Hepatoprotective agent from algae
SUBSTANCE: hepatoprotective agent based on a lipid fraction from an alcohol extract of perforated thallome ulva - Ulva fenestrate P. et R., containing less than 70% membrane-active lipid components, including not less than 20% essential phospholipids with content of polyunsaturated fatty acids of the n-3 series of not less than 55%.
EFFECT: agent has effective hepatoprotective action, speeds up restoration of stages of metabolic reactions, thereby providing normalisation of biochemical properties of carbohydrate and lipid exchange.
The invention relates to biological compositions on the basis of extracts of vegetable origin and can be used as a hepatoprotector and tools that increase the body's resistance to chemicals of anthropogenic origin, the poisoning of industrial poisons and drugs.
Due to progressive deterioration of ecological environment, people are increasingly exposed to various substances of anthropogenic origin. In our country hygienic regulation covers currently about 2 thousand harmful chemicals that have more than 3 thousand hygienic norms of maximum permissible content in various environmental objects. The influence of stressful situations (Hypo - and hyperthermia, high physical activity, breathing hypoxic mixtures, being in the zone man-made disasters and other), unbalanced diet, alcoholism require a search for alternative approaches to pharmacoprophylaxis occurring disorders in the body. It is known that the main barrier to neutralize toxic contamination in humans and animals is the liver. Diseases of the liver and biliary system consists of 40% in the group nosological forms related to the pathology of the digestive with the system.
Thus, the treatment and prevention of liver diseases are one of the most urgent problems of modern pharmacology. Currently there is an active search for means of increasing the stability of liver pathological effects, reinforcing its neutralizing function by increasing the activity of the enzyme system, as well as contributing to the restoration of its functions in various injuries, including the poisoning of industrial poisons.
Currently there are several groups of hepatoprotectors, which are usually classified by origin:
• plant polyphenols;
• synthetic drugs;
• phospholipid preparations;
• organic preparations.
Not all hepatoprotectors studied in adequate clinical trials, therefore, the efficacy and safety of many of them remains unproven. Among the most well-studied drugs in this group include phospholipid hepatoprotectors.
Known drugs that have a hepatoprotective effect, containing as active principle complexes of phospholipids. This number of drugs similar in structure and action, which are produced in different countries under different names: "Essentiale" and a number of its variants (Essentiale-N, Essentiale Forte, and so is.), "Resalat", "asslover", "Phosphogliv", "Gepard" etc.
As funds have hepatoprotective effect by containing in their composition of phospholipids, also known extract from ascidians purple (PRF No. 1522487, op,), "Apler" (vengerovsky A.I., Golovin DEATH, Kovalenko M. and other Joint use of prednisone and hepatic containing phospholipids, in experimental chronic hepatitis // Experimental. and a wedge pharmacology. 1999. No. 2. Pp.28-30.).
Closest to the claimed means is known, widely used in medicine, the drug "Essentiale", containing in its composition as an active agent of polyunsaturated phosphatidylcholine - 1,2-divinelyinspired - phospholipid isolated from soybeans. The drug "Essentiale" (hereinafter Essentiale) is considered the standard hepatoprotector phospholipid nature.
The mechanism of action of Essentiale is connected, mainly, with its ability to provide a membrane and membranoproliferative action. It is achieved by direct injection of the molecules of essential phospholipids (EPL) in the phospholipid structure of the damaged liver cells, replacement of defects and restore the barrier function of lipid bilayer membranes. Unsaturated fatty acids of phospholipids contribute to improving the activity and fluidity of membranes, reduce the density of phospholipid structures, normalizes permeability. Exogenous AFL contribute to the activation located in the membrane phospholipidosis enzymes and transport proteins that, in turn, has a supporting effect on the metabolic processes in the liver cells, promotes its detoxification and excretory capacity.
The objective of the invention is the expansion of the Arsenal hepatoprotective funds. The problem is solved hepatoprotective agent based on the lipid fraction of the alcoholic extract of the thalli of Ulvi perforatum - Ulva fenestrate P. et R. (Chlorophyta - green algae, class Ulotrichophyceae, the order Ulvales - ulvalue), containing 70% active membrane lipid components, including at least 20% of essential phospholipids content of polyunsaturated fatty acid family of n-3 is not less than 55%.
The technical result consists in showing pronounced hepatoprotective effect of the lipid extract of the thalli of Ulvi perforatum - Ulva fenestrate P. et R. (Chlorophyta - green algae, class Ulotrichophyceae, the order Ulvales - ulvalue).
Multi-component phospholipid complex, constituting the active principle of the proposed drug - extract from Ulvi perforatum, is characterized by the presence in its composition of almost all known classes phospholipidosis origin, with reparative properties. The chemical structure of phospholipids contained in the extract of the thalli of Ulivi is similar to the structure of endogenous phospholipids prototype, however, due to the high content of polyunsaturated (essential) fatty acids, phospholipids in the composition of the extract Ulvi perforatum more active. Embedding these high-energy molecules in the cell membrane facilitates the process of regeneration membranes of hepatocytes. Fatty acid composition of the fractions of total lipids funds has a high degree of unsaturation and contains the full range of polyunsaturated fatty acids (Pufas) family of n-3 needed to convert lysophospholipids in the main structural components of membranes, phosphatidylcholine (PC) and phosphatidylethanolamine (PV), as well as metabolically active fraction - phosphatidylserin (PS), phosphatidic acid (FC), phosphatidylinositol (PHI) and diphosphatidylglycerol (FGD).
