Agent possessing anti-inflammatory, antipyretic and antimicrobial action

FIELD: medicine.

SUBSTANCE: agent possessing the anti-inflammatory, antipyretic and antimicrobial action representing a dry extract of drug hedge hyssop leaves and blossom by grinding them, extracting in 96% alcohol on a water bath to a boil, and boiling, evaporating, diluting the evaporated residue by distilled water first, adding chloroform then, cooling to a room temperature and centrifuging, separating a water fraction and drying it in the certain environment.

EFFECT: agent possesses the pronounced anti-inflammatory, antipyretic and antimicrobial action.

5 dwg, 5 tbl, 2 ex

 

The invention relates to medicine and the pharmaceutical industry, namely the creation of medicines on the basis of as novogalenovye drug that has both anti-inflammatory as well as antimicrobial activity.

Search and development of new pharmaceuticals for the treatment and prevention of inflammatory diseases, due to their wide distribution and special severity. Currently, the proven efficacy of medicinal products from vegetable raw materials for the treatment of inflammation.

Among the products from vegetable raw materials there are tools that have anti-inflammatory activity, such as Rotokas, Plantasia (Register of medicines in Russia / CH. Ed. I. F. Krylov. Ed. Nr. Y. C. Boers (Deputy chief editor), H. P. the vishkovsky, H. C., Dogpile, B. N. Vedalken, G. S. Chernov. - M.: ENFERMAGEM, 1993. - 1006 C.). The most famous is the drug based on an extract of plantain (Mashkovsky M. D. Medicines, Moscow, Medicine, 1993). However, the activity of this drug is low. Similar can only be used as an anti-inflammatory. He does not possess antibacterial and antipyretic action.

Known patent RU N 2054945, A61K 35/78, 28.06.95, "Tool "ABISIL-1", which has anti-inflammatory, and is tibacterial and wound healing activity-based extract of Siberian fir. However, the described tool does not have a sufficiently high anti-inflammatory activity and has no antipyretic actions.

Extract of yarrow is used as a styptic and anti-inflammatory drugs (Mashkovsky M. D. Medicines. In two parts. - Kharkov "Torching". - 1997. - ed. the thirteenth. - C. 480). However, the use of the extract of yarrow has a number of contraindications, for example, due to the action of inhibiting the work of the ovaries, and therefore its use is limited to persons of the female sex.

Know the drug Canephron N (Germany) on the basis of the alcoholic extract of the herb centaury, the roots of lovage and flowers of rosemary, containing 19% vol. ethyl alcohol in 100 ml. Disadvantage of this tool is less pronounced anti-inflammatory activity, and the absence of antimicrobial and as well as activity.

Known anti-inflammatory agent-based decoction of marsh cinquefoil used in folk medicine (Century. Century. Teletel. Healing treasures. Irkutsk, 1991, pp. 146-147). However a decoction of medicinal plants does not provide the maximum yield of biologically active substances in the extract and is typically 20-40%. In water extract are transferred mainly substances glycosidic forms./p>

Known means on the basis of vegetative raw material, possessing anti-inflammatory activity, the method which includes three-time extraction of the leaves of bearberry leaf 45-55% ethanol at a ratio of raw materials/extractant 1:(10-14), evaporation of the combined extracts, purification by separation and drying (EN 2064301 C1, 27.07.1996). However, the dry extract, bearberry extract, obtained by the above method contains biologically active substances ginalnogo character, the main one. component of which is arbutin and hydroquinone. It is these substances that have a pronounced antimicrobial, diuretic and anti-inflammatory effect, which determines the application of a dry extract of bearberry only in inflammatory diseases of the urogenital systems caused by bacterial infection.

The Hauran drug (Gratiola officinalis L.) is a herbaceous plant of the family Nalichnaya, widespread in Eurasia and North America. The plant is poisonous. Used in folk medicine in the form of infusions, decoctions, fresh juice, fresh herbs, ointments, powders, essences, fees (http://narodrecept.ru/herbalist/gratiola-officinalis-l.html). For decoctions of herbs is characterized by a strong laxative, diuretic, emetic and anthelmintic activity used for chronic constipation, ascites, helminthiasis. It was established action Speer the OIC leaves tincture Hauran heart similar to the action of digitalis. Roots in folk medicine used as emetic, laxative, diuretic; sagging bowel, hemorrhoids. The above-ground part was part of the collection of Zdrenka - symptomatic remedy for the treatment of bladder papillomatosis, anatsidnyh gastritis, for the treatment of stomach ulcers and certain tumors. Externally the Hauran was used for the treatment of diseases of the skin, with its diseases, for the treatment of bruises, wounds, chronic ulcers, panaritiums.

The plant is poisonous and all previously obtained by extracting from the raw materials of Hauran had from moderate toxicity to a sufficiently high so that when an internal application used together with mucous broths, with great caution and under mandatory medical supervision (http:www.travolekar.ru/articles.php; http://www.ayzdorov.ru/tvtravnik_avran.php).

Known means of fresh herbs Hauran, used previously for the treatment of venous ulcers (Hauran drug was male, was applied to the ulcer and was bandaged; the bandage was changed four times a day; at the same time recommended that 0.2 g of the powder of the herb three times a day).

The disadvantages of using fresh herbs and powder are, on the one hand, restrictions on the use of the tool associated with the vegetation period only in the summer, and, on the other hand, high toxinotypes dry grass due to the presence of toxic compounds, and also the poor yield of the target products (flavonoids) and the use of powder from grass Hauran only for oral administration. In addition, the above methods of application creates a difficulty in calculating the exact dosage. Antipyretic activity the existing funds on the basis of the Hauran was unknown.

