RU2360695C1 - Agent "extraholm" for sugar control in patients suffering from diabetes complicated by hepatopathy and bile passages disorders - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: agent for sugar control in patients suffering from diabetes complicated by hepatopathy and bile passages disorders represents the capsules containing mixed dry extract of hill-growing saltwort and microcrystalline cellulose in ratio 1:1 to 1:2.

EFFECT: agent is non-toxic, does not cause by-effects and has no contra-indications to application.

8 ex, 6 tbl

Description

The invention relates to medicine, in particular to preparations based on the use of plant materials for the treatment of diseases of the liver and biliary tract, including those complicated by diseases of the pancreas.

Currently, a wide range of drugs of various composition and origin are used to treat diseases of the liver and biliary tract (GWP). So, for the treatment of liver ameloidosis, a wide range of corticosteroids, vitamin preparations, diuretics are used; for the treatment of hepatitis - lipamide, methionine, pyridoxine, vitohepat, glucocorticosteroids, etc. (M.D. Mashkovsky, Medicines, in 2 volumes, M .: Medicine, 1990). For the treatment of chronic liver diseases (chronic persistent hepatitis, chronic active hepatitis), accompanied by lesions of the pancreas (chronic pancreatitis) due to a delay in the excretion of pancreatic juice and intraorgan activation of pancreatic enzymes, one tablet is used 4 times a day. However, some patients do not tolerate this drug (Boger M.M. Pancreatitis. Novosibirsk, Nauka, 1984).

Substitution therapy of chronic pancreatitis, occurring against a background of chronic liver diseases, is carried out using panzinorm 1-2 tablets 3 times a day with meals. At the same time, in some cases, the drug is contraindicated in chronic liver diseases, obstructive jaundice, and in some patients hypersensitivity to it is determined (Medications in Russia: Vidal Handbook, 1995).

Various prophylactic and therapeutic agents are known that have a normalizing effect on cholesterol and lipoprotein metabolism. In particular, large doses of vitamin C and linetol (a mixture of ethyl esters of unsaturated fatty acids) contribute to lowering blood cholesterol levels.

Medicines are also known, such as clofibrate (ethyl-i- (parachlorophenoxy) -isobutyrate) and cetamiphene (p-ethanolamine salt of phenylethylacetic acid), polysponin and tribusponin. Clofibrate lowers blood levels of very low density lipoproteins and P-lipoproteins (rich in cholesterol). The drug cetamiphene has a moderate hypocholesterolemic effect. The drug polysponin is a dry extract from the rhizomes and roots of the Dioscorea nippon (Dioscorea nipponica Makino) family of dioscoreic, has a moderate hypocholesterolemic effect.

However, these drugs have toxicity, are characterized by various side effects (skin itching, nausea, vomiting, headache, and others) and have a number of contraindications for use.

In this regard, the use of preparations derived from plant materials for these purposes is promising. In particular, for these purposes it is recommended to use kuroslep, odoriferous woodruff, shepherd’s bag, field larkweed, dawn, dandelion, thuja, verbena and other plants in the form of decoctions and infusions (M.A. Nosal, I.M. Nosal, Medicinal plants and methods of their use in the people, Kiev, GMI, 1959, p.139-153).

However, this effect is not always effective and has a significant number of contraindications.

Of the herbal preparations for the treatment of liver diseases and gastrointestinal tract, the most promising are preparations based on hill hodgepodge (CX). The uniqueness of CX lies in the fact that it has a wide range of biologically active substances that have beneficial effects on such body systems as the immune, endocrine, and nervous.

Moth solyanka (Salsola colina Pall,) - a plant of the crows family (Chenopodiaceae). As a medicinal raw material use the aboveground part - the grass of the plant. The biologically active complex, obtained from the aerial part of the hillwort, contains: salsolin, salsolidin, alkaloids, flavonoids (tricin, isoramnetin, quercetin, rutin); polysaccharides; carotenoids; sterols characteristic only for this type of plant; saponins; lipids; amino acids and microelements (Lavrenov V.K., Lavrenova G.V. Complete encyclopedia of medicinal plants, M., S.-GG., 1999). The microelement composition is represented by 14 microelements, where the bulk belongs to potassium (7-10 times more than dried apricots), calcium, phosphorus, iron, magnesium and silicon. The presence of silicon is very important.

Silicon is a skeleton-forming element that is washed out in the process of human life, which is one of the reasons for the "decrepitation" of the body. It practically does not recover, since there are few natural sources of silicon, assimilated by the body from a biopharmaceutical point of view: there are few sources of silicon: nettle, yarrow, horsetail, larch, highlander, bamboo and some other plants. The silicon content in the grass of hodgepodge - 50 mg / l (more than in nettle).

