The method of obtaining funds, has cardioprotective activity

 

(57) Abstract:

The invention relates to the field of pharmacy. Powdered plant material - leaves-kakali spear extracted with 70% ethanol twice when the ratio of raw material:solvent 1:16 for 16 and 10 h, concentrated, by evaporation under vacuum. Raw materials after alcohol extraction is additionally extracted with boiling water twice for 60 min at a ratio of raw materials:extract 1:15. Water extracts evaporated, combined with the aqueous residue alcohol extraction, darpariaeth and dried in a vacuum drying apparatus. Yield is 40.3% by weight of plant material. The invention allows to realize the specified destination. 7 table.

The invention relates to the field of pharmacy and relates to a method of receiving funds from vegetable raw materials, which has cardioprotective activity.

A method of obtaining hawthorn tincture, which is based on counter-current 3-stage extraction of raw materials 70% ethanol in a battery of three percolation [( N. D., Ant I. A., the Development of technology for production of tinctures from fresh hawthorn fruit // pharmacy. - 1987. - so XXXVI. No. 4. - C. 33-37]. The disadvantages of the known method is the result of invention - receiving funds from the leaves of kamalii spear, with pronounced cardioprotective activity, which is achieved by increasing the output of existing substances.

To achieve the technical result of the crushed plant material (leaves cacalia spear) extracted with 70% ethanol in the ratio of raw material:solvent 1:(16-18) taking into account the coefficient of water absorption at room temperature and constant stirring. Removing the filter in the collection. The extraction was repeated twice. The extraction time at 1st contact phases - 16 h, the 2nd contact phases - 10 PM Alcohol extract are combined and evaporated to 1/4 of the original volume. Meal after alcohol extraction is additionally extracted with water at 100°C in the ratio of raw material:solvent 1:(15-20) with the same coefficient of water absorption and constant stirring. Removing the filter in the collection. The extraction was repeated twice. The extraction time at 1-m and 2-m contacts phase - 60 minutes Water extraction combined with alcohol and evaporated to 1/3 the original volume. The resulting product is distilled separated, dried in a vacuum drying apparatus and crushed in the mill propeller type. Yield sostavlyayuschi decision criterion of "novelty".

The proposed method allows to obtain the substance, which represents a powdery amorphous hygroscopic powder brown with bitter-sour astringent taste and a peculiar smell. Weight loss at drying is 2.14%.

The method is illustrated by the following examples.

Example 1

1 kg leaves cacalia spear crushed in the mill until the particle size diameter (sieve No. 50 GOST 214-83). The crushed raw material is loaded into the extraction apparatus with stirrer and external steam heater and pour 16 l 70% ethanol. Extracted at room temperature with periodic stirring for 16 hours, the Extract is filtered in a collection. Spend another extraction under the same conditions for 10 hours, giving the extractor 70% ethanol in a quantity equal to the amount drained. The first drain - 12.4 l, the second - 11.8 liters United alcoholic extract evaporated to approximately 1/4 of the original volume. Raw materials after alcohol extraction pour 15 l of water. Extracted at 100°C and stirring for 60 minutes. Removing the filter in the collection. Spend another extraction under the same conditions, giving the extractor water in an amount equal to the amount drained retrieval. First SGAs volume. VAT residue of the four extracts purified by separation and dried on stainless steel trays in a vacuum dryer at a temperature of 60°C for 8 hours and pulverized in the mill propeller type. Get 0.403 kg of the finished product, which is 40.3% of extractives by weight of the feedstock. The dry extract is a loose amorphous hygroscopic powder brown with bitter-sour astringent taste and a pleasant aromatic smell. Weight loss at drying is 2.14%.

Example 2

1 kg leaves cacalia spear crushed in the mill until the particle size diameter (sieve No. 50 GOST 214-83). The crushed raw material is loaded into the extraction apparatus with stirrer and external steam heater and fill in 14 l of 70% ethanol. Extracted at room temperature with periodic stirring for 10 hours removing the filter in the collection. Spend another extraction under the same conditions for 8 h, giving the extractor 70% ethanol in a quantity equal to the amount drained. The first drain - 10.7 l, the second - 10.2 HP United alcoholic extract evaporated to approximately 1/4 of the original volume. Raw materials after alcohol extraction pour 20 litres of water. Extraly in the same conditions, feeding the extractor water in an amount equal to the amount drained retrieval. The first drain - 18.5 l, the second drain - 18.2 liters of Alcohol and aqueous extract combine, evaporated to about 1/3 the original volume. VAT residue of the four extracts purified by separation and dried on stainless steel trays in a vacuum dryer at a temperature of 60°C for 8 hours and pulverized in the mill propeller type. Get 0.396 kg of the finished product, which is 39.6% extractives by weight of the feedstock. The dry extract is a loose amorphous hygroscopic powder brown with bitter-sour astringent taste and a pleasant aromatic smell. Weight loss at drying is 2.00%.

