Osmotic diuretic possessing antitoxic activity in case of aliphatic alcohol poisoning

FIELD: medicine.

SUBSTANCE: claimed is remedy possessing antitoxic properties in case of aliphatic alcohol poisoning. As such polyosm - 30% solution of polyethylene oxide 400 is suggested. It is shown that polyosm protects animals against death (100% in control) in case of isopropyl alcohol poisoning.

EFFECT: water content in lungs is analogous to index of intact animals at moderate reduction of respiration rate.

6 tbl, 9 ex

 

The invention relates to medicine, specifically to pharmacology, and relates to agents that have anti-inflammatory, antitoxic and hemorheological properties.

It is known that aliphatic alcohol is isopropyl alcohol and ethylene glycol - cause acute poisoning by ingestion, and their toxic effect on the organism is characterized by swelling of the brain and lungs, acute renal failure, toxic coma, hypothermia, impaired functions of the cardiovascular system and respiratory system, can cause you to stop breathing and the heart [1, 2]. One of the necessary measures if poisoning aliphatic alcohols is the use of forced diuresis [1, 2].

The closest (prototype) is mannitol, used as a means of forced diuresis in case of poisoning[3, 4, 5, 6].

It is known that the use of mannitol for acute conditions involving intracranial hypertension and acute swelling of the brain, also leads to improvement of rheological properties of blood [7]. Thus, there is evidence that when used in early post-stroke period manna moderately reduces blood viscosity and hematocrit, however, the drug does not influence the increased erythrocyte aggregation [9]. Shortcomings in the application of mannitol are electrolyte imbalance, heart-lung is swelling, the syndrome of "impact" [10, 11]. In addition, the use of mannitol in therapeutic doses can cause kidney damage [12, 13] and hypersensitivity reactions [14].

Object of the invention is the expansion of the range of osmotic diuretics with antitoxic action and improves the rheological properties of blood poisoning aliphatic alcohols.

The problem is solved by using osmotic diuretic Prisma® - 30% solution of polyethylene oxide 400 (VFS 42-3631-00).

It is known that polyethylene oxide 400 exhibiting the properties of osmotic diuretics, intravenous in pure form and in the form of a 30% solution (poliom) is a powerful diuretic effect[15, 16, 17].

It is also known that polyethylene oxide 400 intravenously in pure form and in the form of a 30% solution (poliom) has a dehydrating and antitumor activity in models of brain edema, reduces intracranial pressure[16, 17, 18].

The use of polyethylene oxide 400 and polyoma as a means of having a toxic effect in the administration of aliphatic alcohols, and means having a hemorheological activity not described in literature.

Brand new in the present invention is that poliom shows antitoxic effect in the administration of aliphatic alcohols, is AutoRAE is to improve the survival of animals, the elimination of pulmonary edema, increased urine output, restore breathing rate, body temperature, reducing blood viscosity.

Brand new in the present invention is that poliom shows hemorheological properties due to effects on cell hemorheological factors - reducing aggregation of erythrocytes and increased erythrocyte deformability

These properties are not explicitly derived for the expert from the prior art.

The drug poliom can be used for the treatment of acute poisoning aliphatic alcohols as antitoxic agent in order to alleviate the severity of poisoning, reduce swelling of the brain and lungs, restore breathing and body temperature, as well as the weakening of the syndrome increased blood viscosity with improved indicators of cell rheology - reducing aggregation of erythrocytes and increased erythrocyte deformability.

Thus, this solution meets the conditions of patentability: novelty", "inventive step", "industrial applicability".

Acute poisoning in rats produced intragastric introduction of isopropyl alcohol (of 6.6 ml/kg) or ethylene glycol (9 ml/kg). After 30 min after poisoning once intravenously injected mannitol at a dose of 1 g/kg of a 30% solution (group "mannitol"), poliom dose of 1 g/kg of a 30% solution of poly is telenokia 400 (group "poliom") or equiano amount of isotonic sodium chloride solution (group "control"). In addition, intact rats were evaluated, all the studied indicators to establish their normal values ("intact").

Half of the rats in each group "control", "mannitol" and "poliom" before and 4 h after poisoning with isopropyl alcohol or ethylene glycol and 3.5 h after intravenous isotonic sodium chloride, mannitol or polyoma were determined: body temperature, breathing frequency, the osmolarity of plasma. Within 4 h after poisoning was determined amount released urine. After 4 h after poisoning in the blood samples was measured hemorheological parameters: the viscosity of whole blood, plasma viscosity, hematocrit, half aggregation of erythrocytes.

The other half of the animals to establish antitoxic activity at 24 h after poisoning with isopropyl alcohol or ethylene glycol and 23.5 h after intravenous isotonic sodium chloride, mannitol or polyoma determined survival.

Rectal body temperature was measured by elektrotermometria TPAM-1. The respiratory rate was counted visually on the stopwatch for 1 minutes

The water content in the lung tissue of rats was estimated by gravimetric method. Drying of lung tissue was performed in air sterilizer SU-40 at 100°C for 60 minutes Weighting was performed after drying the tissue of rats to posto is authorized mass of dry residue.

To establish the diuretic activity of preparations of the urine in rats was performed by placing the animals in the exchange houses.

