Medicinal mixture, possessing hepatoprotective and anti-inflammatory activity


FIELD: medicine.

SUBSTANCE: invention relates to field of medicine. Mixture consists of medicinal plants: inflorescences of pot marigold, peppermint leaves, Baikal skullcap root, black leaves and root of badan, shoots of shrubby cinquefoil, with the following component ratio, wt fr.: inflorescences of pot marigold 3; peppermint leaves 1; Baikal skullcap root 2; rhizome and black leaves of badan - 1+1; shoots of shrubby cinquefoil 2. Clinical treatment with claimed mixture has resulted in positive effect in case of alcoholic hepatitis in 150 patients.

EFFECT: creation of mixture for treatment and prevention of alcoholic hepatitis.

10 tbl

 

The invention relates to the field of medicine and for the establishment of collection with hepatoprotective and anti-inflammatory activities.

It is known that in the environment, consumed food has a huge number of hepatotoxic xenobiotics with which man comes in contact throughout his life. In the last decades has increased and has a further tendency to spread the proportion of diseases of the gastrointestinal pathology, about half of which are liver disease. Hepatoprotective means of pathogenetic therapy of acute and chronic diseases of the hepatobiliary system and normalize the structure, metabolism, function of the liver parenchyma.

It is known that chronic alcohol consumption is accompanied by liver damage (fatty infiltration, hepatitis), small intestine (motility disorders). The main biological effect of ethanol is associated with impaired tissue and cellular metabolism, suppression of the immune system, toxicity [Collier Jab, Montmor J.M., Harvey JG Oxford Handbook for clinicians. M.: Medicine, 2000]. Chronic alcoholism is often accompanied alcoholic enteritis, the main manifestation of which is diarrhea [Shabanov P.D. Guide to addiction. SPb.: Publishing house "LAN", 1999.- 352 C.]. IP is the use of synthetic drugs (antibiotics, NPVS) does not always provide the desired effect, in some cases exacerbates the disease. In this regard, the timely development and use of herbal medicines differ quite pronounced efficacy and safety in the treatment and prevention of alcoholic liver and intestines. therapeutic effect is achieved through a wide range of pharmacological properties of medicinal plants: hepatoprotective, choleretic, anti-inflammatory, antimicrobial, astringent, immunomodulatory and other

The proposed medical fee (called the "Calendula-6") has a pronounced hepatoprotective and anti-inflammatory activity consists of the following medicinal plants, parts:

Florets of calendula3,0
Peppermint leaves1,0
The roots of Scutellaria baicalensis2,0
Rhizomes of bergenia tolstolistnogo1,0
Leaves black bergenia tolstolistnogo1,0
Shoots facilitycontaining 2,0

To prepare 1000 g of the proposed collection take florets of calendula 306 g; peppermint leaves 102 g; the roots of Scutellaria baicalensis 204 grams rhizomes of bergenia tolstolistnogo 102 g, leaves black bergenia tolstolistnogo 102 g, shoots consisting of five leaves shrub 204 g, mixed, ground in a mill to a particle size of 1.0-2.0 mm sieved through sieve No. 2 and weighed. The loss of raw materials during grinding is 2%.

Part of the collection is composed taking into account the contribution of individual plants in hepato-protective and anti-inflammatory effects collection. Biologically active substances (BAS) of each component make a definite contribution to the normalization of the functions of the hepatobiliary system in alcoholic liver injury. Hepatoprotective and anti-inflammatory activity are BAS (carotenoids, flavonoids, polysaccharides, triterpene glycosides, essential oils, amino acids and other) blossoms of calendula, peppermint, Scutellaria baicalensis [Saakov, Ipomoeae. Handbook of medicinal herbs (Herbal medicine). - M.: Medicine. 1990. 428 S.; Ohanova.av, KLA. Biologically active ingredients Calendula officinalis L. // Raises. resources. 1990. So 26. issue 3. S-463; Addolgar, Amiga, Weitwinkel and other Scutellaria baicalensis. Phitokhimia and pharmacological properties. Tomsk. 1994. 222 S.; IGIC Laeva, Vbobrov, MRA. The consisting of five leaves shrub. Medicinal plants of Tibetan medicine. Series. - Ulan-Ude: Publishing house of the psybnc SB RAS. - 2000. 120 C.]. Anti-inflammatory, astringent and antimicrobial properties - main pharmacological properties of the drugs bergenia root containing phenolic compounds [Plant resources of the USSR: Flowering plants, their chemical composition and use; Family Hydrangeaceae-Haloragaceae. - L.: Nauka, 1987. - P.8-10]. The extract of black leaf bergenia exhibits adaptogenic, anti-stress, together with immunomodulating, anti-inflammatory, antitoxic activity [Publisherdata. Bergenia. Medicinal plants of Tibetan medicine. Series. - Ulan-Ude: Publishing house of the psybnc SB RAS. - 2003. - 90 S.].