It should be noted that the biological activity of the lipid complex Ulvi perforatum Ulva fenestrate P. et R. not previously been studied.
As raw material for tools use the thallus Ulvi perforatum. Ulva perforatum Ulva fenestrate P. R. et refers to the division of green algae. It is widely distributed in the seas of the Far East and is often Senator is based on views, is the most important commercial species of green algae. It is rich in carbohydrates, nitrogenous substances and lipids and is widely used as a food product of high biological value.
The use of thallus, in the opinion of the applicant, because it is the part of the plant, which is in the process of life is characterized by a maximum growth rate that requires constant active membrane biosynthesis of lipids for the construction of cellular and subcellular membranes of newly formed cells. This determines the maximum content of lipids in the organism during the growing season.
The lipid fraction of the alcoholic extract obtained by the method, the usual selection of lipids from plant and animal raw materials (Folch, J., Less, M., Sloane-Stanley GH, A simple method for the isolation and purification of total lipids from animal tissues.//J. Biol. Chem. 1957. 226, N 1. P.497-509).
Samples of algae Ulva fenestrate P. et. R. (type Chlorophyta, class Ulotrichophyceae, order Ulvales) were collected in summer in Peter the Great Bay, sea of Japan. The collected algae were thoroughly cleaned from epiphytes, small invertebrates and particles of sand. The algae were washed in sea water and then heated for 2 min in boiling water to inactivate enzymes. Processed in this way, the algae were dried until dry air condition. The dried thallus was ground using a laboratory mill to the size of the s particles 0.5-1 mm and was extracted with 96% ethanol in the ratio of raw materials - the extractant 1:2 for 8 hours with continuous stirring. The extract was separated on a Buchner funnel under vacuum. The cake was filled with a new portion of alcohol before the mirror and was extragonadal under stirring for two hours. The extracts were combined, then evaporated the alcohol under vacuum at a temperature less than 37°C. the Obtained oily mass was extracted with a mixture of chloroform: ethanol (2:1). Phase separation to the extract was added 20% by volume of 0.73% solution of sodium chloride. After phase separation of the chloroform layer containing the lipids were separated in a separating funnel and evaporated on a rotary evaporator (T <37°C) until no odor of chloroform. The lipid extract is oily mass of greenish-dark green. Extracts for pharmacological testing was pre-dissolved in liquid paraffin 1:2.
The output of the lipid extract was 3.5% by weight of dry algae. In the study of the composition of the obtained extract was found that 80% of the total lipids, 70% of which belong to the category of active membrane components. As active membrane fraction took the amount of essential phospholipids and neutral lipids, less triacylglycerides, which, according to some authors do not directly enter into the composition of biological membranes (Kostetsky DURING, Goncharova S.N., Sanina N.M.,Shnyrov V.L., Season influence on lipid composition of marine macrofites // Botanica Marina. - 2004. - Vol.47, No. 2. - P.134-139). Essential phospholipids accounted for 20% of active membrane fractions of lipids. An important element of this composition is the high content in the composition of the phospholipid PUFA family of n-3 - predecessors of biologically active eicosanoids. It is known that the content of n-3 PUFA in marine organisms, in most cases, determines the value of the latter as a medicinal raw material. The detailed composition of the lipid fraction isolated from thalli of Ulva fenestrata presented in table 1.
The toxicity (LD50is more than 5000 mg/kg) and safety with long-term injections in the stomach and parenteral allowed to conduct experimental studies that have revealed a pronounced hepatoprotective effect of the extract on the model of intoxication by carbon tetrachloride (Chu). As a comparison used the drug "Essentiale"® (rhône-Poulenc Rorer, Germany), which is polyunsaturated phosphatidylcholine soybeans. Essentiale as reference hepatoprotector recommended official publications of the Pharmacopoeia Committee as the comparison drug test new tools that have hepatoprotective properties containing phospholipids (vengerovsky A.I., Markov IV and others, guidelines for the study hepatotomy the activity of pharmacological substances // Guidance on experimental (preclinical) study of new pharmacological substances. Moscow. 2000. S-231).
The experiment was carried out in rats male Wistar weight 130-180 g contained on a standard diet. Experimental model of acute toxic hepatitis (intoxication by carbon tetrachloride-Chu) in animals (rats) and the introduction of the preparations was carried out according to the guidelines for conducting pre-clinical trials (vengerovsky A.I., I.V. Markov, Saratikov A.S. Preclinical study of hepatoprotective funds // Vedomosti of the pharmacological Committee. 1999. No. 1. P.9-12). To create acute hepatitis animals were injected subcutaneously (in the dorsal cervical crease) 2 ml/kg Cho 50% oil solution (olive oil) daily for 4 days. From the 5th day of the experiment rats were treated for 7 days winterization 80 mg/kg Essentiale (in liquid paraffin) (Saratikov A.S., Ratekin A.V., Frolov V., Chuchalin B.C. the Influence of hepatic phospholipid nature on the toxicity of cyclophosphamide // problems of biological, medical and pharmaceutical chemistry. 2004. No. 2. S.43-47) or the lipid extract of the thalli of Ulvi perforatum dose of 80 mg/kg of active membrane fraction (in the form of an oil solution). Animals of the control groups were injected equiano amount of paraffin oil. A day after the last injection, rats were deceptional under ether anesthesia.