The osmotic activity of blood plasma in rats were measured on the device OMCA 1TS-01.

The viscosity of whole blood and plasma were investigated on the viscometer AVK-2 [19]. As the stabilizer used a 3.8% solution of sodium citrate in the ratio of blood 1:9. Erythrocyte aggregation was studied using electrometrical method [20] in our modification [21]. To establish the photometric intensity of the signal used microcalorimeter MKMF-1 with a graphical check on the plotter H306. Criterion aggregation activity of erythrocytes was half aggregation T1/2the time for which the magnitude of the photometric signal is reduced by half.

To assess antitoxic and hemorheological actions polyoma poisoning isopropyl alcohol were 4 series of experiments. In the first series of experiments evaluated the studied indices in intact rats (example 1), in the second series of experiments evaluated the studied parameters in rats poisoned with isopropyl alcohol (example 2), in the third series of experiments evaluated the studied parameters in rats poisoned with isopropyl alcohol and treated with mannitol (prototype, example 3) and four series of experiments evaluated the studied parameters in rats from Alannah isopropyl alcohol and treated with Polycom (example 4).

To assess antitoxic and hemorheological actions polyoma poisoning ethylene glycol performed 3 series of experiments. In the first series of experiments evaluated the studied parameters in rats poisoned with ethylene glycol (example 5), in the second series of experiments evaluated the studied parameters in rats poisoned with ethylene glycol and treated with mannitol (prototype, example 6) and in the third series of experiments evaluated the studied parameters in rats poisoned with ethylene glycol and treated with Polycom (example 7).

To establish mechanisms hemorheological actions polyoma performed 3 series of experiments in vitro. A blood examination was taken under ether anesthesia in rats Wistar from the common carotid artery. As the stabilizer used a 3.8% solution of sodium citrate in the ratio of blood 1:9. In the blood samples was measured indicators of cell rheology - size aggregation of erythrocytes and erythrocyte deformability. Erythrocyte aggregation was studied using Electrometry CPU microcalorimetry MKMF-1 with a graphical check on the plotter H301. The criterion for the aggregation of erythrocytes was half aggregation (the time for which the magnitude of the photometric signal is reduced in two times) [21]. The deformability of erythrocytes was determined by the method of laser estatically; value deformability was assessed by the index the Fund is Miramonti erythrocytes (IDA) [22]. Mannitol (prototype, example 8) and polyethylene oxide 400 (experience, example 9) was added to the blood samples in blood samples in the form of a 30% solution in a volume of 35 ál for 3 min to determine indicators of cell rheology. To control blood sample was added to the physiological solution in equiano number.

Statistical processing was performed using the SRP "Statistica for Windows 4.3". Expected average value, standard error, to identify the differences between groups were using U-Mann-Whitney test.

The results are shown in examples 1-9.

Example 1. The body temperature of intact animals for 4 h did not change and amounted 38,0±0,2°C. the rate of respiration in animals intact group was stable - 115±6 min-1. The osmolarity of the plasma changed within physiological limits. The volume of urine released for 4 h was equal to 1.28±0,14 ml of water Content in the lungs was 79,40±0,06% (table 1, intact).

Blood viscosity at the shear rate of 3-15-1, 7-1, 10-1, 50-1, 100-1and with 300-1was accordingly 7,3±0,1, 6,7±0,2, 6,3±0,2, 6,0±0,1, 4,4±0,1, 4,2±0,1 and 3.9±01 MPa·s when the hematocrit 43±1%. Half aggregation of red blood cells in the group of intact animals to 18.6±1,1 (table 2, intact).

Example 2. In animals poisoned with isopropyl alcohol at a dose of 6.6 ml/kg, 4 h observation noted the deterioration of the General condition of the animal, expressed in statistically significant compared with the original values of the temperature reduction is 15%, respiratory rate by 42% and the increase in the osmolarity of blood plasma by 15%. The volume of urine released for 4 h did not differ from that seen in intact animals and amounted to 1.34±0,04 ml For 4 h revealed pulmonary edema, manifested in increasing water content up to 81,87±0,4%, which was 3% higher (p<0,05)than in intact animals (table 1, control).

When isopropyl alcohol poisoning in animals of the control group had developed symptoms of increased blood viscosity. At shear rates 3-15-1, 7-1, 10-1, 50-1, 100-1and with 300-1blood viscosity increased by 66%, 61%, 57%, 53%, 45%, 33% and 26%, respectively, compared to intact animals, the plasma viscosity and hematocrit did not change. Half aggregation of erythrocytes in the control group was 6.2±0.7 s, which was 67% was significantly lower than the rate in intact animals (table 2, control).

During the first days after poisoning isopropyl alcohol all the animals of the control group died (table 1, control).

Thus, in rats after intragastric administration of isopropyl alcohol at a dose of 6.6 ml/kg acute poisoning, expressed in violation of a number of basic physiological parameters (body temperature, h is the notes of breath, the osmolarity of blood plasma) with symptoms of pulmonary edema and the formation of a syndrome of increased blood viscosity.