Under different methods of extraction from Hauran drug go out and get a different biologically active compositions with different properties: laxative, gag, antispasmodic, diuretic and digitalis effect on the heart (http//www.dorogaistin.ru>index.php...), antioxidant properties (Polukonova N. In., Merkulova E. P., Durnova N. A., Romantsev Y. C., Borodulin Century, the Study of antioxidant activity of extract of Hauran drug on rats with inoculated tumor liver PC-1 // Abstracts of scientific-practical conference "Biologically active substances: fundamental and applied problems of production and application". Novy Svet, Crimea, Ukraine 23-28 may 2011. Kyiv. 2011. S. 585), antitumor and immunomodulatory actions, as described by us previously (Navolokin N. A., Polukonova N. V., Maslyakova G. N., Bucharskaya A. C., Durnova N. A. / Effect of extracts of gratiola officinalis and zea mays on the tumor and the morphology of the internal organs of rats with trasplanted liver cancer // Russian Open Medical Journal. 2012. So 1. No. 2. C. 0203).

The technical task of the present is about the invention is the expansion of the means on the basis of natural plant materials of complex action, simultaneously possessing high anti-inflammatory, antimicrobial and cough active and non-toxic.

Advantages of the proposed medicinal extract are low toxicity, availability of raw materials, of which the tool, along with a wide range of effects: anti-inflammatory, antipyretic, antimicrobial.

We first established property funds, representing one stripped off the extract of the leaves and flowers of the Hauran drug, obtained by grinding herbs of Hauran drug, extraction with alcohol 96%, evaporation of the extract, the addition of chloroform, removing the chloroform, and extracted with alcohol carried out in a water bath to boiling and boiled for 14-15 minutes, is evaporated at a temperature of 55-60°C. the evaporated extract is diluted first with distilled water 40-50°C, then add chloroform in a ratio of 4/5 parts of water and 1/5 parts of chloroform, cooled to room temperature and centrifuged with a speed of 1500 rpm for 15 minutes, next, the separated water fraction and dried it. Derived biologically active composition has new properties: anti-inflammatory, antipyretic and antimicrobial.

The means obtained by this method, has the following chemical composition obtained compositions of the Hauran Lakers the public: 4-vinyl-2-methoxyphenol; 2,3-dihydro-3,5-dihydroxy-6-methyl-4H-Piran-4-one; 2,3-dihydrobenzofuran; 3-francebuy acid; 5-hydroxymethyl-2-furaldehyde; ethyl-α-d-ribose; 4-propylene; pyrocatechin: L-Lukasa (pentose); 6-deoxyhexose L-galactose; benzoyloxy acid ethyl ester; hexadecanoate acid (palmitic acid); HVA acid; glucose; 1,4-anhydrous-d-mannitol; benzoic acid; quercetin.

Thus obtained extract is a biologically active composition with new pharmacological properties (anti-inflammatory, antipyretic, antimicrobial), not previously known as a plant of Hauran drug and the above-described means.

The tool is a one stripped off the viscous extract, yellow-brown, mixed with water and ethyl alcohol in any proportion.

The parameters of authenticity and quality tools

The authenticity of the drug is confirmed by qualitative reactions to the content of bioflavonoids and absence of alkaloids in aqueous solution one stripped off of the extract of Hauran.

Qualitative tests for flavonoids: to 1 ml of the drug was added 1 ml of purified water, 10 mg of crystalline magnesium and 5 drops of concentrated hydrochloric acid, heated on a boiling water bath for 3 min, appeared red-brown staining, positive samples the Synod, what about the content in the obtained solution flavanoids.

Qualitative reactions for alkaloids: a) with a reagent Wagner-Bouchard negative (in the presence of alkaloids, the solution should turn yellow); b) with a solution of 1% picric acid negative (in the presence of alkaloids in solution should be yellow); (C) acid solution phosphomolybdenum negative (in the presence of alkaloids, the solution becomes cloudy).

All 3 qualitative reactions is negative, therefore, the resulting extract no alkaloids.

Compared with the previously received water and alcohol extracts of the herb Hauran received one stripped off the extract of the leaves and flowers of the Hauran is non-toxic, due to chemical composition and confirmed previously in rats [N. A. Navolokin, N. V. Polukonova, G. N. Maslyakova, A. B. Bucharskaya, N. A. Durnova / Effect of extracts of Gratiola officinalis and Zea mays on the tumor and the morphology of the internal organs of rats with transplanted liver cancer // Russian Open Medical Journal 2012; 1:0203].

We have also conducted experimental work to establish the toxicity class received aqueous extract one stripped off of the Hauran based on the definition LD50laboratory white mice. Each group consisted of 6 mice, weighing 25-30 g, the number of groups together with the control was five.1). Aqueous extract of Hauran was administered intraperitoneally, observation of animals is rowdily during the day.

Table 1
The results of the experiment to establish dose LD100, LD50and LD10in mice and rats
No.Dose (mg/kg)Loss (%)
The result of the experiment on mice
14475100
2400080
3300083.33
417000

Thus, on the basis of data obtained by LD50in accordance with GOST 12.1.007-76 and SanPiN 2.1.4.1074-01 aqueous solution of one stripped off of the extract of Hauran can be attributed to class IV toxicity (low hazardous substances).

In the injection of the extract of Hauran at the dosage 1323 mg/kg, which exceeded therapeutic dose (70 mg/kg) in 19 times, was determined individual sites of necrobiosis and severe infiltration of muscle and fatty tissue segmented neutrophils (Fig.1).

All changes are reversible and Loka is iny, this allows us to conclude that therapeutic dosage changes will be even less pronounced or absent. Similar changes are described in the instructions for use of Diclofenac sodium and is considered to be valid with intramuscular injection of funds in this group.

