Cortexin 10 mg (22 mg) 10 pcs lyophilisate for the preparation of solution for intramuscular administration

Cortexin, bottles 10 mg, 5 ml, 10 pcs.

Manufacturer

Geropharm, Russia

Compound

1 bottle of lyophilisate contains:
active ingredient:

cortexin (complex of water-soluble polypeptide fractions) 10 mg,

excipient:

vglycine (stabilizer) 12 mg

pharmachologic effect

CORTEXIN contains a complex of low molecular weight water-soluble polypeptide fractions that penetrate the blood-brain barrier directly to nerve cells. The drug has nootropic, neuroprotective, antioxidant and tissue-specific effects. Nootropic - improves higher brain functions, learning and memory processes, concentration, and resistance to various stressful influences.

Neuroprotective – protects neurons from damage by various endogenous neurotoxic factors (glutamate, calcium ions, free radicals), reduces the toxic effects of psychotropic substances.

Antioxidant – inhibits lipid peroxidation in neurons, increases the survival of neurons under conditions of oxidative stress and hypoxia. Tissue-specific – activates the metabolism of neurons of the central and peripheral nervous system, reparative processes, helps improve the functions of the cerebral cortex and the general tone of the nervous system.

Mechanism of action

CORTEXIN is caused by the activation of neuronal peptides and neurotrophic factors of the brain; optimization of the balance of metabolism of excitatory and inhibitory amino acids, dopamine, serotonin; GABAergic effects; a decrease in the level of paroxysmal convulsive activity of the brain, the ability to improve its bioelectrical activity; preventing the formation of free radicals (products of lipid peroxidation).

Pharmacokinetics

The composition of CORTEXIN, the active substance of which is a complex of polypeptide fractions, does not allow for conventional pharmacokinetic analysis of individual components.

Indications

In complex therapy:

• cerebrovascular accident;
• TBI and its consequences;
• encephalopathy of various origins;
• cognitive impairment (memory and thinking disorders);
• acute and chronic encephalitis and encephalomyelitis;
• epilepsy;
• asthenic conditions (suprasegmental vegetative disorders);
• reduced learning ability;
• delayed psychomotor and speech development in children;
• various forms of cerebral palsy.

Contraindications

Individual intolerance to the drug.

The drug is contraindicated during pregnancy (due to the lack of clinical trial data).

If it is necessary to prescribe the drug during lactation, breastfeeding should be stopped (due to the lack of clinical trial data).

Side effects

There were no reports of side effects.

Individual hypersensitivity to the components of the drug is possible.

How to take, course of administration and dosage

The drug is administered intramuscularly.

Before injection, the contents of the bottle are dissolved in 1–2 ml of 0.5% solution of procaine (novocaine), water for injection or 0.9% sodium chloride solution, directing the needle to the wall of the bottle to avoid foaming, and administered once daily: adults at a dose of 10 mg for 10 days; children with body weight up to 20 kg at a dose of 0.5 mg/kg, with body weight over 20 kg - at a dose of 10 mg for 10 days.

If necessary, repeat the course after 3–6 months. For hemispheric ischemic stroke in the acute and early recovery periods for adults, a dose of 10 mg 2 times a day (morning and afternoon) for 10 days, with a repeat course after 10 days.

Release form

Lyophilisate for preparing a solution for intramuscular administration

Storage conditions

In a dry place, protected from light, at a temperature of 2–20 °C

Best before date

3 years

Active substance

Livestock cerebral cortex polypeptides

Conditions for dispensing from pharmacies

On prescription

Dosage form

injection

Barcode and weight

Barcode: 4607008360011 Weight: 0.091 kg

Cortexin®

This term is often found in medical publications, the media, and in advertising of medicines. The possibilities of neuroprotection are inherent in the very nature of the brain, in genes, at the level of regulatory neuropeptides. The essence of neuroprotection is that the treatment process not only helps protect the affected group of neurons, but also ensures its further functioning. An important question for medicine is: are there adequate pharmacological effects that can trigger these natural mechanisms and maintain them at the required level? In this regard, the search, creation and testing of new pharmaceuticals are and will be one of the most important areas of modern pharmacology.

It is obvious that the search for new neuroprotectors is a complex process that requires the combined efforts of doctors, biologists, and pharmacologists at all stages. In this regard, preparations of peptide nature deserve special attention. Despite their diversity, they are united by a number of common characteristics: low dosage, absence of pronounced toxic effects, gentleness and duration of exposure. In general, it can be argued that the body’s peptide system (Koroleva S.V., Ashmarin I.P., 2006), formed over millions of years of evolution, provides multi-level regulation of all functions, including processes that ultimately lead to a neuroprotective effect . In terms of information, it is peptides that are a universal language, understandable and natural for living organisms both at the systemic level and at the cellular level.

