified with polyphepan from toxins with the remaining lactobacilli and bifidobacteria. This provides a substrate that feeds beneficial bacteria. In addition, during the metabolism of one of the sugar residues of lactose - galactose - galacturonic acid is formed, which has gelling properties and, along with other sugar acids, simultaneously creates an acidic environment favorable for normoflora.

Thus, in the resulting complex, new properties of the known enterosorbent are observed due to the immobilization of lactose on hydrolysis or medical lignin (polyphepan) and the use by the beneficial microorganisms of the gastrointestinal tract of the properties of lactose metabolism products that form a jelly-like medium with acidic properties. Moreover, additional joint or simultaneous administration of probiotic preparations together with enterosorbent is not required at all. In the case of separate use of lactose, this effect is not observed.

Unlike the known enterosorbents, the present enterosorbent does not sorb and does not remove the beneficial microflora from the intestine, but, on the contrary, due to the above mechanism, it enhances the growth of beneficial probiotic microorganisms (without additional administration) in our body and improves the health of the whole organism.

The selected quantitative ratios of the components are optimal for the manifestation of the enterosorbent along with the known properties of hydrolytic lignin (polyphepan) of a new additional prebiotic effect on the human body, which makes this development one of the most promising areas - the introduction of natural food prebiotic components in comparison with the traditional mass introduction of non-individual probiotic microorganisms. Deviations from the stated ratios of the components do not ensure the achievement of the specified technical result. This is due to the fact that the maximum value of the lactose interval is established experimentally and sets the limit of the possible effective immobilization of lactose on the carrier, since a larger amount of lactose can be added, but this will immediately affect the sorption properties of lignin downward, which may result from a decrease in porosity . The minimum amount of lactose has also been established experimentally and it is due to the fact that lactose less than 1% will no longer serve as a filler and exhibit the required prebiotic property. At the same time, a lactose content of 1% or more allows even people with an allergic reaction to milk and milk sugar to take such a drug. This is because lignin will neutralize a possible allergenic reaction to lactose due to its high sorption properties.

Enterosorbent is prepared as follows.

Lactose is added to wet or dry powder of hydrolytic or medical lignin. After mixing the components, if necessary, the mixture is dried, and then it is granulated or, without granulation, direct tableting is carried out immediately. Tableting of the main components is possible without the introduction of dusting substances. In particular cases of the embodiment of the invention, the introduction of additional auxiliary components is carried out in amounts traditionally normalized in the pharmaceutical industry for these substances.

Example 1. To prepare the enterosorbent — the finished tablet dosage form — hydrolyzed lignin 75 wt.% With a moisture content of 65% was used, lactose (milk sugar) - 25 wt.%. The components were mixed, the mixture was dried to a residual moisture content of 5-7%, granulated and tableted. The resulting tablets had the following indicators:

Average tablet weight 0.51 g Disintegration 7 min Abrasion resistance tablets not less than 97% Adsorption capacity 0.041 g methylene blue per tablet

Example 2. Prepared biologically active additive in tablet form. The composition consisted of hydrolytic lignin 99 wt.% With a moisture content of 64%, lactose (milk sugar) - 1 wt.% Powder. After mixing the components, the mixture was dried to a residual moisture content of 5-8% and sent to a tablet press without granulation. Received tablets with the following characteristics: weight 0.48-0.52 g; disintegration 7-10 min; the adsorption capacity of 0.045 g / g of absolutely dry weight, which exceeds this characteristic of tablets based on hydrolytic lignin without the addition of lactose.

Example 3. Prepared the finished dosage form of enterosorbent. For this, medical lignin (polyphepan) 50 wt.% With a moisture content of 72% was used, lactose (milk sugar) - 50 wt.%. To obtain tablets, polyphepan and lactose were mixed, then the mixture was dried to a residual moisture content of 5%, granulation and tabletting were performed. The resulting tablets had the following indicators:

Average tablet weight 0.49 g Disintegration 15 minutes Abrasion resistance tablets not less than 94% Adsorption capacity 0.037 g methylene blue per tablet

Example 4. The composition for the preparation of a biologically active additive in tablets consisted of medical lignin 90 wt.% With a moisture content of 66% and lactose (milk sugar) - powder 10 wt.%. The components were mixed, the mixture was dried to a residual moisture content of 6% and sent without pelletization to a tablet press. Received tablets with the following characteristics: weight 0.48-0.52 g; disintegration - 12 min; the adsorption capacity of 0.035 g / g of absolutely dry weight, which exceeds this characteristic of lignin-based tablets without the addition of lactose.

Example 5. The study of the properties of dietary supplements and drugs with the addition of lactose, obtained in accordance with examples 1-2, was carried out in the Treatment and Diagnostic Center of the General Staff of the Armed Forces of the Russian Federation. For comparison, in the control group of patients used dietary supplements and a drug without the addition of lactose. Drugs were prescribed to patients with severe intestinal dysfunction 3 times a day before meals, 1-2 tablets. A total of 35 people took pills, including 16 patients with gastroenterocolitis of unknown etiology and 8 with ulcerative colitis. In the control group (25 patients), they were taken with drugs without milk sugar.