Hill solyanka is allowed for use in the preparation of alcoholic beverages and beer (Application for a patent of the Russian Federation No. 2001013963, 2001) as a flavoring additive. In folk medicine, an infusion of herb plants is used for diseases of the liver and biliary system (Lavrenov V.K., Lavrenova G.V. Complete encyclopedia of medicinal plants, M., S.-G. G., 1999).

CX preparations are obtained by grinding the herbs of this plant to particles with a size of 3-10 mm and subsequent extraction of the active principle with water or ethanol (Pat. RF No. 2046604, 1995; Pat. RF No. 2118167, 1998). The extract is usually subjected to subsequent purification by filtration (US Pat. RF No. 2111167, 1998; application for US Pat. RF No. 2000110664, 2002), and then either use further to obtain liquid dosage forms, or remove the solvent and use the resulting dry extract to use in the form of powder, tablets or capsules.

Preparations of the hodgepodge have hypotensive, sedative, anti-inflammatory, choleretic and tonic effects.

In particular, CX extract (US Pat. RF No. 2043111, 1995) is used to treat hyperlipidemia, obesity, cholitis, coronary heart disease in the form of a dry, thick or liquid extract. A preferred dosage form is a “liquid extract” containing 3% dry extract of CX. It is possible to use CX in the form of capsules containing a dry extract. The drug is used as a liquid extract of 20-30 drops in 50-100 ml of water or 1-2 tablets or capsules containing 40 mg of CX 3-4 times a day for 15-20 minutes before meals for 1.5-3 months (if necessary, the course of treatment is repeated).

The disadvantage of the drug is relatively low efficiency, which requires the use of long courses of treatment for patients.

Known drug "Extracode", which is a powder containing 2.5 wt.% CX (a mixture of 50 mg CX and 1950 mg filler - the nature of the filler is not given). The powder is used up to 6 packets per day (up to 300 mg CX) for 2-6 weeks as an adjuvant for the treatment of coronary heart disease (CHD), hepatitis, as well as diet therapy (US Pat. RF No. 2152221, 2000).

The disadvantage of the drug is an unpleasant taste, the need to introduce significant amounts of ballast substances into the body, lack of effectiveness, apparently due to the partial destruction of biologically active substances (BAS) contained in SC in the zone of their most effective absorption and low bioavailability of BAS of SC due to their low the content in the mass of the filler.

Currently, the use of CX as a part of more complex mixtures is most widespread. In particular, CX is included, along with other plant components, in tea collections with hepatoprotective and sugar-regulating effects (RF patent application No. 93040379, 1996; RF patent application No. 2003123069, 2004; RF patent application No. 20052221586, 2005; Russian patent. No. 2203676, 2003).

In particular, it is known to use CX together with lake sediment lipids in a ratio of 16: 1 as a hepatoprotector and antioxidant (US Pat. RF No. 2043111, 1995). However, this drug has an unstable composition and a large number of contraindications.

The closest to the claimed drug for the achieved effect is the drug "Chitochol", which has a combined immunomodulating and anti-allergic effect and is intended for the treatment of a wide range of diseases, including viral diseases, cholecystitis, gastritis, biliary tract dyskinesia, nephritis, etc. The drug is used in the form of tablets 3 times a day for 3-4 tablets for 30 days.

The drug "Chitochol" is offered in two versions:

- according to the first embodiment, it contains 67% of CX powder; 15% chitosan, 3% vitamin C and the filler is starch, calcium stearate and about 10% microcrystalline cellulose;

- according to the second embodiment, it contains 8% of CX powder; 8% chitosan, 3% vitamin C and the filler is starch, calcium stearate and about 20% microcrystalline cellulose.

The action of the drug is based on the ability of pectins, the substances that make up SC, to carry out the destruction of chitosan molecules, which ensures its increased bio-permeability and creates better conditions for absorption in the blood and lymph of both the obtained oligomers and other biologically active substances contained in the drug. Chitosan oligomers provide an immunostimulating effect, normalize the condition of joints and the skeletal system, reduce blood cholesterol, and promote the elimination of toxins and pathogens from the body.

The disadvantage of the drug was its relatively weak effect on the condition of the liver and biliary tract, apparently due to the irreversible binding of part of the BAS CX with chitosan, as well as a limited range of therapeutic effects on the body, in particular, the lack of sugar-regulating effect.

The task facing the authors was to create a drug based on CX and a high molecular weight component in which the interaction of BAS CX with it would not only not lead to the loss of their beneficial properties, but, on the contrary, would contribute to their stimulation, as well as expand the range of effects on the body, In particular, it was possible to treat diseases of the liver and biliary tract, complicated by diabetes.

