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Method of secondary prevention of hepatobiliary dysfunctions in children in conditions of increased contamination of biomedia with phenol, formaldehyde, methanol. RU patent 2478395. |
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IPC classes for russian patent Method of secondary prevention of hepatobiliary dysfunctions in children in conditions of increased contamination of biomedia with phenol, formaldehyde, methanol. RU patent 2478395. (RU 2478395):
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FIELD: medicine, pharmaceutics. SUBSTANCE: invention relates to medicine and is intended for prevention of hepatobiliary dysfunctions in children, living in conditions of contamination of atmospheric air with phenol, formaldehyde, methanol. Complex of medications ia applied. Eslidin in introduced perorally in 14-day course in age dosage from 3 to 7 years - 1 capsule 2 times per day, over 7 years - 1 capsule 3 times per day. Canephron N is introduced perorally, diluted in small amount of water, 2 times per day, to children of pre-school age in dose 10 drops, of school age - 20 drops per day with 10 day course; Flamin is introduced perorally 30 minutes before meal in dose 1-2 tablets per day with 10 day course; Jungle is introduced perorally during or after meal in dose 1 tablet 1 time per day with 21 day course; Immunal is introduced perorallyt 1 time per day with 10 day course in age dosage from 1 year to 6 years - 5-10 drops, from 6 to 12 years - 10-15 drops, over 12 years - in dose 20 drops. Course is repeated 1 time per year in children with light degree of disease course and 2 times per year in case of middle-severe disorders. EFFECT: method makes it possible to ensure and prolong remission and reduce frequency of recurrences of hepatobiliary dysfunctions in children. 10 tbl, 1 ex
The invention relates to medicine, in particular to Pediatrics, and can be used for the prevention of hepatobiliary dysfunction in children living in the zone of influence of chemical enterprises, in terms of pollution of atmospheric air phenol, formaldehyde, methanol. The invention is aimed at expanding the base schema prevention of hepatobiliary disorders through a combination of , antioxidant, immune-modulating action of the drugs used. During the last 15-20 years, there has been a trend of growth of prevalence of diseases of gastrointestinal tract, and on territories with high level of technogenic contamination of the environment, the level of gastroenterological morbidity in 3 times higher than in areas with favorable sanitation. It is found that 79% of children with diseases of the digestive system as a primary or secondary diagnosis revealed pathology of the hepatobiliary system. We know that about 95% of all toxic substances, received by the organism, metabolised in the liver its enzymatic systems. Environmental contaminants and with hepatotoxicity are aliphatic aldehydes (formaldehyde), aromatic hydrocarbons (benzene, phenol), alcohols (methanol). These substances because of their lipophilicity easily penetrate through biological barriers, can accumulated during the parenchymatous organs, rich in fats (liver, brain), forming functional and organic disorders. At chronic exposure to chemical factors hepatobiliary system may develop cytotoxic and cholestatic damage to a violation of education and bile secretion, increased permeability of the walls of the bile-excreting channels, dysfunction of the microvilli epithelium biliary moves, ensuring the flow of bile, with the development of steatosis and fibrosis. According to the literature prevention programmes hepatobiliary dysfunction associated with the negative influence of chemical factors of anthropogenic origin in children have not been developed in the Russian Federation are not standardized. Modern protocols of patients, approved by the Ministry of health and social development of the Russian Federation in 2004, relate to chronic inflammatory (cholecystitis) and organic lesions of the gallbladder (cholelithiasis), not focusing the attention of doctors in the early methods of diagnostics and prevention of a dysfunctional disorders of GBS. The basis of the recommended comprehensive measures are dietotherapy, the appointment of enzymes, cholagogue and [1, 2, 3]. Absence of regulated standards for treatment and prevention of hepatobiliary dysfunction associated with adverse chemical factors, causes necessity of optimization of schemes for medical and preventive activities to reduce the incidence of diseases of liver and gall-bladder and improvement of Supervisory activities on the territories of sanitary and hygiene. Of patent literature is a series of patents, aimed at diagnosis of violations of hepatobiliary dysfunction [4, 5], and treatment