Remedy for poisoning and its complications treatment
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.
The invention relates to the field of medicine critical conditions, in particular to the use of a drug of alzola in the treatment of acute poisoning and its complications.
In the structure of causes of death in the working age population (according to 2003), the first place belongs poisoning and injuries (36.8% of men and 28.4% of women), ahead of even the diseases of the circulatory system. The majority (60%) of ecotoxicol comes to share poisoning neurotoxic substances (hypnotics, neuroleptics, and other), including complex toxic chemicals generated during the burning and destruction of organic substances. In 10-20% of cases of such poisoning is fatal. The leading place among the causes of disability are also poisoning.
A serious problem are complications, aggravating the course of acute poisoning. The greatest danger of toxic and hypoxic encephalopathies (TSES) and nosocomial pneumonia (SE). In the analysis of the clinical course of exogenous poisoning by products of thermal destruction is established that changes in the Central nervous system (CNS) remain after the exit of patients from coma. In surviving patients may have long flowing neuropsychiatric disorders, which are considered as variants of TSES. The shaping is their TSEs are directly related to the drop mode, oxygen supply of the cerebral cortex.
In the study of patients with severe poisoning, accompanied by respiratory syndrome, severe encephalopathy and coma lasting more than two days, pneumonia was diagnosed in 50% of cases in the first week after admission and another 30-40% of patients in the second week. Mortality from pneumonia in somatic stage is 2/3 of all deaths.
Currently, the main approach in the treatment of acute poisoning are: active methods of detoxification, aimed at stimulating the excretion of the poison from the body, reducing endotoxemia, antidote therapy.
Existing approaches for the treatment of TSES are in the application of methods of oxygen therapy (normobaric and hyperbaric oxygen therapy). As a pathogenetic drug therapy is applied cytochrome C.
Treatment of pneumonia is difficult, and it depends on predisposing to the development of the disease factors, severity of condition of patients, polymicrobial nature of infections, frequent selection of the "problem" of microorganisms, rapid development of resistance in microbes in the process of treatment, frequent relapses of infection during and after antibiotic therapy.
The decrease in gas exchange function of the lungs and respiratory failure with pneumonia in the children to systemic hypoxia and disturbance of the functional activity of the vital organs and systems (heart, liver, brain and other), as well as the main indicators of homeostasis as the severity of the changes of the immunity, the circulation, the rheological parameters of blood, stimulatie free-radical and lipid peroxidation of biomembranes, etc.
The main etiopathogenetic treatment of SE is antibiotic therapy. There are various schemes antibiotic treatment (monotherapy and in combination), which are not always effective. As a pathogenetic therapy in clinical practice for the treatment of SE methods laser (LGT) and ultraviolet (UFGT) haemotherapy. Known applications of Mexidol in the pathogenetic therapy of complications of acute poisoning neurotoxic substances.
Symptomatic therapy for poisoning and its complications is based on the evidence in each case and is aimed at correcting or maintaining the functions of vital organs and systems.
However, the relevance of improving the treatment of acute poisoning and complications resulting from a continuing high rate of cases of severe and mortality of patients on background of traditional therapy. Thus, mortality in deferred treatment of TSES is from 18 to 40%. The number of deaths in-hospital pneumonia also remain eno is however high. In the Russian Federation it is 42-45%. According to foreign sources, in some cases reaches of 52.9%.
The present invention is to use a drug arizol in the treatment of acute poisoning and complications, aimed at the normalization of indicators of homeostasis, reduced morbidity and mortality.
It is known the use of alzola as an antidote for carbon monoxide. However, in real conditions (fires, industrial smog, automobile exhaust gases and other) on the body is a complex toxic chemicals (such as carbon monoxide, carbon dioxide, acetone, Acrylonitrile, aromatic hydrocarbons, sulfur dioxide, nitrogen dioxide and others) in concentrations capable of causing poisoning of varying severity or substantially modify the toxic action of carbon monoxide.
Antihypoxic effect of alzola associated with its impact on the cooperative interaction of hemoglobin, resulting in increased affinity of hemoglobin to oxygen and improves oxygen transport properties of the blood. The drug reduces the body's need for oxygen increases resistance to hypoxia vital organs and systems (myocardium, Central nervous system, liver and others), induces microsomal mono-oxidase in the liver and replenishes the deficiency of zinc in the body. Azizol oblad is no strong antioxidant and immune stimulating effect, is effective hepatoprotector and adaptogen.
In the examples below we have shown the effectiveness of alzola in the treatment of acute poisoning and its complications.
Example 1. Study the protective efficacy of alzola in case of poisoning by the products of combustion of various materials in the experiment.
To assess the protective properties of alzola held a special experimental Toxicological studies in which laboratory animals were exposed to acute inhalation exposure to carbon monoxide and other toxic volatile substances formed during thermo-oxidative decomposition of combustible natural and synthetic polymeric materials.
Antidote properties arizola was estimated by the integral toxicometric characteristics when the priming experimental animal products of thermal decomposition of combustible materials at 600°C. have been selected For testing three materials: pine wood, insulation material FC-72, manufactured on the basis of phenolic resin rezol type of insulating material Vilares-5, manufactured on the basis of phenol-formaldehyde resin.
Pine wood was selected as the reference source two-component mixture of volatile products of thermal decomposition, because when heated it emits mainly oxide ug is erode, carbon dioxide, water and a small amount of resinous substances. The combustion products of materials FC-72, Vilares-5, in addition to oxide and carbon dioxide contain acetone, Acrylonitrile, aromatic hydrocarbons (benzene, toluene, and others), chloride and hydrogen cyanide in quantities that could significantly modify the toxic action of carbon oxides.