To prove the reasonableness of the proposed composition of the collection the authors performed a series of experiments, data which confirm its efficiency expressed in alcoholic liver injury in experimental animals. Application in clinical conditions collection "Calendula-6 showed its beneficial effect on the functional state of the liver in patients with chronic alcoholism.

The analyzed sample collection, made from a medicinal raw material, which is consistent with the current articles GF XI ed. Quantitative determination of BAS in the collection and broth (1:10) was performed by the method of the GF XI ed. [State Pharmacopoeia of the USSR: issue 1. General methods of analysis. THE USSR MINISTRY OF HEALTH. - 11th ed., extra - M.: Medicine. - 1987. - 337 S.; v.2. General methods of analysis. Medicinal plant raw materials. THE USSR MINISTRY OF HEALTH. - 11th ed., extra - M.: Medicine. - 1990. - 400 C.]. Data analysis to quantify the content of BAS "Calendula-6" are shown in table 1.

Table 1
The quantitative content of biologically active substances in the collection "Calendula - 6"
NameThe content of BAS
In the collection "Calendula-6", %In broth collection (1:10), mg/ml
Flavonoids, in terms of luteolinwas 2.76±0,010,91±0,02
Tanning in society, in terms of tannin7,53±0,083,16±0,75
Polysaccharides4,99±0,351,5±0,02
Ascorbic the1,88±0,060,22±0,01

An example of a specific implementation.

Crushed and sifted through a sieve with diametral,5 mm florets of calendula 3.0 g; peppermint leaves 1.0 g; the roots of Scutellaria baicalensis 2.0 g; rhizomes of bergenia tolstolistnogo 1.0 g; leaves black bergenia tolstolistnogo 1.0 g; shoots consisting of five leaves shrub 2.0 g mixed, placed in a flask with a capacity of 300 ml, add 100 ml of distilled water, the flask connected with a reflux condenser and heated on a water bath, maintaining the boil within 30 minutes After cooling for 10 min, the extract was filtered through a paper filter, the obtained filtrate is used for determination of pharmacological properties.

The study of hepatoprotective activity "Calendula-6". Research conducted on 375 outbred white rats of both sexes with the original weight 150-170, Statistical processing of data carried out using U-test, Mann-Whitney [Sergienko V.I., Bondareva IB Mathematical statistics in clinical research. - M., 2000. 263 C.]. Alcoholic hepatitis in animals caused intragastric introduction of a 40% aqueous solution of ethyl alcohol in a volume of 7 ml/kg weight of the animal 1 time per day for 21 days [Mansurov I.D. Olimova S.O. the Activity of microsomal etnologija system during alcoholic intoxication // Experimental Hepatology. Riga: Zinatne, 1985. P.41]. The study collection "Calendula-6 was introduced in the form of decoction in experimental therapeutic dose in stomach white rats in the volume of 1 ml/100 g of animal 1 time a day for 21 days. The interval between the introduction of broth "Calendula-6 and ethanol corresponded to 5-6 hours. Another group of white rats on a similar scheme was introduced the product comparison - broth collection, intended for the treatment of hepatitis and chronic colitis (called collection FGHC) and consisting of chamomile flowers 2 hours, calendula flowers - 2 hours, peppermint leaves 2 hours, herbs tricolor violet 1 h [A.I. Krylov, V.A. Marchenko Guide to herbal medicine. SPb.: Publishing house of Peter, 2000. 416 C.]. Animals of control group received distilled water in an appropriate amount.

The functional state of the liver of animals were evaluated in the development of the injury at 7, 14 and 21 days from the beginning of the experiment. The activity of alanine aminotransferase (ALT), aspartate aminotransferase (ACT), alkaline phosphatase (apase), cholesterol, β-lipoproteins, bilirubin thymol turbidity test in the serum was determined by conventional methods [Laboratory methods in the clinic: a Handbook /Menshikov V.V., Delektorskaya, L.N., Zolotnitskaya R.P. and others: Ed. by V.V. Menshikov. - M., 1987. - 368 C.]. The intensity of the processes of lipid peroxidation (LPO) was estimated by the content of malondialdehyde (MDA) in the serum [Temirbulatov R.A. Seleznev H. a Method of increasing the intensity of free radical oxidation oil containing blood components and on the agnostic /value/ Laboratory work. - 1981. No. 4. - s-211] and in liver homogenate [I.D. Steel, Garishvili YEAR Method for the determination of malondialdehyde using thiobarbituric acid // Modern methods in biochemistry.- M, Medicine, 1977.- p.66-68]. The catalase activity in blood serum was determined by the method Gasolina, Mincho [Bobenko GA, Heinecke mathematical SCIENCES. Determination of catalase activity in erythrocytes and serum. // Laboratory work, 1976, No. 3]. Data analyses are shown in table 2.

