Cortagen spray

Product status information

Chemical reagent intended exclusively for laboratory tests (Research Use Only). It is not a medicinal product, dietary supplement or food. It is not intended for use on humans or animals. Sales only to registered research units and laboratories.

Regulatory status

As a research reagent, Cortagen has never been registered as a medicinal product in the EU, US or other jurisdiction. It should be clearly distinguished from Cortexin — a peptide preparation registered as a medicine in Russia (and selected countries in the region), used in neurology. Cortexin is a registered medicinal product in a specific jurisdiction; Cortagen in the reagent market – including the nasal spray kit – is a Research Use Only material and is not a substitute for the medicinal product.

No EMA/FDA authorization as a medicine and no EFSA authorization as a dietary supplement ingredient. Communication of the product as a “brain peptide”, “neuroprotector for athletes”, “memory and concentration spray” or “cognitive support” is contrary to the Research Use Only framework.

Cortagen is a synthetic short regulatory peptide derived from the concept peptide bioregulation developed in St. Petersburg Institute of Bioregulation and Gerontology under the supervision of Vladimir Khavinson. In this research school, Cortagen belongs to the family of tissue-specific regulatory peptides (nomenclature ending in “-gene”), traditionally associated with a tetrapeptide with the sequence Ala-Glu-Asp-Pro (AEDP). The conceptual assumption of the entire group is that short, several-amino-acid peptides have affinity for the tissue from which they were originally isolated or to which their design concerns – in the case of Cortagen, this is the cerebral cortex and neuron.

The reagent belongs to the line Endogenic — materials mapping molecules of endogenous origin or directly derived from them, provided for research on peptide bioregulation of nervous tissue. This reagent provides Cortagen in a format consistent with a route of administration widely considered in the short cortical peptide literature – as kit for self-preparation of nasal spray: vial with Cortagen lyophilisate, bacteriostatic water for reconstitution and a glass atomizer with a dosing pump.

This is not a ready-to-use solution: the researcher first reconstitutes the lyophilized product with the included water and then fills the atomizer, preparing the solution for intranasal administration.

This format reflects the nose-to-brain transport logic studied for regulatory peptides: a peptide administered to the nasal mucosa has an alternative delivery route to the central nervous system, partially bypassing the blood-brain barrier. As a product from the group peptides spray is prepared for nasal administration – unlike the vial with the lyophilisate itself (Cortagen 20 mg), which does not contain water or an applicator.

In this kit, both of these elements are included, and the working concentration of the solution is determined by the researcher himself during reconstitution. Purity verified by HPLC ≥98%, identity confirmed by mass spectrometry, COA available for each batch.

The concept of peptide bioregulation is based on the observation that short peptides composed of two to four amino acid residues can influence cell function in a tissue-specific manner. In a series of works (Khavinson 2002; Anisimov, Khavinson 2010), Vladimir Khavinson and colleagues hypothesized that these types of peptides are part of an internal regulatory system that controls gene expression in response to the functional state and age of the tissue.

As part of this concept, a whole family of peptides assigned to specific organs was isolated: the pineal gland, thymus, vessels, heart, liver, bones – and the brain and its cortex, for which the working name became Cortagen.

Mechanistically, this school proposes that short regulatory peptides enter the cell and then interact with specific sites in the DNA strand or with proteins that regulate transcription, thereby modulating the expression of genes relevant to a given cell type. In tissue culture models, the influence of peptides of this family on the proliferation and differentiation of cells derived from the “mother” tissue of the peptide was observed (Khavinson 2002 – tissue-specific peptide effects).

The tissue specificity hypothesis is one of the most distinctive – and at the same time most controversial – elements of this concept, because it requires a mechanism for tissue recognition by a very short peptide sequence.

More broadly, the Khavinson family of short regulatory peptides includes several recurring research themes:

• Tissue-specific modulation of gene expression — hypothesis of the interaction of short peptides with DNA sequences and transcription factors
• Effect on cell proliferation and differentiation in tissue cultures derived from the “parent” organ of the peptide
• Cytoprotective and antioxidant effects in cell models subjected to stress (oxidative, hypoxia, excitotoxicity)
• Gerontological context — peptides as hypothetical modulators of processes related to tissue aging (Khavinson 2002; Anisimov, Khavinson 2010)
• Short sequence and low molecular weight — tetra- and tripeptides, designed as fragments of larger tissue regulators

Cortagen takes the place of a peptide in this family tissue-specific for the cerebral cortex and neuron — tools to study the concept of peptide bioregulation of the nerve cell, its protection, neuroregeneration and resistance to metabolic stress in experimental models. Organ-related bioregulators of the same school – how Cardiogen (peptide assigned to the heart) or Bronchogen (bronchial peptide) – illustrate the same logic of tissue-specific design.

