Cerebral protective and stress-protective medicinal agent "nootril" as injection solution

FIELD: medicine, chemical-pharmaceutical industry, pharmacy.

SUBSTANCE: invention relates to a cerebral protective and stress-protective medicinal agent. Agent comprises an active base as a mixture thiotriazoline with piracetam and water for injection as a forming component. The proposed medicinal agent shows the enhanced bioavailability of active medicinal components, and it shows the cerebral protecting, stress-protective and anti-amnestic effect also.

EFFECT: valuable properties of agent.

12 tbl

 

The invention relates to medicine, in particular to pharmacotherapy, and can be used in solutions for injection combined with an active basis.

Known drug in the form of 1 and 2.5% solutions "Thiotriazoline" for injection (drugs of Ukraine. - Kharkov. - 1999. - Vol.2. - S). The solutions contain as the active ingredient thiotriazoline with antioxidant, hepatoprotective, cardiotonic, anabolic, anti-ischemic, membrane, immunomodulatory and other actions.

Known drug in the form of a 20% solution of piracetam (Mashkovsky PPM Medicines. - M.: 2002. 1. - S). Piracetam has cerebroprotective and stress-protective action, but does not have an antioxidant effect and can cause exacerbation of coronary insufficiency and the occurrence of dyspeptic symptoms.

Known cerebroprotective and nootropic drug "Neotel" tablets, coated (Declarative patent of Ukraine №A). Active ingredients tablets "Neotel" are a mixture of thiotriazoline and piracetam. This drug is taken as a prototype. Pharmacological benefits of this medicinal product is due to article concludes that the effect of the active substances. So, titres the Lin has antioxidant and anti-ischemic actions and also strengthens cerebroprotective action of piracetam, along with metabolic regulatory mechanism of blood circulation contributes to the normalization of the nervous mechanism of its regulation, increases the speed and force of impact of the drug on improving blood flow to the brain.

Drug "Neotel" not only preserves, but also expands the range of pharmacological effects, inherent thiotriazoline, and eliminates the side effects that are possible with the use of piracetam, and also increases the effectiveness of the treatment.

The disadvantages of the known means include delay of pharmacological action tablets for the period of their absorption, decomposition and incomplete bioavailability, because when using the pill is not 100% active ingredients into the blood stream.

Recently, the problem of regulation of cognitive brain functions (attention, memory, orienting-exploratory behavior, learning ability, decision making), violated in extreme conditions and in various diseases (craniocerebral trauma, stroke, chronic cerebrovascular insufficiency, post-hypoxic dementia, neuroinfections, mental retardation in children) has a significant social and medical importance in connection with a wide R is prostrannie these diseases.

It is known that stress is one of the main causes of sudden death. In stress conditions significantly increase energy consumption, catabolic processes, activated lipid peroxidation, increases the amount of modified proteins with antigenic properties, which leads to an immediate reaction from the immune system.

Accordingly, the purpose of the invention is the development of medicines, without delay entering crevoiserat patient and providing maximum bioavailability of its active ingredients.

The solution of this problem provides cerebroprotective and stress-protective drug "Neotel" in a solution for injection that contains the active basis in the form of a mixture of thiotriazoline with piracetam: thiotriazoline 25 g / kg 100 g of water for injection up to 1 litre.

Pharmacological benefits of a medicinal product according to the invention "Neotel" (solution for injection) at a dose of 250 mg/kg weight of the animal has a strong antiamnesic, anti-stress effect, increases the survival rate of premature offspring, providing a positive impact on their mental and physical development, has a more pronounced neuroprotective effect. Use injection solution "Neotel" in acute intracerebral Gravois the economic, as well as in acute ischemia reperfusion brain improves survival, reduces the degree of ischemic damage neurocytol by reducing the level of bioenergetic processes, the reactivation of the antioxidant system and the activation of its own radical scavenging mechanisms.

Solution "Neotel" for injection has a strong cerebroprotective action that ensures the normalization of carbohydrate and energy metabolism and antioxidant system in neurotitan.

The pretreatment solutions piracetam, thiotriazoline and nootie showed that stressprotektivnoe the effect is most pronounced in "Nootie".

Therapeutic anti-stress effect of drugs after short-term immobilization maximally expressed in "Nootie"as indicators of cellular composition of peripheral blood, bone marrow stabilize for 12 hours earlier than after use of piracetam and for 24 hours before using thiotriazoline.

The invention is illustrated below by the description and examples of study drug according to the invention.

Research cerebroprotective steps of injection solution "Neotel"

Nootropic activity of the solution according to the invention was studied in experiments on 114 white Wistar rats of either sex who, weighing 160-180 g, were obtained from the nursery of the Institute of pharmacology and toxicology, Academy of medical Sciences of Ukraine.

