The homogenate and lyophilized drone larvae with hypolipidemic and hepatoprotective activity

 

(57) Abstract:

The invention relates to medical and pharmaceutical industry, namely the use of homogenate and freeze-dried from drone larvae, can be used as sources of highly effective medicinal and therapeutic tools. A means of having hypolipidemic and hepatoprotective effect, represents the homogenate or lyophilized drone larvae and has a hepatoprotective effect in the dose of respectively 200 mg/kg or 50 mg/kg, and lipid-lowering dose of 50 mg/kg or 13 mg/kg Technical result: the tool contains a synergistic complex of biologically active components and provides a pronounced hepatoprotective and hypolipidemic effect. 4 table.

The invention relates to medical and pharmaceutical industry, namely to develop a method of obtaining homogenate and freeze-dried from drone larvae with hypolipidemic and hepatoprotective activity.

In medical practice used to treat liver diseases, restore its functioning LIV-52 representing the integrated product of porosity ordinary, tamarisk Gali) [Mashkovsky M. D. Medicines, 2000]. For the treatment of atherosclerosis apply Lipner (“Ciprofibrate”), which we selected as the analogue of lipid-lowering action.

As a prototype, we made a technical solution disclosed in the patent RU №2084232 from 20.17,97, “a Method for obtaining compounds having hypolipidemic, antioxidant and hepatoprotective activity of the honey bee”) decisive the same task as stated.

It should be noted that these drugs have side effects (dyspeptic symptoms, allergic reactions and others).

In the pathogenesis of liver diseases play a significant role destructive processes caused by local acidification of the environment, destruction of cellular elements and biopolymers, damage to the membranes of liver cells. The basis of the pathogenesis of atherosclerosis is the increase in the content of cholesterol in serum and liver, beta-lipoproteins and prebeta-lipoproteins in the serum.

The purpose of this invention is the use as means, with pronounced hypolipidemic and hepatoprotective activity of homogenate and lyophilized drone larvae.

The homogenate is a homogeneous liquid creamy mass, light beige or yellow color, characteristic odor.

The lyophilization is conducted in the following way. Native homogenate was freeze for 2-3 hours at a temperature of minus 35 to 40°C. Then out of the frozen produce sublimation in vacuum at a residual pressure of 0.1-0.6 mm RT.article in 40-48 hours, bringing the temperature to the end of drying to +25-30°C. the residual moisture content of the resulting lyophilisate is 1-3%. In appearance the lyophilisate is an amorphous yellow powder, characteristic odor with high hygroscopicity. Due to the high hygroscopicity of the lyophilisate should be stored at a temperature of +7°C in sealed form. Installed the full chemical composition of these objects, both qualitatively and quantitatively determined the content of biologically active components: proteins, amino acids, is), trace elements and other compounds, causing high pharmacological activity of the drone larvae.

The study of the hepatoprotective action of the substances of the drone larvae (homogenate and freeze-dried) was performed on a model of acute toxic liver injury by carbon tetrachloride, which is one of the most frequently used models for evaluation of hepatoprotective activity of the connection.

In the experiment used white rats-males and females Wistar rats weighing 180-200 g contained in the standard mode of the vivarium. As control was used intact animals and animals with hepatopathies. Toxic hepatopathy caused a threefold intragastric probe introduction through day 50% oil solution of carbon tetrachloride at a dose of 0.3 ml per 100 g body weight. Experimental animals within 14 days intragastrically injected aqueous homogenate of the drone larvae (GTL) at a dose of 200 mg/kg, or lyophilized drone larvae (LTL) at a dose of 50 mg/kg (which corresponds to the dry residue dose GTL) or comparator drug LIV-52 in a dose of 50 mg/kg (single dose). Model of acute hepatic toxicity caused by the second week of the introduction of the investigated substances.

the functional status of the liver: the activity of alanine aminotransferase (ALT) Reitman and Frenkel using a standard set of firm "LACHEMA", the activity of Alp (alkaline phosphatase) - with a set of firm "LACHEMA" and TBA-active products spectrophotometric method using a standard set of "agate".

Data on the comparative impact of GTL, LTL and LIV-52 on the indicators of the functional status of the liver are presented in table 1. Acute toxic hepatopathy caused by the introduction of carbon tetrachloride (“control”), accompanied by a sharp increase in the activity of enzymes: ALT 208% (P<0,001), Alp 115% (P<0.001) and the increase in the content of TBA-active products (TBCAP) - by 138% (P<0,001). Welcome GTL at a dose of 200 mg/kg and LTL dose of 50 mg/kg had a protective effect, as manifested in lower metabolic shifts. ALT activity groups “GTL+CCI4and LTL+CCI4” decreased compared to the control at 60% (P<0.001) and 55% (P<0,001), respectively. The activity of alkaline phosphatase in groups “GTL+CCI4and LTL+CCI4” decreased by 55% (P<0.001) and 50% (P<0,001) compared to the benchmark. Accumulation TBCAP decreased in the group “GTL+CCI4” by 63% (P<0,001), the group “LTL+CCI4” by 55% (P<0,001) in relation to the performance of the control group animals. The performance of the group “LIV+CCI4” were changed as follows: M.