The introduction of ethanol per os white rats causes a 7 day observation accelerating FLOOR in membranes: the MDA content in the liver homogenate of white rats in the control increased by 43% and stored in all subsequent periods of observation at a high level (table. 2). With the intensification of GENDER related manifestations of the syndrome of cytolysis. So, on day 7 of the experiment on the background of the introduction of ethanol in serum increases the activity of membrane-bound enzymes (AST and Alt) in 4.2 and 4.6 times compared with the intact group of animals. Simultaneously, increases blood alkaline phosphatase activity 1.6 times that of cholesterol by 22%, which indicates the development of cholestasis, which is due to impaired secretion and flow of bile. The development of cytolysis, cholestasis and strengthening processes the FLOOR accompanied by a decrease in the rate reception is tion of bile, inhibition of synthesis and release of bile bilirubin, cholesterol and bile acids, Thus, animals treated with ethanol for 7 days reduced the rate of secretion of bile by 16%, the content of bile acids, bilirubin and cholesterol, respectively, 36%, 33% and 22% compared with the control (table 3).

Course introduction "Calendula-6 in experimental therapeutic dose significantly reduced the toxic effect of ethanol. On day 7 of the experiment observed the inhibition of peroxidation processes: the MDA content in the liver homogenate of animals treated "Calendula-6", was significantly lower than in animals in the control. Along with this there is a decrease in activity levels of Alt, AST. The most pronounced therapeutic effect "Calendula-6" used in the dose has on the symptoms of cholestatic syndrome and phenomena of dysproteinemia. In addition, said reduced cholesterol, alkaline phosphatase and bilirubin 36%, 24% and 26% respectively compared with the corresponding figures in the control (table 2). In subsequent follow-up period (14-21 days) changes of biochemical parameters in the experiment indicate favorable dynamics involution signs of cholestasis in animals treated with "Calendula-6", than the comparison drug FGHK when ethanol hepatitis.

Thus, "Calendula-6" in experimentally-terapi the practical dose has a beneficial effect on the functional state of the liver of animals in the early stages of the development of ethanol-induced hepatitis.

2. The study of anti-inflammatory activity "Calendula-6". Experiments conducted on rats of both sexes of Wistar weighing 160-170, Antiexudative activity "Calendula-6" was determined on a model of acute aseptic inflammation of the hind limbs of rats using phlogogenic agent formalin. Play acute aseptic inflammation of the limb was performed according to the method Yevstratov [Manual on experimental (preclinical) study of new pharmacological substances. - M., 2005. 832 C.]. Decoctions "Calendula-6", FGCH (experimental group) and distilled water (control group) was administered intragastrically in a volume of 1 ml/100 g animal mass for 3 hours before subplantar of rats in the right hind paw with 0.1 ml of 3% formalin solution, and then through 5 and 18 h after that. After 24 h after injection of formalin assessed antiexudative effect of herbal ecometrics method. The obtained data are given in table 3

Table 3
The effect of decoction collection "Calendula-6" per phase exudation when "formalin" the swelling of the paws of rats
№№ p/pConditions of experienceThe volume of the displaced water, ml The percentage inhibition of edema
prior to the introduction of formalinafter injection of formalin
1Control (H2O)0,64±0,030,98±0,05-
2"Calendula-6"0,85±0,061,02±0,04*33%
3FGHK0,76±0,050,95±0,07*28%

A decoction of the collection "Calendula-6 provides antiexudative action, reducing the swelling of the paws of rats by 33% as compared with rats in the control group (table 3).

To study the effect of "Marigold-6" per phase of alteration of the inflammatory process conducted experiments on rats of both sexes of Wistar weighing 150-170, the Inflammatory process was reproduced by the method Mancina [Manual on experimental (preclinical) study of new pharmacological substances. - M., 2005. - 832 S.] by subcutaneous injection of 0.5 ml of 9% solution of acetic acid in the back area with a pre-cropped hair. Simultaneously to rats intraperitoneally injected with a solution dextrans dose of 300 mg/kg First intragastric administration "Calendula-6" in the amount of 1 ml/200 g was carried out for 1 hour before injection of acetic acid, and then daily 1 time per day for 29 days. Animals of the control group received water, purified on a similar scheme in equianharmonic quantities. 9, 20, 29, the day of the experiment was estimated area of necrotic tissue planimetric method. The obtained data are given in table 4.