To assess antiamnesic activity used conditional response passive avoidance (passive avoidance reaction). The animal was placed in the bright compartment, double chamber installation and recorded the latency time of entry into the dark compartment of the chamber where the rat received a single shock through electrodes floor (training).

Directly after training, electrocution (110 V, 50 Hz, 500 MS). Play reflex was performed 24 hours after training.

In another series of experiment amnesia passive avoidance reaction was caused by abdominal injection of scopolamine dose of 2.5 mg/kg

Study of the effect of the solution according to the invention on the activity of the higher nervous system were also carried out on the model of a single learning passive avoidance reaction without the use of amazonvideo factor. The ability of the animal to memorize caused electrobalance irritation was calculated by the difference of latency time before and after the training within 24 hours.

At the end of the experiment in brain tissues was determined the basic parameters of carbohydrate and energy metabolism - the content of ATP, glycogen, malate and lactate.

The solution according to the invention and analogues was administered intraperitoneally: "Neotel" - 250 mg/kg piracetam 10% - 200 mg/kg, thiotriazoline 2,5% - 50 mg/kg, calculated on the dry matter active phrases is tov.

Also the study of the neuroprotective activity was investigated in the simulation of extreme conditions. The training was conducted using the technique of passive avoidance reaction described above, but when entering the dark compartment, the rat immediately got a shock, bypassing a single shot through the electrode floor, and ran out into the bright compartment.

Play passive avoidance reaction was checked after 24 hours. About the safety of skill to be judged by the change in the latent time in the dark compartment. The drugs were injected in doses: "Neotel", as in the first experiment, 250 mg/kg piracetam - 10 % - 400 mg/kg, phenazepam - 1.0 mg/kg

In the first series of experiments the extreme conditions created by the method of Juve restriction of motor activity and sleep. For this purpose, rats were placed on a platform with a diameter of 6.0 cm (1 rat on the platform) in the Plexiglas pool filled with water (t≈5°C). The platform rises above the pool 1.5-2 cm In the pool was 5 sites. In this case occurred selective deprivation of paradoxical sleep phase (SFC), because during the SFC muscles of animals were relaxed and they fell into the water. Deprivation SFC was carried out directly after training. The drugs were injected 30 minutes prior to training.

In the second series of experiments extreme situation created in terms of collision drinking and defensive reflexes according to the standard technique of "Conflict situation".

The experiment starts and after training rats to develop their skill of taking water from the trough. To improve drinking motivation and feelings of thirst within 2 days the animals were kept on a dry diet. Then at the same time, within 3 days, animals were placed for 10 minutes in a cage for receiving the water, on the 4th day of the training the rat after 5 sec after the onset of drinking was hit by the current through the electrode near the nose of the drinker. Thus, the collision of two reflexes (drinking and defensive) has led to the creation of an extreme situation in which the fear of getting painful irritation kept the animal from thirst.

In the future (after 30 min) for 20 min was recorded the number of takes of water, a number of approaches to the drinker and the cumulative amount of motor activity by the number of crossed squares. The drugs were injected during the entire period of training once a day.

Influence of solution "Neotel" according to the invention in premature rats was studied using the definition in the dynamics of the main indicators of their functional development and growth: the floor by the hair, cutting teeth, opening his eyes, the number of horizontal displacements, ustavni on his hind legs, looking at the hole in the floor, survival.

For selected rats female rats male placed in cells at a ratio of 1 male to 5 females. Just was simulated 5 families, which contained the standard race is not vivarium.

First signs of pregnancy was carried out to check the time. On 19-20 day pregnant rats caused a premature birth. Control rats were given birth in the period. Women with offspring odarivali in separate cells and perform the observation.

Solution "Neotel" and the Comparators was administered to newborns from the first day of life in doses: Neotel - 62.5 mg/kg piracetam - 50.0 mg/kg, thiotriazoline - 12.5 mg/kg, calculated on the dry matter. Each group was under the supervision of 12 newborn rats.

The study cerebroprotective activity of the solution according to the invention is performed on 245 white Wistar rats, weighing 180-200 g in terms of the modeling of acute ischemic and hemorrhage in the internal capsule of the brain. Cerebral blood flow was modeled with surgery: 1) bilateral ligation of the internal carotid arteries under debutalbum anesthesia; 2) the introduction of autologous blood into the region of the internal capsule brain by drilling holes in the skull of the rat, which in the region of the internal capsule was administered 0.2 ml of blood obtained from the tail vein of the animal.

The drugs were injected intraperitoneally daily for 4 days after modeling in doses: thiotriazoline 2,5% - 50 mg/kg piracetam 10 % - 200 mg/kg, the solution "Neotel" 12.5% in the 250 mg/kg

The slaughter of animals produced put the feet of decapitate under Nembutal anesthesia (40 mg/kg) on the 4th day of observation. Blood and brain after homogenization investigated biochemically according to the usual method.