Example 3. In animals poisoned with isopropyl alcohol at a dose of 6.6 g/kg and received intravenous mannitol for 4 h observation occurred naturally (p<0.05) decrease in body temperature by 9%, respiratory rate by 34% and increased plasma osmolarity by 12% compared with the original values. The volume of urine released within 4 h after intravenous injection of mannitol, was 2.0±0,21 ml, which was higher by 56% and 49% of the intact and control animals, respectively (p<0,05). For 4 h, the water content in the lungs was 79,51±0,18%, which was similar to the rate in intact animals and in 3% significantly below control values (table 1, mannitol).

When isopropyl alcohol poisoning in animals after intravenous mannitol was developed symptoms of increased blood viscosity. At the shear rate of 3-15-1, 7-1, 10-1, 50-1, 100-1and with 300-1blood viscosity increased by 40%, 43%, 48%, 40%, 39%, 29% and 26%, respectively, compared to intact animals. The viscosity of the blood of the animals of the experimental group was lower than control values on 4-16%, which, however, did not reach significant difference. The half-life of RBC aggregation was statistically significantly decreased by 53% as compared with intact animals. Comparedwith the control group, this figure was increased by 42%, however, this value did not reach the level of statistical significance (table 2, mannitol).

Intravenous mannitol at a dose of 1 g/kg increased the survival of animals during the first days after intragastric administration of isopropyl alcohol at a dose of 6.6 ml/kg 30% compared with the control group (table 1, mannitol).

Thus, after intragastric administration of isopropyl alcohol at a dose of 6.6 ml/kg intravenous mannitol at a dose of 1 g/kg increased diuresis and weakened pulmonary edema, however, positive developments of the basic physiological parameters (body temperature, breathing rate, the osmolarity of blood plasma) and rheological parameters did not reach the level of statistical significance compared to control.

Example 4. In animals poisoned with isopropyl alcohol at a dose of 6.6 ml/kg treated poliom to 4 h of observation was the decrease in body temperature from 37.9±0.1°C to 36.3±0.3°C, which was 4% below the original value, but exceeded the control group by 12% (p<0.05), and was also 5% higher values in the group with intravenous mannitol. Noted moderate decrease in respiratory rate from 115±3 102±7 min-1that was 11% below the original value of the group and 62% (p<0,05) higher than in control animals. The osmolarity of the plasma was increased by 15% from the original values. The amount of mo and, released for 4 h, amounted to 2.94±0,24 ml and was more than in intact rats by 130% (p<0.05), and control rats at 119% and in rats treated with mannitol, at 47%. For 4 h, the water content in the lungs was 79,72±0,20%, which was similar to the rate in the intact animal and 3% below control values (p<0,05) (table 1, poliom).

When isopropyl alcohol poisoning in animals after intravenous polyoma noted limitation of the syndrome of increased blood viscosity. At the shear rate of 3-15-1, 7-1, 10-1, 50-1, 100-1and with 300-1blood viscosity was 7,9±0,6, 7,6±0,7, 7,1±0,4, 6,8±0,4, 4,6±0,1, 4,2±0,1 and 3.9±0.1 MPa·s, respectively. The viscosity of the blood of the animals of the experimental group in the range of shear rates 7-300 with-1was lower values in control rats by 20-30% and values in rats treated with mannitol, 19-25% (p<0,05). Half aggregation of erythrocytes remained reduced compared to the intact animals level (40%), however, compared with the control group, this figure increased significantly to 81% (table 2, poliom).

In the group of animals poisoned with isopropyl alcohol at a dose of 6.6 ml/kg and treated poliom, all animals survived (table 1, poliom).

Thus, intravenous polyoma dose of 1 g/kg after intragastric administration of isopropyl alcohol at a dose of 6.6 is l/kg protected the animals from death, increased diuresis, prevented development of pulmonary edema and improved basic physiological parameters (body temperature, respiratory rate, the osmolarity of blood plasma). This poisoning poliom limited the development of the syndrome of increased blood viscosity.

Example 5. In animals poisoned with ethylene glycol at a dose of 9 ml/kg, 4 h observation noted the deterioration of the General condition of animals, expressed in statistically significant compared with baseline values decrease body temperature by 9%, respiratory rate of 24% and the increase in the osmolarity of blood plasma by 36% from the original values. The volume of urine released for 4 hours, 5 times the rate in the intact animal. For 4 h revealed persistent pulmonary edema, manifested in increasing water content up to 81,69±0,91%, which was 3% higher (p<0,05)than in intact animals (table 3, control).

In case of poisoning by ethylene glycol in animals of the control group had developed symptoms of increased blood viscosity. At the shear rate of 3-15-1, 7-1, 10-1, 50-1, 100-1and with 300-1blood viscosity increased by 101%, 89%, 81%, 65%, 43%, 33% and 26%, respectively, compared to intact animals. The hematocrit increased by 21%. Half aggregation of erythrocytes in the control group after poisoning isopropyl alcohol was 6.2±0.5 s, which bladestore 67% lower than intact animals (table 4, control).

During the first days after poisoning with ethylene glycol at a dose of 9 ml/kg mortality of animals in the control group (table 3, control) was close to 80%.

Thus, in rats after intragastric administration of ethylene glycol at a dose of 9 ml/kg acute poisoning, expressed in violation of a number of basic physiological parameters (body temperature, breathing rate, the osmolarity of blood plasma) with symptoms of pulmonary edema and the formation of a syndrome of increased blood viscosity.