Table 4
The influence of complex Fiorella "Calendula-6" per phase of alteration of the inflammatory response
No.Conditions of experienceThe area of necrotic tissue, cm2
9th day20 days29th day
1Control (H2O)3,61±0,382,42±0,131,50±0,11
2"Calendula-6"2,82±0,201,95±0,15*1,06±0,11*
3FGHK 2,21±0,231,91±0,160,94±0,09*

Course introduction Calendula-6" within 29 days reduces the extent of tissue damage when exposed phlogogenic agent and significantly reduces the area of the ulcer surface. So, after 9 and 20 days after injection of acetic acid area of alteration was decreased by 39 and 21%, respectively, compared with rats in the control group. A more pronounced anti-inflammatory effect of the tested tools were observed on the 29th day, when the area of alteration was decreased by 37%, the comparison drug has a less significant antiulcerative action (table 4).

To study the effect of "Marigold-6 proliferative processes in the inflammatory process conducted experiments on Wistar rats of both sexes weighing 170-180, Inflammatory reaction caused by the method of Trinus et al. [Manual on experimental (preclinical) study of new pharmacological substances. - M., 2005. - 832 C.]. For this purpose, sterile cotton balls weighing 15 mg implanted under the skin of rats in the back under aseptic conditions. Decoctions fees were injected intragastrically in a volume of 1 ml/100 g of 1 times a day for 7 days. Animals of the control group were injected in equianharmonic quantities on a similar scheme purified water. After 7 days was extracted Gran is the problem and were weighed on an analytical balance in raw form (immediately after extraction) and after drying at 70°C for 24 h to constant weight. The proliferative response was assessed by the difference between the dry weight of the granuloma and the original weight of a cotton ball, antiexudative activity - the difference between wet weight and dry granulomas. The obtained data are given in table 5.

Table 5
The effect of decoction collection "Calendula-6 on the proliferation phase of the inflammatory response
Conditions of experienceControl (H2O)"Calendula-6"FGHK
Wet balls mg198±4,2150±0,7to 139.3±8,3
Dry the balls mg32,1±2,734,3±1,225,3±1,8
The difference from the original mass mg17,119,410,3

The experimental data shown in table 6, indicate that "Calendula-6" compared with the collection FGCH more beneficial to the formation of fibrous granulation tissue phase chronic proliferative inflammation in rats.

Thus, the data of the conducted research is Avani show what the test collection "Calendula-6" has a more pronounced anti-inflammatory effect compared to the comparison drug.

3. Study of influence "Calendula-6" on the condition of patients with chronic alcoholism (clinical observation).

Crushed and sifted through a sieve with a diameter of 2.0 mm florets of calendula 3.0 g; peppermint leaves 1.0 g; the roots of Scutellaria baicalensis 2.0 g; rhizomes of bergenia tolstolistnogo 1.0 g; leaves black bergenia tolstolistnogo 1.0 g; shoots consisting of five leaves shrub 2.0 g mix. Brew Calendula-6" for clinical studies prepared in the form of tea: 1 teaspoon of the mixture is placed in infantery apparatus, add 100 ml of water, heated on a water bath, maintaining the boil within 30 minutes After cooling for 10 min, the extract was filtered through cheesecloth or a piece of cotton wool, the obtained filtrate is used for clinical studies.

Clinical study of the effectiveness of this herbal remedies conducted in 2001-2003, on the basis of the Republican narcological dispensary Ulan-Ude. Were examined 150 patients with alcoholism men aged 21 to 47 years, 54 men who ethanol occasionally (table. 6). Patients for the duration of the disease were divided into 2 groups: group 1 - the duration of the disease up to 5 years; group 2 - duration C is the disease from 6 to 11 years and more. In turn, patients who were divided into 2 groups according to the duration of the disease were divided into 2 subgroups: in addition to the same type of detoxification treatment "taking Calendula-6 (subgroup a) and the second subgroup of patients who did not take the remedy Calendula-6 (subgroup B). All patients diagnosed II expanded stage of alcoholism, the duration of binge 14-20 days. Almost all patients, according to the anamnesis, clinical examination was detected signs of alcoholic liver injury: a sudden loss of appetite, nausea, vomiting, coated tongue, pain and heaviness in the right hypochondrium, hepatomegaly, yellowness of the skin, interesest sclera, urine bile pigments.