The technical result was achieved due to the creation of EXTRAHOLM, which is a capsule containing a mixture of dry extract of hillwort with microcrystalline cellulose (MCC) in a ratio (wt.%) From 1: 1 to 1: 2, i.e. in a concentration of 33.3 to 50% CX.

The MCC used in the preparation is used as dietary fiber, capable of activating the motor-secretory and evacuation function of the intestine, improve digestion, and prevent constipation. MCC fibers help to eliminate toxic substances, metabolic products, cholesterol, heavy metals and radionuclides from the body. Cellulose promotes the exchange of fats and lipoprotein in the blood. In medicine, it is used for functional disorders of the gastrointestinal tract. (V.A. Tutelyan, B.P. Sukhanov et al. Biologically active additives in human nutrition, Tomsk, 1999).

Improving the effectiveness of the claimed drug is based on the ability of SC lectins - metal-containing protein complexes, whose presence is characteristic of plants growing on silicas (Western Ukraine, Siberia, Moldova) - to partially degrade the polymer molecules of cellulose in the gastrointestinal tract. Moreover, the resulting oligomers are characterized by increased sorption ability and bioavailability. This allows them to sorb the biologically active components of CX, in particular betain, on their surface and ensures their better penetration into the blood and lymph, and also contributes to improved detoxification of the body and normalization of the blood formula.

The achievement of the technical result was made possible by selecting a ratio of ingredients in which the lectin content in the mixture was sufficient for partial cleavage of the MCC and activation of the resulting product, in particular due to sorption of microelements and other biologically active substances, in particular betaines, on its surface. When the ratio is less than 1: 2, or in the presence of chitosan, CMC cleavage does not occur and no additional effect from the interaction of the ingredients is observed.

A ratio greater than 1: 1 is not economically feasible, because leads to costs of the CX extract, while further improvement in the properties of the drug is not observed, which, apparently, is due to the ability of lectins, etc. CX ingredients affect only certain areas of MCC macromolecules. (Data on the effect of the composition of the drug on its properties are given in example 2 of the present invention.).

The drug is obtained by weighing a given amount of ingredients and thoroughly mixing them or co-grinding.

As a rule, 2 g capsules containing 618 mg CX-preparation EXTRAHOLM are used, however, when conducting studies in some cases, the ratio of ingredients may change (in these cases, the composition of the drug is specified).

The inventive drug is not toxic, does not cause side effects, has no contraindications. It can be recommended for the prevention and treatment of diseases caused by impaired cholesterol metabolism in the body: primary hyperlipidemia, hypercholesterolemia; obesity: cholesterol cholelithiasis, coronary heart disease; atherosclerosis of the vessels of the brain and coronary vessels, as well as for viral hepatitis and other similar diseases in combination with diabetes.

Features of the use of the drug and its effectiveness are illustrated by the following examples.

Example 1. The effect of the drug on the antitoxic function of the liver of mice.

Tests were carried out using preparations of various compositions containing SC MCC.

To detect violations of the antitoxic function of the liver, the hexenal test method was used. The criterion for evaluating it is the duration of hexenal sleep, expressed in minutes. Hexenal is known to break down mainly in the liver.

In the experiments, drugs were used at a dose of 13.62 mg / kg orally, which corresponds to the maximum therapeutic dose for humans. A hepatoprotector, an ampoule solution of essentiale (500 mg in 10 ml), at a dose of 7.14 mg / kg, widely known in practical medicine, was used as a positive control.

The experiments were performed on outbred mice, females, weighing 20-22 g. Conditioned individuals with a smooth coat and body weight were selected for the experiments within the average age indices (M + SD). Groups were formed by randomization by body weight. The animals were kept in standard plastic cages (10 mice per cage) with free access to water and feed. The diet included a grain mixture, briquettes, vegetables according to average feed consumption standards. The course of treatment was 10 days.

Animals were divided into 8 groups (20 mice per group). The preparations were injected with a probe into the stomach at a dose of 0.30 mg / mouse (the route of administration corresponded to the recommended route of administration of the drug).

As a positive control, animals were used, which were injected intravenously with essential at a dose of 0.14 mg / mouse (group 7). As a negative control, a 0.9% NaCl solution was used in the same volume doses (group 8).

On the 10th day of the experiment, 2 hours after the last injection of the preparations, a hexenal test was performed. Hexenal was injected intraperitoneally at a dose of 1.6 mg / mouse in both control and experimental animals.

The latent period and duration of anesthesia was determined by the moment of loss and restoration of the gravitational reflex. Statistical analysis of the results was carried out by t-student test.

The data on the study of the antitoxic function of the liver of mice are presented in the table.