Therapeutic effect and the activity of hepatic evaluated for their impact on the survival of animals, weight characteristics and biochemical parameters of the liver. In the serum was determined by the activity of alanine aminotransferase (ALAT) and the content of malondialdehyde (MDA)in the liver was determined in lipid metabolism.
Animals were divided into following groups: 1 - control (intact); 2-I - introduction Chu for 4 days; 3-I - introduction Chu further cancellation (deprivation) within 7 days; 4-I - doing extract from Ulivi in the period of deprivation within 7 days; 5-I - introduction Essentiale in the period of deprivation within 7 days.
In the course of the experiment, after 4-day introduction of Chu weight of the animals was reduced by 21% (p<0,001), and weight of the liver of animals increased by 19% (p<0,05) (table 2).
During visual inspection of the animals coat was dull, stuck in some education. Animals were poorly mobile, bad eating food. In the liver was observed continuous grain fat inclusions, that is manifested severe fatty infiltration, characterized by intoxication, Chu. This is confirmed by the fact that the amount of total lipids in the liver exceeded the control level 3.5 times (table 3).
About the development of toxic hepatitis in this experimental model shows increased activity in the blood marker of liver enzyme Alt 7-fold (p<0,001), due to release of the enzyme from hepatocytes in Rove the result of increasing the permeability of membranes. One of the indicators of toxic hepatitis is the activation of lipid peroxidation. The increase in the number of malondialdehyde (MDA) 2 times (p<0,001) with the introduction of Chu characterized by high activity of the peroxide oxidation of fatty acids included in the composition of membrane phospholipids, which is accompanied by increased permeability of the membranes of hepatocytes.
The development of toxic hepatitis accompanied by an increase in the number of triacyl glycerine (TAG), free fatty acids (FFA) and cholesterol (LDL) while lowering their esterified forms (ask and EHS) in connection with the oppression tarifitsiruemih liver (table 4).
As can be seen from table 4, after the intoxication of Chu in rat liver by 11% (p<0,01) increased the number TAG on 15-16% (p<0,01-0,001) increased the number of FFA and cholesterol, while reducing ASC by 16% (p<0.01) and AHS by 25% (p<0,01). The mechanism of data breaches were caused by the collapse of triacylglycerides in adipose tissue (chemical stress), the release of fatty acids and glycerol into the blood and resynthesis in triacylglyceride in the liver. Since the synthesis of phospholipids from triacylglycerides violation of fatty acids and TAG accumulate in hepatocytes, which leads to the development of fatty infiltration. The low level EHS (25%reduction, p<0,001) indicates a violation tarifitsiruemih functions pécs and in connection with the inhibition of the enzyme ACAT (acyl-COA: cholesterol-acyltransferase) with intoxication of Chu.
In phospholipid spectrum of liver should be noted that among cholinesterase factions significant decrease in PF 7% (p<0,01) while increasing LFH by 36% (p<0.001) and CM by 26% (p<0,05) (table 5).
PF is included in the structure of the outer monolayer of the membrane and is the predominant number of phospholipid. It is known that activation of free radical processes in the first place, undergo oxidation of polyunsaturated fatty acids (Pufas) phospholipids membranes, causing a reduction in the content of their main structural components, in particular, PF. Among ethanolamine fractions should be noted the reduction in the number of PV at 10% (p<0,05), FS 23% (p<0.01) and an increase LFE 50% (p<0,001). The increase literacy phospholipids (LFH and LFE) due to increased activity of phospholipase A2. The accumulation of literacy phospholipids in the membrane of hepatocytes increases the permeability of their membranes. Compensatory mechanism to increase the permeability of membranes is an increase in CM, which together with cholesterol its stabilizer.
The high activity of phospholipases with intoxication of Chu is an increase in phosphatidic acid (FA), which is the basis of the structure of phospholipids. Reducing the number of diphosphatidylglycerol (FGD) by 24% (p<0,001) Nar determines the solution in the system of phosphorylation and ATP synthesis, since this phospholipid is a marker of mitochondria and is essential for the functioning of enzymes in the respiratory chain.
Based on the above, it should be noted that the experimental model of intoxication, Chu really contributed to the development of toxic hepatitis with impaired metabolic reactions in the liver. This manifested itself:
• to increase the mass of the liver due to fatty infiltration of hepatocytes;
• in violation of the membrane permeability and the release of markers of cytolysis in the blood (Alt);
• activation of lipid peroxidation;
• to increase the intensity of lipolytic processes;
• in violation of tarifitsiruemih liver function.
7 days after discontinuation of Chu (the period of deprivation) in the liver of experimental animals (group 3) most of the studied parameters are not normalized, testified to the continuing toxic stress and failure of protective forces of an organism to resist the development of toxic pathology.