Example 6. In animals poisoned with ethylene glycol at a dose of 9 ml/kg and received intravenous mannitol for 4 h observation occurred naturally (p<0.05) decrease in body temperature by 6%, respiratory rate by 14% and increased plasma osmolarity by 26% compared with the original values. The volume of urine released within 4 h after intravenous mannitol, amounted to 21.8±4,0 ml, which was 5.5 times greater than that of intact animals. For 4 h, the water content in the lungs was 77,00±0,27%, which was less than 3% of the value of intact animals and in 6% of the control rats (p<0,05) (table 3, mannitol).

In case of poisoning by ethylene glycol in animals after intravenous mannitol was developed symptoms of increased blood viscosity. At the shear rate of 3-15-1, 7-1, 10-1, 50-1, 100-1and with 30 -1blood viscosity increased by 73%, 63%, 63%, 57%, 39%, 21% and 21%, respectively, compared to intact animals. The viscosity of the blood of the animals of the experimental group in the range of shear rates 3-7-1was lower values in control rats to 3-14% (p<0,05). Half aggregation of erythrocytes remained reduced compared to the intact animals level (48%), however, compared with the control group, this figure increased by 55% (table 4, mannitol).

Intravenous mannitol at a dose of 1 g/kg increased the survival of animals during the first days after intragastric administration of ethylene glycol at a dose of 9 ml/kg of 25% compared with the control group (table 1, mannitol).

Thus, after intragastric administration of ethylene glycol at a dose of 9 ml/kg intravenous mannitol at a dose of 1 g/kg weakened pulmonary edema, however, positive developments of the basic physiological parameters (body temperature, breathing rate, the osmolarity of blood plasma); decrease of blood viscosity was significantly in the range of low shear rates.

Example 7. In animals poisoned with ethylene glycol at a dose of 9 ml/kg and fed policy, to 4 h of observation was the decrease in body temperature from 37.6±0.1°C to 35.6±0.2°C, which was 5% below the original value, but exceeded the control group by 4% (p<0,05). Noted moderate decrease is astate breath - with 116±3 103±6 min-1that was 14% below the original value of this group, but by 11% (p<0,05) higher than in control animals. The osmolarity of the plasma was increased by 26% from the original values. The volume of urine released for 4 h, amounted to 16.4±1.7 ml, which was more than 4.1 times the rate intact. For 4 h, the water content in the lungs was at 76.00±0,72%, which was lower by 4% and 7% of the performance of the intact and control animals, respectively (p<0,05) (table 3, poliom).

In case of poisoning by ethylene glycol in animals after intravenous polyoma noted limitation of the syndrome of increased blood viscosity. At the shear rate of 3-15-1, 7 c-1, 10-1, 50-1, 100-1and with 300-1blood viscosity was 11,6±0,2, 9,9±0,5, 9,2±0,3, 8,5±0,3, 5,7±0,1, 5,1±0,1 and 4.7±0.1 MPa·s, respectively. The viscosity of the blood of the animals of the experimental group in the range of shear rates 3-100 with-1was lower values in control rats on 9-24% and values in rats treated with mannitol, in the range of shear rates 7-100 with-17-11% (p<0,05). Half aggregation of erythrocytes remained reduced compared to the intact animals level (29%). Compared with the control group, this value significantly increased by 113% (p<0,05) (table 4, poliom).

In the group of animals poisoned with ethylene glycol at a dose of 9 ml/kg and treated poliom, yilo 60% of the animals, it was 50% higher than the control group and 33% in the group of rats treated with mannitol (table 3, poliom).

Thus, intravenous polyoma after intragastric administration of ethylene glycol at a dose of 9 ml/kg protected the animals from death, prevented development of pulmonary edema and improved basic physiological parameters (body temperature, respiratory rate, the osmolarity of blood plasma). This poisoning poliom limited the development of the syndrome of increased blood viscosity.

Example 8. In blood samples was added mannitol at a final concentration of 1·10-3g/ml (35 µl of 30% solution). To the test sample were added equiano amount of saline. Adding to the blood mannitol increased the half-life of aggregation of red blood cells compared to the control sample at 100%, which indicates a significant weakening of the aggregation of erythrocytes (table 5). The increase in the index of deformability of erythrocytes in shear 180 and 890 with-1tended to increase (table 6).

Example 9. In blood samples was added poliom (35 µl of a 30% solution of polyethylene oxide 400) at a final concentration of 1·10-3, To the test sample were added equiano amount of saline. Adding to the blood solution of polyethylene oxide 400 has led to an increase of the half-period aggregation of erythrocytes with whom avanyu with the control sample at 80% (table 5). The index of deformability of erythrocytes in shear 90 and 180-1increased by 7% and 4%, respectively (p<0,05) (table 6).

The resulting shifts of the investigated indicators suggest that poliom has a distinct impact on the performance of cell rheology, namely reducing the aggregation of red blood cells and increases their deformability. On hemorheological activity of the polyethylene oxide 400 is not inferior to mannitol.