When using the drugs and dietary supplements, the periods for eliminating the symptoms of dysfunction were shorter than in the control group and amounted to an average of 2 days in case of moderate intestinal infections and 3 days in severe cases. In the control group, these terms were equal to 5 and 9 days, respectively.

During the observation period, patients in the experimental group observed changes in the initial and final levels of bifidobacteria and lactobacilli.

1. The number of bifidobacteria when taking dietary supplements from 3 × 10 ² before taking increased to 1.5 × 10 ⁷ after taking, when taking a drug with lactose, their number increased from 4.5 × 10 ² to 6.2 × 10 ⁹ , respectively (in experiments with lactulose, this indicator increased slightly).

2. The initial number of lactobacilli was before the start of taking 2.6-3.5 × 10 ⁴ . On the 10th day after taking dietary supplements, their number increased to 1.4 × 10 ⁸ , when taking the drug, respectively, to 8.7 × 10 ⁹ (in similar studies with lactulose, the indicators increased to 5 × 10 ⁶ ).

Intoxication syndrome was stopped earlier in the group of patients taking the drug with lactose: in moderate cases of the disease - in 2 days, dietary supplements with lactose - in 3.5 days, in severe cases, respectively - in 4.9 and 6 days, while in the control group, these indicators were 5 and 7.2 days, respectively.

At the same time, there was a lack of cases of intestinal dysbiosis in patients taking the studied drugs. Here, with a comparative assessment, it was proved that the intake of these enterosorbents is not inferior in its effectiveness to treatment with antibiotics and sulfa drugs, and in some cases is preferred.

The results of clinical trials allowed us to conclude that the drug and dietary supplement with the addition of lactose are highly effective non-specific agents and can be included in the complex of therapeutic measures for acute intestinal infections. In this case, the administration of drugs is not accompanied by side effects.

In addition, studies were conducted on the treatment of chronic enterocolitis and food allergies, as a result of which, in 28 patients with atonic dermatitis, the use of drugs led to a quick relief of exacerbation (within 7-10 days). Repeated courses at the outpatient stage allowed lengthening periods of disease remission.

Thus, the unexpected results on increasing the titer of beneficial microflora - lacto- and bifidobacteria in the gastrointestinal tract of patients using hydrolytic or medical lignin (polyphepan) tablets with the addition of lactose, are evidence that this composition has improved pharmacological properties compared with lactose-free polyphepan tablets.

The use of the above dietary supplements and drugs makes it possible to expand the class of enterosorbents, interest in which from the side of physicians in recent years has increased due to the ease of their administration, the absence of side effects, and their high effectiveness in various types of intoxication.

Compared with other known enterosorbents, lignin-based products in the above composition have several advantages:

- are issued in a convenient form - tablets,

- the composition includes disaccharide-lactose (milk sugar), which during the metabolism and due to immobilization creates favorable conditions for the development of beneficial intestinal microflora,

- greater sorption ability in relation to microorganisms and toxins, which is associated not only with the presence of a significant amount of macropores, but also with the presence of various functional groups in the lignin macromolecules,

- in their physical condition, dietary supplements and the drug are drugs that do not injure the mucous membranes of the gastrointestinal tract, which makes it possible to take it for a long period of time, due to the course of the disease,

- To obtain drugs, a cheap source of raw materials is used - hydrolysis and medical lignin, which is a natural polymer.

Claims (5)

1. Enterosorbent in tablet form containing the following composition of the components, wt.%: Hydrolysis lignin or medical lignin (polyphepan) 50-99 Lactose (milk sugar) 1-50 2. Enterosorbent according to claim 1, characterized in that it is a drug. 3. Enterosorbent according to claim 1, characterized in that it is a biological food supplement. 4. Enterosorbent according to claim 1, characterized in that it as an additional auxiliary component contains a substance from the following series: starch, polyvinylpyrrolidone, calcium stearate, lauryl sulfate, magnesium stearate, sugars, carbohydrate derivatives, microcrystalline cellulose, calcium phosphate, calcium carbonate , calcium sulfate, magnesium carbonate, magnesium oxide, natural gums, alginates, alginic acid, pectin, amylose, dextrose, polyethylene oxide-400, polyglycol, sodium chloride, sweeteners, tween-80, talc, hydroxypropylmethyl llyuloza, carboxymethylcellulose, stearyl alcohol, stearic acid, glycol, polyethylene glycol, aerosil, titanium dioxide, ethylcellulose. 5. Enterosorbent according to claim 4, characterized in that it contains a substance from the following series as sugar and carbohydrate derivatives: sucrose, mannitol, glucose, fructose, sorbitol, saccharin.