Acute ischemia and reperfusion brain was modeled temporary shutdown of blood flow through the carotid arteries.

Operations were performed under Nembutal anesthesia. Made a longitudinal incision in the neck, was isolated carotid artery, which imposed a ligature for 30 minutes. Then the ligature was removed and sutured to the skin. After recovery from anesthesia, rats were placed in a cell for 6 animals. On the 3rd day after surgery, animals were deceptional under Nembutal anesthesia and removed ishemizirovanne hemisphere. Animals were collected blood from the carotid artery 0.2-0.3 ml during surgery, after 30 min after the application of ligatures and 30 min after removal of the ligatures.

In addition, were drawing blood from the abdominal artery on the 3rd day after the operation at the time of slaughter. Blood and brain after homogenization investigated biochemically by standard methods.

The drugs were injected intravenously, twice for 30 minutes before applying ligatures and before reperfusion: thiotriazoline 2,5% - 50 mg/kg piracetam 10% - 200 mg/kg, Neotel 250 mg/kg

To assess cerebroprotective action of the drugs was determined by the status of bioenergy in content Danilovich nucleotides, activity of glycolysis (lactate piruw is that), oxidation in the Krebs cycle (the content of malate), and the intensity of free radical oxidation (CPO) on the content of malondialdehyde (MDA), diene conjugates (DC) and transitonal (TC) and the antioxidant system in the activities of superoxide dismutase (SOD), catalase, glutathione peroxidase (SNR) and content α-tocopherol. About ischemic brain damage was assessed by indicators giperfermentemii (activity of the brain isoform of creatine phosphokinase - ck).

The study of the anticonvulsant activity was carried out on white rats male Wistar rats weighing 180-220 g Model GABA-deficient cramps reproduced by injecting animals with thiosemicarbazide subcutaneously at a dose of 30 mg/kg

Solution "Nootie" according to the invention was administered intraperitoneally at a dose of 250 mg/kg 30 minutes prior to the introduction of thiosemicarbazide. Comparators - piracetam 200 mg/kg and phenobarbital 20 mg/kg intraperitoneally and medical 25 mg/kg) was subcutaneously injected as "Neotel", 30 minutes prior to the introduction of thiosemicarbazide.

Picture of seizures was assessed by time of occurrence and duration of the individual components of convulsive seizure - clinical and tonic phases.

At the peak of convulsive seizure animals taken out of the experiment. They removed the cortex of the brain and put it in liquid nitrogen. The cortex of the brain is homogenized in idcom nitrogen and processed by conventional biochemical methods.

The intensity processes of the SRO in the cerebral cortex of rats at the peak of convulsive seizure to be judged by the accumulation of products of this process - DK, TC, MDK, about the intensity of formation of nitric oxide (NO) in the tissue of the cerebral cortex of rats on the accumulation of its stable metabolite of nitration-NO3-.

The results are shown examples of research solution Neotel according to the invention and comparative drugs are shown in tables.

The study of the neuroprotective properties of the drug "Neotel"

The study antiamnesic properties of the drug "Neotel conducted on the model of stun and tropenbos amnesia.

Studied the effect of injection solutions thiotriazoline, pyracetam and Nootie" to eliminate the CPAR amnesia, caused by atropine and shock.

Studies have shown that shock immediately after learning of passive avoidance reaction, as well as the introduction of atropine causes forgetting of skill in control animals when playing 24 hours after training (table 1, 2).

Introduction thiotriazoline, pyracetam and nootie experimental animals to study and subsequent conduct of the shock (or the introduction of atropine) caused a significant increase in latency time response compared to control animals (table 1, 2). The most effective was the introduction of the drug "But is home to the thrill" as when conducting the electric shock, and with the introduction of atropine.

Table 1.

The effect of study drug on amnesia passive avoidance reaction caused by atropine
The injectable preparationDose, mg/kgThe latent time of reflex when playing passive avoidance reaction, s
Control without amnesia (n=6)-136,5±21,6
Control with amnesia (n=6)-22,5±2,4
Piracetam (n=6)200,037,0±6,2*
Thiotriazoline (n=6)50,057,8±7,6*
Neotel (n=6)250,074,8±6,2*
Note: * - p<0.05 with respect to control with amnesia.
Table 2.

The effect of study drug on amnesia passive avoidance reaction caused by electroshock
The injectable preparationDose, mg/kgThe latent time of reflex when playing passive avoidance reaction, s
Control without amnesia (n=6)-120,6±14,5
Control with amnesia (n=6)-20,7±2,6
Piracetam (n=6)200,028,6±3,7*
Thiotriazoline (n=6) 50,042,6±4,8*
Neotel (n=6)250,061,6±5,2*
Note: * - p<0.05 with respect to control with amnesia.