Table 1
The impact of intravenous mannitol (1 g/kg, 30% solution) and polios (1 g/kg, 30% solution of polyethylene oxide 400) on mortality and major pharmacological indicators for poisoning by isopropyl alcohol (of 6.6 ml/kg)
GroupBody temperature, °CRespiratory rate, min-1The osmolarity of plasma, mm/kgThe amount of excreted urine, mlThe water content in the lungs, %Mortality, %
Original value4 hOriginal value 4 hOriginal value4 h
Intact (n=5)38,0±0,237,9±0,1113±8115±6306±2311±31,28±0,1479,40±0,06-
Control (n=5)38,0±0,132,4±1,2*109±563±9*303±2348±5*1,34±0,0481,87±0,40*100
Mannitol (n=5)37,9±0,134,5±0,8*116±377±18*306±1342±7*2,0±0,21*+79,51±0,18+70
Poliom (n=5)37,9±0,136,3±0,3*+115±3102±7+305±1 352±5*2,94±0,24*+•79,72±0,20+-
Note: * - p<0.05 compared with values in the intact animals;
+ - p<0.05 compared with values in the control group;
- p<0.05 compared with values in the group of animals with intravenous mannitol.

Table 2
The impact of intravenous mannitol (1 g/kg, 30% solution) and polios (1 g/kg, 30% solution of polyethylene oxide 400) on indicators of blood rheology in case of poisoning by isopropyl alcohol (of 6.6 ml/kg)
GroupBlood viscosity, MPa·sPlasma viscosity, MPa·sHtT1/2with
3-15-17-110-150-1100-1300-1
Intact (n=5) 7,3±0,16,7±0,26,3±0,26,0±0,14,4±0,14,2±0,13,9±011,3±0,143±118,6±1,1
Control (n=5)12,1±1,5*10,8±1,1*9,9±1,0*9,2±1,0*6,4±0,5*5,6±0,4*4,9±0,2*1,4±0,144±16,2±0,7*
Mannitol (n=5)10,2±0,4*9,6±0,3*9,3±0,3*8,4±0,1*6,1±0,2*5,4±0,1*4,9±0,1*1,4±0,145±18,8±1,7*
Poliom (n=5)7,9±0,6+•7,6±0,7*•7,1±0,4+• 6,8±0,4+4,6±0,1+4,2±0,1+•3,9±0,1+•1,4±0,144±111,2±2,3*+
Note: * - p<0.05 compared with values in the intact animals;
+ - p<0.05 compared with values in the control group;
- p<0.05 compared with values in the group of animals with intravenous mannitol.

Table 3
The impact of intravenous mannitol (1 g/kg, 30% solution) and polios (1 g/kg, 30% solution of polyethylene oxide 400) on mortality and major pharmacological indicators for poisoning by ethylene glycol (9 ml/kg)
GroupBody temperature, °CRespiratory rate, min-1The osmolarity of plasma, mm/kgThe amount of excreted urine, mlThe water content in the lungs, %Mortality, %
And the initial value 4 hOriginal value4 hOriginal value4 h
Intact (n=5)38,0±0,237,9±0,1116±5115±6306±2311±34,0±0,879,40±0,06-
Control (n=5)37,7±0,134,3±0,1*119±491±4*308±1419±28*19,8±1,3*81,69±0,91*80
Mannitol (n=5)37,6±0,135,4±0,2*+117±5101±7307±4387±16*21,8±4,0*77,00±0,27*+60
Poliom (n=5)37,6±0,1 35,6±0,2*+116±3103±6308±3391±13*16,4±1,7*at 76.00±0,72*+40
Note: * - p<0.05 compared with values in the intact animals;
+ - p<0.05 compared with values in the control group

Table 4
The impact of intravenous mannitol (1 g/kg, 30% solution) and polios (1 g/kg, 30% solution of polyethylene oxide 400) on indicators of blood rheology in case of poisoning by ethylene glycol (9 ml/kg)
GroupBlood viscosity, MPa·sPlasma viscosity, MPa·sHtT1/2c
3-15-17-110-150-1100-1300-1
Intact (n=5)7,3±0,16,7±0,26,3±0,26,0±0,14,4±0,14,2±0,13,9±0,11,3±0,143±118,6±1,1
Control(n=5)14,7±0,5*12,7±0,3*11,4±0,3*9,9±0,3*6,3±0,1*5,6±0,3*4,9±0,1*1,5±0,152±2*6,2±0,5*
Mannitol (n=5)12,6±0,2*+10,9±0,3*+10,3±0,2*+9,4±0,2*6,1±0,1*5,3±0,1*4,7±0,1*1,5±0,152±1*9,6±1,5*
Poliom (n=5)11,2±0,6*+9,9±0,5*+ 9,2±0,3*+•8,5±0,3*+•5,7±0,1*+•5,1±0,1*+4,7±0,1*1,5±0,152±3*13,2±0,6*+
Note: * - p<0.05 compared with values in the intact animals;
+ - p<0.05 compared with values in the control group;
- p<0.05 compared with values in the group of animals with intravenous mannitol.