Table 6
Clinical characteristics of the patients
Distribution of patients according to parametersThe number of patients, anti-lock brakes.(%)
1. Age, years
21-3019 (12,7)
31-3952 (34,7)
40-4979 (52,6)
2. The duration of Soboleva what I years
To 542 (28,0)
From 6 to 1131 (20,7)
More than 1123 (15,3)
Consume alcohol occasionally54 (36,0)

All patients received the same type of detoxification treatment; no other means of affecting the hepatobiliary system, was not appointed. Patients received "calendula-6" 100 ml in the form of tea 3 times a day for 7 days. To determine the functional state of the liver was determined by the activity of some biochemical parameters of blood serum in patients. To assess the validity of differences between average values of the sample used nonparametric criterion Wilkinson (Mann-Whitney) [Lakin K.M. Krylov Û.F. Biotransformation of drugs: General questions. M: Medicine. 1981. 342 C.]. In addition to biochemical parameters, information about the treatment tool "calendula-6" are recorded in a special map clinical observations. Carried out the score of each characteristic: 0 - no, 1 - weak expression, 2 - medium, 3 - high severity. Survey data are shown in tables 7 and 8.

Table 7
Action calendula-6 clinical signs of hepatotoxicity in patients with chronic alcoholism for up to 5 years
Clinical signsBefore the treatmentThe effectiveness of treatment in points *
3-day treatment5-day treatment7-day treatment
subgroupsubgroupsubgroup
AndBAndBAndB
Pain and heaviness in the right hypochondrium3,02,52,51,51,801,0
Liver enlargement2,32,22,22,0 2,01,82,0
Yellowness of the skin2,01,82,01,61,81,21,6
Interesest sclera2,42.22,41,82,01.21,8
The presence of bile pigments in urine2,82,22,41,51,501,0
Note: sub-group A - patients who received detoxification therapy+"calendula-6"; subgroup B patients who received the same type of detoxification therapy. * assessment of severity of symptoms in points: 0 - absent; 1 - weakly expressed; 2 - moderately expressed; 3 - strongly pronounced

When the analysis results to assess the effectiveness of "Calendula-6" in the first place was determined by its ability to influence the pain and heaviness in the right hypochondrium. The survey in most of the observations already the 3rd day there was a marked influence of the "Marigold-6" on the heaviness and pain in the right hypochondrium. To 7-th day pain was completely absent (PL. 8). Also clearly observed from the 3rd day tending to decline and other clinical signs.

Table 8
The action of Calendula-6 clinical signs of hepatotoxicity in patients with chronic alcoholism duration from 6 to 11 years or more
Days of treatmentClinical signs
Pain and heaviness in the right hypochondriumLiver enlargementYellowness of the skinInteresest scleraThe presence of bile pigments in urine
The effectiveness of therapy in points*
Before the treatment3,02,82,62,83,0
Day 3
subgroup a2,82,82,62,42,2
subgroup B2,82,82,62,62,8
Day 5
subgroup a2,42,62,42,21,8
subgroup B2,42,62,22,42,8
Day 7
subgroup a1,22,4 1,81,61,2
subgroup B1,52,62,02,01,8
Note: sub-group A - patients who received detoxification therapy + "calendula-6"; subgroup B patients who received the same type of detoxification therapy. * assessment of severity of symptoms in points: 0 - absent; 1 - weakly expressed; 2 - moderately expressed; 3 - well-defined.

The action of Calendula-6 clinical signs in patients with disease duration of 10 years or more also had a positive trend, although the clinical symptoms persist longer than in patients of group I (table 7). In table the data of biochemical analyses of patients during treatment "marigold-6".

Dynamics of changes of biochemical parameters of blood were characterized by the following: enzyme activity of AST in the serum at the time of treatment with herbal "Calendula-6 was decreased to 41-43%, Alt on 45-59% (table). In patients of group B, who did not take study vitorello, respectively decreased AST at 32-36%, Alt on 38-50%. Also clearly observed decline in cholesterol, sell the manual phosphatase, β-lipoproteins in 1.5 times, and the content of bilirubin in 4 times. The levels of total protein and thymol turbidity tests were equivalent to patients of the control group (who incidentally) (table. 9).

Thus, the use of herbal "Calendula-6" in the prevention and treatment of alcoholic liver damage in patients with chronic alcoholism in clinical conditions made it possible to achieve the correction of the main symptoms of liver damage, normalization of its functional state.