The influence of the drug "Neotel on learning and memory, impaired deprivation of paradoxical sleep phase and in the "conflicts"

Analysis of the results in groups of control animals (with deprivation and without) showed that deprivation SFC conducted immediately after the training session, leads to disruption of skill passive avoidance reaction. When comparing the performance of two control groups can be noted that in animals not exposed to deprivation SFC, latency time of entry into the dark compartment when playing passive avoidance reaction increases significantly compared with the same indicators in the study (table 3). This indicates intact rats skill passive avoidance.

Table 3.

The influence of the drug "Neotel" latent times of rats in the dark compartment when producing passive avoidance reaction
The group of animalsLutetiae time, sec
TrainingPlayback
Control without deprivation SFC (n=6)1,52±0,4258,3±4,35*
Control with deprivation SFC (n=6)1,73±0,343,50±0,54*
With deprivation SFC receiving Neotel (n=6)3,53±0,7972,2±of 5.84*
With deprivation SFC treated with piracetam (n=6)of 4.44±0,8314,5±1,17*
With deprivation SFC receiving phenazepam (n=6)2,05±0,682,20±1,01
Note: * - p<0.05 with respect to the value of the latency time in the period of study.

In animals subjected to deprivation SFC, latency time of entry into the dark compartment when playing passive avoidance reaction was slightly different from the values obtained when training, indicating a distinct shortage of playing passive avoidance reaction.

Introduction nootie 30 minutes before training, would eliminate the deficit playback passive avoidance reaction caused by deprivation SFC. Deprivileging animals treated Neotel when playing skill latent period of time in the dark compartment of the camera significantly increases compared with the same parameters of the control deprivileging animals and approaches to data of the control groups (animals without deprivation SFC) (see table 3).

Piracetam has a less noticeable antiamnesic activity in rats subjected to deprivation SFC.

Phenazepam, n is against, does not affect violated skill passive avoidance reaction in rats subjected to deprivation SFC. The latent period of time in the dark compartment when playing skill passive avoidance reaction in rats does not differ from the parameters of the control deprivileging animals.

Thus, studies have shown that under extreme impacts caused by the deprivation SFC, along with sleep disorders there is a shortage of playing passive avoidance reaction. Neotel and piracetam eliminate the deficit playback passive avoidance reaction. This Neotel exceeds piracetam power antiamnesic activity, and tranquilizer phenazepam generally does not have one.

The obtained results in terms of "conflict situation"created by the collision of drinking and defensive reflexes showed that getting painful shock when drinking water is in animals, the sense of fear accompanied by a distinct tachycardia, changes in breathing, inadequate response. Control animals in this situation do another 1-2 attempts to get water and then abandon them.

Phenazepam, with a distinct anti-stress effect, in this situation reduces the feeling of fear in animals, resulting in a significant increase in attempts to take on water. General locomotor activity are lower than in the control belly is s.

Neotel also has anti-stress effect, several yielding phenazepam. This significantly increased the number of approaches to drinking and General locomotor activity of the animals (table. 4).

Table 4.

Anti-stress effect of the drug "Neotel" on the behavior of rats in a collision drinking and defensive reflexes in the "conflicts"
The injectable preparationThe number takes the waterA number of approaches to the drinkerMotor activity
Control1,7±0,865,7±0,8613,0±2,97
Neotel9,7±3,09*24,8±4,17*56,2±5,49*
Piracetam8,5±1,96*15,0±2,2038,8±2,77*
Phenazepam13,8±11,68*5,7±1,275,5±1,72
Note: * - p<0.05 with respect to control.

Piracetam had a similar focus, but a less pronounced anti-stress effect (see table 4).

Thus, Neotel has expressed antiamnesic action in conditions of deprivation SFC, excelling in efficiency is piracetam and phenazepam. Besides, having a stress-protective effect in terms of "conflict situation", surpassing in some indicators piracetam (the amount of water taken and phenazepam (General motor activity).

The study of the neuroprotective activity of the drug "Neotel" influence on mental and physical development in premature rats

Exchange application (30 days) injection solution "Neotel" had a beneficial effect on physical and mental development in premature rats. On the main indicators of physical development of animals treated Neotel, did not lag behind of pups born at full term, and was significantly ahead of the coating coat, teething and opening the eyes of premature rats not treated with the drug, and treated with piracetam and thiotriazoline (table 5).

Table 5.