To describe the overall toxicity of the extract solution after removal of animals from the experiment (24 hours from the start time), also climbed the internal organs were weighed and calculated the index To the index of mass of body (=mbody/manimalfor liver, kidney and spleen (Fig.2). It was found that the introduction of diclofenac sodium causes a significant increase in the mass of the liver compared with the control at 30% at that time, as the introduction of the extract of the Hauran was observed a slight increase in liver by 12% compared to control, indicating a lower toxicity of the extract in comparison with diclofenac sodium and less load on the main detoxification organ (liver).

a) Antipyretic and anti-inflammatory activity of the extract.

Under the guidance of the Pharmacological Committee of Ministry of health of Russia as a pilot was used formalin model of inflammation [Manual on experimental (preclinical) study of new pharmacological substances / C. P. Fisenko, the.In. Arzamastsev, E. A. Babayan [and others]. - M MZ the Russian Federation, JSC "JJA Remedium", 2000. 398 S.; Methodological materials of the Pharmacological Committee of the Russian Federation on experimental (preclinical) study of non-steroidal anti-inflammatory pharmacological substances. - M., 1983. 18 S.;

Methods of screening and pharmacological study of anti-inflammatory, analgesic and fever-reducing drugs (methodical recommendations). Kiev, 1974. 27 C.].

Materials and methods: 30 outbred rats-males with an average body weight 163,5±6,8,

The design of the experiment: all animals (30 pieces) had previously introduced subplantar 0.1 ml of a 3.0% solution of formalin, and then the animals were divided into 3 groups of 10 male outbred rats in each group: 1-I - control group without treatment; group 2 - standard: was intramuscularly administered a solution of diclofenac sodium at a dose of 3 mg/kg; group 3 - experienced: intramuscular injection was administered an aqueous solution of one stripped off of the extract of Hauran drug in the dosage of 70 mg/kg

About Arapongas the effect was judged by the decrease in rectal temperature, anti - reduction of the degree of swelling of the foot, the hind limbs of the animals after 1, 2, 3 and 24 hours after injection phlogogenic agent [Tkachenko, K., 2003], and changes leukocyte formula. As phlogogenic agent used 3.0% solution is armaline, which in a volume of 0.1 ml was injected subplantar in the aponeurosis of the left hind limb of the rat, right arm served as a control. As standard anti-inflammatory activity used diclofenac sodium. Diclofenac sodium was injected once intramuscularly at a dose of 3.0 mg/kg immediately after the injection of formalin.

Analysis of the results was performed by comparing the data in the experimental and control groups between the initial and subsequent temperature, the volume of a limb, changes in leukocyte and morphological changes in the muscles. Statistical processing of results was performed using generally accepted methods of medical and biological statistics by calculating the median, maximum and minimum, the significance of the differences with non-parametric distribution was determined using the criterion of Moses.

It is established that the average rectal temperature in rats before the start of the experiment amounted to 35.0±0.5°C, which corresponds to the average parameters of the specific provisions.

In the control group without treatment, the infusion of phlogogenic agent, the temperature began to rise, reaching a maximum of 38°C, 2 hours, and was maintained until the end of the experiment.

In the comparison group with the introduction of diclofenac sodium on the background of the introduction of phlogogenic agent, the temperature was changed zigzag: maximum was nigeriaafplagos 1 hour after beginning of the experiment, reaching nearly normal numbers after 2 hours, and then again there was a decline in temperature, with the gradual restoration of the initial values by the end of the experiment.

In the group with the introduction of the aqueous extract of the Hauran on the background of the introduction of phlogogenic agent, it was found that the temperature of the animal during the first two hours did not change, then for 3 hours was a significant reduction of the temperature to the same values as with the introduction of diclofenac and further dynamics of temperature was similar to the dynamics of temperature changes in the group of animals with the introduction of diclofenac sodium (Fig.3, PL.2).

Table 2
The dynamics of the animals ' body temperature
Groups of animalsT °C
Prior to the experimentAfter 1 hour2 hoursAfter 3 hoursAfter 24 hours
Control35,0ME - 36,5 (Max=36,3 Min=35,4) +++ME - 36,8 (Max=37,3 Min=35,1) ++ME - 36,8 (Max=36,6 Min=35,6) +++ ME - 36,8 (Max=36,7 Min=35,8) +
Diclofenac sodium35,0ME - 32,4 (Max=35,2 Min=33,7) +++ME - 34,2 (Max=37,6 Min=34,8) ++ME - 33,2 (Max=35,9 Min=34,6) +++ME - 33,7 (Max=36,3 Min=34,7) +
An aqueous solution of one stripped off of the extract of Hauran35,0ME - 35,1 (Max=37,3 Min=34,9) +++ME - 34,9 (Max=37,2 Min=35,2) ++ME - 33,3 (Max=34,7 Min=33,9) +++ME - 33,8 (Max=Min 35,0=33,7) +
Note: + - P<0,05; ++ P<0,005; +++ - P<0.001 significance of the differences in the comparison between the experimental and control parameters.

Thus, the analysis of the dynamics of rectal temperature of the animals in the experiment, one can conclude that significant Arapongas the effect of the extract on the background of the introduction of phlogogenic agent. In this extract begins from the moment of introduction, maintains a normal temperature for two hours, followed by a decline after three hours and the effect lasts for up to 24 hours.

We also determined the rate of reduction of swelling in a limb compared to the control group and the comparison group (diclofenac sodium). After the introduction of the aqueous solution of the former is rakta Hauran was established, what anti-edematous effect of the extract begins to emerge after hours after injection, reaching a maximum after 3 hours, statistically different from the control group and the comparison group (table.3, Fig.4). This effect of the extract remains stable and within 24 hours from the beginning of the experiment.