It is known that alcohol intoxication is accompanied by a pronounced activation of free radical oxidation of lipids in biological membranes of liver cells [.Loguerco, A.Federico. Oxidative stress in viral and alcoholic hepatitis.// Free Rad.Biol. and Med. 2003. 34. No 1. P.3-10]. With the purpose of the research intensity of the processes of lipid peroxidation in the serum was determined by the content of secondary products of lipid peroxidation - malonic dialdehyde - HMM. To assess the status of antioxidant defense system in the blood serum was determined by the activity of catalase. The results are shown in table 10.

In the study of GENDER indicators in the serum of patients receiving "Calendula-6", the detected decrease in MDA content on 23-24%, while in patients with subgroup B by 17-20%. It was also noted increased activity of catalase the patients subgroups And 27-35%, patients subgroup B 10-29%, indicating that activation of the endogenous antioxidant system (table. 10).

Thus, taking into account experimental and clinical studies "Calendula-6" set his pronounced anti-inflammatory and hepatoprotective effect in the liver by alcohol.

Drug collection with hepatoprotective and anti-inflammatory activities based on vegetable raw materials blossoms of calendula, peppermint leaves, characterized in that the quality of plant raw material additionally contains the roots of Scutellaria baicalensis, black leaves and rhizomes of bergenia tolstolistnogo, shoots consisting of five leaves shrub in parts:

Florets of calendula3,0
Peppermint leaves1,0
The roots of Scutellaria baicalensis2,0
Rhizomes of bergenia tolstolistnogo1,0
Leaves black bergenia tolstolistnogo1,0
Shoots consisting of five leaves shrub

 

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1 tbl, 9 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel compounds of formula (I), where R2 denotes H, [(C1-C6) alkylene]0-1-R'; R3 denotes H; R4 denotes H, halogen or (C1-C6) alkyl; R5 denotes H or halogen; R6 denotes H, (C1-C8) alkyl, R', (C1-C6) alkylene-R'; R7 and R8 independently denote H, halogen, (C1-C6) alkyl, O-(C1-C6) alkyl, R'; R9 denotes (C1-C6)alkyl; n equals 0 or 1; L denotes O or O-(C1-C6)alkylene; where R' denotes (C3-C8) cycloalkyl; (C5-C10)heterocyclyl, which denotes an aromatic or saturated mono- or bicyclic ring system which, besides a carbon atom, includes one or more heteroatoms such as nitrogen, oxygen and sulphur atoms; or (C6-C10) aryl; where in the heterocyclyl is unsubstituted or substituted with (C1-C6)alkyl, and the aryl is unsubstituted or substituted with a halogen, (C1-C4)alkyl, -O-(C1-C4)alkyl, SO2- (C1-C4) alkyl or N[(C1-C4) alkyl]2; and where in groups R4, R6 and R7 the alkyl can be halogenised in one or more positions; or pharmaceutically acceptable salts and/or stereo isomer forms thereof. The invention also relates to use of formula (I) compounds, as well as a medicinal agent.

EFFECT: obtaining novel biologically active compounds having Rho-kinase inhibiting activity.

21 cl, 320 ex, 3 tbl

FIELD: medicine, veterinary science.

SUBSTANCE: invention refers to veterinary science, namely to therapy of internal nontransmitting diseases, particularly to drugs for chicken hepatosis prevention. The agent for chicken hepatosis prevention contains the ingredients in the following relation: antihepatotoxic serum 0.9-1.15 titre units; antisplenotoxic serum 0.9-1.15 titre units; phenol 0.004-0.005 mg; physiological solution up to 1 ml. The agent is introduced to chickens and chicks in dose 0.2 ml/kg of body weight subcutaneously or intramuscularly.

EFFECT: invention allows higher effectiveness of chicken hepatosis prevention.

4 tbl

FIELD: medicine.

SUBSTANCE: invention relates to medicine, namely to hepatology, and can be applied in treatment of chronic hepatitis, caused by TTV virus. Method consists in simultaneous application of medication Amixin 0.125 in dose 1 pill every second day during 3 months in combination with medication fosfogliv in dose 2 pills 3 times per day during 3 months, with simultaneous treatment of sex partner.

EFFECT: application of invention allows to reach eradication of TTV form patient's organism with reduction of treatment time and reduction of complication quantity.

1 tbl, 3 ex

FIELD: medicine.