The composition and level of concentration of toxic products of combustion of the test materials shown in table 1.
Experimental evaluation of the toxicity of the products of thermal decomposition of all three investigated materials was performed on the unit with closed circuit gases construction research Institute FOR satisfying the requirements of GOST 12.1.044-89. The experiments were carried out on outbred white rats and white mice of both sexes. Before each series of experiments the animals of both species were formed two groups with body weight: for rats 190-240 grams, for mice 18-22 grams. Animals in the experimental group 30 minutes before the dose was administered intramuscularly azizal (rats at a dose of 30 mg/kg to mice at a dose of 40 mg/kg). Control groups of rats and mice were administered the same volume of isotonic sodium chloride. The duration of seed in all experiments was 30 minutes.
The integral indicator of the toxicity of combustion products of material HCL50(mass toxicometric the index or weight of material in grams, thermal decomposition which in standard conditions leads to the creation of the air volume of one cubic meter concentrations of toxic substances that cause the death of 50% of the animals) was calculated according to the results of experiments by the method of probit analysis. Antidote action of arizola was assessed by the magnitude of the protective index (RFI), whose calculation is made according to the formula:
Integral toxicometric index of NCL50pine wood in experiments on rats, which is 30 minutes before the seed products of combustion introduced azizol amounted to 73.2±3,9 g/m3and in experiments on rats, which were injected with isotonic sodium chloride solution - 59,8±3.4 g/m3. The difference between these two indicators assessed by student's t-test-Fisher, significantly (P<0,02). Protective index - 1,22 (table 2).
Similar results were obtained in experiments on white mice. HCL50pine wood protected etizolam mice was equal 44,6±2.0 g/m3and for unprotected mice - 38,7±1,9 g/m3and the difference between them was also significant (P<0,01). The protective index (RFI) was equal to 1.15 (table 3).
When seeds animal products thermo-oxidative degradation of polymeric insulation material FC-72 indicator of the toxicity of HCL50for rats, protected and unprotected etizolam, RA is enterprising, respectively 27,9± 1.5 g/m3and 23.9±1.8 g/m3. The values ZI of arizola was 1.17. In experiments on mice, which before the seed was introduced azizol, HL50equal 25,32±1,5. In experiments with unsecured drug mice indicator HCL50material FC-72 was equal to 19.9±1,3. Protective index in this case was equal to 1.27 (table 3).
The preliminary introduction of rats alzola increased their resistance to the action of combustion products material Vilares-5. Weighed samples of this material, the seed products of combustion which caused the death of 50% of the rats in the experimental and control groups statistically differed and was equal respectively to 20.6±1.0 g/m3and 17.1±1.2 g/m3and the value ZI of arizola was the value of 1.20. In experiments on mice, the value ZI of alzola when the seed products of thermal decomposition of hanging material Vilares-5 was 1.13 (table 3).
Comparison of the protective indices (table 2 and 3), obtained in experiments with seed rats and mice products thermo-oxidative degradation of wood, foam, FC-72 and material Vilares-5, allows to conclude that the introduction of experimental animals alzola increases their resistance to the combined toxic effects of complex mixtures of chemical compounds formed during thermal-oxidative decomposition of combustible materials.
Thus, ACI is ol exerts its antidote properties not only in case of poisoning by oxides of carbon, but when the intoxication complex mixtures of products of combustion of synthetic polymer materials (foams FC-72, Vilares-5), which are classified as highly toxic (the values of HCL50are in the range of from 10 g/m3to 50 g/m3at 600°).
Example 2. Clinical study of the effectiveness of alzola in the treatment of TSES, complicating the course of acute poisoning by products of thermal destruction.
The study included 63 patients with TSEs are associated with acute poisoning by combustion products. Patients were divided into 2 equal groups. In the first group (control) consisted of 32 patients, aged 15 to 85 years (mean age of 42.3±3,66 years), of which 23 men and 9 women who received traditional treatment methods. 17 patients in the combined therapy were included sessions of hyperbaric oxygenation (HBO) from 0.6 to 1 excess atmosphere from 2-10 sessions. All patients in this group are assigned cytochrome C in doses of 15-60 mg per day.
The second group (the study group) amounted to 31 patients aged 15 to 85 years (mean age 46,6±2,79 years), of which 21 men and 10 women in the complex treatment that has been on azizol dose 120-480 mg per day to positive dynamics of consciousness. 14 patients received sessions of HBO. The effectiveness of alzola researched blind.
According to the severity of pathological processes both gr is PPI were comparable. Basic therapy was carried out using complex intensive (including infusion) therapy for patients with acute poisoning by products of thermal destruction and TSES.
The results showed that the inclusion in the complex therapy of TSES drug arizol was accompanied by a rapid recovery of consciousness prevented the development of severe neurological complications in 70% of patients, a third reduced risk of developing mental disorders, was 2.4 times reduced the number of pneumonia and was accompanied by a decrease in mortality 2.75 times compared with the control group (table 4). On the background of treatment with etizolam the development of disabling complications, in particular acute neuropsychiatric syndrome, compared with the control group decreased in 2 times.
Thus, shows a pronounced therapeutic effect of the drug arizol when toxic and hypoxic encephalopathy due to acute poisoning by combustion products.