of these disorders [6, 7, 8]. However, all of these well-known technical solutions are not focused on secondary prevention of hepatobiliary dysfunction in children. The technical result is achieved by the invention consists in increasing the effectiveness of secondary prevention of hepatobiliary dysfunction in children living in the zone of influence of chemical enterprises in conditions of pollution of atmospheric air phenol, formaldehyde, methanol, due to the extension of the duration of remission, to reduce the frequency of relapses, prevention of formation of concomitant gastroduodenal pathology. The specified the technical result is achieved by the proposed method of secondary prevention of hepatobiliary dysfunction in children in conditions of high contamination phenol, formaldehyde, methanol by prescribing, according to which in the period of remission carry out the combined use of children following drugs: oral course of 14 days in the age dosage of 3 to 7 years old - 1 capsule 2 times a day, over a 7 - 1 capsule 3 times a day; Canephron N orally, diluted in a little water, 2 times a day for children of preschool age 10 drops, school-age - 20 drops per day course of 10 days; Flamin oral, 30 minutes before meals for 1-2 tablets 2 times a day rate of 10 days; Jungle orally during or after meals to 1 1 tablet once a day course for 21 day; Immunal orally 1 time per day rate 10 days in the age dosage of 1 to 6 years - 5-10 drops from 6 to 12 years - 10-15 drops, over 12 years - 20 drops, and the course of combined application of the medicines exercise 1 once a year in children with mild course of the disease and 2 times a year when moderate violations. This technical result is achieved due to the following. Thanks to the combined application of medication recommended by the proposed method provides high effectiveness of secondary prevention of hepatobiliary dysfunction in children living in conditions of ecological trouble. In the pathogenesis of hepatobiliary disorders dominate the processes of damage and dysfunction of hepatocytes, developing against the background of activation of lipid peroxidation, a breach of the functioning of the immune and autonomic nervous systems. Taking into consideration the effects of the negative effects of chemical components, contaminating the environment, hepatobiliary system, and their ability to enhance the peroxide oxidation of lipids and the formation of free radicals of oxygen, forming intoxication, and syndromes, justified the inclusion in the proposed scheme for the secondary prevention of hepatobiliary dysfunction in children residing in the zone of influence of chemical enterprises and contamination of the blood phenol, formaldehyde and methanol, drugs with , antioxidant and membranostabilizing properties. Moreover, the proposed method is recommended for use in combination of the following medicines: ® (ESLIDINE) is a combined drug, including essential phospholipids and methionine, to restore the function of the liver and increase its detoxifying ability, normalization of lipid, carbohydrate and protein metabolism in the body. ® - active substances - PPL-400 300 mg, methionine 100 mg - capsules; BL. 10 cor. 3 pieces; LSR - 001048/08 on 26.02.2008; manufacturer: JSC «3-PHARMA» (Russia); Canephron® H (Canephron N) - the combined means of plant origin, has a diuretic, spasmolytic, anti-inflammatory and antimicrobial action. Contains active substances zolototysjachnika (Centaurium umbellatum, Gentianaceae), drug (Levisticum officinale, Apiaceae), rosemary (Rosmarinus officinale, Lamiaceae). Canephron® N - solution for the reception inside; FL. 50 ml doses. pipette cor. 1; P # 014244/01; manufacturer Bionorica D-92318 NEUMARKT, Germany); Jungle - Polyvitamin preparation (vitamin A, D3, E, C, Vs, H, B1, B2, PP, B6, B12) with micro - and macro-elements (iron, magnesium, iodine, copper, phosphorus, calcium, zinc) to meet the vitamin balance and normalize metabolism. Jungle - chewing table.; the ban. 100 Pach. cardboard. 1; # N014491/01 from 04.04.2008; manufacturer: , Inc., Chicago (USA); Flamin - zhelchegonnoe means of plant origin, possesses hepatoprotective, spasmolytic and anti-inflammatory action. Contains flavonoid glycosides, flavonoids from inflorescences bessmertnika (limits) sand (Helichrysum arenarium L./Moench./). Flamin (Flaminum) - table; .10 .3 PCs; P # 014599/01; manufacturer: LLC «Pharmaceutical company «Zdorovie» (Ukraine); Immunal® - immune-stimulating drug vegetable origin, stimulates the phagocytic activity of granulocytes and macrophages, and causes an increase in the number of lymphocytes in human body, thereby inhibiting the reproduction and contributing to destroy microorganisms, stimulates the production of native interferon. Contains active substances of purple Echinacea (Echinacea purpurea (l.) Moench)enhancing the natural protective forces of the body and act as stimulators of the immune system. Immunal® (Immunal®) - drops for reception inside; FL. 50 ml doses. pipette cor. 1; EAN code:3838957873913; No. P N013458/01, 2007-11-26 from Lek (Slovenia). Novelty of the proposed method consists in that for the first time for the secondary prevention of hepatobiliary dysfunction in children with contamination phenol, formaldehyde, methanol, living in conditions of adverse effects of chemical technological factors, used pathogenetically substantiated complex scheme, including a combination of hepatoprotector («») and («Canephron N»). This scheme is aimed to elimination of contaminants («Canephron N»), restoration of function of hepatocytes (methionine), improving metabolism and vegetative reactivity («Jungle», methionine), normalization of motor-evacuation function («Flamin»), redox (essential phospholipids) and immunological homeostasis («Immunal»). The choice of drugs for preventive measures is determined by their age regulations, ease of use in outpatient settings, including in children's preschool establishments, and low toxicity. It was found experimentally that only use of a complex scheme for the application of the above drugs creates synergies in achieving delivered a technical result. Use them separately or with the scheme only of the range of instruments not achieved an increase in the remission periods is not provided with the maximum possible impact at all stages of pathogenesis of formation of hepatobiliary pathology, caused by the influence of adverse chemical factors of anthropogenic origin. The proposed method is as follows, by selling it at a specific example: 2. Produce selection of patients from this territory for conducting of preventive measures. Were examined 85 children (48 girls and 37 boys) with dysfunction aged 4 to 12 years and the level of toxins in the blood (phenol, formaldehyde, methanol) above the regional background levels that were examined in the clinic. Clinical and anamnestic criteria for selection of children: - the collection of complaints the complaints of occasional pains in the abdomen without clear localization arising after eating or not connected with meals; electoral appetite and nausea; tearfulness, nightmares, night sweats and sweating of the hands and feet; - at the stage of study of anamnesis - reduction of immune resistance (frequent acute respiratory diseases); accommodation in the zone of influence of chemical enterprises and highways; - the physical examination - intoxication and syndromes, the presence of shadows, dry skin and cracked in the corners of the mouth, diffuse light yellow coating on the tongue, pain in pane, right upper quadrant and pressure points (.Б), positive symptom Ortner-Grekov; - when laboratory study of selected children turned out to be the excess of the regional background levels of toxicants in children: phenol more than 4.7 times, formaldehyde 1.7 times, methanol more than 1.8 times; the presence of inflammatory reaction (increase in the level of leukocytes by 15% or more of the norm); in biochemical studies increasing the activity of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) is more than 10%, violation of oxidant- processes (increased antioxidant activity (AOA) more than 10%, lipids malondialdehyde (MDA) in plasma blood more than 20%), changing regulatory immunological mechanisms (General improvement of sensitization in 1,5-2,0 times, absolute and relative phagocytosis by 10-15%; increase levels of IgA-10%; functional studies: - by ultrasound scanning of the gastrointestinal tract increase in the tail of the pancreas, jet liver changes (hardening of the walls of blood vessels of the system of portal vein, hepatic veins), the presence of (visualization of loose sediment over 1/4 of the volume of the gallbladder or high density sludge); - dynamic ultrasound study trial choleretic Breakfast - a hyperkinetic type of hepatobiliary disorders cessation increase the volumetric flow of bile size of allocated bile (over 0.24 ml/min). Clinical laboratory diagnostics is performed using the analyzer Hematology AcT5diff AL (USA, France, Backman Coulter), the automatic device "Stat Fax-2600», photoelectric photometer KFK-3, biochemical Konelab analyzer, flowing FACS Calibur company "Becton Dickinson", immunoassay "Stat Fax-2100 (USA) analyzer. Activity of oxidative processes and antioxidative system were determined by the level of the AOA plasma lipids and MDA content in blood serum. A fermentative function of a liver evaluated by the level of activity of ALT, AST, alkaline phosphatase. The functional activity of the kidney on the level of creatinine. The state of humoral immunity was assessed on the content of serum immunoglobulins