Table 3
The dynamics of limb girth
Groups of animalsThe limb girth (cm)
Prior to the experimentAfter 1 hour2 hoursAfter 3 hoursAfter 24 hours
Control2.53.5 (Max=3.7 Min=3.2) +++3.4 (Max=3.5 Min=3.3) +++3.55 (Max=3.7 Min=3.5) +++2.95 (Max=3.1 Min=2.5) +++
Diclofenac sodium2.52.65 (Max=2.9 Min=2.4) +++3 (Max=3.2 Min=2.8) +++3.2 (Max=3.4 Min=3.1) +++2.65 (Max=2.8 Min=2.5) +++
Water is a solution of one stripped off of the extract of Hauran 2.53.15 (Max=3.5 Min=2.9) ++3.2 (Max=3.4 Min=2.8) +++2.9 (Max=3.1 Min=2.7) +++2.95 (Max=3.1 Min=2.7) ++
Note: + - P<0,05; ++ P<0,005; +++ - P<0.001 significance of the differences when comparing the values of the experimental and control groups.

The analysis of the dynamics of swelling of the paws of the animals in the experiment allows to make a conclusion about a significant and sustainable anti-edematous effect of the extract on the background of the introduction of phlogogenic agent, even greater than the effect of diclofenac sodium after 3 hours from the beginning of the introduction.

Were obtained reliable results for a number of blood parameters (table.4, Fig.5). The content of monocytes in animals treated with the solution of the extract of the Hauran, is reduced compared with the control group, which probably indicates a rapid migration of monocytes into the tissue. So, it is known that monocytes, after maturation in the red bone marrow, extend in the peripheral direction of blood flow and circulate in the blood from 36 to 104 hours, after which they migrate into tissues, where their further differentiation into tissue macrophages, which performs the basic functions of phagocytic defenses against microbial infection; participate in immune and inflammation, etc. That is, under the action of the m extract Hauran processes are accelerated immune response of the body and reduce inflammation.

The content of basophils in the group of animals treated with the solution of the extract of the Hauran, increases in comparison with other groups.

The number of neutrophils as segments and sticks insignificant changes in all compared groups. Although the group of animals treated with diclofenac, and a decrease of segments, severe neutropenia, evidence of immunosuppression, no. In General, the same as in the group treated with the extract solution of the Hauran, and diclofenac tends to increase the number of sticks that reflects the strengthening of the protection of the body from the beginning of inflammation.

Table 4
WBC
Groups of animalsThe content elements of blood
LymphocytesMonocytesBasophilsEosinophilsNeutrophils
SegmentsWand
ControlME - 47 (Max=57 Min-37) -ME - 8 (Max=2 Min=4) +++ IU - 3 (Max=4 Min=2) +++ME - 1 (Max=2 Min=1) +++ME - 34 (Max 44) (Min=27) -ME - 4 (Max 6) (Min-2) +++
The solution of diclofenac sodiumME - 60 (Max=65 Min=40) -ME - 8 (Max=15 Min-4) +++ME - 4 (Max=4 Min=0) +++ME - 1 (Max=1 Min=0) +++ME - 22 (Max=43) (Min=21) -ME - 5 (Max=8) (Min=3) +++
The solution of the extract of HauranME - 47.5 (Max=57 Min=42) -IU - 3 (Max=5 Min=2) ++ME - 11 (Max=15 Min=1) +++ME - 1 (Max=1 Min=0) +++ME - 31 (Max=36) (Min-29) -ME - 5 (Max=7) (Min=3) ++
Note: + - P<0.05; ++ P<0.005; +++ - P<0.001 significance of differences when comparing the values of the experimental and control groups.

b) antimicrobial activity

Determination of antimicrobial activity of the drugs was performed according to the methods recommended by the State Pharmacopoeia (GF) 11 editions (GF USSR: Vol.2 - M.: Medicine, 1989. - 398 C. Il.). Antimicrobial activity was determined against three standard strains: Staphylococcus aureus was ATSS R, Pseudomonas aeruginosa was ATSS 27835, Escherichia coli was ATSS 25922 taken of ismuse living cultures of the Department of Microbiology, Virology and immunology GBOU VPO Saratov state medical University n.a. C. I. Razumovsky.

Determining the sensitivity of bacteria was performed by the method of twofold serial dilutions in medium Mueller-Hinton. Was preparing a series of dilutions, the concentration of the drug from 337.5 to 10.38 mg/ml in a volume of 0.9 ml of the bacterial Strains was pre-cultured for 24 h in the incubator for sloped agar. From overnight cultures of the studied strains was prepared a suspension according to the turbidity standard 0.5 McFarland, leading to a concentration of 2·106CFU/ml In each tube with dilution of the extract were made in 0.1 ml of the prepared bacterial suspension. The experience was accompanied by control cultures of microorganisms without the content of the studied extract. To determine the effect of antimicrobial action of the control tube before incubation was performed measuring the plating on a dense nutrient medium for counting the grown colonies. Crops were incubated in a thermostat at 35°C for 20-24 hours. In a series of dilutions of the drug was said tube with the lowest concentration of the extract, in which there was no growth of bacteria. The amount of substance in the test tube was regarded as minimum inhibitory concentration (MIC). Of tubes in which no visible growth of bacteria, producing dimensional seeding on solid nutrient media and incubated in the incubator for 20-24 hours The number of grown colonies was compared with the amount raised from the test tubes. If the number of colonies was less in 2-3 times in comparison with the control, the nature of the antimicrobial action was regarded as bactericidal, if the number of colonies in the seeding of the control and experimental tubes was equal to as bacteriostatic.