Example 3. The influence of arizola on the state of the Central nervous system after acute intoxication by combustion products in the experiment.
In connection with a particular complexity of monitoring patients with TSES after discharge from the hospital we studied therapeutic effect of the drug arizol on the status of processes of long-term memory and other indicators of the functional activity of the Central nervous system in the experiment.
The most reliable is the service provider state of the memory function in animals is a conditioned reflex of passive avoidance (passive avoidance reaction). Analysis of the latent period (LP) in animals with developed passive avoidance reaction gives the basis to judge the degree of damage to the Central nervous system at different times after intoxication.
Experimental study of the effect of arizola on the state of the Central nervous system after acute intoxication by the products of combustion carried out in experiments on Mature white outbred rats male weighing 180-220 g Seed animals was carried out in a cell volume of 0.5 m3where from the muffle furnace was supplied products of thermal decomposition of polyurethane foam stamps-306. During the combustion of materials of this type are characterized by high concentrations of carbon monoxide and carbon dioxide, hydrogen cyanide, hydrogen chloride, acetone, aromatic hydrocarbons. The duration of the seed was 30 minutes. Mounting material for incineration was selected in such a way as to cause acute severe poisoning complex products of combustion. Formed three groups of animals 10 animals in each group. One group was not exposed to combustion products ("control"). Animals of the second group ("seed") after intoxication was administered isotonic solution of sodium chloride, the third group ("treatment etizolam") received azizol intramuscularly at a dose of 30 mg/kg immediately after a dose and again after two hours.
Data on the effect of therapeutic applications azizol is on the processes of long-term memory in the passive avoidance reaction rate is presented in table 5.
As follows from table 5, passive avoidance reaction in animals of the control group, not exposed to the priming persisted throughout the observation period, and the duration of the latent period has not changed and amounted to 180 seconds. In animals, after which the seed products of combustion is not carried out pharmacological therapy etizolam, there was a decrease in PL 53% at the end of the first hour after a dose. After the first day after exposure to combustion products and the occurrence of retrograde amnesia was observed in 40% of animals that did not enter azizol. Later on the third day after priming all untreated animals recovering skill and elongation PL, but then again indicates a progressive decrease in LP (up to 20% of control at the end of the observation), indicating that the disruption of the processes of information storage in animals undergoing acute toxicity of the combustion products severe.
However, in the group of animals, which at the end of the seed was introduced azizol, retrograde amnesia is expressed to a much lesser extent. The recovery of the PL occurs already by the end of the first day after priming and lasts for one week. Less affected are also the processes of information storage. At the end of the observation PL 67% of the control level, which was significantly higher than in the group without treatment.
Thus, the test of saving passive avoidance reaction is logged therapeutic effect of arizola on the processes of reproduction and storage of information.
An important criterion of preservation functions of the Central nervous system is the ability of laboratory animals to study. To assess this ability, experiments were carried out, where the model was used conditional reflex active (AVOIDANCE) avoidance, which has been developed in three groups of Wistar rats (10 animals in each group) after a certain time after the seed products of combustion. The results of the experiment are presented in table 6.
As follows from the presented data, the acute effects of combustion products dramatically reduces the ability of white rats to learn. Thus, study 3 hours after the dose, indicates an increase of more than 2 times of combinations required to produce AVOIDANCE. In addition, in this group there is a violation of the subsequent storage of conditional connection. So, a day after intoxication indicator save the AVOIDANCE 3.8 times less than in the control group. However, after 7 days after priming observed recovery AVOIDANCE almost to control values.
In animals treated with curative intent were introduced azizol, there is a slight difficulty in learning 3 hours after the end of intoxic the tion, however, the number of combinations required to produce AVOIDANCE, they are not significantly different from the control. After 1 day after priming the percentage preservation AVOIDANCE 2 times higher than in the group of untreated animals, and a week later, this figure did not differ from the level of intact, which testifies to the effectiveness of therapeutic applications of alzola according to the criterion production and preservation of AVOIDANCE.
With the purpose of monitoring remote consequences of intoxication combustion products investigated the processes of memory and learning on the 7th, 21st and 45th days after priming. Found that on the 7th day after intoxication observed recovery processes of learning in both groups exposed to complex toxic substances. However, after 1 day after training in the group of untreated animals was observed the decrease of conservation AVOIDANCE, which is also celebrated in a week. In the group of animals that received azizol, these indicators do not differ from the control.
When testing animals on the 21st and 45th day after the intoxication has a positive dynamics of the number of combinations required to produce the reflex, increases the speed of learning.
However, in the group of animals who were not treatment etizolam, indicators of the ability to learn and security processes specific long the AI remain below than in the group of animals that received azizol.
Thus, the experiments show the positive impact of alzola in acute poisoning by combustion products in the processes of short-term and long-term memory, learning ability, stabilization preserving conditional connection.
Definition approximately locomotor activity was investigated using the test "open field". The results of the study are presented in table 7.
As follows from the presented data, the acute toxicity of the combustion products leads to significant changes in performance of psychomotor activity of animals. So, after 4 hours after intoxication in untreated animals there has been a sharp increase in horizontal activity, which is reflected in the increase in the number of crossed squares and zaglyadyvanie in mink almost 2-fold relative to control. This increased activity can be regarded as neurotoxic phenomenon, because in this case the increase in horizontal activity was not associated with increased vertical activity. Natural tentatively locomotor response is characterized by a direct correlation between these two parameters. The animals, which were introduced azizol, there was a slight decline in horizontal and vertical activity in relation to the structure to control.