SUBSTANCE: invention relates to medicine, namely to pharmacology and cell technologies. Medication, possessing regenerative activity, represents granulocytic colony-stimulating factor, immobilised on water-soluble polymers with molecular weight 400-4000 Da. Granulocytic colony-stimulating factor is immobilised on water-soluble polymers by means of ionising radiation - flow of accelerated electrons with energy 2.5 MeV, absorbed dose from 2 to 10 kGy and rate of dose gain 1.65 kGy/hour.

EFFECT: medication by claimed invention does not have immunogenicity, is highly efficient both in parenteral and peroral introduction.

10 tbl, 10 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to medicine, namely to pharmacology. An agent represents an aqueous solution of molecularly capsulated dihydroquercetin in the form of a water-soluble associate. Dihydroquercetin is homogenised in a melted surfactant or in a general solvent ethanol in the relation of the surfactant to dihydroquercetin 5:1 in a temperature range 40-70°C to be mixed with water and concentrated by water evaporation.

EFFECT: invention allows higher bioavailability and activity of the agent, simplified technology.

4 cl, 3 ex, 3 tbl, 8 dwg

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to pharmaceutical industry, in particular to hepatoprotective medication. Medication, which has hepatoprotective action, represents product of extraction by ethanol of thalli of Cha-Kombu - Laminaria japonica Aresch., of laminarian family -Laminariaceae, which contains to 30 % of polyphenol compounds.

EFFECT: medication possesses efficient hepatoprotective action, favours accelerated restoration of metabolic reactions cascade, ensuring normalisation of biochemical characteristics of carbon and lipid exchange, as well as endogenous antioxidant protection system.

6 tbl

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to chemical-pharmaceutical industry, namely to creation of composition of dense extract of conifer needles for capsulation. Composition of dense extract of conifer needles contains the following ingredients: dense extract of conifer needles, emulsifier, a-tocopherol (vitamin E), retinol (vitamin A), naphthoquinones (vitamin K), essential fatty acids (vitamin F), vegetable oil. Microelements can be included additionally.

EFFECT: composition improves state of mucous membranes and enhances protective properties of organism.

2 ex

FIELD: medicine.

SUBSTANCE: invention relates to field of pharmacology, medicine and food industry and deals with medicine for reduction of visceral fatty tissue accumulation, which contains compounds of formula or extract of plant Liliaceae, which includes these compounds, application of said compounds or extracts for inhibition of visceral fatty tissue accumulation as well as product on their basis.

EFFECT: invention insures efficient reduction of visceral fatty tissue accumulation.

19 cl, 2 tbl, 2 ex

FIELD: medicine.

SUBSTANCE: invention relates to field of pharmacology, medicine and food industry and deals with medicine for reduction of visceral fatty tissue accumulation, which contains compounds of formula or extract of plant Liliaceae, which includes these compounds, application of said compounds or extracts for inhibition of visceral fatty tissue accumulation as well as product on their basis.

EFFECT: invention insures efficient reduction of visceral fatty tissue accumulation.

19 cl, 2 tbl, 2 ex

FIELD: medicine.

SUBSTANCE: invention relates to veterinary and can be used for external application in treatment of dogs, cats, fur-bearing animals and other small pets with disease of bacterial-mycotic-mite etiology. Cream for treatment of skin disease of small pets, contains acaricidic, anti-mycotic-antimicrobial substances, wt %: 20% Roksacin 1.8-2.1; 1% Aversect-2 7.8-8.1; child's cream on grease base - the remaining part.

EFFECT: invention insures increasing of efficiency and reduction of treatment terms.

1 tbl, 2 ex

FIELD: medicine.

SUBSTANCE: invention relates to medicine, namely to urology and rehabilitation medicine, and deals with prevention and complex treatment of urolithiasis after distant lithotripsy. For this purpose after distant-shock-wave lithotripsy carried out is litholytic, antibacterial, antispasmodic, analgesic therapy with administration of a diet. Additionally introduced is infusion of medicinal plants, which contains bearberry leaves, leaves of Indian kidney tea, knotweed grass, dill fruits, burdock root, nettle leaves, rowan fruits, taken in equal component ratio. Infusion is introduced in dose 100 ml 3 times for day 30 min before meal for 10 days at the background of carried out basic therapy and for 4 weeks after its withdrawal, basic therapy.

EFFECT: method ensures efficient prevention and treatment due to complex impact on all links of urolithiasis pathogenesis.

3 cl, 1 tbl, 1 ex

FIELD: medicine.