Dynamics of physical development in premature rats
The injectable preparationFloor coat (d)Teething (d)The opening of the eyes (d)
Control (full-term)11,0±0,311,0±0,213,6±0,2
Control (premature)12,1±0,112,4±0,115,6±0,1
Piraceta the 12,0±0,212,0±0,115,6±0,1
Thiotriazoline12,0±0,111,7±0,114,7±0,2
Neotel11,7±0,111,2±0,113,6±0,2

A very important action nootie was that he increased the survival rate of premature rats in the first 7 days after birth (table 6). Effectiveness Neotel excelled as piracetam and thiotriazoline.

Table 6.

The survival rate of premature rats early after birth
The injectable preparationOnlyThe number of surviving rats in the different periods of life (day)
1234567
Control (full-term)1212121010101010
Control (premature)12121088764
Piracetam121212 111111109
Thiotriazoline1212121212111111*
Neotel1212121111111111*
Note: * - p<0.05 with respect to preterm animals.

Exchange application nootie also had a positive impact on the processes of GNI in preterm animals. Application nootie had a positive effect on the orienting-exploratory behavior in premature rats. While this is most clearly manifested on the 30th day after the injection. In the group of rats not receiving treatment, dynamics of development was the lowest (table 7).

td align="left" morerows="1"> Control (full-term)
Table 7.

Orienting-exploratory behavior in premature rats at different periods of observation
MedicationNight observationThe number in 15 minutes
Horizontal movementsStevani on his hind legsZaglyadyvanie into the hole in the floor
21st36,6±2,9310,3±1,0929,4±2,33
30th42,5±3,0616,1±1,0136,7±2,58
Control (premature)21st23,6±2,319,0±1,7623,4±3,38
30th28,8±2,9714,0±1,4726,1±3,40
Piracetam21st26,4±2,5811,8±1,7128,8±2,13
30th29,8±2,1814,3±1,6331,7±3,15
Thiotriazoline21st29,8±2,6111,5±1,0530,1±3,30
30th36,0±2,34*16,0±1,3336,3±3,23*
Neotel21st36,6±2,4313,9±1,6333,5±and 2.26*
30th40,0±2,27*16,3±1,22*41,5±3,11*
Note: * - p<0.05 with respect to preterm animals.

The test passive avoidance reaction, the increase in latency time after training was observed in all groups of animals. P and as at the 21st day of life, and on the 30th the maximum growth rate was observed in the group with the introduction of nootie (table 8).

At the end of the experiment was a study of basic biochemical indicators of the level of carbohydrate and energy metabolism in the brain tissue of animals (table).

Table 8.

Latency time passive avoidance reaction in premature rats at different periods of observation
MedicationNight observationThe latent time
before trainingafter training
Control (full-term)21st20,4±4,0325,3±3,62
30th12,4±3,02115, 8mm±17,6*
Control (premature)21st13,6±3,1615,7±2,63
30th11,0±1,9072,0±11,20*
Piracetam21st14,2±2,7318,0±2,30
30th8,6±1,5487,5±9,73*
Thiotriazoline21st16,2±2,8126,3±3,22
30th11,4±,17 104,7±10,2*
Neotel21st17,0±3,0334,5±6,0
30th7,6±1,41132,4±14,0*
Note: * - p<0.05 with respect to the results to training.

However, premature animals revealed a decrease in the content of ATP, glycogen, pyruvate, malate and increased lactate, indicating that metabolic changes in the brain. Such shifts are characterized by moderate hypoxia nervous tissue preterm animals.

Course 30-day introduction Nootie" fully normalized content in the brain of the main indicators of carbohydrate and energy metabolism.

The results of the study indicate a positive impact of "Nootie" on a variety of hand mental and physical development in preterm animals. The drug in exchange contributes to accelerated development in premature rats and eliminates the lag from animals born in the period, on indicators such as coverage wool, teething, opening his eyes. "Neotel increases survival of animals in the first days of life.

Table 9.

The carbohydrate-energy is static metabolism in the brain tissues of rats at 30 days of observation
The injectable preparationATP, µmol/g tissueGlycogen (mg/g tissueLactate, mmol/g tissueMalate, µmol/g tissuePyruvate, µmol/g tissue
Control (full-term)2,84±0,093,61±0,172,77±0,210,42±0,030,28±0,02
Control (premature)2,22±0,073,07±0,113,00±0,110,37±0,020,22±0,01
Piracetam2,70±0,033,26±0,103,14±0,130,36±0,020,29±0,02
Thiotriazoline2,30±0,073,10±0,072,78±0,220,39±0,010,27±0,01
Neotel2,90±10,04*3,70±0,15*2,80±0,140,44±0,010,30±0,02*
Note: * - p<0.05 with respect to preterm animals.

On the background of the injection solution nootie animals faster than normal orienting-exploratory behavior, quickly develops the ability to memorize and training, produced a more stable passive avoidance reaction than even the full-term newborn rats.

Study of the effectiveness of the drug "Neotel" on the model of acute disorders of cerebral circulation

According to modern concepts on the 4th day after bilateral ligation completed the acute phase of development of ischemic brain lesions.