The study tentatively locomotor activity of animals, obtained after priming azizol, have not revealed their behavior on the 7th, 21st and 45th day of observation. Indicators of behavioral activity in animals of this group were not significantly different from the corresponding parameters in intact animals (control). However, a similar study of a group of untreated animals reveals hyperactivity their behavior. Indicators of horizontal and research activity on the 7th, 21st day, significantly higher than those in the control group and normalized to 45 days, although the number of crossed squares, indicating persistent motor excitation. In addition, there is a dissociation of horizontal and vertical activity in the tested animals.
The results of the experiment for determining the state of emotional and behavioral reactions at different times after acute intoxication by the products of combustion are presented in table 8. The study of these reactions in experiments on animals allows us to assess the impact of toxic substances on the subcortical structures of the brain - the thalamus, reticular formation in the remote terms after suffering intoxication combustion products. Assessment of motor threshold reactions, rage, and aggression allows you to define the dynamics of processes of emotional response.
From the data of table 8, it follows that 4 hours in groups of animals undergoing acute toxicity of the combustion products, there was a decline in the level of emotional and behavioral reactions, which is expressed in the increase of thresholds of motor reactions, squeak, fights, and indicates the toxic effects of carbon monoxide and other toxic substances on the brain structures. Moreover, the average thresholds defined in the animals treated with curative intent were introduced azizol was even slightly higher than in untreated. A study conducted on 7th, 21st, 45 days after intoxication, shows the full normalization of the studied processes in the group that received azizol. Thresholds emotional and behavioral reactions in this group do not differ from those in the group of intact animals (control) after 7 days and remained stable throughout the study.
However, in the group of animals that did not receive treatment, on the 7th day and then throughout the study observed a significant drop thresholds of excitability that, accordingly, shows the development of emotional and behavioral instability in the late periods after intoxication.
Thus, in animals undergoing intoxication combustion products, changes occur in the Central nervous system, affecting such critical brain function is AK long-term memory, the ability to learn, about physical activity, emotional and behavioral reactions. The study of these functions indicates a significant breach in the immediate and long term after intoxication in a group of animals who were not therapeutic measures. The introduction of alzola with the purpose of treatment significantly reduces the severity of these changes in the coming days and in the more distant (up to 45 days) time after suffering intoxication.
Order pathological evaluation of the effectiveness of drug therapy etizolam acute poisoning by combustion products studied drugs parietal areas of the cerebral cortex of Wistar rats in the remote terms after suffering intoxication. The slaughter of animals and the selection of brain tissue for research was carried out 45 days after priming.
Morphological picture of brain tissue in animals undergoing intoxication combustion products differed from that of healthy animals (control). To the greatest extent changes have been expressed in animals, which at the end of the seed was not conducted medical treatment. Vascular changes were observed in 60% of untreated animals, and the severity of violations is approximately the same in all studied drugs. With the UDA Pia mater and brain capillaries moderately full. Capillaritis met in some areas of the cerebral cortex and, in General, was not expressed. In such cases, the capillaries extended, Packed red blood cells, endothelial cells moderately flattened. In venules and arterioles small diameter also noted similar changes. In areas with signs of violation of microcirculation was observed lots of diapedesis red blood cells in the perivascular space. Slightly pronounced perivascular edema.
In the fourth and fifth layers of the crust was noted neurocity with a pronounced chromatolysis and vacuolization of the cytoplasm. In General, degenerative changes in the nerve cells expressed moderately. The reaction neuroglial elements toxicity was manifested as the presence of a small number of foci with high density of cells glial cell has.
In animals, after which the seed was twice introduced azizol, morphological changes in brain tissue were expressed to a lesser extent. While the structure of the Pia mater and the feeding vessels is practically not changed. In some capillaries of the cerebral cortex was observed accumulations of erythrocytes with signs of capillaroscopy, witnessed a slight flattening of endothelial cells. Arterioles and venules were no signs of dilation and stasis, although in some cases took place perivascular edema. Minor chromatosis with aqualisa is her neurocytol granular layers of the cerebral cortex was observed in 20% of animals in this group. In General, cytoarchitectonic and the histological pattern of the study area of the cerebral cortex in animals that received after priming azizol, had no such significant damage, which was observed in animals not receiving treatment.
Thus, the use of alzola for therapeutic purposes can reduce the degree of damage to the Central nervous system, caused by the action of toxic products of combustion, resulting in improved long-term memory, learning ability, the normalization of spontaneous motor activity, normalization of emotional behavior compared with the control. Data pathomorphological studies indicate less severe structure damage target organs at the tissue, cellular and subcellular levels, which allows to make a conclusion about the appropriateness of alzola early after intoxication combustion products to reduce the risk of complications and reduce the severity of late effects of intoxication.
Clinical study of the effectiveness of alzola in the treatment of pneumonia, complicating the course of acute poisoning.
In the treatment of patients with pneumonia in the complex therapy included arizol in medicinal forms "Azizol, solution for intramuscular injection of 60 mg/ml and Azizol, capsules 120 mg. Injectable form of alzola who has oznaczali from receipt of patients in the intensive care unit or intensive care. Capsulated form of the drug used after the patient into a regular room. The most demonstrative examples, confirming the high efficiency of arizola was its use in the most difficult cases: in patients with pneumonia, complicating the course of acute poisoning by combustion products and psychopharmacological drugs.