The presence of antimicrobial action of an aqueous solution of the extract against all of the tested microorganisms (table.5).

The greatest activity of aqueous extract of Hauran demonstrated against S. aureus: IPC was 20,45 mg/ml (it was noted bacteriostatic effect). Higher concentrations of the extract (135 mg/ml and above) had a bactericidal effect against Staphylococcus aureus. Against P. aeruginosa IPC was 75 mg/ml, while the maximum concentration (337.5 mg/ml) exerted a bactericidal effect. The lowest antimicrobial activity of the extract showed against E. coli: IPC was 337,5 mg/ml against Escherichia coli this concentration also had a bactericidal effect).

Table 5
Antimicrobial activity of aqueous extract of Hauran dosage
Type of bacteriaThe concentration of the aqueous extract one stripped off of Hauran (mg/ml)
337.52251357539.7120.4510.38
Escherichia coli-±±++++
Pseudomonas aeruginosa-±±±+++
Staphylococcus aureus-----±+
"-" - total lack of culture growth (bactericidal effect), " ± " is the number of colonies is the same as in the control (bacteriostatic action), " + " culture growth exceeds the growth in the control

In financial p is Tata established the electoral activity of aqueous extract of Hauran against different strains while the lowest activity was observed for conditionally pathogenic E. coli strain.

Thus, the obtained extract Hauran drug has both a set of new properties, not previously known to him: anti-inflammatory, antipyretic and antimicrobial activity needed for the prevention and treatment of inflammatory diseases.

Example 1

The grass of the Hauran were crushed and sieved through a sieve with a mesh size of not more than 3 mm. Weighed 10 g of the crushed material, put it in a flask with a volume of 500 ml, was added 100 ml of ethyl alcohol 96%, in a water bath and brought to the boil and boiled for 14-15 minutes Extract of the bulb strain into a glass container through 4 layers wide bandage, the remainder of the plant material carefully pressed, poured 100 ml of ethanol 96%. Brought to the boil and again was filtered in the same glass container. The extract obtained was boiled away to dryness in a thermostat at a temperature of 55-60°C. In a glass bowl with the evaporated extract was added 8 ml of distilled water, then with a syringe suffered the resulting solution in a plastic centrifuge tube with a volume of 11 ml, was added 2 ml of chloroform, shake a few times until homogeneous, cooled to room temperature and centrifuged for 15 min (to remove non-polar premise the (chlorophyll) and others) at a speed of 1500 revolutions per minute. The aqueous fraction was collected with a syringe, placed in pre-weighed Petri dish, dried and kept until the beginning of the experiment. The weight of the dried extract was calculated as the difference between the weight of a weighted Petri dish with dry extract and weight of empty Petri dishes. Received 225 mg of dry extract of Hauran.

Received 225 mg of dry extract from herbs of Hauran drug was investigated by gas chromatography-mass spectrometer, model Trace GC - Trace DSQ (firm ThermoFinnigan, USA). In the framework of the performed works were selected organic substances: 4-vinyl-2-methoxyphenol; 2,3-dihydro-3,5-dihydroxy-6-methyl-4H-Piran-4-one; 2,3-dihydrobenzofuran; 3-francebuy acid; 5-hydroxymethyl-2-furaldehyde; ethyl-α-d-ribose; 4-propylene; pyrocatechin; L-Lukasa (pentose); 6-deoxyhexose L-galactose; benzoyloxy acid ethyl ester; hexadecanoate acid (palmitic acid): HVA acid; glucose; 1,4-anhydrous-d-mannitol; benzoic acid; quercetin.

Was taken rat weighing 160 grams, which previously introduced subplantar 0.1 ml of a 3.0% solution of formalin, and then was injected intramuscularly aqueous solution of one stripped off of the extract of Hauran drug in the dosage of 70 mg/kg found that the rectal temperature of the rats before the start of the experiment amounted to 35.0° C, which corresponds to the average species norms. It was setup the network, the temperature during the first two hours have not changed, then at 3 PM there was a decrease of temperature to 33.3° C, and further dynamics of the temperature was not changed up to 24 hours from the beginning of the experiment.

In the determination process of reducing swelling of the limb, with the introduction of aqueous extract of Hauran, it was found that anti-edematous effect of the extract was beginning to occur in rats 1 h after injection (girth hind legs 3,15 mm), reaching a maximum after 3 hours (girth hind legs 2.9 mm). This effect of the extract remains stable and within 24 hours from the beginning of the introduction (girth hind legs 2.95 mm).

Example 2

The means obtained in example No. 1, was tested for antimicrobial activity.

From the daily culture of the studied strain Staphylococciis aureus ATCC 6538P prepared suspension standard turbidity of 0.5 McFarland, leading to a concentration of 2·106CFU/ml was taken as the test tube containing an aqueous solution of a dry extract of Hauran. In a test tube with dilution of the extract was made 0.1 ml of the prepared bacterial suspension of S. aureus. Crops were incubated in a thermostat at 35°C for 24 hours.

Was investigated aqueous solution of Hauran in a concentration - 39,71 mg/ml test-tube, in which no visible bacterial growth, productivity dimensional seeding on solid nutrient medium and incubated in thermostat in accordance with the s 24 PM The presence of antimicrobial action of an aqueous solution of the extract against S. aureus: IPC was 39,71 mg/ml (reported bactericidal effect), since there was no bacterial growth after 24 hours.