To this period in the control group were lost 70% of the rats in the groups of animals that received piracetam - 50%, thiotriazoline - 43% and Neotel" - 10% (table 10). On the 4th day after surgery behavioral responses of experimental and control rats did not differ from intact animals except for the consumption of a smaller amount of feed control rats.

Table 10.

The dynamics of survival of animals on the 4th day after bilateral ligation of the common carotid arteries and the introduction of the studied drugs
The group of animalsBilateral ligation of the common carotid arteryIntroduction autologous blood into the internal capsule brain
Before surgeryAfter surgeryBefore surgeryAfter surgery
Control103104
Piracetam105 105
Thiotriazoline106*107*
"Neotel"109*109*
Note: * - p<0.05 with respect to control.

Course introduction pyracetam, thiotriazoline and nootie animals in acute animal experimental cerebral circulation led to the normalization of many carbohydrate and energy metabolism, inhibition of SRO and reactivation of the antioxidant system, as well as lower giperfermentemii (table, 12).

In General the positive direction in the action of drugs on bioenergetic processes are identified and quantified differences in their effect on the studied parameters.

Thus, it is extremely important moment in the action of piracetam, thiotriazoline and nootie was increased in treated animals the level of ATP in the background of the increase in the content of its predecessor - ADP and reduce the number of AMF compared with untreated animals. These changes were most pronounced when the drug "Neotel". The lowest level of lactic acid and the highest level of pyruvic and malic acids in animals with the introduction of drugs have been reported with use is the so called "Nootie" (table).

Table 11.

The influence of the drug "Neotel" on carbohydrate and energy metabolism in ischemic brain tissue of animals on the 4th day of the experiment (µmol/g tissue)
The group of animalsLactatePyruvateMalateATPADPAMP
Control7,11±0,320,11±0,010,16±0,031,05±0,060,31±0,030,24±0,01
Piracetam6,57±0,190,15±0,03*0,18±0,02*1,50±0,06*0,40±0,020,21±0,04
Thiotriazoline5,17+0,12*0,17±0,04*0,28±0,05*1,82±0,07*0,42+0,04*0,20±0,02*
Neotel4,78±0,24**0,26±0,03**0,37±0,02**2,00±0,08* 0,47±0,02*0,14±0,01**
Intact animals2,60±0,180,27±0,020,33±0,012,88±0,070,43±0,040,14±0,02
Note: * - p<0,05; ** - p<0,001 compared to control.
Table 12.

The influence of the drug "Neotel" on the performance of the antioxidant system and the activity of SRO in ischemic brain tissue of animals on the 4th day of the experiment
The group of animalsSOD, cu/mg protein minCatalase, mkat/mg protein minHLOOKUP, umol/mg protein minα-tocopherol, µmol/g tissueDK, µmol/g tissueTC, µmol/g tissuehmm,

µmol/g tissue
Control56,2±3,81,77±0,4236,2+8,43,00±0,332,56±0,101,24±0,031,23±0,07
Piracetam102,6±11,8*5,0±0,33*42,2±2,7 3,64±0,312,0±0,080,89±0,04*0,78±0,02*
Thiotriazolineof 148.6±13,0*6,0±0,42*58,6±4,3*4,00±0,22*1,81±0,07*0,70±0,02*0,70±0,03*
Neotel311,6+21,6*of 7.64±0,21*70,8±6,8*4,77±0,15*1,58±0,03*0,62±0,03*0,53±0,04*
Intact animalsbr220.6±18,36,82±0,2277,5±5,64,92±0,111,28±0,040,48±0,010,54±0,05
Note: * - p<0.05 with respect to control.

With the drug "Neotel" there is a stronger positive influence on the processes of aerobic and anaerobic oxidation of carbohydrates and, consequently, significantly increases the energy Fund of cells.

The result of improving the energy status of brain cells and reduce the severity of their ischemic damage is the reduction in the possession of products SRO and reactivation of the antioxidant system.

All prescribed drugs increased the activity of SOD, catalase, SNR, reduced the expenditure of a-tocopherol and accumulation DK, TC and MDA in brain tissue, and the greatest effect was observed after the introduction of nootie. Simultaneously with the decrease in the degree of damage of the cytoplasmic membrane in reactions SRO occurred a significant decline giperfermentemii, which was more pronounced under the influence of the drug "Neotel".

As you can see from the results of the research are shown in the tables, the solution nootie on pharmacological effectiveness exceeds all contained in the description drugs-analogues, significantly expands the range of pharmacological actions, and therefore, its application, eliminating the disadvantages inherent in the Comparators, and can be widely used in medical practice.