Comprehensive treatment of pneumonia in patients with acute poisoning were included etiological, pathogenetic and symptomatic treatment.
To reduce critical and lethal concentrations of the toxicants were conducted treatments aimed at the elimination of toxic substances from the body: washing stomach through a tube, the introduction of chelators, salt and oil laxatives, use of specific antidotes. Implemented various methods of artificial detoxification. Conducted sessions of HBO.
All patients with impaired respiratory function was performed diagnostic and rehabilitation of fibrobronchoscopy (FBS). The number of sessions FBS was determined by the severity of the pulmonary system and averaged from 2 to 5 treatments.
In the complex of measures aimed at improving the drainage of the lung, were used methods of stimulation of natural sputum discharge: postural drainage, percussion and vibration massage of the chest.p> For edema toxic coagulation and stabilization of microcirculation in the lungs was used heparin in a dose of 5,000 IU to 10,000 IU per day.
Mild edema of the lungs was performed by injection of furosemide at a dose of 0.5 mg/kg of body weight of the patient.
Antibacterial therapy in patients with acute respiratory failure started in the first hours after admission, appointment of a combination of antibiotics, taking into account the composition of the microflora in the Department. After receiving data bacteriological examination was made a corresponding adjustment of the mode of antibacterial therapy. Used aminoglycoside antbiotic in combination with semi-synthetic penicillins, cephalosporins II, III and IV generation macrolides. In severe pneumonia antibiotic therapy combined with intravenous dioksidina and / or metronidazole.
Example 4. The study included 20 patients with acute poisoning by combustion products. The control group consisted of 10 patients who had only conventional therapy. The studied group consisted of 10 patients in whom conventional therapy combined with the introduction of alzola in a daily dose of 120-480 mg of receipt to the clinic prior to their release. The average age in the treatment group ranged from 43 to 50 years in the control group from 45,6 to 61 years.
The clinically is Skye characteristic of poisoning are shown in tabl
In the control group the disease was complicated by pneumonia in 30% of cases and in all cases ended in death on 14-17 day, and 20% of patients died from heart failure. In the study group of inflammatory processes in the lungs occurred in 40% of patients, the duration of treatment was 26-30 days, the outcome of the disease in all cases was favorable.
The data of table 10 and 11 show that the use of the drug arizol has a beneficial effect on the disease that is characterized by positive dynamics of indicators of blood: the content of diene conjugates, lymphocytes, urea and creatinine, transaminase activity, the level of medium molecular peptides, i.e. endotoxicosis in the background of daily use of the drug is less pronounced.
Thus, the use of alzola in exchange of his appointment, significantly improves survival and makes the disease in patients with acute poisoning by combustion products, including complicated by pneumonia.
Example 5. Based on high performance alzola shown in example 4, we have conducted research on its use in the treatment of pneumonia, complicating the course of acute poisoning psychopharmacological drugs (hypnotics, neuroleptics, and so on), as specified poisoned whom I have the highest percentage (70%) among all cases of poisoning neurotoxic substances.
The study included 72 patients with pneumonia, as a complication of acute poisoning psychopharmacological drugs. The control group consisted of 30 patients in the treatment which was applied to conventional treatment methods. In the groups studied in addition to the basic therapy were assigned Mexidol in a daily dose of 600 mg (28 patients) and Aziza in a daily dose of 120-480 mg (13 patients). By severity of pneumonia, age and sex of the patients in all groups were comparable.
The results of these studies showed that the use of alzola in treatment of pneumonia in acute poisoning vesselname neurotropic action leads to a significant reduction of deaths - 5.6 times compared to traditional treatment and 1.9 times in comparison with the use of Mexidol (table). This is achieved through its favorable effect on some indicators of homeostasis, which play an important role in the pathogenesis of inflammatory processes in the lungs of such patients.
From table 13 it follows that azizol at all stages of treatment supports the content of cells in patients ' blood at a normal level. Along with Mexidol contributes to a more rapid increase in blood lymphocytes. Oxybiotic metabolism of neutrophils source in all of the studied group the Ah of patients were above normal from 2 to 4 times. The smallest changes occurred with the introduction of arizola. This drug is maintained at a normal level blood concentration of immunoglobulin M and restrained growth in the blood of most pathogenic circulating immune complexes of small and medium size
The data presented in table 14 demonstrate positive impact of arizola on specific and relative blood viscosity, which at all stages of the study was lower than in the comparison groups. Azizol, as well as Mexidol, restrained the growth of the aggregation activity of erythrocytes and 3rd days contributed to the normalization aggregation activity of platelets.
From table shows that the use of alzola marked the highest values as indicators of lipid peroxidation, and indicators of the antioxidant system of blood, indicating the high activity of the whole system during all periods of the study conducted.
Thus, it is shown expressed the effectiveness of alzola as therapeutic agents in the treatment of pneumonia, complicating the course of acute poisoning neurotropic drugs.
Conclusions: studies have shown that Aziza is a highly effective prophylactic and therapeutic agent in acute poisoning and its complications.
1. The health status of the Tr is of working age. Izmerov, the front national, Uniform Russia - 2006.
2. Poisons and antidotes. Oksenhendler GI, L., 1989.
3. Acute poisoning: Guidance for doctors. Iagno, Lgucosamine. - 2nd ed., revised and enlarged extra - M.: Medicine, 2000. - 434 S.