As follows from the table, the most prolonged narcotic sleep was observed in control mice of group 8. This indicator is 21.0 ± 4.1 minutes.

In animals of groups I and II (experiment) and group III (positive control), the duration of sleep was significantly lower than in group 3 and corresponded to 13.2 ± 2.5 and 15.7 ± 2.7 (for groups I and II, respectively ) and 14.9 ± 3.1 (for group III), which is a statistically significant result with respect to the negative control (p <0.05).

Table 1
The effect of the composition of CX preparations on the antitoxic function of the liver of mice No. Injectable drug Hexenal sleep duration (in minutes) Ratio Latent Duration % (in relation to the negative control I CX: MCC = 1: 0.75 2.2 ± 0.6 19.2 ± 2.5 87.23 2 CX: MCC = 1: 1 2.3 ± 0.6 17.7 ± 2.5 77.73 3 CX: MCC = 1: 1.5 2.5 ± 0.6 14.2 ± 2.5 64.55 four CX: MCC = 1: 2 2.4 ± 0.6 14.4 ± 2.5 65.45 5 CX: starch = 1: 1.5 2.3 ± 0.8 18.2 ± 2.8 82.72 6 Hitochol 2.9 ± 0.6 18.6 ± 2.7 84.54 7 Essentiale (w / w) 2.4 ± 0.4 14.9 ± 3.1 70.95 8 Fiz. rr (control) 2.2 ± 0.8 22.0 ± 4.4 one hundred

From the results of the studies presented in table 1, it follows that the drug “Extraholm” significantly changes the action of hexenal and, therefore, affects the system of non-specific liver oxidoreductases that metabolize foreign substances. The best results, comparable with the intravenous administration of essential, are achieved with a ratio of CX: MCC from 1: 1.5 to 1: 2.

Example 2. Evaluation of the clinical effectiveness of the drug "Extraholm"

A clinical assessment was carried out on the basis of an analysis of the data of a clinical study conducted at the Central Research Institute of Epidemiology of the Ministry of Health of the Russian Federation.

Clinical studies were conducted at the Scientific Advisory Clinic and Diagnostic Department of the Central Research Institute of Epidemiology of the Ministry of Health of the Russian Federation. Under observation were 40 patients with chronic viral hepatitis C.

20 patients comprised the main observation group, 20 - the comparison group. The compared groups were comparable in sex and age composition, duration and severity of the underlying disease, the nature of the concomitant pathology

All patients received a similar course of rehabilitation therapy, which included traditional antiviral drugs.

In the main observation group, patients received an additional 1 package of “Extraholm”, dissolved in 100 ml of boiled water, 3 times a day. The observation course was 3 weeks.

Efficiency criteria were indicators of clinical, biochemical, laboratory research methods, analyzed before and at the end of the observation period.

Tolerance "Extraholm" was good. There were no allergic reactions or any side effects associated with its administration.

During the observation period, an improvement in the clinical condition was observed in all observed patients. However, in the group of “Extraholm” patients, a more rapid relief of dyspeptic symptoms, a decrease in pain, and earlier positive dynamics of laboratory parameters (ACT, ALT, thymol test) were observed compared with the comparison group.

Based on the foregoing and in accordance with the provisions of paragraph 2.1 SanPin 2.3.2 1290-03 "Hygienic requirements for the organization of production and turnover of dietary supplements for food" Extraholm can be used as dietary supplements, an additional source of betaine that improves the functional state of the liver and bile ways.

Example 3. The use of the drug "Extraholm" for the treatment of acute and chronic hepatitis.

Tests of the possibility and prospects of using the Extraholm drug for the treatment of acute and chronic hepatitis were carried out on the basis of the Central Research Institute of Epidemiology of the Ministry of Health of the Russian Federation and St. Petersburg State Medical Institute named after II Mechnikov in patients with acute forms of viral hepatitis A (HAV) and chronic forms of viral hepatitis C (CHC) .

The drug was used as follows:

- for patients with HAV - starting from 20-21 days from the onset of the disease after completion of detoxification therapy, 2 capsules three times a day before meals for 4 weeks;

- for patients with chronic hepatitis C - from the first day of hospitalization, 2 capsules three times a day before meals for 4 weeks.

Basic therapy (control) included a medical and protective regimen, detoxification therapy, enzymes, vitamins according to the traditional scheme.

Assessment of tolerance and effectiveness of the drug was carried out according to the following parameters:

analysis of clinical symptoms during treatment with cholesterol extract; subjective complaints of the patient - general health, temperature reaction, condition of the skin, etc., subjective assessment of patient tolerance to the drug; a clinical blood test (white blood cells, red blood cells, platelets, erythrocyte sedimentation rate (ESR) leukocyte formula);

biochemical blood tests (bilirubin, alanine aminotransferase (ALT), aspartate aminotransferase (ACT), etc.