Cerebroprotective and stress-protective drug containing the active basis in the form of a mixture of thiotriazoline with piracetam and formative component, characterized in that the active base and forming the basis of water for injection, amount, g/l solution ±10%:

Thiotriazoline25,0
Piracetam100,0
WaterThe rest is up to 1 l


 

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3 cl, 9 tbl

FIELD: medicinal industry.

SUBSTANCE: the present innovation deals with manufacturing medicinal preparation containing drotaverin hydrochloride to be applied for interrupting spasms of smooth musculature. Mass for tableting should be prepared due to mixing the powder of drotaverin hydrochloride with that of dyed granulate at the ratio of 1:3 to 2:1. One should obtain the dyed granulate by moisturizing inert pharmaceutical filler with binder's solution dyed with quinoline yellow dyestuff. Then comes drying up to 0.1-2.5% followed by granulation and tableting. The innovation enables to obtain tablets of drotaverin hydrochloride upon industrial equipment at its degradability being below 15 min, being stable during manufacturing and at storage. Quality of tablets meets all the requirements of pharmacopoeic article.

EFFECT: higher efficiency of manufacturing.

2 cl, 4 ex, 3 tbl

Antispasmodic drug // 2232018
The invention relates to the medical industry, namely antispasmodic drug, containing drotaverine hydrochloride used for relief of muscle spasm

The invention relates to medicine, specifically to vascular surgery, and relates to methods of conservative treatment of occlusive arterial disease of the limbs

The invention relates to the field of organic chemistry and medicine and relates to new mono - and disulfonated of anthraquinones, are useful for the treatment of pathologies associated with erosion of cartilage and bone matrix, the method of their derivation and farbkomposition containing these compounds

The invention relates to medicine and can be used in preparation for surgery and during surgery, revascularization on the beating heart using a system of mechanical stabilization of the myocardium "Осtopus-2"

The invention relates to an improved process for the preparation of collagen from solubilizing and purified, may pasensyahan extract non-sterile native or telopeptide collagen, including: i) the stage of mixing and shearing of the extract in mixer with dual lateral incisors with the gradual increase of the initial rate of mixing at 500-1000 rpm without exceeding the speed of 10000 rpm and the gradual increase of temperature for 2-10oWith, preferably 3-5oWith, thus, to increase the initial ambient temperature of the extract to the maximum controlled temperature, component not exceeding 50oWith, and then (ii) the stage of sterilization in the liquid environment of the extract with obtaining sterile collagen in native or telopeptides, native or telopeptide collagen type I, obtained with the above method, with the following characteristics or properties: ratio2(I)1/1(I)2from 0.48 to 0.52; sterility in accordance with the standard of the European Pharmacopoeia; total nitrogen from 17,0 to 18.7%; hydrox

The invention relates to medicine, in particular it is proposed to use derivatives of the formula I, where R = CH3or6H5and n = 0 or 1, as vasodilator, hypotensive, antispasmodic, anti-means and platelet aggregation inhibitors and pharmaceutical compositions on their basis

FIELD: medicine.

SUBSTANCE: method involves administering preparation like 1% histochrome solution in the amount of 5 ml daily during five days. The first intravenous histochrome injection is carried out slowly. The following ones are intravenously introduced drop-by-drop.

EFFECT: enhanced effectiveness of treatment; no adverse side effects.

2 cl, 4 dwg, 5 tbl

FIELD: pharmaceutics.

SUBSTANCE: the suggested powder consists of crystals of one component amiphostin, the length of crystalline granule corresponds to 300-700 mcm at the content of 1-3 molecule of crystalline water. In method for obtaining amiphostin powder for injections one should apply the process of vacuum drying. The innovation provides resistance of the product obtained, the crystals obtained have got moderate length and acceptable mobility without any reduction.

EFFECT: higher efficiency of application.

6 cl, 5 dwg, 13 ex, 3 tbl

FIELD: neurological diseases.

SUBSTANCE: composition contains therapeutically effective amount of anticonvulsant agent dissolved or dispersed in aqueous carrier containing 10-80 vol % aliphatic alcohol, 10-80 vol % ethylene glycol, and 0.1-5 vol % bile acid salt or lecithin. Indicated carrier ensures increased access of anticonvulsant agent (such as benzodiazepin, in particular diazepam, clonazepam, phoenitoin, mephoenitoin, ethotoin, phenobarbital, carbamazepin, ethosuccinamide, valproic acid, gabapentine, trimethadion, lamotrigin) into blood and rapid pharmacological response when using nasal administration.

EFFECT: accelerated anticonvulsant effect.

11 cl, 9 dwg, 10 tbl, 13 ex

FIELD: medicine, pharmacy.