4. The toxicity of combustion products of polymeric materials. Principles and methods of determination. Lickin B.C. SPb., Chemistry, 1993. - 136 C.
5. GOST 12.1.044-89 SSBT. Pozarovzryvobezopasnost substances and materials. The range of indicators and methods of their determination.
6. Patent No. 2038079. The antidote carbon monoxide, 1988.
7. Patent No. 2260427. The use of alzola as hepatoprotector.
8. Patent No. 2279877. Adaptogen, 2006.
9. The effectiveness of Roncoleukin in the prevention of pneumonia in acute poisonings. Maaloula, Vbeprobe, Avicennasis and other abstracts. Dokl. 2 Congress of toxicology Russia. - M., 2003. - S-313.
10. Toxic damage of the respiratory system in acute poisoning. Cle, Iagno. - M.: Malpractice - M, 2004., 176 C.
11. Application AUTOC in the rehabilitation of patients protracted pneumonia. Emelianov, Aaahaha, Opimanova, Avilova. Experimental and clinical use of optical radiation in medicine: Meiwes. sbornik nauch. Tr. - Saransk, 1991. - P.85 - 88.
12. Physiogeography acute poisoning. E.A. Luzhniki stadium, Ussoldiers. - M, Malpractice - M, 2002. - 200 S.
13. Experience and prospects endovenous laser about the doctrine of blood (ILIB) in patients with burns. Ligamasiva, WAV, Tashkalova and other proceedings of the ninth conference. Mosk. society of gemafereza. - M., 2001. p.17.
14. Use of the drug "Mexidol" in complex treatment of patients with acute exogenous intoxications. Iagno, Cle, Tuppeny, Tvermashina. Bulletin of the experiment. biology and medicine. Appendix 1. M., 2006. - S-198.
15. Sanogenetic mechanisms of hyperbaric oxygenation in acute exogenous intoxications. Yepifanov, N.M., Hyperbaric, Fiziol. and the honey. - 1999. No. 4. - P.31-32.
16. The state of emergency in acute poisoning. Iagno, Unescaping, Genshtab. M: Malpractice - M, 2001. 219 S.
17. Management of carbon monoxide poisoning. A.L. llano, T.A. Raffin Chest. - 1990. - Vol.97, No. 1. - P.165-169.
18. Oxygen affinity and acid. - base ststus of human blood during exposure to hypoxia and carbon monoxide R.O.Mulhausen, P.Astrup, K.Millemgaard Scand. J din. lab. Inverst. - 1968. - Vol.22, Suppl. 103. - p.9-15.
19. Coma reversal with cerebral dysfunction recovery after repetitive hyperbaric oxygen therapy for severe carbon monoxide poisoning (see comments). B.S.Dean, V.P.Verdile, E.P.Krenzelok. Am J Emerg Med. - 1993. - Vol.11, No. 6. P.616-61.
20. Nosocomial pneumonia is not prevented by protective contact isolation in the surgical intensive care units. W.G.Koss, T.M.Khalili, J.F.Lemus et al. Am. Surg. - 2001. - Vol.67. - P.1140-1144.
21. Acute poisoning in patients of a medical intensive care unit. S.Furst, W.Habscheid Dtsch. Med. Wochenschr. - 1993. - Jun 11; 118 (23). - P.849-853
22. Longing bronchopneumonia as complication of the sharp poisoning with psychotropic medicine. V.Todorovic, T.Dragovic, S.Randelovic et al. Vojnosanit Pregl. - 1995. - Jul. - Aug., 52 (4). - P.341-348.
The use of alzola as a preventive and therapeutic agent for poisoning neurotoxic substances and their complications.
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.
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
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.
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: veterinary science.
SUBSTANCE: in case of dioxine intoxication animals should be prescribed with dimephosphon at the dosage of about 50-150 mg/kg body weight daily for 10-30 d. The innovation provides decreased embryonic lethality in animals.
EFFECT: higher efficiency of therapy.
3 ex, 1 tbl
FIELD: medicine, toxicology.
SUBSTANCE: invention proposes applying 15% aqueous solution of 1-methyl-5-[2'-(benzyldimethylammonio)ethyl]carbamoyl pyridinium-2-aldoxime dichloride that exceeds the 15% solution of dipiroxime (TMB-4, trimedoxime bromide) used in native medicinal practice by the curative effectiveness. Invention can be used in urgent treatment of acute poisoning with organophosphorus poisonous substances eliciting neuroparalytic effect.
EFFECT: enhanced effectiveness, valuable medicinal properties of agent.
SUBSTANCE: invention relates to medicine, namely to surgical stomatology and can be used for treatment of chronic periodontitis. For this purpose operative access to teeth roots with root canals which are difficult or impossible to reach, complicated by radicular cyst, is performed. Prepared cavity is processed with constant current of 4-5 mA during 15 minutes through isotonic solution of sodium chloride with trypsinum in ratio 0.1:2 by apparatus "Potok-1". Retrograde filling of root canal is fulfilled with glassionomeric cement "ProRoot". Then it is processed with semi-conductive laser diode, generating pulse light with wave frequency from 0.85 to 0.98 mcm, pulse power 2-4 Watt, pulse duration 40-100 Ns, pulse frequency 1.5-2.0 kHz, magnetic field strength 35 mT during 5 minutes by apparatus "Optodan". After that, it is filled with osteoinducing bioresorbing material "Osteoplast-K" at 2/3 of bone wound, covered with bioresorbing membrane "Paradoncol" and film "Diplen-denta" with metronidasole from oral cavity. The method ensures effective tooth-preserving treatment and reduction of number of post-operative complications due to reliable sterilisation of micro-canals of tooth root and bone wound cavity, obturation, biointegration and angio-osteogenesis, stimulation of osteoreparative process in bone wound, as well as due to preservation of stability and occlusive integration of tooth in tooth arch.