The weight of the animals during the period of deprivation (table 2) has changed little relative to the 2-nd group (Cho) (an increase of 8%), whereas relative to the control remained significantly low (15%, p<0,001). The weight of the liver of animals decreased by 6% (p<0,05) relative to the 2-nd group (Chu), but at the same time, yet were significantly higher than control the initial level of 12%. In the liver at autopsy, there were grainy inclusion of lipids. Animals during external examination were poorly mobile, bad eating food, the coat was dull. The number of total lipids (table 3) in the liver relative to the 2-nd group decreased by 15%, while relative to the reference level of their value exceeded 3 times (p<0,001). On the conservation of toxic hepatitis in this group of animals shows significantly high relative to controls (32%, p<0.05) activity of a marker of liver enzyme Alt. Also retained a high level of MDA (64%, p<0,001), which determines the ongoing process of lipid peroxidation. That is, in the period of deprivation, toxic stress continues because of the presence of the products of metabolism of xenobiotics, as well as due to the depletion of antioxidant defenses.
In the period of deprivation number TAG is even higher than in the 2nd group (an increase of 22%, p<0,001) (table 4). Also increased the number of FLC (26%, p<0,001). At the same time, the magnitude ask and AHS remained at the level of those registered in the 2nd group (intoxication, Cho). That is, tarifitsiruyutsya liver function has not recovered and the process of development of fatty infiltration continued.
Analysis of the fractional composition of liver phospholipids in the cancellation period, Chu showed that the content LFH and LFE was even higher (2 times control UB is the tier). This indicates a further increase in lipid peroxidation and activity of phospholipases. The content of the basic structural components of membranes of hepatocytes - PF and PV has undergone further decline compared with the 2nd group, as compared to control significantly decreased on average by 9-12% (p<0,01-0,001). Also even lower than in the 2nd group, there were a number PHI, FS and FGD necessary for the functioning of membrane-bound enzymes. Draws attention to the fact that the number of CM was higher (48% compared to control; p<0,001), due to a compensatory response to impaired membrane permeability.
Thus, the data analysis of the investigated biochemical parameters of the liver indicate a continuing and deepening disorders metabolic reactions even in the absence of a toxic agent (the period of deprivation).
Research on the application of known hepatoprotector Essentiale and extract from Ulivi in the cancellation period, Chu showed that the resulting biological effect was, in General, identical, but in some cases had different severity (tables 1-4; 4-I and 5-I group). Under the action of both drugs there was a strong tendency to normalization of the studied indicators. So, there has been a restoration of weight of animal performance (weight gain relative to 3rd group), on average, 19% (p<0.001) in the 4th group (the extract of the thalli of Ulvi) and 9% (p<0.01) in the 5th group (Essentiale). Draws attention to the compliance of the weight of the liver of animals from the control values. Animal fur was smooth, fluffy, they have a good start there and move actively. At the same time with the introduction of the extract from Ulvi the amount of total lipids in the liver relative to the control is fully normalized, whereas the introduction of Essentiale this value was 20% (p<0,05) above. However, when compared with a group of deprivation (group 3) values were reduced by almost 3 times.
The fact that the activity of the marker enzyme of toxic hepatitis B was not significantly different from control values with the introduction of the extract from Ulvi, testifies to its membrane-stabilizing properties. At the same time with the introduction of Essentiale the activity of Alt was significantly higher than the control level by 23% (p<0,05), indicating that not the full restoration of the structure of membranes of hepatocytes. When comparing indicators of lipid peroxidation of membranes (MDA) it should be noted that in the 4th group (extract Ulivi) was a restoration of this indicator to the control values. At the same time, in the group of animals with the introduction of Essentiale the amount of MDA was 20% (p<0,05) higher than the control. However, regarding the 3rd group (deprivation) is MDA b is lo reduced with the introduction of both drugs accordingly, 40 and 26% (p<0,001).
In the study of indicators of neutral lipids in the liver after injection of medications draws attention to the marked reduction in the number TAG, FFA and cholesterol while increasing ask and AHS regarding the 3rd group (table 4). Compared with the control, significant differences exist in the 5th group (Essentiale). Thus, the number of TAG remained increased by 7% (p<0.01), and the number of FLC - 11% (p<0.05)and cholesterol by 7% (p<0,05). The number EGK was reduced by 13% (p<0.01)and EHS - 12% (p<0,001). Thus, Essentiale not completely removed fatty infiltration and not permanently reinstated aeriferous liver function. The extract of the thalli of Ulvi fully normalized investigated biochemical parameters of neutral lipids and showed higher efficiency in the recovery of liver function.
When comparing the phospholipid fractions in the liver tissue of the 4th group with those in the control it should be noted that administration of the extract of the thalli of Ulvi fully normalized studied parameters (table 5). With the introduction of Essentiale noted significant differences in the indicators of phospholipid exchange from control values: content LFH exceeded by 20% (p<0.01)and the number of LFE - 35% (p<0,001). Especially significant differences were observed in the content of metabolically active fractions: if estvo FS was lower than the control levels by 14% (p< 0,05), PHI 20% (p<0,001), FC - 29% (p<0,001), FGD by 31% (p<0,001).