Thus, the extract obtained by extraction with 96% ethanol leaves and flowers of the Hauran drug, under certain conditions, with chloroform purification from toxic substances with their full subsequent removal together with the solvent by centrifugation, followed by evaporation of the water fraction in a water bath at a temperature not exceeding 60° C, has a complex of new properties: anti-inflammatory, antipyretic, antimicrobial and is not toxic, which is necessary for the prevention and treatment of inflammatory diseases.

The tool, which has anti-inflammatory, antipyretic and antimicrobial activity, representing the dry extract of the leaves and flowers of the Hauran drug, obtained by crushing them, extraction with alcohol 96% on a water bath to a boil and boil for 14-15 minutes, evaporation at a temperature of 55-60°C, cultivation evaporated residue first with distilled water at a temperature of 40-50°C, then add chloroform in a ratio of 4/5 parts of water and 1/5 parts of chloroform, cooled to room temperature and centrifugation at 150 rpm for 15 minutes, with the subsequent separation of the water fraction and drying it.



 

Same patents:

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to the pharmaceutical industry, in particular to a medication, possessing a nephroprotective action. The medication with the nephroprotective action, contains an extract of grass with roots and rhizomes of slender-leaf iris (Iris tenuifolia), stabilising agents and preservatives, taken in a certain ratio, where the extract is obtained by extraction of the grass with roots and rhizomes of slender-leaf iris (Iris tenuifolia) with a 30-70% water solution of polyol.

EFFECT: medication possesses an effective nephroprotective action.

3 cl, 3 dwg, 7 tbl, 14 ex.

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to the pharmaceutical industry, namely to a method of obtaining a preparation, possessing an antimicrobial activity. The method of obtaining the preparation, possessing he antimicrobial activity, where an aboveground part of freshly harvested bear leek (Allium ursinum L.) or victory onion (Allium victoriale L.) is crushed to a paste-like state, poured with ethyl alcohol, infused tree times, under certain conditions, after each extraction the extracts are poured off, the obtained extracts are combined.

EFFECT: medication, obtained by the claimed method, possesses an expressed antimicrobial activity.

2 cl, 1 tbl, 6 ex

FIELD: food industry.

SUBSTANCE: method involves raw material milling, extraction of useful substances, filtering and drying. The method characterisation is as follows: extraction is performed in an ultrasonic bath with a food acid with concentration not in excess of 5% in conversion to adipic acid at a temperature of 20-40°C during 15-30 min while drying is performed by high-temperature spraying method at a temperature of 70-100°C in a flow of extract ensuring production of a powered product. The food acid may be represented by adipic, orthophosphoric, malic, ascorbic, amber or acetic acid.

EFFECT: method enables production of powered preparations of non-fruit sea-buckthorn parts with high serotonin content.

2 cl, 1 tbl, 1 ex

FIELD: agriculture.

SUBSTANCE: method of complex processing of rice production wastes in the form of rice hulls and straw comprises preparing raw material by screening hulling bran or dust and washing with water, processing the prepared raw material to produce a solid phase and solution of organic compounds, at that in preparing the raw material the rice straw is crushed, the prepared raw material is treated with 0.5 N ammonium oxalate solution, the solid phase is separated from the solution by filtration and sent to the recovery of silicon-containing products, the filtrate is dialyzed against running water and then against distilled water, concentrated, treated with acetone or alcohol, the resulting precipitate is separated by centrifugation, dissolved in water and lyophilized to obtain the polysaccharides under certain conditions.

EFFECT: method enables to increase the number of target products extracted during processing of rice production wastes, to improve environmental security of production by minimizing the amount of wastes, while simultaneous expanding the resource base through the use of rice straw.

4 cl, 2 ex

FIELD: medicine.

SUBSTANCE: invention represents a natural antioxidant preparation technology for cosmetic applications. The presented method for preparing a biologically active extract of grape berries or secondary wine making products - husks of grapes - provides drying the raw material, grinding, mixing it with an extactant in a ratio of 1:2.

EFFECT: method provides producing the all-purpose antioxidant for all types of cosmetics rich in biologically active substances with the relatively simple technological process requiring no organic acids used.

1 cl, 2 ex, 1 tbl, 1 dwg

FIELD: chemistry.

SUBSTANCE: invention relates to extraction of valuable substances, primarily phosphate, from products contained in waste water sludge or formed from treating waste water, specifically: waste water sludge, ash formed from burning waste water sludge, or slag formed from treating waste water sludge or contained therein, by extraction. The method includes preparing a suspension of a product contained in waste water sludge or formed from treating waste water in water, alcohol, water-alcohol mixture or aqueous solution, adding to said suspension carbon dioxide (CO2) gas or supercritical carbon dioxide (scCO2) as an extraction agent, separating undissolved solid substances from the liquid suspension agent, removing carbon dioxide from the suspension agent, precipitating valuable substances dissolved in the suspension agent and separating said substances from the suspension agent.

EFFECT: economically effective method for selective separation, recuperation of valuable substances, primarily phosphorus, and also, at certain conditions, metals and nonmetals from waste water sludge or ash formed from burning waste water sludge.

11 cl, 3 ex

FIELD: biotechnology.

SUBSTANCE: method of processing wood green of fir to obtain fir oil, chlorophyll-carotene paste, aqueous extract of fir, comprising the sequential extraction of wood green with aqueous isopropanol, extraction with water, concentration of the isopropanol extract, hydro-distillation of the volatile components from the concentrate of the isopropanol extract to obtain fir oil, washing with water of hot bottom products for extraction of hydrophilic components and their separation from the lipophilic part, combining of hydrophilic components with an aqueous extract of wood green and concentration in vacuum to obtain the total aqueous fir extract, saponification of lipophilic part with aqueous solution of sodium hydroxide to obtain chlorophyll-carotene paste, under certain conditions.