Table 5
The effect of mannitol (10.5 mg/ml of blood) and polyoma (10.5 mg of polyethylene oxide 400 /ml of blood) on the bottom half of aggregation of erythrocytes in vitro
GroupT1/2c
Control10,4±1,4
Mannitol20,8±1,6+
Poliom18,0±1,5+
Note: +p<0.05 compared with control

Table 6
The effect of mannitol (10.5 mg/ml of blood) and polyoma (10.5 mg of polyethylene oxide 400/ml of blood) on the index of deformability of erythrocytes at different shear rates in vitro
GroupShear rate, c-1
90180360890
Controlof 0.133±0,0040,206±0,0040,303±0,0200,394±0,021
Mannitolof 0.133±0,0050,210±0,0040,303±0,0200,426±0,016
Poliom0,143±0,001+0,214±0,001+0,310±0,0010,416±0,016
Note: +p<0.05 compared with control

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19. Dobrovolsky N.A., Lopukhin, Y.M., Parfenov A.S., ALEXANDER Peshkov Analyzer blood viscosity. // Rheological studies in medicine. - M., 1997. - Issue 1. - P.45-51.

20. Gabrielian ES, Akopov SE blood Cells and circulation. - Yerevan: Hayastan, 1985. - P.71-78.

21. Carpenter MB, I. Aliyev, F. W. Popiel Modification microcalorimetry MKMF-1 for registration of aggregation of erythrocytes. // The wedge. lab. diagnosis. - 1995. No. 3. - S-458.

22. Belkin AV, a Pointer S.A., Katugin LN. Estationery - objective method of assessing the ability of RBCs to deform. // Fiziol. Journe. Of the USSR. - 1991. - T, No. 1. - S-138.

Application polyoma as an antitoxic agent with poisoning aliphatic alcohols.



 

Same patents:

FIELD: chemistry.

SUBSTANCE: invention refers to veterinary science, in particular to products intended to increase capacity for survival and yield of poultry. For this purpose common composition 1,3-di(3-piperidine-2-hydroxypropyl)-6-methyluracil of formula: is used. Composition is characterised by natural resistance, antioxidant activity, activates nonspecific factors of immune system, as well as possesses medicinal properties to provide detoxification of nitrates and nitrites. Composition has the appearance of white powder, is highly soluble in water and can be added in specified doses to chickenfeed.

EFFECT: production of composition providing increase of capacity for survival and yield of poultry.

6 tbl, 5 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to pharmaceutical industry and deals with acizol application as preventive and therapeutic means in neurotoxin poisoning cases. The present invention showed high efficacy of acizol in complex treatment for toxico-hypoxic encephalopathy and pneumonia (normalisation of homeostasis indices, lowering of mortality and disabling complications).

EFFECT: lowering of the risk of complications in neurotoxin poisoning cases.

15 tbl

FIELD: medicine; pharmacology.

SUBSTANCE: wood of Siberian or Daurian larch is debarked, cleaved and dried at 40-50°C to residual moisture 23-27%. Dried wood is chopped, and soluble substances are extracted with 75-85% ethyl alcohol aqueous solution at temperature 45-50°C in ratio raw material:extracting agent 1:(7-10). Further extracting agent is distilled off, and sawdust is supplied to press for additional alcohol return. Then extract aqueous part is cooled to 20-25°C within 20-30 minutes for isolation of resinous impurity accompanying dihydroquercetin (DHQ). Deresined extract aqueous part is added with methyltertbutyl ether (MTBE) in ratio 1: (0.3-0.45), and DHQ is reextracted within 2-3 hours. Extract ether part is isolated separate from aqueous part through sedimentation within 2-2.5 hours and supplied to MTBE evaporation, while target product is crystallised of hot water. Invention enables to produce DHQ with yield 2.2-2.5% of bone-dry wood mass with grade 90-96%.

EFFECT: simplification of process and production of high-quality product.

4 cl, 2 ex

FIELD: medicine; veterinary.

SUBSTANCE: method describes the use of 2,4-diphenyl-7,8-benzo-5,6-dihydroselenochromen as a means of treatment and prevention of poisoning with heavy metal compounds.

EFFECT: higher resistance in animals and humans to poisoning with heavy-metal compounds.

8 tbl, 1 ex

FIELD: organic chemistry, toxicology.

SUBSTANCE: invention describes a method for using 2,4,6-triphenyl-4H-selenopyrane as an agent for treatment and prophylaxis of poisoning with arsenic compounds. Sodium arsenite was used as a toxicant. Using the claimed preparation reduces lethality of animals up to 40-60% (100% in control group). Also, significant improving blood indices and visceral organs of animals occurred, i. e. the severity degree of poisoning was decreased.

EFFECT: enhanced effectiveness of agent.

2 tbl

FIELD: medicine, pharmacy.

SUBSTANCE: invention relates to biologically active substances displaying perspective using medicine, veterinary science, cosmetics and dairy industry. Agent comprises polyoxyarylene ester and hydroquinone in their ratio from 83:17 to 5:95, respectively. Agent comprises 2-(1-oxy-4-hydroxyphenylene)benzoquinone or 4-hydroxyphenylene-2,4-dioxybenzene as a polyoxyarylene ester. Method for preparing agent involves mixing polyoxyarylene ester with hydroquinone and wearing the prepared mixture up to formation of the uniform mass. Invention provides creature of a novel agent of the broad spectrum of effect, namely: antioxidant, antihypoxic, antitumor, radioprotective, immunostimulating and biocide effects.