Thus, therapeutic and prophylactic administration of GTL and LTL animals with hepatopathy has a hepatoprotective effect by reducing cytolysis and cholestasis [Loginov A. C. et al. A new method of assessing the functional status of the liver in the clinic of internal medicine in medical examination of some patients, 1990], the decrease in peroxidation of membrane lipids. This effect is comparable with the action official hepatoprotective drug LIV-52, and in the case of GTL even slightly exceed it.

"Tenova" hypercholesterolemia in rats was established by intraperitoneal injection of tween-80 at the rate of 250 mg of tween-80 on a 100 g weight of the animal in 1 ml of purified water. Hypercholesterolemia developed later, 12 hours after injection of tween-80 [Poliakoff, E. D., Klimov, M. A. Pat. physiology and experimental. therapy, 1973, No. 1]. Animals with "tinuloy" hyperlipidemia was investigated the influence of different doses of drugs. For this animal within 7 days of the injected aqueous homogenate of the drone larvae (TTL) in the dose of 50 mg/kg of lyophilized drone larvae (LTL) at a dose of 13 mg/kg (1/4 of the dose homogenate) and the reference product “Lianor” in a dose of 13 mg/kg (single dose). The control were intact animals and animals Pochereth 12 hours produced decapitation, the study took the serum and liver. Total cholesterol and triglycerides were determined using a standard set of "Lachema".

Determination of cholesterol in the liver was performed after removal of diethyl ether after a preliminary alkaline hydrolysis [Kolmakova Century. N. The matters. the honey. chemistry, 1957, No. 6], a colorimetric method for color reaction Lieberman-Burchard [Stroev, E. A., Makarova Century, Workshop on biological chemistry, 1986].

Determination of triglycerides in the liver was performed using a standard set of "Lachema" after extracting them is similar to removing cholesterol [Kolmakova Century. N. The matters. the honey. chemistry, 1957, No. 6].

The calculation was carried out according to standard, the results were expressed in µmol/g

The experiments showed that the content of cholesterol and triglycerides in the serum and in the liver of control animals with "tinuloy" hyperlipidemia compared with corresponding levels in intact animals has increased dramatically (table 2 and 3). Introduction LTL resulted in decrease in serum total cholesterol 32.3% (p<0,001), triglyceride - 42.1% (p<0,001). In liver cholesterol decreased by 38.1% (p<0,001), and triglycerides - 56.9% (p<0,001) compared with the control group. G is the Cheney - on 94,1% (p<0,001); the content of triglycerides in serum decreased 36.6% (p<0,001), and in liver - 56.9% (p<0,001).

It is noted that the content of cholesterol and triglycerides in the experiments with the introduction of lyophilized drone larvae in most cases, recovered to the level of intact animals or even lower.

Studies have shown that the introduction of the drone larvae and drug comparisons Lianora at doses of 13 mg/kg obtained similar results. With the introduction of Leanora the level of cholesterol in blood serum decreased 59.5% (p<0,001), triglyceride - 58.8% (p<0,001), and the introduction of LDL cholesterol decreased by 54.5% (p<0,001), triglycerides - 51.4% (p<0,001). The difference in the values of indices were not statistically significant (p<0,5). A similar pattern of changes was observed in the liver.

Hypolipidemic properties LTL confirmed and chronic models of hyperlipidemia caused by the combined application of cholesterol, thiuragyl pain and stress [Denisenko, p. P. et al., 2000]. As follows from table 4, in the control group of animals treated with saline, after 1 month there was a significant increase in the content of cholesterol in 84,4% (p<0,001) against the source, and the cholesterol level was lower compared to control 25.1% (p<0.01), and triglycerides - by 9.2% (p<0,5), prebeta - and beta-lipoproteins 40.0% (p<0,001).

Significant changes in lipid content in serum was observed in the second month of experience. In the control group, the cholesterol level was above the original 134,1% (p<0,001), triglycerides by 11.0% (p<0,05), prebeta - and beta-lipoproteins - 60.0% (p<0,001). Introduction LTL resulted in the normalization of the studied indicators: compared to control cholesterol level decreased by 49.6% (p<0,001), triglyceride - 25.5% (p<0,001), prebeta - and beta-lipoproteins by 34.7% (p<0,001), and almost reached the initial level (p<0,5). In the liver, with the introduction LDL cholesterol decreased by 23.3% (p<0,001), triglycerides by 17.5% (p<0,001) compared with the control experiments.

Therefore, the study of the hypolipidemic activity of the drone larvae in the form of homogenate and lyophilized allow to conclude that they have a unidirectional effect in animals with different models of hyperlipidemia by reducing the amount of cholesterol, triglycerides, prebeta - and beta-lipoproteins in blood serum, as well as cholesterol and triglycerides in the liver.

This effect is not inferior to the official action of lipid-lowering Ave is askoy and hepatoprotective activity.

This demonstrates the feasibility of further study of this material with the aim of creating effective medicines.

A means of having hypolipidemic and hepatoprotective effect, characterized in that it is a homogenate or lyophilized drone larvae and has a hepatoprotective effect in the dose of respectively 200 or 50 mg/kg, and lipid-lowering - dose respectively 50 or 13 mg/kg



 

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