EFFECT: method enables to extract efficiently fir oil, chlorophyll-carotene paste, aqueous fir extract of wood green of fir.

1 tbl, 2 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to the pharmaceutical industry, namely to an extract of Nerium oleander in aloe. A method of obtaining the extract of Nerium oleander in aloe includes mixing vegetable material, which contains leaves and stems of the Nerium oleander plant, with vegetable mucus of aloe with obtaining an extraction mixture, conditioning the said extraction mixture with obtaining the extract of Nerium oleander in aloe. The composition of cardiac glycosides and aloe for treatment of a pathological state of skin, selected from sun-damaged skin, ageing skin, acne, age spots, liver spots, sunburn and herpes. A pharmaceutical composition for treatment of the pathological state of skin. A method of treating the pathological state of skin. A method of the cosmetic composition application.

EFFECT: described above extract and based on it preparations are efficient.

14 cl, 7 ex

FIELD: chemistry.

SUBSTANCE: method of producing a fraction of phenol substances from shelf fungus includes grinding fungus, extracting the material with water, separating the aqueous extract from the extraction cake, boiling the extraction cake in an organic solvent, separating the organic extract, wherein before boiling the extraction cake is dried, the organic solvent used is ethyl acetate, the solvent is removed from the obtained extract under defined conditions.

EFFECT: method provides effective extraction of a fraction of phenol substances from shelf fungus, containing flavonoids, phenolcarboxylic acids, phenols with a simple structure, having marked biological activity.

1 tbl, 2 ex

FIELD: chemistry.

SUBSTANCE: ground shelf fungus is extracted with water; the obtained aqueous extract is separated from the extraction cake; the extraction cake is dried; petroleum ether is added to the extraction cake and boiled; the obtained organic extract is separated; the solvent is removed to obtain a dry residue a fraction of lipophilic substances under defined conditions.

EFFECT: method enables to extract a fraction of lipophilic substances from shelf fungus, which includes sterine compounds, having a marked biological activity.

2 tbl, 4 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to medicine and represents a composition possessing the antioxidant and antibacterial activity and containing lithium ascorbate, differing by the fact that it additionally contains lithium benzoate in the following proportions, wt %: lithium ascorbate - 50; lithium benzoate - 50.

EFFECT: invention provides extending the range of antioxidants with antibacterial activity possessing normothymic activity.

1 ex, 2 tbl

FIELD: medicine.

SUBSTANCE: method involves recovering choleragen anatoxin by tangential ultrafiltration with the use of a membrane with the rated cut-off of a molecular weight of 300 kDa, concentrating by tangential ultrafiltration with the use of the membrane with the rated cut-off of a molecular weight of 30 kDa and purifying by diafiltration with a triple volume of sterile purified water by tangential ultrafiltration with the use of the membrane with the rated cut-off of a molecular weight of 30 kDa.

EFFECT: higher yield of choleragen anatoxin, reduced time and number of technological stages for preparing it.

1 dwg, 2 tbl, 1 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to the pharmaceutical industry, namely to a method of obtaining a preparation, possessing an antimicrobial activity. The method of obtaining the preparation, possessing he antimicrobial activity, where an aboveground part of freshly harvested bear leek (Allium ursinum L.) or victory onion (Allium victoriale L.) is crushed to a paste-like state, poured with ethyl alcohol, infused tree times, under certain conditions, after each extraction the extracts are poured off, the obtained extracts are combined.

EFFECT: medication, obtained by the claimed method, possesses an expressed antimicrobial activity.

2 cl, 1 tbl, 6 ex

FIELD: medicine.

SUBSTANCE: pharmaceutical composition possessing antiviral and antibacterial activity and containing L-N-2,6-diamino-hexanoyl-D-glucosamine, L-y-glutamyl-cysteinyl-glycyl-proline, lysine glycyrisinate, desoxyribonuclease, palmitoyl hydroxypropyl trimmonium amylopectin/glycerin cross polymer, hydroxypropyl-beta-cyclodextrin, D,L-pyrrolidone carboxylate N-cocoyl ethylarginate, escin, an emulsifying agent, a preserving agent, a pH control agent, demineralised water in certain amounts. The pharmaceutical composition possessing antiviral and antibacterial activity and containing L-N-2,6-diamino-hexanoyl-ascorbyl phosphate, N-pyrrolidine-carbamoyl-D-glucosamine, lysine ursolate, ribonuclease, a modified acrylic thickening agent, hydroxypropyl-beta-cyclodextrin, D,L-pyrrolidone carboxylate N-cocoyl ethylarginate, glycyrrhizic acid, an emulsifying agent, a preserving agent, a pH control agent, demineralised water in certain amounts. The pharmaceutical composition possessing antiviral and antibacterial activity and containing L-N-2,6-diamino-hexanoyl-hinokitiol, N-pyrrolidine-carbamoyl-D-glucosamine, lysine betulinate, collagenase, palmitoyl hydroxypropyl trimmonium amylopectin/glycerin cross polymer, hydroxypropyl-beta-cyclodextrin, chlorhexidine bigluconate, D-panthenol, an emulsifying agent, a preserving agent, a pH control agent, demineralised water in certain amounts. The pharmaceutical composition possessing antiviral and antibacterial activity and containing fusidoyl lysine, lysyl-valyl-proline pomolate, proline escinate, lysozyme, hydroxypropyl trimmunium maltodextrin, cross polymer, hydroxypropyl-beta-cyclodextrin, D,L-pyrrolidone carboxylate N-cocoyl ethylarginate, cedar extract, an emulsifying agent, a preserving agent, a pH control agent, demineralised water in certain amounts.