SUBSTANCE: invention relates to medicine, namely to urology and rehabilitation medicine, and deals with prevention and complex treatment of urolithiasis after distant lithotripsy. For this purpose after distant-shock-wave lithotripsy carried out is litholytic, antibacterial, antispasmodic, analgesic therapy with administration of a diet. Additionally introduced is infusion of medicinal plants, which contains bearberry leaves, leaves of Indian kidney tea, knotweed grass, dill fruits, burdock root, nettle leaves, rowan fruits, taken in equal component ratio. Infusion is introduced in dose 100 ml 3 times for day 30 min before meal for 10 days at the background of carried out basic therapy and for 4 weeks after its withdrawal, basic therapy.

EFFECT: method ensures efficient prevention and treatment due to complex impact on all links of urolithiasis pathogenesis.

3 cl, 1 tbl, 1 ex

FIELD: medicine.

SUBSTANCE: invention relates to medicine, namely to urology and rehabilitation medicine, and deals with prevention and complex treatment of urolithiasis after distant lithotripsy. For this purpose after distant-shock-wave lithotripsy carried out is litholytic, antibacterial, antispasmodic, analgesic therapy with administration of a diet. Additionally introduced is infusion of medicinal plants, which contains bearberry leaves, leaves of Indian kidney tea, knotweed grass, dill fruits, burdock root, nettle leaves, rowan fruits, taken in equal component ratio. Infusion is introduced in dose 100 ml 3 times for day 30 min before meal for 10 days at the background of carried out basic therapy and for 4 weeks after its withdrawal, basic therapy.

EFFECT: method ensures efficient prevention and treatment due to complex impact on all links of urolithiasis pathogenesis.

3 cl, 1 tbl, 1 ex

FIELD: medicine.

SUBSTANCE: invention relates to cosmetology and represents gel from natural polysaccharide for injections in cosmetology, different due to the fact that it contains water solution, which contains 0.1-5% in weight/volume of hyaluronic acid or its salts and 0.5-5% in weight/volume of biologically compatible, highly hydrophilic viscous alcohol, obtained from water solution of hyaluronic acid or its salt and alcohol and optionally additives, conventional in cosmetology, with further sterilisation of said solution, with considerable increase of obtained gel viscosity resulting from sterilisation of components after mixing.

EFFECT: invention ensures skin rejuvenation.

5 cl, 3 ex, 3 dwg

FIELD: medicine.

SUBSTANCE: invention relates to cosmetology and represents gel from natural polysaccharide for injections in cosmetology, different due to the fact that it contains water solution, which contains 0.1-5% in weight/volume of hyaluronic acid or its salts and 0.5-5% in weight/volume of biologically compatible, highly hydrophilic viscous alcohol, obtained from water solution of hyaluronic acid or its salt and alcohol and optionally additives, conventional in cosmetology, with further sterilisation of said solution, with considerable increase of obtained gel viscosity resulting from sterilisation of components after mixing.

EFFECT: invention ensures skin rejuvenation.

5 cl, 3 ex, 3 dwg

FIELD: medicine.

SUBSTANCE: invention relates to field of cosmetology and represents method of obtaining emulsion cosmetic preparation, including step-by-step dispersion in solvent at room temperature of poorly soluble components, components being introduced into installation with powerful hydroacoustic impact, in which carried out are dispersion of components and cavitation homogenation of emulsion with further packing, characterised by the fact that mode of resonance acoustic cavitation is formed inside flowing mechanic fluctuation system-canal of rectangular section with larger side a and smaller side b respectively, generation of acoustic fluctuations is realised in phase on both opposite sides a with amplitude exceeding threshold of acoustic cavitation for moving multi-phase medium, consisting of mixed ingredients, amplitude of fluctuations is selected optimal for different stages of emulsion preparation, frequency f of acoustic fluctuations is selected equal to resonance frequency of entire canal with elements of added mass, which is determined by any known method, smaller distance b between canal walls is selected multiple to one fourth of wavelength, excited in said multi-phase medium, where f is frequency of generated fluctuations, Hz, C is sound velocity in multi-phase medium, m/s, b is distance between canal walls, m.

EFFECT: invention ensures obtaining the finest monodisperse cream emulsions with submicronic size of disperse phase, coalescence-resistant.

7 dwg

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to chemical-pharmaceutical industry, namely to creation of composition of dense extract of conifer needles for capsulation. Composition of dense extract of conifer needles contains the following ingredients: dense extract of conifer needles, emulsifier, a-tocopherol (vitamin E), retinol (vitamin A), naphthoquinones (vitamin K), essential fatty acids (vitamin F), vegetable oil. Microelements can be included additionally.

EFFECT: composition improves state of mucous membranes and enhances protective properties of organism.

2 ex

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