EFFECT: increased effectiveness of tooth-preserving treatment in case of chronic periodontitis and reduction of number of post-operative complications.
4 ex, 1 dwg
FIELD: medicine; stomatology.
SUBSTANCE: local medicinal therapy is performed within three stages. Thus the first stage implies usage of medicinal mixture injected to parodontal recess and applied on gums, containing in mass %; perfloxacin - 0.5÷1.0, trichopol - 0.5÷1.0, chlorhexidine bigluconate - 0.001÷0.01, silicon glycerates - the rest up to 100. Procedures number thus is 5-6. The second stage implies usage of medicinal mixture injected to parodontal recess and applied on gums, containing in mass %: vitamin agent "Aecolum" - 50÷52, chlorhexidine bigluconate - 0.001÷0.01, silicon glycerates - the rest up to 100. Procedures number thus is 3-4 procedures. The third stage implies usage of of medicinal mixture injected to parodontal recess and applied on gums, containing in mass %: hydroxyapatite 7.0÷20.0, chlorhexidine bigluconate - 0.001÷0.01, silicon glycerates - the rest up to 100. Procedures number thus is 2-3 procedures.
EFFECT: method provides high efficiency of treatment at considerable reduction of therapy time.
SUBSTANCE: invention refers to medicine, gastroenterology and concerns methods of stomach ulcer treatment. For this purpose, patient with suffering from mediagastral localisation of ulcer defect which is not cicatrising within six weeks, or from piloroduodenal ulcers which are not cicatrising within four weeks, in addition to traditional pharmacotherapy is prescribed with fluconasol. Single dose of fluconasol is 150 mg. Preparation is introduced once a week, within three weeks. Method provides effective utilisation of antithymicotic agents within stomach ulcer therapy based on first formulated specific indications for introduction, without preliminary examination of stated categories of patients.
EFFECT: development of effective method of stomach ulcer treatment due to antithymicotic agents.
7 tbl, 3 ex
FIELD: chemistry; pharmaceutical compositions.
SUBSTANCE: imidazole derivatives have general formula (I) where each of R1 and R2 independently represents hydrogen, (C1-C6)alkyl or (C3-C8)cycloalkyl; n=0.1 or 2; each of R3, R4, R5 and R6 independently represents hydrogen or (C1-C6)alkyl, halogen, cyano, (C1-C6)alkoxy, trifluoromethyl, (C1-C6)alkylthio, (C1-C6)alkylsulphonyl or (C1-C6)alkoxycarbonyl; R3 and R6 together with their carrier phenyl ring can also form N-methylbenzotriazole and to its acidic-additive salts, solvates and stereoisomer forms. Also, the given invention relates to pharmaceutical compositions, inhibitory aromatiser and application of derived imidazole of formula (I) for producing of medication.
EFFECT: new compounds, with useful biological properties.
23 cl, 2 tbl, 33 ex
FIELD: medicine; pharmacology.
SUBSTANCE: medicinal agent for various suppulative-inflammatory skin and mucous process treatment is characterised by the fact that it has gel consistency and contains metronidazole or biocomplex of metronidazole and zinc, or biocomplex of metronidazole and cobalt, or biocomplex of metronidazole and copper, or biocomplex of metronidazole and manganese, trimecaine, ascorbic acid, spirulyna platensysm, clove essence, or peach essence, or rose essence, water, as well as hydrophilic base - water-soluble devivative of cellulose, or methylcellulose, or carboxymethyl cellulose, or carboxymethyl cellulose sodium salt, taken in specified ratio. Medicinal agent for various suppulative-inflammatory skin and mucous process treatment, is characterised by the fact that it has ointment consistency contains metronidazole or biocomplex of metronidazole and zinc, or biocomplex of metronidazole and cobalt, or biocomplex of metronidazole and copper, or biocomplex of metronidazole and manganese, trimecaine, ascorbic acid, spirulyna platensysm, clove essence, or peach essence, or rose essence, water, as well as hydrophilic base - fusion of polyethylene oxide-400 and polyethylene oxide-1500 taken in specified ratio.
EFFECT: agents described above are effective for various suppulative-inflammatory skin and mucous process treatment.