An experimental and control group of patients was formed both from patients with chronic hepatitis C with an actively ongoing process, and from individuals with signs of moderate and low activity of the pathological process. All patients with HAV suffered a moderate icteric form of the disease. Patients of all the studied groups at the time of starting treatment did not show significant complaints, however, in some cases with an active survey, some patients noted periodically arising weakness, decreased appetite, heaviness and pain in the right hypochondrium, and bitterness in the mouth. Symptom data are given in tables 2 and 3.

table 2
THE FREQUENCY OF IDENTIFICATION OF THE MAIN CLINICAL SYMPTOMS IN PATIENTS WITH JAUNDICE FORM OF HEPATITIS A ON THE BACKGROUND OF TREATMENT WITH EXTRACHOLM Clinical symptoms Detection Rate (%) The main group (n = 15) Control group (n = 8) before treatment After before treatment After Headache 17.6 17.3 Dizziness 11.8 10.3 Weakness 41.2 9,4 37.9 10.7 Decreased appetite 52.9 62.0 6.9 Nausea 64.7 58.6 6.9 Vomiting 23.5 20.7 Pain in the right hypochondrium 52.9 48.3 24.1 Itchy skin 41.2 34.5 Hepatomegaly> 4 cm 64.7 41.2 75.9 62.1 Bitterness in the mouth 23.5 17,2 6.9

Table 3
FREQUENCY OF IDENTIFICATION OF KEY CLINICAL SYMPTOMS IN PATIENTS WITH CHRONIC VIRAL HEPATITIS WITH EXTRACHOLM TREATMENT BACKGROUND Clinical symptoms Detection Rate (%) The main group (n = 15) Control group (n = 8) before treatment after treatment before treatment after treatment Headache 11.6 13.3 Dizziness 4.8 6.3 Weakness 85,2 7.6 79.9 31,0 Decreased appetite 62.9 59.0 7.5 Nausea 44.3 48,4 12.3 Vomiting 2.5 3,7 Pain in the right hypochondrium 74.7 - 69.3 34.1 Itchy skin 21,4 18.5 Hepatomegaly> 4 cm 87.6 31.1 81.9 56.1 Bitterness in the mouth 13.5 4.7 11.1 5.9

On the background of Extraholm therapy, almost all patients noted a subjective improvement in well-being. The index for improving the quality of life has been rising. (In the comparison group, all these symptoms persisted for a longer time and required continued infusion therapy.)

In the group of HAV patients treated with Extacholm, there was a significant improvement in well-being, pain in the right hypochondrium, bitterness in the mouth, i.e. complaints of dyspeptic and asthenovegetative nature disappeared.

All patients with chronic hepatitis C had moderate intoxication, dyspeptic, and holistic manifestations. In the group of patients who received the drug Extraholm, there was a significant decrease in the symptoms of intoxication and dyspepsia (anorexia, nausea, vomiting, weakness, sleep disturbances), characteristic of viral hepatitis. On average, these symptoms in patients treated with ectraholm disappeared 5 days earlier than in individuals in the control group. The positive effect of the drug on the disappearance of the right hypochondrium syndrome in patients was especially noted. In patients who received the drug, after 10-12 days from the start of administration, a significant improvement in well-being and quality of life was noted and dyspeptic symptoms disappeared.

In the comparison group, all these symptoms persisted longer and required continued infusion therapy. After a month-long course of treatment, dyspeptic symptoms were not detected in any of the patients of the experimental group.

Evaluation of the effectiveness of Extraholm was also carried out according to the indicators of biochemical research. It was established that the initial level of bilirubin significantly exceeded the indices of healthy individuals and amounted to 106.3 ± 8.5 μmol / L in the group of patients with HAV and 22.5 ± 2.6 μmol / L in chronic hepatitis C patients.

In patients of the control group with HAV, the average bilirubin values also exceeded those of healthy individuals and amounted to 92.4 ± 7.5 μmol / L; in patients with chronic hepatitis C who did not receive the drug, it was 28.5 ± 3.6 μmol / L. After a month of treatment with Extraholm in all patients with HAV and chronic hepatitis C, the level of bilirubin did not exceed the values of healthy individuals and amounted, respectively: chronic hepatitis C - 18.2 ± 2.3 and HCV - 16.4 ± 4.3. In half of the patients who received basic therapy, the average bilirubin values exceeded the normal level and amounted to 27.2 ± 2.4 in the HCV group and 21.6 ± 5.3 in the HCV group (Tables 4, 5).