Example 3

1 kg leaves cacalia spear crushed in the mill until the particle size diameter (sieve No. 50 GOST 214-83). The crushed raw material is loaded into the extraction apparatus with stirrer and external steam heater and fill in 14 l of 60% ethanol. Extracted at room temperature with periodic stirring for 12 hours, the Extract is filtered in a collection. Spend another extraction under the same conditions for 10 hours, giving the extractor 60% ethanol in aliceanna to 1/4 of the original volume. Raw materials after alcohol extraction pour 18 l of water. Extracted at 100°C and stirring for 75 minutes. Removing the filter in the collection. Spend another extraction for 30 minutes under the same conditions, giving the extractor water in an amount equal to the amount drained retrieval. The first drain - 16.5 l, the second drain - 15.8 liters of Alcohol and aqueous extract combine, evaporated to about 1/3 the original volume. VAT residue of the four extracts purified by separation and dried on stainless steel trays in a vacuum dryer at a temperature of 60°C for 8 hours and pulverized in the mill propeller type. Get 0.392 kg of the finished product, which is 39.2% of extractives by weight of the feedstock. The dry extract is a loose amorphous hygroscopic powder brown with bitter-sour astringent taste and a pleasant aromatic smell. Weight loss at drying is 2.16%.

1. We carried out phytochemical analysis of dry extract. On the basis of qualitative phytochemical analysis of dry extract revealed the presence of:

1) organic acids

By chromatography on paper (FN-16, 10°C, the upward current muraviinaya acid water (18:5:9) (II direction) after treatment with 0.5% solution of bromophenol blue (pH 9.2) was found tartaric acid - Rf=0.32 (I), Rf=0.45 (II); citric acid - Rf=0.48 (I), Rf=0.56 (II); oxalic acid - Rf=0.53 (I), Rf=0.60 (II); malic acid - Rf=0.68 (I), Rf=0.63 (II); fumaric acid - rf=0.82 (I), Rf=0.96 (II); succinic acid - Rf=0.85 (I), Rf=0.90 (II); pyruvic acid - Rf=0.91 (I), Rf=0.98 (II). Identification was carried out in comparison with authentic samples.

2) -carotene

0.05 g of the obtained extract was dissolved in 10 ml of hexane, 2 ml pour 2 ml of saturated solution of chloride of antimony (III) in chloroform, shake it vigorously, developing blue staining (-carotene).

By chromatography in thin layer of sorbent (plate mark "Sorbfil PTSH-P-a-UV) in the system chloroform - ethanol (19:1) for the manifestation of the chromatograms 10% solution phosphomolybdenum acid in ethanol and curing in a drying Cabinet at a temperature of 80°With 5 minutes found 2 areas blue on yellow-green background with Rf=0.87 (-carotene) and Rf=0.92 (unidentified).

3) phenolic acids

By chromatography on paper (FN-6, vaasna acid (II direction) while browsing the chromatogram in ultraviolet light before and after application of 10% potassium hydroxide solution in 96% ethanol discovered coffee acid Rf=0.80 (II), Rf=0.30 (II); chlorogenic acid - Rf=0.63 (I), Rf=0.56 (II). Identification was carried out in comparison with authentic samples.

4) tannins

0.05 g of the obtained extract was dissolved in 5 ml of purified water, 2 ml of the solution add 10 ml of 10% solution of acetic acid and 5 ml of 10% solution of lead acetate, the precipitate formed (hydrolyzable tannins). The reaction mixture was filtered and to the filtrate add 2 drops of 1% solution salesonline alum and 0.1 g of lead acetate, developing black-and-green staining (condensed tannins).

5) coumarins

By chromatography in thin layer of sorbent (plate mark "Silufol") in the system chloroform - ethanol (9:1) after processing the chromatograms reagent Pauli and curing in a drying Cabinet at a temperature of 105°With 10 minutes found three red zone with Rf=0.50 (esculetin), Rf=0.76 (umbelliferone), Rf=0.88 (scopoletin). Identification was carried out in comparison with authentic samples.