When comparing the investigated parameters between the 4th and 5th groups (extract of the thalli of Ulvi with Essentiale) were expressed significant differences. So, with the introduction of Essentiale weight of animals after the intoxication of Chu was 8% (p<0,01) lower, and the weight of the liver by 7% (p<0,01) more than those figures with the introduction of the extract of the thalli of Ulivi. The amount of total lipids in the liver was higher by 18% (p<0.05)and the activity of Alat - 15% (p<0.05), and the number of MDA - by 22% (p<0,001). Among the neutral lipids, draws the attention of a higher level of cholesterol (4%, p<0.05) and low - cholesterol esters (9%, p<0,01). Differences were observed in the fractions of phospholipids: number LVH was higher by 37% (p<0,001), LFE - 30% (p<0,001). At the same time had lower content of FCS (20%, p<0,001), PHI (15%, p<0.05), and FC (32%, p<0,001), FGD (33%, p<0,001).
Benefits administration of an extract of the thalli of Ulvi perforatum during the period of deprivation compared with Essentiale were as follows:
• weight of animals and the liver, the activity of Alat, the value of MDA fully recovered;
• the value of XC is lower (4%, p<0,05), EHS higher (9%, p<0,01);
• the number of literacy phospholipids lower by 20-30% (p<0,001);
• the number of metabolically active fractions (FS, FI, FC, FGD) is higher by 15-33% (p<0,001).
The introduction is xtracta thalli of Ulivi and Essentiale helped correct the violations, caused by the intoxication of Chu, however, restore the changed settings under the action of the extract of the thalli of Ulvi was more effective.
Apparently, the main reason for the observed differences is that the biological activity of polyunsaturated phosphatidylcholine soybeans, part of Essentiale, as opposed to the multi-component complex extract of the thalli of Ulvi perforatum. High efficiency of the extract according to the applicant, due to the presence in its composition of almost all known classes of phospholipids of marine origin, with reparative properties. Their fatty acid composition has a high degree of unsaturation and contains PUFA family of n-3 needed to convert lysophospholipids in the main structural components of membranes - PF and PV, as well as metabolically active fraction, FS, FC, FI and FGD.
In addition, n-3 PUFA metabolites included in the composition of phospholipids of the proposed drug, show anti-inflammatory action, in contrast to fatty acid family of n-6 included in the active agent Essentiale.
Thus, the obtained experimental data follows:
1. The extract of the thalli of Ulvi perforatum has a pronounced hepatoprotective effect in the liver chetyrehhloristy the second carbon.
2. The mechanism of therapeutic action of the extract of the thalli of Ulvi perforatum due to the restoration of violated toxicant metabolic reactions of the liver:
• Stabilizes membranes of hepatocytes due to the embedding of the phospholipids within the lipid bilayer of the plasma membrane;
• Normalizes the structure of the membranes of hepatocytes and inhibits the release into the blood liver enzymes (Alat);
• Removes fatty infiltration of the liver;
• Activates aeriferous liver function, which contributes to the synthesis of phospholipids from triacylglycerides.
3. By the investigated indicators extract of the thalli of Ulvi perforatum shows a higher biological activity than Essentiale.
|The chemical composition of the lipid fraction of the thallus of Ulvi perforatum (Ulva fenestrate)|
|Total lipids||to 28.05 mg per 1 g of dry cloth|
|Total phospholipids||3,41 mg per 1 g of dry cloth|
|General matrilineality||24,64 mg per 1 g of dry cloth|
|The fraction of neutral lipids (% of sum of all fractions)|
|Free fatty acids||to 11.11±1,02|
|Esters of fatty acids||9,24±0,81|
|Esters of cholesterol||8,75±0,62|
|The residual fraction||11,93±1,00|
|Fractions of phospholipids (% of sum of all fractions)|
|Fatty acids (% of sum of all fractions)|
|16:1 n-7||of 3.60±0,07|
|16:4 n-3||14.24 from±0,85|
|20:5 n-3||of 3.60±0,43|
|Weight characteristics of rats after lesions of carbon tetrachloride and administration of an extract of the thalli of Ulivi and Essentiale (g; M±M)|
|Groups of animals||Lots of animals||The mass of the liver|
|group 2||195,83±4,36***||of 9.21±0,44*|
|group 3||210,83±4,90***||to 8.62±0,23|
|Deprivation + extract thallus|
|group 5||**230,00±4,00**, 2||*8,00±0,132|
|Deprivation + Essentiale|
|Note: differences are statistically significant at *., 1-p<0,05;**, 2-p<0,01; ***,3-p<0,001. Asterisks on the right compared with the control group, the asterisk on the left is the comparison with the 3rd group (deprivation), numbers on the right compared with the 4-th group.|
|Biochemical parameters of rat liver after the defeat of carbon tetrachloride and the administration of the extract of the thalli of Ulivi and Essentiale (M±M)|
|Groups of animals||Total lipids (mg/g tissue)||The activity of Alat (U/l)||MDA (nmol/ml plasma)|
|group 1 Control (intact)||42,17±1,97||43,80±4,25||3,43±0,30|
|2 group Chu||142,09±7,22***||307,71±65,30***||7,27±0,15***|
|group 3 Deprivation (Chu)||120,46±of 12.33***||58,03±1,75***||5,61±0,19***|
|group 4 Deprivation+extract of the thalli of Ulivi||***42,87±2,20||***46,79±2,54||***3,38±0,10|
|5 group Deprivation + Essentiale||***50,68±of 2.51*, 1||53,77±of 2.51*, 1||***4l3±0,11*, 3|
|Note: differences are statistically significant at *, 1-p<0,05; **-p<0,01; ***p<0,001. Asterisks on the right compared with the control group, the asterisk on the left is the comparison with the 3rd group (deprivation), numbers on the right compared with the 4-th group.|
|The fractions of neutral lipids in the liver of rats after lesions of carbon tetrachloride and the administration of the extract of the thalli of Ulivi and Essentiale (M±M)|
|Para-meters||group 1||group 2||group 3||group 4||group 5|
|Control (native)||Chu||Deprivation||Deprivation + extract of the thalli of Ulivi||Deprivation + Essentiale|
|SJK||14,26||16,55**||17,90***||**15,42||*trend of 15.87*|
|Note: differences are statistically significant at *,-p<0,05;**-p<0,01;***p<0,001. Asterisks on the right compared with the control group, the asterisk on the left is the comparison with the 3rd group (deprivation), numbers on the right compared with the 4-th group.|
Abbreviations: TAG - triacylglyceride, FFA - free fatty acids, ASC - esters of fatty acids, LDL - cholesterol, EHS - esters of cholesterol.