A positive effect of Extraholm on the severity of the cytolytic syndrome, manifested by a decrease in ALT activity, was observed in almost all patients. When assessing the dynamics of ALT during treatment, it was found that only in 30% of patients, ALT activity did not reach normal values after a month from the start of therapy, however, in the comparison group, 58% of patients retained elevated ALT values. In patients with chronic hepatitis C, receiving Extraholm, by the end of therapy, ALT activity decreased by 2 times, while in the comparison group this indicator decreased only by 1.5 times (Table 6). A significant decrease in cytolysis syndrome in patients receiving Extraholm indicates the membrane-stabilizing effect of this drug. The positive effect of the drug on the biochemical markers of cholestasis indirectly indicates its positive effect on the enterohepatic circulation of bile acids, the improvement of lipid and pigment metabolism.

Table 6 presents the indicators of changes in the thiol disulfide equilibrium during treatment with Extraholm compared with the control group. As can be seen from the data presented, in almost all patients there is an increase in the content of the SH-group and a decrease in the SS-groups.

Table 4
Dynamics of changes in biochemical parameters in patients receiving EXTRAHOLM. Indicators Analysis time Basic therapy Extraholm treatment CHC (n = 8) CAA (n = 8) CHC (n = 10) CAA (n =, 158) Bilirubin, μmol / L Before treatment 28.5 ± 3.6 92.4 ± 7.5 22.5 ± 2.6 106.3 ± 8.5 After treatment 27.2 ± 2.4 21.6 ± 5.3 18.2 ± 2.2 16.4 ± 4.3 ALT, Unit / L Before treatment 789.3 ± 15.5 1203 ± 12.7 647.3 ± 14.6 1159 ± 11.3 After treatment 413.1 ± 10.7 202.2 ± 10.3 475.8 ± 9.7 62.6 ± 9.3 ACT, U / L Before treatment 603.3 ± 9.5 835.4 ± 11.2 544.3 ± 8.5 633.1 ± 10.4 After treatment 488 ± 6.4 386.5 ± 9.8 258 ± 4.4 224.7 ± 8.9 Alkaline phosphatase Before treatment 88.4 ± 9.3 2165 ± 16.0 98.9 ± 12.5 206.7 ± 14.2 After treatment 62.8 ± 10.1 89.4 ± 9.1 76.9 ± 10.4 111.8 ± 10.2 Cholesterol Before treatment 7.9 ± 0.2 8.6 ± 0.5 7.6 ± 0.3 9.3 ± 0.4 After treatment 6.3 ± 0.3 6.9 ± 0.4 6.9 ± 0.4 6.4 ± 0.3 Prothrombin index,% Before treatment 75.0 ± 6.1 76.4 ± 6.9 75.6 ± 5.2 80.3 ± 5.4 After treatment 88.4 ± 5.8 89.4 ± 7.1 80.4 ± 5.4 92.4 ± 8.3

Table 5
Dynamics of changes in the thiol disulfide equilibrium in patients receiving EXTRAHOLM. Indicators Analysis time Basic therapy Extraholm treatment CHC (n = 8) CAA (n = 8) CHC (n = 10) CAA (n = 15) SH Before treatment 325 ± 20.5 389.2 ± 17.3 331.3 ± 21.6 395.7 ± 18.4 After treatment 330.7 ± 23.1 397.3 ± 15.3 398.4 ± 23.1 465.7 ± 15.3 SS Before treatment 172.4 ± 16.9 177.3 ± 18.4 174.2 ± 17.5 179.8 ± 15.9 After treatment 175.0 ± 16.9 189.2 ± 16.1 181.0 ± 16.9 186.4 ± 16.1 SH / SS Before treatment 1.8 ± 0.13 2.0 ± 0.08 1.9 ± 0.13 2.0 ± 0.09 After treatment 1.88 ± 0.09 2.1 ± 0.12 2.2 ± 0.11 2.5 ± 0.12

The dynamics of AlAt changes in patients receiving Extraholm changes for the group with HCV from 647.3 to 475.8 (in the control from 789.3 to 313.1), and for the group with HCV it changes from 1159 to 62.6 (in the control from 1203 to 202 ); the dynamics of changes in bilirubin in patients receiving Extraholm changes for the group with HCV from 22.5 to 18.2 (in the control from 28.5 to 27.2), and for the group with HCV it changes from 106.3 to 16.4 (in the control from 92.4 to 21.6). The SH / SS ratio increases by 15%, which indicates the activation of the antioxidant defense system. In patients receiving basic therapy, the change did not exceed 3%. The positive effect of Extraholm on these indicators indicates the presence of a pronounced hepatoprotective effect. Its use has been effective both in terms of the disappearance of cholestatic syndrome, and in terms of stopping the cytolysis syndrome.