EFFECT: valuable properties of agent.

7 cl, 20 tbl, 16 ex

FIELD: medicine.

SUBSTANCE: claimed adsorbent contains spherical activated carbon having size diameter of 0.01-1 mm, specific surface determined in accordance to Langmuir equation of 1000 m2/g or more, ratio of diffraction intensities R of 1.4 or more (R is determined as R = (I15-I35)/(I24-I35) (1), wherein I15 is diffraction intensity at diffraction angle (2θ) of X-ray diffraction is 15°C; I35 is diffraction intensity at diffraction angle (2θ) of X-ray diffraction is 35°C; I24 is diffraction intensity at diffraction angle (2θ) of X-ray diffraction is 24°C), and pore volume having diameter of 7.5-15000 nm is less than 0.25 mg/ml. In another embodiment claimed adsorbent contains abovementioned spherical activated carbon with modified surface. Also disclosed are pharmaceutical composition and method for prevention or treatment of kidney or liver diseases containing said adsorbent.

EFFECT: new adsorbent for peroral administration.

20 cl, 5 ex, 2 tbl, 12 dwg

FIELD: organic chemistry, medicine, hepatology.

SUBSTANCE: invention relates to using 2-methylthiopyrimido[4,5-b]indole of the formula (1): showing melting point at 243°C (with decomposition) and value LD50 > 1000 mg/kg used in liver protection from poisoning with carbon tetrachloride. Proposed compound exceeds activity of the "Essentiale" as a comparison preparation.

EFFECT: valuable medicinal property of compound, enhanced effectiveness.

1 tbl

FIELD: pharmaceutical industry.

SUBSTANCE: claimed adsorbent contains spherical active carbon, obtained from thermosetting resin as carbon source, having particle size of 0.001-1 mm, specific surface determined by Langmuir adsorption equation of 1000 m2/g or more and pore volume of 7.5-15000 nm in diameter less than 0.25 ml/g. Also disclosed is adsorbent being similar to abovementioned one, wherein total content of acidic groups is 0.40-1.00 meq/g; total content of basic groups is 0.4-1.1 meq/g. Pharmaceutical compositions contain said adsorbents and pharmaceutically acceptable carriers and recipients. Agents of present invention are useful in treatment of kidney or liver diseases or disorders associated with uremic substance by administration of said adsorbents.

EFFECT: products of increased selectivity.

21 cl, 5 ex, 2 tbl, 11 dwg

FIELD: chemical and pharmacological industry.

SUBSTANCE: invention relates to encapsulated form of Acyzol containing Acyzol and pharmaceutically acceptable fillers in specific component ratio.

EFFECT: encapsulated mass with high technological characteristics, high biological availability and effectiveness of Acyzol component.

5 tbl, 3 dwg

FIELD: medicine.

SUBSTANCE: present invention refers to medical products, particularly to large depletion mixture containing the following components per litre of aqueous solution: polyethylene glycol 90 to 150; ascorbic acid and/or ascorbic acid salt 5 to 15; alkaline or earth metal sulphate or mixed alkaline or earth metal sulphates 5 to 10; and electrolyte (sodium chloride, potassium chloride and sodium hydrocarbonate). The mixture agents are chosen so that the osmolarity of the aqueous solution reduced to 1 litre is within 300 to 550 mOsmoles/litre. Besides the invention concerns a cleaning agent, a component set for large intestine depletion, to application of polyethylene glycol as a large intestine depletion agent and to method of large intestine depletion.

EFFECT: higher mixture safety and tolerance.

39 cl, 29 tbl, 6 ex

FIELD: medicine.

SUBSTANCE: treatment or prevention of epithelial disorders mediated by microorganisms, such as enterogenous sepsis, burns, necrotising enterocolitis and many other pathological conditions, is ensured with polyethylene glycol of molecular weight 8000-20000 dalton applied as an active agent in methods and pharmaceutical compositions, and for production of medical products. Polyethylene glycol of specified molecular weight provides complete inhibition of virulence manifestation of microorganisms, including Pseudomonas aeruginosa, without destruction thus preserving individual natural microflora.

EFFECT: higher efficiency.

36 cl, 6 dwg, 8 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to chemical-pharmaceutical industry and concerns composition, production method and application of agent based on perfluorcarbon-fat emulsions, used for blood substitute parenteral nutrition. Perfluorcarbon-fat emulsion composition can include one perfluorcarbon only, and mixed two, three or four perfluorcarbons: "ПФД" or "ПФТБА", either "ПФОБ", or "ПФМЦП", in ratio 1:1 to 10:10 and one oil selected of group: either soy, or cottonseed, or corn, olive oil, or cod-liver oil, and besides, can include sodium chloride, proxanole and/or phospholipids (soy or egg) as emulsifier; and in addition can contain either glycerol or sorbitol, or xylitol.

EFFECT: can be used for blood substitute parental nutrition.

96 cl, 13 ex, 1 dwg

FIELD: medicine.