A, M, G (Mancini et al., 1965); system nonspecific defense - on indicators of phagocytosis (the method Douglas, 1983). Chemical-analytical survey included in the definition of the content in the blood 3 components: formaldehyde by high performance liquid chromatography, phenol and methanol by capillary gas chromatography method. Determination of toxic organic compounds in blood was performed in accordance with the guidelines of the «Determination of chemical compounds in biological media», approved by the Ministry of health of Russia, 2000 (MUK 4.1.763-4.1.779-99) and the «Definition of harmful substances in biological media», approved by the Ministry of health of Russia, 2008 (MUK 4.1.2102-4.1.2116-06) method analysis with different variants of preparation. Mean daily concentrations of toxicants in the atmospheric air in areas inhabited by selected patients accounted for formaldehyde 1,2 x 10 2 mg/m 3 , phenol 10,0 x 10 3 mg/m 3 , the average annual concentrations of formaldehyde were registered at the level of 2.4 MPC S.S., phenol - up to 3.5 MAC, S.S., the Total index of hazard when combined and intake amounted to 1,88 units By the combined action of substances in case of chronic exposition there is the risk of the development of liver pathology (HI, to 1.88). Ultrasound examination of hepatobiliar zone held ultrasonic scanner Toshiba APLIO XG» and Toshiba «Viamo SSA-640A» using linear sensors frequency from 7.5 to 13 MHz standard method assessing topographic anatomic relations, the macrostructure of the liver, biliary tract. The mathematical treatment of the evidence base the evaluation of the effectiveness of the recommended method is performed with the use of nonparametric statistical methods to the construction and analysis of two-dimensional contingency tables, the method of one-way ANOVA, methods of linear and non-linear regression analysis. To assess the reliability of the results used the criterion of Fisher's assessment of the adequacy of models), student's criterion (comparison group on quantitative criteria), criterion ^ 2-square (comparison of patterns of characteristics). Comparative assessment of probabilistic relationship between the signs in the groups assessed the relative odds (odd ratio - OR) with the analysis of the confidence interval (CI). 3. Spend the prevention of children on the territory of ecological trouble by complex appointment of the five drugs (table 1). All children receive the preparations of the proposed medical technologies on the basis of children's institutions. Table 1 Scheme of secondary prevention, conducted by the children in group №1 No. Drug Dosage and administration 1 ® Inside, at the time of delivery, are proglatawaya, with sufficient water. Children 3-7 years - 1 capsule 2 times a day for children after 7 years of age - 1 capsule 3 times day. Drug is taken for 14 days. 2 Canephron® H Inside, diluted in a little water. Children of preschool age 10 drops - 2 times during the day. Children of school age - 20 drops 2 times a day. The drug is taken within 10 days. 3 Flamin Inside on the 1-2 tablets 2 times a day, 30 minutes before eating, squeezed small amounts of water. The drug is taken within 10 days. 4 Jungle® Inside, and 1 tablet of 1 times a day during or after delivery. Drug is taken for 21 days. 5 Immunal® Inside, with a small amount of liquid, children over 12 years - 20 drops of 1 time per day. Children 1-6 years in the 5-10 drops, 6-12 years - 10-15 drops 1 time per day. The drug is taken within 10 days. Evaluation of the effectiveness of the proposed method of prevention was based on the analysis of the dynamics of complaints, the data of objective inspection, the results of laboratory methods of examination after 3 months. To assess the clinical effectiveness of the proposed treatment-and-prophylactic schemes, all patients were divided into 3 groups depending on the combination of drugs. Group №1 included 32 children, receive the whole complex of preparations for the proposed method (table 1). Group №2 selected 16 children in the scheme of reception of preparations listed in the table 2. Table 2 Scheme of secondary prevention, conducted by the children in group-2 No. Drug Dosage and administration 1 Flamin Inside on the 1-2 tablets 2 times a day, 30 minutes before eating, squeezed small amounts of water. The drug is taken within 10 days. 2 Jungle® Inside, and 1 tablet of 1 times a day during or after delivery. Drug is taken for 21 days. Children (37 persons)who received the scheme of secondary prevention, including Flamin, Jungle and immunomodulator Immunal, but do not use drugs, contributing to the elimination of chemical compounds, strengthening their metabolism, having hepatoprotective action ( and Canephron) (table 3), amounted to a group study №3. Table 3 Scheme of secondary