2. The method of quantitative determination of the amount of organic acids (in terms of malic acid) using potentiometrical the cost of 250 ml with a glass stopper, add 100 ml of distilled water, heated the contents of the flask in a water bath to 70°C and maintain this temperature for one hour. After cooling, the extract was filtered into a volumetric flask with a capacity of 200 ml through a paper filter, washed with 10 ml of distilled water and bring the volume of the solution up to the mark with distilled water (solution A).

10 ml of the solution And passed through an ion exchange column, which was washed with 50 ml of water. The eluate and the washing water is transferred into a glass for potentiometric titration. The titration is carried out with 0.1 N NaOH solution to pH 7.0. The titer of NaOH solution set for hydrofolate potassium (the State Pharmacopoeia T. 11. - vol.1. - 1990).

The total content of organic acids X (%) dry extract in terms of malic acid is calculated by the formula

where VNaOH- the volume of 0.1 N NaOH, followed by bringing the pH of the investigated solution to a value of 7.0, ml;

V' - volume of a solution of dry extract, ml (200 ml);

V'' - volume of sample passed through the ion exchange column, ml (10 ml);

K - correction on the titer of 0.01 N NaOH;

0.0067 - the amount of malic acid in g corresponding to exactly 1 ml of 0.1 N NaOH;

m- 5±0.23%

3. The method of quantitative determination of the amount of carotenoids (in terms of-carotene) using spectrophotometric method.

About 0.200 g (accurately weighed) of dry extract is placed in a flat-bottomed conical flask with a capacity of 250 ml with a glass stopper, add 50 ml of hexane, mix thoroughly in shaker for one hour. After removing the filter into a measuring flask of 100 ml capacity through a paper filter, washed with 10 ml of hexane and bring the volume of the solution up to the mark with distilled water (solution A).

The optical density of a solution is measured on a spectrophotometer at a wavelength of 450 nm in a cell with a layer thickness of 10 mm

As the reference solution using hexane.

The total content of carotenoids X (mg%) in terms of-carotene in the dry extract is calculated by the formula

where D is the optical density of the investigated solution;

V - volume of solution of dry extract, ml (100 ml);

m is the mass of a sample of dry extract, g;

W is the loss in weight on drying of raw materials, %;

2770 - specific absorption of beta-carotene at a wavelength of 450 nm in hexane.

Found with purification, allows you to extract the maximum quantity of active substances through the use of two extractants, allows to obtain a product of constant composition. The technology can be implemented at the enterprises for the production of medicines and Wellness resources.

To establish the optimal technological regimes was studied the influence of main factors: the composition and nature of the extractant, the ratio of raw materials, temperature, degree of grinding of raw materials, duration, and frequency of extraction on the processes of extraction of plant material.

Quantitative evaluation was carried out according to the amount of organic acids (in terms of malic acid) and total carotenoids (in terms of-carotene).

Metrological characteristics determine the amount of organic acids and the amount of carotenoids was carried out on samples of leaves cacalia lanceolated collected in muhorshibirskom of the Republic of Buryatia in 2002 (table 1).

One of the main factors determining the completeness of extraction, is the type and concentration of the extractant, which acts as an active component of the system, exerting a significant influence on the quality, completeness and / min net is carried out with hot water and ethyl alcohol the following concentrations: 20, 30, 40, 50, 60, 70, 80, 90, 95%. The results are presented in table 2.

It is established that the extraction with ethyl alcohol in a concentration of above 70% yield of carotenoids is not significantly increased; hot water to extract the maximum amount of organic acids. Based on the obtained results, for the extraction of carotenoids selected 70% ethanol, and for the extraction of organic acids with hot water.

Grinding the solid product with the aim of accelerating the diffusion of extraction of biologically active substances is one of the important stages of preparation of raw materials, which ensures the full release of extractives. To study the effect of the degree of grinding of plant material at the exit of the amount of organic acids and the sum of carotenoids raw material was subjected to grinding to particles passing through a sieve with the hole diameter of 0.5; 1.0; 2.0; 3.0; 5.0 mm found that the optimal degree of grinding for this raw material is a particle size of 0.5-1.0 mm (table 3).

We studied the dependence of the output of BAS on the ratio of raw material and extractant, resulting in the optimal ratio for the extraction of alcohol 1:(16:18) and for the extraction voicelog raw materials must take into account the temperature factor. With increasing temperature the extraction of the soluble components is increased. Based on the data analysis revealed that the optimal extractant for the extraction of organic acids is boiling water, while for the extraction of the alcohol is selected room temperature to avoid the formation of artifacts and destruction of heat-sensitive carotenoids (table 5).