EFFECT: compositions possess expressed antiviral and antibacterial activity and are stable.

4 cl, 2 tbl, 11 ex

Antimicrobial gels // 2535013

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention refers to medicine, particularly to aspects covering antimicrobial compositions, and described antimicrobial compositions, antimicrobial silicone gel based on the above antimicrobial composition, a wound dressing and methods for preparing them. Among other things, the antimicrobial compositions contain at least one alkenyl- and/or alkynyl-substituted polysiloxane, at least one polysiloxane containing silicone-linked hydrogen atoms, and at least one hydroxylation catalyst, at least one hydrophilic ingredient, at least one silver salt.

EFFECT: invention can be used for preparing a drug preparation to be used in treating burns, scars, bacterial infections, viral infections and/or mycotic infections.

19 cl, 5 dwg, 8 ex, 6 tbl

FIELD: veterinary science.

SUBSTANCE: method involves intramuscular injections of a drug preparation. The drug preparation is presented by a mixture of a medical solution of formaldehyde and normal saline at the weight portion ratio (2-6):(994-998). First, the preparation is injected into ill, latently ill and healthy animals starting from 3-month-old calves in two doses of 5-6 ml every 7-8 days during the period from September to November. Thereafter, the injections are continued for the ill animals only, but for no more than 5 weeks, and 5-7 days after the last injection the remaining ill animals are detected and isolated.

EFFECT: method enables recovering the farm effectively from necrobacteriosis.

1 tbl, 5 ex

FIELD: medicine.

SUBSTANCE: group of inventions refers to veterinary science and aims at treating subclinical mastitis in cows. A preparation and a method for using it are declared. The preparation contains silver nanoparticles stabilised by submicrone titanium dioxide particles, poly-N-vinylpyrrolidone-2, and water in the following proportions, wt %: silver nanoparticles having a size of 200-300 nm 2.0×10-3, titanium dioxide particles having a size of 2-4 mcm 60.0×10-3, poly-N-vinylpyrrolidone-2 10.0, water - the rest up to 100.0. The method involves intracisternal introduction of the declared drug preparation in a dose of 10.0 ml twice a day for 2-4 days.

EFFECT: using the method enables providing the higher clinical effectiveness and reduces the length of recovery.

2 cl, 4 dwg, 7 tbl, 5 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: declared group of inventions refers to veterinary science and is applicable for treating the animals suffering from bacteriosis and yeast mycosis. A declared preparation contains oxytetracycline hydrochloride, sulphadimine, ampicillin sodium, nistatine, a solvent and the active substance conduit dimethyl sulphoxide, the quick-relief anaesthetic lidocaine in the following proportions, wt %: ampicillin sodium 4.0-8.0, oxytetracycline hydrochloride 2.0-4.0, nistatine 1.0-2.0, sulphadimine 2.0-4.0, novocaine 0.25-0.5, lidocaine 0.25-0.5, dimethyl sulphoxide 10.0-20.0, 1,2-propylene glycol - the rest. A method of treating the animals consists in administering the declared preparation in a dose of 0.1-0.2 cm3 per 1 kg of body weight.

EFFECT: using the declared group of inventions is high-efficiency for treating the animals suffering from bacteriosis and yeast mycosis and enables improving livestock farms with an unfavourable incidence of bacteriosis and yeast mycosis.

5 cl, 9 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a method of obtaining a polymer conjugate of an indolocarbazole compound of formula (I), where R1, R2, R3, W1 and W2 represent hydrogen, X represents methoxy-polyethyleneglycol. The method includes the interaction of a polymer compound of formula (II) with an indolocarbazole compound of formula (III), where Y stands for a methoxygroup. The nvention also relates to a polymer conjugate of formula (I), a pharmaceutical composition, containing the conjugate of formula (I) as an active ingredient, and to the application of the polymer conjugate of formula (I).

EFFECT: obtaining the polymer conjugate of the formula with a high output, the polymer conjugate of the formula for treatment of skin pathologies and HMGB1-associated pathologies.

48 cl, 7 dwg, 7 tbl, 15 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to medicine, namely to broad-spectrum antibacterial preparations. What is presented is an agent representing sodium dihydroxocystine diaminodiargenate possessing the antibacterial activity. The agent represents a complex C6H12Ag2N2Na2O6S2 of two silver ions with a disodium salt of natural amino acid L-cystine being coordinately linked. The method for preparing the agent involves adding an estimated amount of argentous oxide to a solution of cysteine disodium salt, mixing a reaction mixture at room temperature until argentous oxide dissolves completely, and precipitating a target product in alcohol.

EFFECT: new agent, sodium dihydroxocystine diaminodiargenate possesses the evident antibacterial action on the pathogenic strains of Staphylococcus, Proteus, Salmonella typhimurium, Pseudomonas aeruginosa, and also inhibits the yeast growth, has low toxicity and storage-stability.

1 tbl, 4 ex

FIELD: biotechnology.

SUBSTANCE: invention is a composition having antibacterial, immunostimulating, anti-allergic and anti-inflammatory action, containing bacterial waste products useful for human body, in the form of exometabolites and fermentolysis products, characterised in that it is a culture medium of lactic acid bacteria, containing laxarane in an amount of 5-10 g/ml, caseicyne, isracydine or their mixture and lectins in an amount of 0.05-2.5 mol/l, histamine in an amount of 0.8-2.0 mmol/l and monocarboxylic fatty acid with an unbranched chain, namely, acetic acid, propionic acid, butyric acid and valeric acid - in an amount of 10-20 mg/ml.

EFFECT: expanding the range of agents having complementary antibacterial, immunomodulating, anti-allergic and anti-inflammatory action.

4 cl, 5 ex

Up!