Cerebroprotective and nootropic medicinal agent "nootril" in envelope-covered tablet

FIELD: medicine, pharmacy.

SUBSTANCE: invention relates to nootropic, cerebroprotective medicinal agents as tablets. Tablet of a medicinal agent comprises thiotriazoline and piracetam as active components and accessory components used for formation of core and applying an envelope on it. Invention provides elevating rate and power of a medicinal agent effect on the brain blood supply, expanding spectrum of its pharmacological effect and excludes negative adverse effects.

EFFECT: improved and valuable medicinal properties of agent.

6 tbl

 

The invention relates to medicine, in particular to pharmacotherapy, namely, nootropic, cerebroprotective medicines.

Known nootropic drug tablets “Piracetam”, registration No. 95/174/6/82/624/24 from 29.09.95, (drugs of Ukraine 1999-2000, 2, str-306). Piracetam has a positive effect on metabolism, blood flow and bioenergetic processes of the brain.

The disadvantages of this drug are: he has an antioxidant effect, pharmacological effect is manifested only in an hour, and adverse effects of severe coronary insufficiency and the occurrence of dyspepsia.

Known drug “Thiotriazoline” tablets, registration No. 94/85/4 (drugs of Ukraine - Kiev, 1995.. Pharmaceutical journal No. 4 - p.43). Tablets Thiotriazoline contain as the active ingredient thiotriazoline.

Thiotriazoline has antioxidant, hepatoprotective, cardiotonic, anabolic, anti-ischemic, membrane, immunomodulatory, galatasarays, wound healing, antiviral and other actions.

Lack of thiotriazoline as piracetam is slow pharmacological action.

Tablets titre the Zolina adopted for the prototype.

The basis of the invention is the task of the drug development with cerebroprotective, neuroprotective and antioxidant effects.

The solution of this problem provides the creation of the combined drugs “Neotel” in the form of tablets containing triazoline with piracetam.

The composition of the tablets Neotel”coated wt. g ±5%:

Thiotriazoline 0,05 (~14% mass)

Pyracetam 0,2 (~56% mass)

Additional ingredients:

(microcrystalline cellulose,

the low molecular weight polyvinylpyrrolidone,

the methylcellulose or Oxymetazoline,

stearic acid or magnesium stearate,

the polyethylene oxide 400) 0,106 (~30% mass)

Pharmacological benefits of a medicinal product according to the invention due to the article concludes that the action of thiotriazoline, providing antioxidant and cerebroprotective action, and piracetam with nootropic action, along with metabolic regulatory mechanism of blood circulation contributes to the nervous mechanism of its regulation, increases the speed and force of impact of the drug on improving blood flow to the brain.

This medicinal product according to the invention not only preserves, but also expands the range of pharmacological actions, pessegueiro, and eliminates the aggravation of coronary insufficiency and dyspepsia possible when using piracetam.

The essence of the invention is illustrated below by the results of pharmacological tests.

Research nootropic and cerebroprotective of drug action “Neotel” tablets was carried out on 285 white Wistar rats weighing 180-200 g, were obtained from the nursery of the Institute of pharmacology and toxicology, Academy of medical Sciences of Ukraine.

Evaluation of the neuroprotective actions

To assess neuroprotective actions used method of conditional reactions passive avoidance (passive avoidance reaction) followed by the application as amazonvideo factor shock and scopolamine.

To this end, 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 had received an electric shock through the floor electrode (training).

The experimental group of animals 60 minutes before training received inside investigational drugs - thiotriazoline dose of 50 mg/kg piracetam 200 mg/kg, Neotel 250 mg/kg in terms of the content of the active ingredients.

Directly after training amnesia caused by electroshock (110 V, 50 Hz, 500 mA). And another group of rats received an injection of scopolamine (2.5 mg/kg). The safety play reflex was carried out by the 24 hours after training.

Studies have shown that the shock and scopolamine cause forgetting of skill in animals when playing passive avoidance reaction 24 hours after training (table 1 and 2). Preliminary introduction thiotriazoline, piracetam or nootie experimental animals and the subsequent application of amnestic factors caused a significant increase in the latency time of reflex, i.e. saving skill learning compared to control animals.

The most effective was a preliminary introduction Nootie”, which is almost 2 times increased time saving skill training in the induction of amnesia by scopolamine and more than 3 times increased retention of skill in the induction of amnesia with electroshock (tables 1 and 2).

Assessment cerebroprotective actions.

Cerebroprotective properties nootie studied in two models of experimental stroke in rats.

The first brain ischemia caused by bilateral ligation of the common carotid artery.

The second was caused by hemorrhagic brain damage by injecting autologous blood into the region of the internal capsule.

The study was performed under Nembutal anesthesia (40 mg/kg). The drugs were injected daily for 18 days after surgery orally in doses: thiotriazoline 50 mg/kg piracetam 200 mg/kg, Neotel 250 mg/kg Slaughter of animals was carried out on 4-th and 18-th day of the experimental the NTA under Nembutal anesthesia, for studies used blood and brain tissue. About cerebroprotective drug action was tried to reduce giperfermentemii cerebral isoenzyme CPK (BB-ck) in the blood plasma and to reduce the accumulation in the brain of the end product of free radical oxidation of malonic dialdehyde (MDA), as well as for the overall indicator is the percentage of survival of animals in terms of experimental acute disorders of cerebral circulation (cerebral vascular accident).