To determine the duration and the ratio of the number of extraction the dependence of time to achieve equilibrium concentration in the system raw material:extractant for alcohol (And) water and (B) extraction.

A. Carried out the extraction of the crushed material 70% ethyl alcohol in a ratio of 1:16 at room temperature with periodic mixing. Intervals of time(1, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24 h) removing the filtered (1 contact phases), was evaporated to an aqueous residue was added hexane and determined the amount of carotenoids in terms of-carotene. Similarly spent two subsequent extraction of the pressed raw material, adding each time 70% ethanol in a volume equal to the slit (2nd and 3rd contacts phases), while also analyzed the content of total carotenoids.

B. Conducted extracontent stirring. Intervals of time(30, 45, 60, 75, 90, 120 min) the extract was filtered (1 contact phases) and determined the amount of organic acids in terms of malic acid. Similarly spent two subsequent extraction of the pressed raw material, adding each time the water in a volume equal to the slit (2nd and 3rd contacts phases), while also analyzed the total content of organic acids.

Experimental evidence suggests that the equilibrium state occurs when the ground contact phase after 16 h and the second contact phase after 10 h in the case of alcohol extraction (table 6); when the first and second contact phase after 60 minutes in the case of water extraction (table 7).

In the case of alcohol and water extraction during the first contact phase is extracted with about 75 and 60% of the amount of carotenoids and organic acids (respectively), the second - to 25 and 35%, third to 5%, i.e. up to 95% of carotenoids and organic acids extracted during the first two contacts of the phases, so in order to save the use of a third contact of the phases was considered inappropriate for both extractants.

The proposed method is compared with the known allows you to obtain the product of constant composition expressed CLASS="ptx2">

To calculate the economic feasibility of the proposed method is currently not possible, however, the foregoing advantages, in combination with a simple scheme to obtain promote the rational use of medicinal plants and determine the prospects of implementation of this method in the pharmaceutical industry.

PHARMACOLOGICAL STUDY OF THE EXTRACT FROM THE LEAVES OF KAMALII SPEAR.

The cardioprotective effect of the extract of kamalii spear

The experiments were carried out on 50 white Wistar rats of both sexes weighing 180-200, the Object of the research was dry extract, isolated from the leaves of kamalii spear. To evaluate its pharmacological activity was reproduced acute myocardial injury by catecholamines [Artykov, 1999]. Model adrenal necrosis infarction was induced by single intramuscular in the thigh animals 0.1% solution of epinephrine hydrochloride at a dose of 2 mg/kg rats. With pharmacotherapeutic purpose of the experimental group rats, intragastric was administered 1 time per day of the extract from the leaves of kamalii spear at a dose of 5 mg/kg rats, in the form of an aqueous solution in a volume of 1 ml, for what I was used amiodarone at a dose of 9 mg/kg [Mashkovsky, 1993]. Control group animals received distilled water in aquioben number on a similar scheme. Study of the functional state of the myocardium of animals was performed after 2, 8, 24 and 72 h after injection of adrenaline.

To estimate the functional state of the myocardium and pharmacological effects of the extract from the leaves of kamalii lanceolated following methods were used: a) determination of biochemical parameters of blood serum: the activity of aspartate aminotransferase (AST) and alanine aminotransferase (Alt), lactate dehydrogenase and its fractions LDH1and expected de Ritis coefficient standard methods [Menshikov and others, 1987]; b) the study of the levels of malondialdehyde (MDA) in the homogenate of the heart muscle [Steel and others, 1977], diene conjugates (DC) [Gavrilov and others, 1983] and MDA in serum [Temirbulatov and others, 1981]; C) study the content of serum cholesterol and total lipids standard methods [Menshikov and others, 1987]; g) registration electrocardiographic indicators on the electrocardiograph ACC - 1 in six standard leads. It was estimated the rate and rhythm of heart contractions, changes in the QRS complex, ST segment and activity of the tested tools [Avtandil, 1976; Selye, 1950]; (e) study of the mechanism of coagulation of blood with anticoagulant test Berkarda modified by Barkagaon [research Methods of hemostasis, 1993]; W) a study of the development and severity of stress reactions. Taking into account the following criteria: increased adrenal masses, the involution of the thymus, the appearance of ulcerative lesions in the gastric mucosa.