2 cl, 5 tbl
SUBSTANCE: invention relates to heterocyclic compounds with general formula (I) or its pharmaceutically acceptable salts; and including its any stereoisomer forms;X and Y are independently N or CR1; Z represents S, O, NR1 or CR1 2;every R1-R6 represent independently H or not influencing substitute, which is alkyl (C1-10), allkenyl (C2-10), alkynil (C2-10), aryl ("C'5-12), arylalkyl, arylalkenyl or arylalkynil, each of which can not obligatorily contain one or more heteroatoms selected from O, S and N and each of which can be substituted further one; or not obligatorily substituted forms of acyl, arylacyl, alkyl,alkenyl alkynyl or arylsulphonyl or their forms which contain heteroatoms in alkyl,alkynyl or aryl fragments or representing OR, SR, NR2, COOR, CONR2, where R is N or alkyl alkenyl, alkynyl, or aryl not obligatorily substituted, as defined above, when C is a substituted atom not influencing substitute can be a halohen, OOCR, NROCR, where R is H or its substitute shown above, or can equal 0; nl is equal to 0-4; n2 is equal to 0-1, where * means that CR5=CR5 can be substituted by C=C; n3 is equal to 0-4;where nl+n2+n3 exceeds or equals 2; b is equal to 0-2; where the following combinations of R-groups can be associated with cycle formation, which can saturated or unsaturated R2-R2, one R2+R3, R3+ one R4, R4+R4, one R5 + the other R5, one R5 + one R6 and R6+R6; where cycle can not be aromatic, when the cycle formation components are represented by two R5; and where, when n2 is unity 1, neither of n1 nor n3 can be equal to 0, the invention also relates to pharmaceutical composition, based on these compounds, possessing a modulating ability relative to CXCR4- and/or CCRS-receptor; to modulation method CXCR4- and/or CCRS-receptor; to method of treatment of a statec described by unusual activity CXCR4- and/or CCR5-receptor and application of the described compounds for production of pharmaceutical.
EFFECT: new compounds feature useful biological properties.
36 cl, 171 ex
SUBSTANCE: invention relates to new derivatives of benzimidazol of the general formula I R1 designates phenyl group which unessentially contains up to three substitutors independently chosen of the group including F, Cl, Br, J, R4; R2 designates monocyclic or bicyclic 5-10-terms heteroaryl group which contains 1-2 heteroatoms, chosen of N, S and O; R3 designates H; R4 designatesC1-6alkyl; A designates C2-6 alkylene group; B designates group COOH, CONH2, CONHR5 or CONR5R5, in each case attached to atom of carbon of group A; R5 and R5 ' independently designate the residue chosen from group includingC1-6 alkyl where one C-atom can be replaced by O, and(C0-3 alkandiil-C3-7 cycloalkyl); and to their pharmaceutically acceptable salts, except for following compounds: 6 [[1-phenyl-2 (pyridine-4-il)-1H-benzimidazol-6-il] oxi] hexanic acid and 6 [[1-phenyl-2 (benzothien-2-il)-1H-benzimidazol-6-il] oxi] hexanic acid. The invention relates also to pharmaceuticals and to application of compounds of general formula I.
EFFECT: new biologically active compounds possess inhibiting effect on activation of microglia.
10 cl, 34 ex
SUBSTANCE: invention relates to new displaced heterocyclic derivatives that can be used in treatment of diabetes and to reduce the content of cholesterol. In formula m is 1; n is 1; Q is C; A is -(CH2)x 2-0-(CH2)x 3-, where x2 varies from 1 to 3 and x3 is 0; B is a bond or it is (CH2)x 4, where x4 varies from 1 to 2; X represents CH or N; X2, X3, X4, X5, X6 represent C, N, O; provided that one from X2 X3 X4 X5 and X6 represents N; and at least one of X2, X3, X4, X5, and X6 represents C; R1 represents H or C1-C6alkyl; R2 is H; R2a, R2b and R2c can be equal or different and selected from H, C1-C6alkyl, C1-C6alkoxy, halogen or thyano; R3 is selected from phenyloxycarbonile, C1-C6alkyloxycarbonile, phenylcarbinol, phenyl, alkoxy; Y represents CO2R4 (where R4 represents H or C1-C6alkyl); (CH2)m can be not necessarily displaced by 1 substitute.
EFFECT: produced are pharmaceutical composition for treatment of diabetes and to reduce the content of cholesterol.
13 cl, 2 tbl, 22 dwg, 88 ex
FIELD: medicine; veterinary medicine.
SUBSTANCE: invention refers to heterocyclic compound specifically to application of 2-imidozolylpropan-2-sulphacid formula: as bacteristatic, immunostimulating, antiaggregatory, thrombocytes deaggregatingagent stimulating contractive activity of skeletal muscles.
EFFECT: more wide application of combination for medicine and veterinary medicine.
1 cl, 9 tbl, 6 ex
FIELD: medicine; gastroenterology.
SUBSTANCE: invention concerns selection of eradication therapy for ulcer patients associated with Helicobacter pylori. Invention implies that patients with exacerbation rates more than two times per year are initially prescribed four-component therapy, and patients with two and less exacerbation annually are initially prescribed with three-component therapy.
EFFECT: method provides registration of established dependence between therapeutic effect and annual exacerbation rate, simplification of eradication therapy regardless severity of clinical semiotics.
1 tbl, 4 ex
FIELD: medicine; pharmacology.
SUBSTANCE: composition for prevention and treatment of asthma and upper airways diseases is characterised by that it includes incense tree Boswellia serrata dry extract solution with Boswellia acids content in terms of β- Boswellia acid not less than 80%, in wheat germs oil mixed with pharmaceutically acceptable selenium source and encapsulated containing glycerine, gelatin, pharmaceutically acceptable zinc source and chicory dry extract. Composition production implies that pharmaceutically acceptable zinc source, chicory dry extract gelatin, glycerine are sequentially dissolved renovated water. Agitated mixture is used to make capsule thereafter filled with capsulation solution produced by stirring of wheat germs oil and pharmaceutically acceptable selenium source followed by gradual addition of incense tree Boswellia serrata dry extract, with Boswellia acids content in terms of β- Boswellia acid not less than 80% till it is completely dissolved. Produced capsules are kept at temperature 5-10°C and dried out.
EFFECT: produced composition has improved efficiency.
4 cl, 4 ex