It was shown that the drug has a combined detoxification, antioxidant, hepatoprotective and choleretic effect and is promising for the treatment of patients with acute and chronic forms of viral hepatitis, as well as persons suffering from cholecystitis and biliary dyskinesia. The use of the drug for the treatment of hepatitis patients reduces the duration of the icteric period, intoxication and pain syndromes, which can significantly reduce the treatment time.

Example 4. Patient F., 55 years old, was admitted for treatment on February 4, 2003 with a diagnosis of chronic persistent hepatitis; chronic recurrent pancreatitis in the acute phase.

Complains of weakness, itching of the skin, pain in the epigastric region with radiation to the right scapula, loss of appetite, unstable stool. He was also treated on an outpatient basis in a hospital, where histological data for the presence of chronic persistent hepatitis were obtained with a liver biopsy. About a month ago, epigastric pain appeared with irradiation in the right scapula.

Objectively: the condition is satisfactory, the skin is icteric, traces of scratching. The abdomen is slightly swollen. The liver protrudes from the edge of the costal arch by 2 cm, pain in the projection of the pancreas is determined, a positive symptom of Mayo-Robson. In the Hb analyzes, 124 g / l, erythrocytes 3.8 × 10 ¹² / l, white blood cells 888 × 10 ⁹ / l, platelets 210.0 · 10 ⁹ / l, ESR 27 mm / h, total protein 69.0 g / l , globulin 24%, AlAt 1.6 mmol / L, AcAt 1.4 mmol / L, sublimate titer 1.9 U, thymol sample 45 ALL, bilirubin 31.9 mmol / L, amylase 162 units, coprogram - pancreatic syndrome , abdominal echography - chronic diffuse enlargement of the liver, chronic diffuse compaction of the pancreas.

The patient received treatment: 2 capsules EXTRAHOLM 3 times a day for 20 days. After the therapy, the condition improved - weakness, itching of the skin, pain in the epigastric region decreased, stool returned to normal.

In the Hb analyzes, 150 g / l, red blood cells 4.8 × 10 ¹² / l, white blood cells 7.6 × 10 ⁹ / l, platelets 125.0 × 10 ⁹ / l, ESR 22.0 mm / h, total protein 65.0 g / l, globulin 21%, AlAt 1.05 mmol / L, AcAt 1.1 mmol / L, sublimate titer 1.8 U, thymol sample 42 ALL, bilirubin 27.6 mmol / L, amylase 78.0 units. After the course of treatment, the patient was in remission for 3 months.

Example 5. Patient K., 45 years old, was admitted for treatment on March 14, 2004. Diagnosis: chronic persistent hepatitis: chronic recurrent pancreatitis in the acute phase. Complaints of yellowness of the skin, aching pain in the epigastrium. Unstable stool 2-3 times a day. Sick for about a year. Morphological examination of the liver revealed the availability of data for chronic persistent hepatitis. Objectively: the condition is satisfactory, the skin is icteric, the stomach is regular in shape, an enlarged liver is palpated, the lower edge of which extends 1.5 cm from the edge of the costal arch, and a painful pancreas is palpated.

In the analyzes: Hb 110 g / l, red blood cells 3.4 × 10 ¹² / l, white blood cells 6.5 × 10 ⁹ / l, platelets 240 × 10 ⁹ / l, ESR 33 mm / h, total protein 78.0 g / l, - globulin 21%, AlAt 1.3 mmol / L, AcAt 1.4 mmol / L, thymol sample 52.0 VSE, sublimate titer 1.7 U, bilirubin 59.0 mmol / L, blood amylase 187 units, ultrasound imaging abdominal organs - an increase in the size of the liver, pancreas. The patient underwent treatment: Karsil, Eufilin, Vit. B1, B6, C - without significant effect.

After admission to the hospital received treatment: for 3 weeks - 3 times a day, 2 capsules EXTRAHOLM, then another 2 weeks 3 times a day, 1 capsule EXTRAHOLM.

After treatment, the patient's condition returned to normal, pain in the right and left hypochondrium disappeared, appetite and stool returned to normal.

In the analyzes: Hb 128 g / l, erythrocytes 4.0 × 101 ² / l, white blood cells 7.0 × 10 ⁹ / l, platelets 320 × 10 ⁹ / l, ESR 13 mm / h, total protein 70.0 g / L, globulin 22%, AlAt 1.0 mmol / L, AcAt 1.0 mmol / L, thymol sample 35.0 VSE, sublimate titer 1.3 U, bilirubin 24.0 μmol / L, amylase 62.0 units. Remission lasting about 10 months.