One example of a successful development based on the principles listed above is Cortexin, a drug whose effectiveness has been proven at all possible levels of research: clinical, biological, cellular, genetic and molecular.

According to MRI data, a lesion is identified in the right temporal region of the brain, the volume of which clearly increases by the 3rd day. With such a lesion, the formation of a glial scar and post-stroke cysts is usually observed on day 28. When using Cortexin, when a patient with an ischemic stroke begins to receive the drug from the first hours of the disease, along with a noticeable improvement in general well-being, clinical and neurological picture, the volume of the brain lesion by 28 days decreases by 40%. This observation illustrates the striking effect of the neuroprotective action of Cortexin (Skoromets A.A., Skvortsova V.I. et al., 2008).

Terminology: Ischemia - Insufficient blood supply to any organ or tissue area caused by blockage or narrowing of the corresponding artery; ATP - Adenosine triphosphate - a nucleotide that plays an extremely important role in the exchange of energy and substances in organisms; First of all, the compound is known as a universal source of energy for all biochemical processes occurring in living systems. Depolarization of the cell membrane is a change in the electrical potential on the cell membrane; Glutamate is an amino acid and the main excitatory neurotransmitter. The binding of glutamate to specific neuronal receptors results in neuronal excitation. NMDA and AMPA glutamate receptors are receptors that ensure the conduction of an excitatory impulse by neurons when glutamate is bound; Caspases and NO synthases are intracellular enzymes involved in the processes of cell death and the development of oxidative stress.

Neuroprotective anti-apoptotic effect

Cortexin ® is a neuroprotector that has a therapeutic effect starting from the first hours after ischemic brain damage. This means that its main target is the penumbra zone - a section of nervous tissue surrounding the lesion, experiencing oxygen and energy starvation, but temporarily, up to 6 hours, remaining alive. The possibility of subsequent restoration of nervous functions, life and death of the patient depends on the outcome of this process. Cortexin ® affects all links in the pathological chain of molecular events leading to the death of neurons. Cortexin ® to reduce the level of neuronal apoptosis (programmed cell death) caused by excessive accumulation of glutamate (Pinelis et al., 2008).

Glutamate is the main excitatory neurotransmitter of the nervous system. During a stroke, glutamate is released excessively, triggering a cascade of processes that underlie neuronal death. In the culture of nervous tissue, the introduction of glutamate into the medium also leads to the death of neurons. If a substance with a neuroprotective effect is administered simultaneously with glutamate, the death of neurons is reduced. This figure shows the results of a study of the neuroprotective properties of Cortexin ® in vitro: when administered simultaneously with glutamate, Cortexin ® has a pronounced neuroprotective effect in the nanogram concentration range (* p < 0.05 compared to the control group) (Granstrem O.K. et al. , 2008).

Restoration of ATP synthesis

Adenosine triphosphate (abbr. ATP) is a nucleotide that plays an extremely important role in the metabolism of energy and substances in organisms, a universal source of energy for all cells of the body. A decrease in the ATP content in brain cells is the central link in all pathological processes occurring against the background of cerebral ischemia. A decrease in synthesis and an increase in ATP consumption is shown immediately after the onset of ischemia of nervous tissue (Sorokina et al., 2007). Recent studies have demonstrated that Cortexin ® is capable of restoring ATP content in neurons.

The study demonstrated the ability of Cortexin ® to trigger the processes of natural ATP recovery in the mitochondria of nerve cells. Since a drop in ATP levels is one of the main reasons leading to the death of nerve cells during stroke, the restoration of this indicator under the influence of Cortexin ® explains its clinical effectiveness (Granstrem O.K. et al., 2008).

Suppression of delayed calcium dysregulation (DCD)

During cerebral ischemia and stroke, active penetration of calcium ions into neurons occurs, which leads to an irreversible increase in their concentration in the cell and subsequent disruption of mitochondrial functioning associated with a drop in mitochondrial potential (ΔΨm) (Khodorov et al., 2001; Krieger C. & Duchen MR , 2002). As a rule, cells in which ΔΨm collapse occurs do not restore their original potential after glutamate withdrawal and ultimately die—the so-called delayed calcium dysregulation (DCD) occurs (De Wied D., 1997; Sorokina E. G. et al. ., 2007).