Obtained during the experiments, the data processed by the method of variation statistics using t-student criterion [Sergienko, C. I., I. Bondarev B. Mathematical statistics in clinical research. - M.: GEOTAR-MED. 2001. - 256 S.].

During the experiment established that already 2 hours after the introduction of the white rats of dry extract of this plant in the dose decreased the toxic effects of adrenaline on the heart. Noted a decrease in the intensity of peroxidation processes: reduction of MDA in the homogenate of the heart muscle, MDA and DC in the serum of animals at 6, 47, 46%, respectively, than rats in the control. Along with this, we observed a trend towards reduction in the activity of AST, and decreased de Ritis coefficient of 23% compared with the control. Furthermore, the activity of LDH decreased by 16% and her heart fraction was 19% in rats, 21 and 14%, respectively, compared to control. Marked beneficial effect of the investigated extract on myocardial function in rats observed after 8-24 hours after injection of adrenaline. After 72 hours surveillance study Fiorello contributes to the reduction in the activity of AST and Alt by 36% and 23%, decrease in serum MDA and DC by 5 and 34%, respectively. In addition, observed in animals decrease in the level of LDH activity and LDH1at 22 and 43%, reduction of cholesterol and total lipids by 36% and 67% respectively during the introduction of the dry extract of kamalii spear. Comparison drug amiodarone significantly inferior in the degree of influence on the similar parameters of myocardial function in rats with myocardial injury.

When electrocardiographic study observed that in the control group of animals in 1 case out of 5 in the first 2 hours after administration of adrenaline signs of transmural myocardial infarction (increase of S-wave and the formation of a negative prong type QS). In all other cases there was a strong myocardial ischemia - rise of the ST segment on the contour of 2.5-4 mm and inversion of the T wave, reflecting diffuznye metabolism in the myocardium of white rats. Registered rhythm disturbance in the form of single and group achislo PVCs decreased in 3 and 4-fold compared with control. The formation of tooth QS was not observed in groups of animals treated with amiodarone and analyzed Fiorello. Signs of myocardial ischemia were less pronounced on the background of the application of these tools, lifting ST was 1-3 mm, and inversion of the T wave was recorded with a smaller constant.

In the study of the mechanism of blood coagulation revealed that at 2 h experience in animals of the control group decreases the rate of formation of thromboplastin and thrombin by 16%. The infusion of dry extract and amiodarone accelerates the coagulation of blood plasma. After 8 h from the start of injection of adrenaline in the control group of rats observed activation of fibrinolysis in the face of moderate activation of the clotting plasma. With the introduction of these tools (extract, and drug comparisons) is the conjugacy of the coagulation and fibrinolytic systems. At 24 h from the start of injection of adrenaline in the control group of rats is high clotting activity of plasma. With the introduction of the dry extract of kamalii spear liquid state of the blood was provided higher hemostatic potential. With the introduction of the extract observed inhibition of the formation of thromboplastin and thrombin by 76% compared with control. Drugs the VA, with cardioprotective activity by extraction with ethanol and water, evaporation and drying, characterized in that the pre-crushed to a particle size of 0.5-1.0 mm dry plant material - leaves-kakali spear - extracted twice with room temperature 70% ethanol at the ratio of raw material:solvent (1:16) during 16 h and 10 h, respectively, then combined extracts by distillation of ethanol, and twice at 60 min of boiling water at a ratio of raw material:solvent (1:15) then combined extracts by filtration, Association with a water balance alcohol extraction, evaporation and drying in a vacuum drying apparatus.



 

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FIELD: medicine, cardiology, phytotherapy, pharmacy.

SUBSTANCE: invention relates to the field in development of an agent of vegetable origin used for improvement of the functional state and prophylaxis of organic alterations in cardiovascular system, in particular, atherosclerosis. The biologically active supplement used for prophylaxis of cardiovascular diseases, in particular, atherosclerosis comprises clover dry extract, haw-thorn flowers powder, ascorbic and nicotinic acids, and accessory substances taken in the definite ratio. The biologically active supplement is made in the form of tablet or capsule. No adverse responses observed in intake of the supplement. The blood cholesterol level was reduced to the normal value in 68% of patients and reducing morbidity with acute respiratory-viral infections has been noticed. In patients with ischemic heart disease with cholesterolemia the improvement of the state is noted on the background of conventional therapy: the moderate reducing the arterial pressure value in its elevation, improved in the state of health, enhanced working capacity, reduced retrosternal pains, ear noise, vertigo, headache.

EFFECT: valuable medicinal properties of supplement.

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