|The fractions of phospholipids in rat liver after the defeat of carbon tetrachloride and the administration of the extract of the thalli of Ulivi and Essentiale (M±M)|
|Show-teli||group 1||group 2||group 3||group 4||group 5|
|(native)||+extract||+e is Soziale|
|Feh||22,57||on 20, 23"||19,90||*22,63||**22,55|
|LFE||3,41||5,1 G"||5,80""||***3,55||***4,60***, 3|
|FC||2,99||of 5.89"""||4,21||***3,11||***2,13***, 3|
|***4,54||is 3.08***, 3|
|Note: differences are statistically significant at *, 1-p<0,05; **,2-p<0,01; ***, 3-p<0,001. Asterisks on the right compared with the control group, the asterisk on the left is the comparison with the 3rd group (deprivation), numbers on the right compared with the 4-th group.|
Of C is: PF - phosphatidylcholine, LFH - lysophosphatidylcholine, SM - sphingomyelin, PV - phosphatidylethanolamine, LFE - lysophosphatidylethanolamine, FS - phosphatidylserin, PHI - phosphatidylinositol, FC - phosphatidic acid, FGD - diphosphatidylglycerol.
Hepatoprotective agent based on the lipid fraction of the alcoholic extract of the thalli of Ulvi perforatum - Ulva fenestrate P. et R. (Chlorophyta - green algae, class Ulotrichophyceae, the order Ulvales - ulvalue), containing 70% active membrane lipid components, including at least 20% of essential phospholipids content of polyunsaturated fatty acid family of n-3 is not less than 55%.
SUBSTANCE: hepatoprotector is used as peptide ACTH (4-7) -PGP (Semax) having the formula Met-Glu-His-Phe-Pro-Gly-Pro.
EFFECT: use of the said peptide with the aim of hepatoprotection under condition of the development of free-radical oxidation of hepatocytes enables to improve the efficiency of treatment of liver diseases accompanied by intensification of free radical oxidation processes.
1 tbl, 1 ex
FIELD: medicine, pharmaceutics.
SUBSTANCE: invention refers to a new compound of formula [I] or to its pharmaceutically acceptable salt, wherein A represents optionally substituted alkyl, wherein the substitute represents identical or different 1-3 groups specified in aryl optionally substituted by 1-3 groups specified in alkyl, halogen, alkoxy and alkanoyl; cycloalkyl optionally substituted by 1-3 groups specified in alkyl and halogen; hydroxy; alkoxy; halogen; an amino group and oxo; an optionally substituted carbocyclic group specified in a mono- and bicyclic group, wherein an aromatic ring and cycloalkyl are condensed; optionally substituted aryl, an optionally substituted completely saturated 5- or 6-merous monocyclic heterocyclic group each of which contains 1 heteroatom specified in nitrogen and oxygen, wherein the substitute of optionally substituted aryl, the optionally substituted carbocyclic group and the optionally substituted heterocyclic group for A represents identical or different 1-3 groups specified in alkyl, optionally substituted hydroxy, alkoxy, cycloalkyl or halogen; cycloalkyl optionally substituted by alkyl or alkoxy; alkoxy optionally substituted by halogen; halogen; hydroxy; oxo; heterocycle; alkyl sulphonyl; and mono- or dialkylcarbamoyl, optionally substituted amino, wherein the substitute represents identical or different 1 or 2 alkyl or aryl, or optionally substituted carbamoyl, wherein the substitute represents identical or different 1 or 2 alkyls optionally substituted by aryl, X represents optionally substituted methylene or -O-, wherein the substitute of optionally substituted methylene for X represents alkoxy or hydroxy, Q represents N or C-R4, L1 represents a single bond, methylene, -CH=CH-, -O-, -CO-, -NR11-, -NR11CO-, -CONR11- or -CH2NR11-, L2 represents a single bond, -CR6R7- or a bivalent 5- or 6-merous completely saturated monocyclic heterocyclic group each of which contains 1 heteroatom specified in nitrogen and oxygen, R1 and R2 are identical or different, and each represents hydrogen, alkyl or halogen, R3 and R4 are identical or different, and each represents hydrogen, alkyl, alkoxy, cyano or halogen, R1 and R3 are optionally bond thereby forming 5- or 6-merous cycloalkane, or a 5- or 6-merous aliphatic heterocycle containing oxygen atom, R5 represents a carboxyl group, an alkoxycarbonyl group or a bioisosteric group of the carboxyl group, R6 and R7 are identical or different, and each represents hydrogen or alkyl, or R6 and R7 are bond thereby forming cycloalkane, R8 represents hydroxy, alkanoylamino or alkyl sulphonylamino, R9 and R10 represent hydrogen or halogen, and R11 represents hydrogen or alkyl. Besides, the invention refers to specific compounds of formula [I], a drug based on the compound of formula [I], using the compound of formula [I], a method of treating based on using the compound of formula [I], and an intermediate compound of formula [II].