SUBSTANCE: method involves giving patient to drink 100 ml of lactulose syrup with 250 ml of liquid at the day before examination. 2-3 h later, intestinal lavage is carried out with 10-15% aqueous lactulose solution being prepared as 100 ml of the syrup diluted with water to volume of 1 l, giving 250 ml to drink every 15 min. Next day, intestinal lavage is carried out with 1 l of aqueous polyethylene glycol solution 3-4 h before performing examination.

EFFECT: enhanced effectiveness in cleaning large intestine with smaller volume drugs consumed; improved aged patient tolerance to the procedure.

FIELD: cosmetology, medicines.

SUBSTANCE: claimed agent represents composition containing mixture of 4-hydroxyphenylene-2,4-dioxybemzene or 2-(1-oxy-4-hydroxyphenylene)-benzoquinone with hydroquinone in ratio from 99:1 to 1:99. Preparation for treatment of body external tissues contains said agent in amount of 0.5-10 g in daily dose. Composition of present invention are useful in treatment of wound, burn, in surgery, stomatology, etc.

EFFECT: agent of increased effectiveness.

3 cl, 4 tbl, 11 ex

FIELD: medicine.

SUBSTANCE: method involves opening suppuration focus with following pus evacuation, necrectomy and washing with antiseptic solution. Bandage impregnated with antimicrobial ointment on hydrophilic polyethylene oxide base is applied over injured region. The ointment contains 0.2 g of Ciproflaxin, 5 IU of Oxytocin, 19.05 g of polyethylene oxide-1500, 76.2 g of polyethylene oxide-400.

EFFECT: enhanced effectiveness of treatment.

1 dwg, 2 tbl

FIELD: medicine, ophthalmology.

SUBSTANCE: method involves using water-soluble ointment as a combined medicinal antibacterial preparation comprising the following components, g: chinosol, 0.005; streptomycin, 0.015; polyethylene oxide-400, 7.53; polyethylene oxide-1500, 1.87, and distilled water, 0.58. Ointment is placed into conjunctival cavity of eye in the dose 0.5 g, 4 times per a day, every day. Treatment course is 12-17 days. Method provides enhancing effectiveness of treatment, reducing period of treatment based on broad spectrum of antibacterial effect of ointment with respect to pathogenic microflora and with reciprocal enhancing activity of its components. Invention can be used in treatment of cornea suppurative ulcer.

EFFECT: enhanced effectiveness of treatment.

1 ex

FIELD: organic chemistry, chemical-pharmaceutical industry, medicine, oncology.

SUBSTANCE: invention relates to a conjugate containing N-terminal fragment of hepatic growth factor (HGF/SF) that consists of "pin-like" domain and four cringle-like regions of α-chain and one polyethylene glycol group of the general molecular mass about 20-40 kDa and of the formula -CO-(CH2)x-(OCH2CH2)mOR or wherein -CO-group forms an amide bond with one of amino-group of N-terminal fragment of hepatic growth factor wherein X means 2 or 3; or y means 1-10; m has value from about 450 to about 950; or n and p in common have value from about 450 to 950; R means (C1-C6)-alkyl. The growth factor shows improved properties and it can be used as a therapeutic agent in treatment of cancer and metastasis of tumor cells.

EFFECT: valuable medicinal properties of conjugates.

7 cl, 1 tbl, 4 dwg, 9 ex

FIELD: medicine, pharmacy.

SUBSTANCE: invention relates to a liquid pharmaceutical composition comprising pegilated erythropoietin as a conjugate in pharmaceutically acceptable buffer at pH from 5.5 to 7.0 and optionally one or some pharmaceutically acceptable excipients. Proposed composition is used in treatment and prophylaxis of diseases associated with erythropoiesis injury. The advantage of invention involves enhancing stability of the preparation.

EFFECT: improved and valuable property of preparation.

59 cl, 4 tbl, 11 dwg, 13 ex

FIELD: medicine, polypeptides.

SUBSTANCE: invention relates to fusion polypeptides with enhanced pharmacokinetic properties. Fusion polypeptides comprising enhancing peptide sequences associated with the core polypeptide possess with the enhanced pharmacokinetic properties, such as prolonged half-time period. Also, invention relates to methods for enhancing pharmacokinetic properties of any core polypeptide by binding the enhancer peptide sequences with the core polypeptide. Proposed core polypeptides can comprise any pharmacologically useful peptide that can be used, for example, the therapeutic or prophylactic agent. The advantage of invention involves the enhancing of pharmacokinetic properties of polypeptides.

EFFECT: enhanced pharmacokinetic properties of polypeptides.

52 cl, 18 dwg, 14 tbl, 11 ex

FIELD: medicine, hematology.

SUBSTANCE: polyfunctional blood substitute for treatment of blood loss and shock comprises polyethylene glycol with molecular mass 20 000 ± 3 000 Da. As saline base electrolytes the blood substitute comprises sodium chloride, potassium iodide and iodine additionally in the following ratio of components, g/l: polyethylene glycol, 13.5-16.5; sodium chloride, 8.6-9.6; potassium iodide, 0.45-0.55; iodine, 0.05; water for injection, up to 1 l. Invention provides hemodynamic effect and simple medicinal formulation providing good injection usefulness.

EFFECT: valuable medicinal properties of blood substitute.

1 tbl, 3 ex

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