prevention, conducted by the children in group №3 No. Drug Dosage and administration 1 Flamin Inside on the 1-2 tablets 2 times a day, 30 minutes before eating, squeezed small amounts of water. The drug is taken within 10 days. 2 Jungle® Inside, and 1 tablet of 1 times a day during or after delivery. Drug is taken for 21 days. 3 Immunal® Inside, with a small amount of liquid, children over 12 years - 20 drops of 1 time per day. Children 1-6 years in the 5-10 drops, 6-12 years - 10-15 drops 1 time per day. The drug is taken within 10 days. Against the background of the use of preventive schemes there was a positive dynamics of clinical symptoms, more expressed in group 1 compared with groups №2 and №3. Decreased number of children, responding to complaints of nausea - 2.6, 1.3 and 1.9 times respectively (p<0.02), and occasional abdominal pain in the abdomen - 1.8, 1.2 and 1.5 times (p<0.05), 65,5% of children of group №1 normal appetite (p=0.05), while in the compared groups of improvement of appetite noted in 33,0% and 51.0% respectively. The number of children with intolerance to fatty foods decreased from 28,45±3,74% of children under 15,52±3,45% (p<0.05) in group 1, with 30,38±2,17% of children under 22,67±3,11% (p>0.05) in group №2, from 29.38±2,51% of children under 19,33±1,82% (p<0.05) in group 3. Table 4 The dynamics of chemical contaminants in (blood) children of group №1 (mg/dm3 ) before and after the treatment and prevention Toxicant The background level The average value of the course (Pitch m) The average value after the course (Pitch m) The significance of differences before and after the course (p) Phenol 0,01±0,011 0,047±0,010 0,036±0,009 0,037 Formaldehyde 0,0050±0,0014 0,010±0,002 0,007±0,001 0,001* Methanol 0,369±0,12 0,667±0,015 0,514±0,018 0,013 * - p - reliability of differences indicators before and after the course Table 6 The dynamics of chemical contaminants in (blood) group children №2 (mg/dm3 ) before and after the treatment and prevention Toxicant The background level The average value of the course (Pitch m) The average value after the course (Pitch m) Differences before and after the course (p) Phenol 0,01±0,011 0,043±0,010 0,046±0,009 0,12 Formaldehyde 0,0050±0,0014 0,010±0,002 0,017±0,001 0,56 Methanol 0,369±0,12 0,417±0,032 0,414±0,027 0,91 * - p - reliability of differences indicators before and after the course Table 7 Dynamics of laboratory parameters in children group №2 before and after the treatment and prevention Indicator The physiological norm The average value to the course and isolating The average value after the course (Pitch m) Differences before and after the course (p) Leukocytes, 10 9 DM 3 5,5-7,5 7,37±0,33 7,12±0,29 0,15 IgA, g/dm3 0.68 to 1,44 1,33±0,04 1,01±0,08 0,17 Phagocytic index, USD 1,5-2 2,09±0,05 1,89±0,1 0,18 Malonic dialdehyde plasma mol/cm 3 1,8-2,5 3,09±0,17 2,47±0,37 0,05 Antioxidant activity of plasma, % 36,2-38,6 41,16±1,42 36,77±2,83 0,05 lipids, mkmol/DM 3 0-350 349,4±35,31 239,55±3,29 0,09 * - p - reliability of differences indicators before and after the course As can be seen from the tables, the most pronounced effect to the elimination of formaldehyde, phenol and methanol achieved in group №1 in children receiving proposed scheme of prevention, based on a combination of drugs that enhance the metabolism of chemical substances, their elimination with immunomodulatory and hepatoprotective action. Against the background of preventive measures 1.4 times decreased levels of formaldehyde in the blood 0,010±0,007 0,002 to±0.001 mg/DM 3 (p<0.001). In 1, 2 times as compared with the initial level decreased concentration of phenol with 0,047±0,01 to 0.036±0.01 mg/DM 3 (p<0,037), 1.3 times the concentration of methanol with 0,667±0.25 to 0,514±0.25 mg/l (p<0,13). The level of the AOA decreased from 41,64±1,88% to 33,17±2,44% (p<0,042). Indicator lipids decreased in 3 times (p<0.01) and reached the physiological norm. Significantly elevated levels of MDA 3.12 to±0.19 mmol/cm fell 2.52±of 0.27 mmol/cm (p<0,027). Evaluation of the immunological parameters against the background of prevention shows a significant reduction in 1.6 times (p<0.01) content IgA (1,0±0.06 g/dm3 ) (p<0.01). In group 1 showed a significant decrease in phagocytic index 1.2 times (p<0.0001) (p<0,018), the level of leukocytes in the blood from 7.22±0,49 10 9 /DM 3 to 6.38 ħ 0,49 10 9 /DM 3 (p<0,013). The children in the group-2 statistically significant dynamics of the indicators analyzed after the course prevention is not installed (p>0.05), except for normalization of metabolic processes, reduction of initially high antioxidant activity 41,16±1.42% to 36,77±2,83% (p=0.05) and the level of MDA in plasma with 3,09±0,17 umol/cm 3 to 2,47±0,37 umol/cm 3 (p=0.05). Strengthening prevention schemes at the expense