The use of “Nootie” had a significant cerebroprotective effect in experimental cerebral vascular accident, as evidenced by the decrease in MDA level in ischemic brain tissue and giperfermentemii in plasma at different times of the experiment.

So, when bilateral ligation of the common carotid arteries on the 4th day of the experiment Neotel reduces MDA content by 52.3%and antioxidant drug thiotriazoline 38.1%. During these periods of observation “Neotel” reduced HyperTerminal BB-ck 55.1%, thiotriazoline 47.6%, piracetam 17.5%, respectively (table. 3).

On the model of hemorrhagic stroke “Neotel” reduced MDA by 35.1%, BB-ck 48.8%, than surpassed by the action of the thiotriazoline and piracetam (table 4).

The result of such actions nootie was to increase the survival of animals in the conditions of the experts who ment of stroke.

So, on the 4th day of ischemic stroke survival of animals in the appointment of “Nootie was 88,8%, on the 18th day of the same model - 77,7%, which was significantly higher than similar indicators thiotriazoline and pyracetam (table 5).

In terms of hemorrhagic model of stroke survival of animals in the appointment of “Nootie” was 83.0 per cent, pyracetam - 50.0% and thiotriazoline - 33,3% (table 6).

Thus the medicinal product according to the invention pills “Neotel”coated possesses nootropic, cerebroprotective, antioxidant effects, according to the power pharmacological action than individual piracetam and thiotriazoline, refers to a relatively harmless means, has a weakly expressed in species sensitivity, not qualitaets in the body and may find wide application in medical practice.

Acute toxicity nootie when administered orally to rats is 32600 mg/kg

Table 1

Effects of drugs on amnesia passive avoidance reaction caused by scopolamine.
MedicationDose mg/kgThe latent time of reflex when playing passive avoidance reaction, s
Control without amnesia-118,6±16,5
Counter the al with amnesia (scopolamine) 2,547,2±8,7
Piracetam20056,7±9,1
Thiotriazoline5060,8±9,7
Neotel25082,6±8,8*

* p<0.05 with respect to control with amnesia.

Table 2

Effects of drugs on amnesia passive avoidance reaction caused by the electric shock.
MedicationDose mg/kgThe latent time of reflex when playing passive avoidance reaction, s
Control without amnesia-97,2±7,6
Control with amnesia (electroshock)2,516,8±1,0
Piracetam20021,6±2,3
Thiotriazoline5037,3±4,7*
Neotel25058,6±4,4*

* p<0.05 with respect to control with amnesia.

Table 3

The cerebral activity of the enzyme creatine phosphokinase (BB-ck) in serum and the content of malondialdehyde (MDA) in brain tissue of experimental animals at 4 and 18 days of observation after bilateralropejedi common carotid arteries.
No.The group of animalsThe BB-ck (mmol/l/hour) at the follow-up periodMDA (µmol/g tissue)
  4 days18 days4 days18 days
1.Control0,107±0,0050,048±0,0071,26±0,070,68±0,02
2.Piracetam0,088±0,0030,046±0,0060,81±0,08*0,64±0,05
3.Thiotriazoline0,056±0,0020,044±0,0030,78±0,05*0,60±0,07
4.Neotel0,048±0,0040,041±0,0020,60±0,02*0,50±0,02*
5.Intact animals0,042±0,0060,042±0,0060,62±0,070,62±0,07

* p<0.05 with respect to control with amnesia.

Table 4

The cerebral activity of the enzyme creatine phosphokinase (BB-ck) in serum and the content of malondialdehyde (MDA) in the tissues of the head is on the brain of experimental animals on the 4th day of observation after injection of autologous blood into the region of the internal capsule of the brain.
No.The group of animalsThe BB-ck (mmol/l/h)MDA (µmol/g tissue)
1.Control0,090±0,0040,94±0,04
2.Piracetam0,070±0,003*0,74±0,05*
3.Thiotriazoline0,051±0,002*0,70±0,06*
4.Neotel0,046±0,005*0,63±0,07*
5.Intact animals0,042±0,0060,61±0,05

* p<0.05 with respect to control.

Table 5

The dynamics of the survival of animals after bilateral ligation of the common carotid arteries and the introduction of the studied drugs.
No.The group of animalsOnly animalsThe number of rats that survived to day observations in parentheses %
   4 days18 days
1.Control93(33)1(11)
2.Piracetam95*(55)3*(33)
3.Thiotriazoline96*(67)5*(55)
4.Neotel98*(89)7*(78)
5.Intact animals99(100)9(100)

*p<0.05 with respect to control.

Table 6.

The dynamics of survival of animals on the day of observation after injection of autologous blood into the region of the internal capsule of the brain and the introduction of the studied drugs.
No.The group of animalsOnly animalsThe number of surviving rats on days of observations in parentheses %
   1234
1.Control64 (66,6)2(33)2 (33)1(16)
2.Piracetam65 (83)4 (66,6)3 (50)3*(50)
3.Thiotriazoline65 (83)3 (50)2 (33)2 (33)
4.Neotel65 (83)5 (83)5 (83)5 (83)
5.Intact animals66 (100)6 (100)6 (100)6 (100)

*p<0.05 with respect to control.

Cerebroprotective and nootropic drug coated tablets containing the active ingredient - thiotriazoline and auxiliary ingredients to form the tablet core and applying to a shell, characterized in that as the active ingredient contains piracetam in the following ratio of ingredients, wt.%:

Piracetam 53,6-59

Thiotriazoline a 13.3-14,7

Auxiliary ingredients the Rest



 

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