EFFECT: there are prepared new compounds possessing the agonist activity on thyroid hormone β receptor.
18 cl, 36 tbl, 344 ex
SUBSTANCE: managing pregnancy in females suffering from overweight on their 26-30 weeks of pregnancy involves measuring an S-wave velocity in the hepatic tissue by acoustic pulse-wave elastometry. If an average value is 1.41 ms or more, hepatic protectors are administered.
EFFECT: reducing a rate of obstetric complications in the pregnant women suffering from overweight.
FIELD: veterinary medicine.
SUBSTANCE: method comprises complex pathogenetic therapy. Additionally, the specific biological preparation is used. The preparation is prepared according to the principle of production of cytotoxic serum from donor blood by hyperimmunisation of their antigens prepared from liver and spleen tissue. The antihepatotoxic serum and serum antisplenotoxic serum are obtained. They are mixed with sterile saline solution preserved with phenol to 0.5% concentration on the basis of the content in 1.0 ml of 0.9-1.15 its titrated units of antihepatotoxic and antisplenotoxic sera by reaction of binding the complement. The preparation is administered to animals once subcutaneously in the area of the withers at a dose of 0.45-1.1 ml per 1 kg of live weight. The method provides a higher immune status of the animal organism and high efficacy of treatment.
EFFECT: invention enables to improve the efficiency of treatment of liver steatosis in cats.
4 tbl, 1 ex
FIELD: medicine, pharmaceutics.
SUBSTANCE: invention refers to a therapeutic agent for preventing and treating chronic liver diseases. The above agent represents amaranth oil prepared by cold pressing of amaranth seed kernels and coats, to be used in a dose of 62.5 - 250 mg/kg of body weight.
EFFECT: declared invention provides higher positive effect on biochemical processes in blood and liver tissues in treating toxic hepatitis.
SUBSTANCE: method involves simulating hepatitis by 7-day alcoholisation in female rats. A hepatoprotective agent is presented by an api-phytocomposition in the form of an aqueous suspension of honey, lecithin and licorice root extract in the ratio of 10:2:1. The composition is introduced twice a day intragastrically before feeding in a dose of 200 mg/kg of body weight 5 days before ethanol introduction and for 7 days one hour before ethanol introduction.
EFFECT: effective treatment of hepatitis with no side effects.
1 ex, 1 tbl, 1 dwg
FIELD: medicine, pharmaceutics.
SUBSTANCE: claimed invention relates to a pharmaceutical, dietary, nutritional orally soluble composition for peroral intake, which contains at least one S-adenosylmethyonine (SAMe) salt in a combination with physiologically acceptable excipients and optionally other active ingredients. The physiologically acceptable excipients include light magnesium oxide.
EFFECT: compositions of the claimed invention have high taste qualities, which provides easier peroral introduction The compositions by the invention are characterised by the higher systemic bioavailability of S-adenosylmethyonine.
15 cl, 2 dwg, 13 ex
FIELD: medicine, pharmaceutics.
SUBSTANCE: invention relates to the field of pharmaceutics. An extract of Fraxinus excelsior seeds, capable of activating PPAR-alpha, which contains nuzhenide GI3, oleoside methyl ester, excelside B, GI5, salidroside, in effective quantities. An application of the extract of Fraxinus excelsior seeds to obtain a medication for treating a state, in which the PPAR-alpha activation is useful, is described. Also described is a method of treating a subject with the state, in which the PPAR-alpha activation is useful. A method of obtaining the extract of Fraxinus excelsior seeds is disclosed.
EFFECT: application of the claimed extract makes it possible to treat states, in which the PPAR-alpha activation is useful in an efficient way.
14 cl, 11 dwg, 2 tbl, 13 ex
SUBSTANCE: viral hepatitis in simulated in laboratory animals (rats) with D-galactosamine. Hepatitis is treated by single oral administration of immobilised hyaluronidase 25 unit/kg. Administration either precedes simulation, or is combined with the beginning of stimulation.
EFFECT: method enables reducing a severity of metabolic and morphological hepatic disorders effectively in stimulating hepatitis identical to viral hepatitis in a human with underlying reduced xenobiotic load on the body.
1 ex, 3 tbl
SUBSTANCE: invention relates to a compound of formula II, methods of producing a compound of formula I
and formula II
a pharmaceutical composition and versions of use for treating inflammation and/or liver damage. In the compound of formula II, R1 is H; R2 is a linear or branched C1-C18alkoxy; C-18 is in an α-configuration.
EFFECT: high efficiency of the method.
18 cl, 7 tbl, 8 ex
FIELD: medicine, pharmaceutics.