of the drug immunomodulating action, used in children in group №3, contributed to the normalization of immunological and biochemical indicators, however, did not lead to elimination from the body of the studied chemical substances that in the future could lead to a resumption of pathological changes homeostatic parameters and exacerbation of the disease. During the ultrasound scanning of the hepatobiliary system in group №1 in 2 times fewer children with reactive changes in the liver (with 26,72±4,15% to 13,79±3,13%, p<0,03). Decreased to normal values previously increased size of the pancreas every third child with dysfunction (p<0.01). Was 1.7 times less likely to register in the gall bladder (p<0.05). Comparative evaluation of the functional state of the gall bladder in the dynamic ultrasound with the reception of bile stimulus showed a significant reduction of the volume flow of bile in 1,8 times (p<0.001). In the compared groups of # 2 and # 3 on the background of care also noted the positive dynamics of indicators of the ultrasound scan of the liver (the proportion of children with was reduced by 1.3 and 1.5 times) and biliary tract ( disappeared 19% and 23% respectively). However, the differences were statistically insignificant, except dynamic investigations of the function of the gallbladder. A significant reduction of the volume flow of bile installed in 56% and 71% of children groups # 2 and # 3, respectively (p=0,01-0,03). Thus, the combined use of ®, ® H, produced cholelithiasis, Jungle and in the scheme prevention of hepatobiliary dysfunction, unlike standard methods, not taking into account the pathological effects of chemical factors of technogenic origin, helps reduce the severity of the disease, prevents the transformation in severe and chronic forms. For the proof of the synergistic effects in the proposed method, exactly five medicines below table 10, reflecting the clinical effectiveness of the follow-up (in a year) with different schemes of receiving drugs for the prevention of hepatobiliary dysfunction in children. Table 10 Clinical efficacy of prophylaxis regimen of hepatobiliary dysfunction in children in the follow-up (after 1 year) under different combinations of drugs Regimen of medicines The number of children without complications, % The number of children with mild forms of the disease (not more than 1 time in the year),% The number of children with a frequency of exacerbation more than 2 times, % The number of children with the formation of chronic cholecystitis in the follow-up Group №1 52,0 34,0* 14,0* 0* Group №2 22,0 38,0 36,0 14,0 Group №3 37,0 39,0 24,0 10,0 * - p<0.05, compared with other groups The proposed method is recommended for use in outpatient and inpatient departments practical level health care, in profile departments consultative-diagnostic centers specialized care for the child population living in the zone of influence of the enterprises of a chemical profile (phenol, formaldehyde, methanol). Sources of information 1. Maev A.A., Samsonov A. Diagnosis and treatment of diseases of biliary tract // Educational-methodical manual. - M - 2003 - .125. 2. Mikhailov S.M., Trush O.V. Quality medical care to patients with chronic gastroduodenitis // Vestnik of Saint Petersburg state medical Academy. 2006, №2. - P.17-19. 3. E.A. Medical and biological fundamentals of prevention and correction of functional changes of the hepatobiliary system in young athletes: abstract of Diss. kand. honey. Sciences. Moscow, 2008, - P.30. 4. Patent of Russian Federation №23 89029. 5. Patent of Russian Federation №2393 775. 6. Patent of Russian Federation №2132198. 7. Patent of Russian Federation №2193386. 8. Patent of Russian Federation №2197265. Method of secondary prevention of hepatobiliary dysfunction in children in conditions of high contamination phenol, formaldehyde, methanol by prescribing characterized by the fact that in the period of remission carry out the combined use of children following drugs: oral course of 14 days in the age dosage of 3 to 7 years old - 1 capsule 2 times a day, over a 7 - 1 capsule 3 times a day; Canephron N orally, spreading in the a small amount of water, 2 times a day for children of preschool age 10 drops of school-age - 20 drops per day course of 10 days; Flamin orally for 30 minutes before eating 1-2 tablets 2 times a day rate of 10 days; Jungle orally during or after meals to 1 1 tablet once a day course for 21 day; Immunal orally 1 time per day rate 10 days in the age dosage of 1 to 6 years - 5-10 drops from 6 to 12 years - 10-15 drops, over 12 years - 20 drops, and the course of combined application of these drugs carry 1 year in children with mild the course of the disease and 2 times a year when moderate violations.
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