Fluorescence microscopy studies of mitochondrial potential (ΔΨm) demonstrate that Cortexin significantly slows the development of delayed calcium dysregulation under the influence of glutamate. The recording of mitochondrial potentials of neurons shown in the figure indicates the sparing, protective effect of Cortexin ® by delaying the onset of calcium dysregulation. Thus, it has been proven that the use of Cortexin ® can expand the therapeutic window for ischemic damage to nervous tissue (Report on the study of the neuroprotective effects of Cortexin ® , State University Scientific Center for Children's Health of the Russian Academy of Medical Sciences, Moscow, 2008).

Neurotrophic effect

® peptides have direct and indirect neurotrophic effects on cells. The main mechanisms of this influence are based on changes in the work of genes that regulate the synthesis of intrinsic neurotrophic factors such as brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF).

Stimulation of neurite growth in chicken embryo brain culture. In culture

In nervous tissue, the growth of neurites (the processes of a nerve cell along which nerve impulses travel from the cell body to organs and other nerve cells) occurs only in the presence of neurotrophic factors.
In this test, a test with Cortexin ® allows you to determine the degree of its neurotrophic effect: in the right microphotograph, the entire field around the island of nervous tissue is occupied by a branched network of neurites, while in the control (left microphotograph) the growth of neuronal processes is practically not observed ( The photographs show the results of testing a batch of the drug. Such testing is regularly carried out in the analytical laboratory of the research and development laboratory.
Thus, numerous independent studies convincingly demonstrate the presence of Cortexin ® multiple effects affecting the cascade regulation of apoptosis, the expression of neutrophic factors, the energy supply of the nerve cell and mitochondrial potential , the functioning of glutamate receptors and regulation of the concentration of calcium ions in the cell, which together provides the neuroprotective and neurotrophic effects of the drug, and, ultimately, high treatment efficiency and improved quality of life for the patient.

Specific results of clinical experience in domestic medicine using Cortexin ® are reflected in more detail in the Scientific publications section

Literature:

1. Gerasimova M. M., Petushkov A. Yu. / Effect of Cortexin on cytokine metabolism in lumbosacral radiculopathies. // Neuroimmunology. - 2004. - volume II. - No. 2. - P. 26.
2. Granstrem O.K., Sorokina E.G., Storozhevykh T.P., Shtuchnaya G.V., Pinelis V.G., Dyakonov M.M. / Latest news about Cortexin (neuroprotection at the molecular level). // Terra Medica Nova. - No. 5. - 2008. - pp. 40-44.
3. Koroleva S.V., Ashmarin I.P. / Development and application of an expert system for analyzing the functional continuum of regulatory peptides” // Bioorganic chemistry. - 2006. - T. 32. - No. 3 - P. 249–257.
4. Skoromets A. A., Stakhovskaya L. V., Belkin A. A., Shekhovtsova K. V., Kerbikov O. B., Burenchev D. V., Gavrilova O. V., Skvortsova V. I. / New opportunities neuroprotection in the treatment of ischemic stroke // Journal of Neurology and Psychiatry named after S. S. Korsakov. 2008. - T. 22. - P.32–38.
5. Sorokina E. G., Reutov V. P., Senilova Ya. E., Khodorov B. I., Pinelis V. G. / Changes in ATP content in cerebellar granule cells during hyperstimulation of glutamate receptors: possible involvement of NO and nitrite ions // Bulletin let's experiment biol. and honey - 2007. - No. 4. - P. 419-422.
6. Khodorov B.I., Storozhevykh T.P., Surin A.M., Sorokina E.G., Yuravichus A.I., Borodin A.V., Vinskaya N.P., Khaspekov L.G., Pinelis V. G. / Mitochondrial depolarization plays a dominant role in the mechanism of disturbance of neuronal calcium homeostasis caused by glutamate // Biol. membranes. - 2001. - T. 18, N 6. - P. 421–432.
7. De Wied D. / Neuropeptides in learning and memory processes. //Behav. Brain. Res. - 1997. - Vol. 83. - P. 83–90.
8. Krieger C. and Duchen M.R. / Mitochondria, Ca2+ and neurodegenerative disease. //Eur. J. Pharmacol. - 2002. - Vol. 447. - P. 177–188.
9. O'Collins VE., Macleod MR., Donnan GA., Horky LL.,. van der Worp B.H., and Howells D.W. "1,026 Experimental Treatments in Acute Stroke" // Annals of Neurology. - 2006. - 59:467–477.
10. Pinelis VG, Storozhevykh TP, Surin AM, Senilova Ya.E., Persiyantzeva NF, Tukhmatova GR, Andreeva LA, Myasoedov NF, Granstrem O. “Neuroprotective effects of cortagen, cortexin and semax on glutamate neurotoxicity” / 30th European Peptide Symposium (30EPS ), Helsinki, 30 August — 5 September 2008.