SUBSTANCE: invention refers to the pharmaceutical industry, namely to an ointment for burns, folliculitis, furunculosis, vasculitis treatment and wound healing. The ointment for burns, folliculitis, furunculosis, vasculitis treatment and wound healing containing: bees wax, line seed oil, kerosene and visceral fat of pig taken in certain proportions.
EFFECT: ointment possesses a biostimulating effect, reduces the wound healing time with no post-therapeutic cicatrisation with good fixation, uniform distribution on the skin surface and ease of use.
9 dwg, 9 ex
SUBSTANCE: experimental wound is cleaned daily, first with normal saline (NaCl), and then coated with modified montmorillonite clay containing 0.1 to 4.35 wt % of silver. The preparation is introduced into the wound in an amount of 0.1 g per a wound of 1.5 cm in diameter.
EFFECT: higher rate of septic wound healing.
3 tbl, 3 dwg
FIELD: medicine, pharmaceutics.
SUBSTANCE: invention refers to pharmaceutical industry, namely to using smectite for treating or preventing celiac disease. Using smectite known as diosmectite for preparing a therapeutic agent for treating or preventing celiac disease.
EFFECT: agent is effective in preventing and treating celiac disease.
SUBSTANCE: invention refers to medicine, namely to obstetrics and gynaecology, and may be used for preconception preparation in early recurrent miscarriage caused by chronic genital inflammation or inflammatory hormonal ovarian insufficiency. That is ensured by 12 intravaginal introductions of disposable injectors with Dead sea mud gel as a therapeutic agent daily for 30 minutes within one therapeutic course upon completion of the anti-inflammatory treatment following the early miscarriage.
EFFECT: invention provides 50% higher safety and effectiveness of preconception preparation in the given group of patients.
SUBSTANCE: method of treating periodontitis provides professional hygienic oral cleansing, antiseptic therapy, local drug-induced therapy. The local drug-induced therapy is two-staged with the use of zeolite-containing fossil flour with particle size of 0.3-0.4 mm. The first stage involves gingival infriction of a mixture consisting of zeolite-containing fossil flour and distilled water taken in equal weight parts for 10-15 min; the second stage includes applications of tampons impregnated with a mixture containing 2.5-3 weight parts of fossil flour and 1-1.5 weight parts of distilled water on the affected gingiva; the length of the local drug-induced therapy is 12-14 days.
EFFECT: effective treatment of periodontitis enables stable reduction of periodontal inflammation, fastening the remission time and reducing the number of aggravations.
2 tbl, 4 ex
FIELD: medicine, pharmaceutics.
SUBSTANCE: invention refers to pharmacological and cosmetic industry, namely to a dermatological agent. The dermatological agent containing antler deer's dry blood plasma, Mumiyo, D-Panthenol, Sea buckthorn oil and additives in certain proportions.
EFFECT: above dermatological agent possesses higher bioavailability and biological activity, as well as extends the range of similar products.
SUBSTANCE: invention refers to medicine, gynaecology and concerns treating non-specific cervicitis in nulliparae. What is involved is an etiotropic therapy according to the microscopic and bacterioscopic findings in a combination with a 10-day course of laser photophoresis started in the first phase of menstrual cycle for two menstrual cycles. For this purpose, the involvement area is coated with the balneological product 'Elton-gel' with the uterine cervix to be thereafter exposed to laser light at wavelength 0.9 nm, pulse power 5 Wt, pulse repetition frequency 600 Hz. The length of exposure for each locus makes: 2 minutes in first cervicitis, 3 minutes in the process of more than 1 year or the disease suffered for more than one year and the presence of more than two episodes of recurrence.
EFFECT: method provides reducing the length of treating subsacute and chronic non-specific cervicitis (SANC and CNC) in the given category of patients from 6-9 to 2-3 months, reducing the rate of the disease, providing noninvasiveness, safety and availability of the treatment.
3 ex, 2 tbl
SUBSTANCE: invention refers to radiation biology and radiation hygiene, namely the use of the fine (4 mcm) natural zeolite mineral cremcep for the prevention and treatment of radiation pathologies caused by the ingestion of iodine, cesium, strontium radionuclides.
EFFECT: invention provides reducing the internal exposure of both organs and tissues, and a body.
FIELD: medicine, pharmaceutics.
SUBSTANCE: invention refers to pharmaceutical industry, particularly to therapeutic preparations of mumiyo. The therapeutic preparation which contains purified mumiyo, grapefruit citrosept, edible glycerol, ethanol and water at specific proportions.
EFFECT: preparation has a prolonged shelf life.
FIELD: medicine, pharmaceutics.
SUBSTANCE: invention refers to medicine, and aims at preventing gastric mucosa ulceration. The method involves the use of 0.5% aqueous sodium salts of humic acids produced industrially from the bottom mud, in a single dose of 5.0 mg/kg orally 50 minutes before the administration to the ulcerogenic substance sodium diclofenac.
EFFECT: method is safe and high-effective.
2 dwg, 2 tbl, 2 ex
SUBSTANCE: method comprises introducing glauconite into diet of milk cows in ecologically unfriendly zone in amount corresponding to 0.15-0.20 g per 1 kg cow's weight once a day over a 25-30 day period.
EFFECT: reduced level of lead both in body and in blood of cows.