SUBSTANCE: pharmaceutical composition possesses an anti-estrogenic effect. The composition comprises fulvestrant in ricinoleate vehicle, a pharmaceutically acceptable anhydrous ester solvent and pharmaceutically acceptable alcohol. The composition is adopted for intramuscular administration and maintains the therapeutically significant blood plasma fulvestrant concentration for at least 2 weeks. The composition for intramuscular injection provides satisfied releasing fulvestrant for prolonged time.

EFFECT: valuable medicinal and pharmaceutical properties of composition.

32 cl, 4 tbl, 1 ex

FIELD: medicine, pharmacy.

SUBSTANCE: invention relates to a medicinal preparation comprising propolis, dimethylsulfoxide and accessory substances as active substance and it comprises novocaine, anaesthesin as additional active components, and glycerol and 70% ethyl alcohol as accessory substances. The preparation can comprise 1% aqueous solution of ionized silver. The proposed treatment method is realized by applying the indicated preparation, once per 24 h, for 30 min, treatment course involves 7-10 procedures. Invention provides reducing treatment period of patients with diseases of locomotor system, peripheral nervous system and skin integuments and enhancing effectiveness of the preparation also.

EFFECT: improved treatment method, enhanced and valuable properties of preparation.

5 cl, 7 ex

FIELD: medicine, dermatology.

SUBSTANCE: invention proposes an anti-infectious preparation comprising the combination of active substances with topical and systemic antifungal agents and a water-insoluble film-forming agent. The systemic antifungal agent is taken among the group including intraconazole, terbinafine and fluconazole or their salts. The topical antifungal agent is taken among the group including ciclopirox, 6-(2,4,4-trimethylpentyl)-1-hydroxy-4-methyl-2(1H)-pyridone, amorolfine and butenafine or their salts. The preparation is used as lacquer for nails in therapy of onychomycosis. The lacquer preparation provides high concentration of systemic antifungal agents in nails after its topical applying. The significant advantage of the preparation involves short time in treatment of anychomycosis.

EFFECT: enhanced effectiveness and valuable medicinal properties of preparation.

6 cl, 6 ex

FIELD: medicine; medical engineering.

SUBSTANCE: method involves locally administering 30-50% hypertonic solution of xymedon hydrochloride, combined smoothly corrugated draining device, introducing gauze drain into upper part of wound cavity and intra-drain ultrasonic cavitation.

EFFECT: enhanced effectiveness of treatment; reduced risk of complications.

5 cl, 4 dwg

FIELD: medicine, pharmaceutical industry, pharmacy.

SUBSTANCE: invention relates to a pharmaceutical composition used in stomatology in the topical anesthesia. The pharmaceutical composition comprising articaine hydrochloride and epinephrine hydrochloride and accessory substances, such as sodium metabisulfite, sodium chloride and water for injection involves additionally glycine and pH-regulating substance taken in the definite ratio of components. Invention provides preparing the preparation that is stable, non-toxic and doesn't cause allergic response reactions and elicits highly expressed infiltration and conducting anesthetic activity, good tissue tolerance and activity promoting to accelerated wound-healing in the post-operative period.

EFFECT: improved and valuable medicinal properties of composition.

3 cl, 3 ex

FIELD: medicine, pharmacy.

SUBSTANCE: invention relates to an aqueous composition consisting of moxifloxacin hydrochloride and sodium chloride and comprising from 0.04% to 0.4% (mas/vol) (as measured for the amount of moxifloxacin) of moxifloxacin hydrochloride and from 0.4% to 0.9% (mas/vol) of sodium chloride. Also, invention relates to applying this composition with the aim for preparing a medicinal agent used for prophylaxis or treatment of bacterial infections in humans or animals. Invention provides stability of the prepared moxifloxacin solution as moxifloxacin hydrochloride in the presence of iron ions.

EFFECT: improved properties of compositions.

6 cl.

FIELD: chemical-pharmaceutical industry, pharmacy.

SUBSTANCE: invention relates to a new pharmaceutical composition comprising benzamide derivative and one or some additives taken among the following substances: 1) mixture of polyethylene glycol and surface-active substance; 2) amino acid or inorganic acid salt, and 3) propylene carbonate. The composition comprises benzamide derivative taken in the amount from 0.001 to 1000 mg per a single dosing formulation. The composition shows the enhanced solubility and absorption capacity in oral route of administration.

EFFECT: improved medicinal and pharmaceutical properties of composition.

9 cl, 4 tbl, 1 dwg, 5 ex

FIELD: medicine, gynecology, surgery.

SUBSTANCE: one should introduce 3.5%-chitosan ascorbate gel into fistulous channel that contains metronidasol at the dosage of 2 mg/ml, at the volume up to 20 ml once/2 d till complete fistula's closing. The present innovation enables to activate reparative processes and fistulous epithelization that favors for closing fistulous channel in earlier terms.

EFFECT: higher efficiency of therapy conducted.

2 ex

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