Example 6. To assess the prospects of using the drug "Extraholm" for the treatment of diabetes, experiments were conducted on the treatment of artificial diabetes in rats. The results obtained in comparison with the drug "Chitochol" are shown in table 1 (calculated dose of 1 capsule "Extraholma" or tablet "Chitochol" per day).

Table 6
DYNAMICS OF THE CONTENT OF GLUCOSE IN THE BLOOD IN RATS RECEIVED WITH HOLMA SOLA. A drug Label Source Hyperglycemia Level after administration of mg / ml 2 day % 4 day % Extraholm one 2.9 23.2 9.2 39.7 13.5 58.2 2 3.4 23.0 9.7 42.2 16.7 72.6 3 3.2 20.8 18.1 87.0 15.4 74.0 four 3.9 22.5 11.2 49.8 16.6 73.8 5 4.0 18.2 9.6 52.7 18.4 101.1 6 5.3 17.4 16.0 92.0 17.6 101.2 7 3.8 22.1 11.6 52.5 19.1 86.4 average 3.8 ± 1.5 21.0 ± 1.8 12.2 ± 3.0 59.4% 13.9 ± 6.2 81.1% Hitochol 1a 3.4 22.4 16.6 74.1 2a 2.5 21.0 20.2 96.2 3a 4.6 21.6 16.6 76.9 4a 3.4 22.8 19.5 85.5 5a 3.8 25.2 25.2 100.0 6a 4.9 24.6 23.7 96.3 7a 5.2 19.0 22.1 116.3 average 4.0 ± 1.5 22.4 ± 3.4 24.2 ± 4.0 92.2%

From these tests it is evident that Extraholm has a clearly and unambiguously pronounced effect on the 2nd day of administration in lowering blood glucose, and the protective effect of Hitochol is practically absent.

Example 7. Patient E., 40 years old, was admitted for treatment on 04/14/2006. Diagnosis: chronic persistent hepatitis. Type 2 non-insulin dependent diabetes.

Complaints of yellowness of the skin, aching pain in the epigastrium. Morphological examination of the liver revealed the availability of data for chronic persistent hepatitis.

Objectively: the condition is satisfactory, the skin is icteric, an enlarged liver is palpated, the lower edge of which extends 1.3 cm from the edge of the costal arch, and a painful pancreas is palpated.

In the analyzes: Hb 116 g / l, red blood cells 3.6 × 10 ¹² / l, white blood cells 6.4 × 10 ⁹ / l, platelets 210 × 10 ⁹ / l, ESR 32 mm / h, total protein 69.0 g / l, thymol test 52.0 ALL, sublimate titer 1.6 IU, bilirubin 59.6 mmol / l, blood amylase 140 units, glucose 7.5 mmol / l, ultrasound of the abdominal organs - an increase in the size of the liver, pancreas.

After admission to the hospital received treatment: for 3 weeks - 3 times a day, 2 capsules EXTRAHOLM, then another 2 weeks 3 times a day, 1 capsule EXTRAHOLM.

After treatment, the patient's condition returned to normal, pain in the right and left hypochondrium disappeared, appetite and stool returned to normal.

In the analyzes: Hb 130 g / L, red blood cells 4.2 × 10 ¹² / L, white blood cells 7.0 × 10 ⁹ / L, platelets 304 × 10 ⁹ / L, ESR 12 mm / hour, total protein 70.2 g / l, thymol sample 36.2 VSE, sublimate titer 1.2 IU, bilirubin 24.4 μmol / l, amylase 85.0 units, 5.6 mmol / l.

Thus, against the background of hepatitis treatment, the patient additionally observed normalization of blood sugar.

Example 8. A study of the effect of "Extraholm" on the level of blood glucose in patients with diabetes mellitus.

Patient K., born in 1958. Non-insulin-dependent diabetes mellitus since 1998. Over the past week, I took 5 mg 3 times a day. In this case, the blood glucose level varied from 11.4 to 12.4 mM / L. Before taking Extraholm, the initial level was 12.2 mM / L. Extraholm was administered orally in the form of 2 capsules daily 1 time per day. On the 5th day of treatment, the glucose level decreased to 8.4 mM / L. The dose of mannyl was reduced by 2 times (2.5 mg 3 times a day), treatment with Extraholm continued. 14 days after the start of treatment, the blood glucose level was 9.2 mmol / L.

As shown by experiments, the drug "EXTRAHOLM" has shown high efficiency for the treatment of diseases of the liver and gastrointestinal tract, especially in the treatment of diseases complicated by diabetes. The drug is non-toxic, not addictive.

Claims (1)

Means for lowering blood sugar in patients with diabetes complicated by diseases of the liver and bile ducts, which consists in the fact that it is a capsule containing a mixture of dry extract of hodgepodge and microcrystalline cellulose in a ratio of 1: 1 to 1: 2.