In the line of neuro/cortical bioregulators, the literature of the bioregulation school also considers Cortexin – a product with registered medicinal status in Russia, which should not be confused with a research reagent (distinction discussed below).

Chemically, Cortagen is traditionally associated with a linear tetrapeptide with the sequence Ala-Glu-Asp-Pro. In this kit, it is supplied as a lyophilized product in a vial along with bacteriostatic water and a glass atomizer, from which the researcher prepares a solution for intranasal administration after reconstitution.

• Common name: Cortagen, cortical/brain bioregulator peptide, cortical peptide
• Sequence (traditionally assigned): Ala-Glu-Asp-Pro (AEDP) – alanyl-glutamyl-asparaginyl-proline; sequence for verification in the batch COA
• Chemical class: synthetic short regulatory peptide (tetrapeptide); family of bioregulator peptides of the Khavinson school, tissue-specific lineage for the cerebral cortex/neuron
• CAS number: for verification in the batch COA
• Molar mass: dependent on confirmed sequence; for the AEDP variant of approximately 430 g/mol (indicative value – the mass from the MS analysis of the batch is binding)
• Supplied form: set – vial with Cortagen lyophilisate + bacteriostatic water for reconstitution + glass nasal atomizer (for self-preparation of the solution); peptide content according to COA; purity ≥98% HPLC
• Conceptual origin: Khavinson’s concept of peptide bioregulation (St. Petersburg Institute of Bioregulation and Gerontology); Endogenic line; medicinal equivalent: Cortexin (registered drug in Russia)

Characteristics table

Cortagen is considered in the literature through the prism of the concept of tissue-specific peptide bioregulation. The following description refers to hypotheses and observations from preclinical models – not to a validated human clinical mechanism. Profile observed and postulated in preclinical models:

1. Tissue-specific peptide bioregulation of the neuron — the central hypothesis of the Khavinson school assumes that short regulatory peptides enter the cell and modulate gene expression by interacting with specific DNA sequences or with the transcription apparatus. In the case of Cortagen, this concerns genes important for the function, survival and differentiation of cerebral cortex cells. Mechanism: postulated modulation of transcription, not classic stimulation of the membrane receptor (Khavinson 2002; Anisimov 2004 – Cortagen modulating gene expression)
2. Modulation of neuroregeneration and neuronal protection — the influence of peptides of this family on the survival of neurons, regrowth of processes and protection against apoptosis was studied in tissue culture models and in models of neural tissue damage; for Cortagen, the research context is neuroprotection and renewal of cerebral cortex cells in experimental conditions
3. Antioxidant and anti-inflammatory effects — the protective potential of the peptide against cellular damage was tested in models of nervous tissue subjected to oxidative stress or hypoxia; the research context includes the protection of the neuron against reactive oxygen species and the modulation of inflammatory markers in the nervous tissue (Kozina 2007 – tetrapeptides and free radical processes)
4. Modulation of cognitive functions and neuroplasticity — postulated impact on parameters related to synaptic plasticity and cognitive processes, considered in animal models as part of the general concept of bioregulation of nervous tissue

Characteristics of peptides of this family (based on the literature of the bioregulation school):

• Short sequence (tetrapeptide) and low molecular weight – typical for the designed regulatory fragments
• Postulated ability to penetrate the cell and interact at the nuclear level – a hypothesis requiring further mechanistic verification
• The action is described as modulatory and contextual, rather than classically stimulating – the peptide is intended to “normalize” cell function, not to force a one-way response
• Human pharmacokinetic profile: not characterized for the reagent; no data from randomized clinical trials

The intranasal administration format for which this kit is prepared reflects the route of administration widely considered in the neuropharmacology of short regulatory peptides. Most peptides cross the blood-brain barrier (BBB) poorly after peripheral administration – they are too polar, and short peptides are also quickly proteolyzed. Intranasal administration offers an alternative delivery route to the central nervous system (CNS), partially bypassing the BBB. Two parallel nose-to-brain transport pathways have been described in research models:

• Olfactory pathway (olfactory) — a peptide applied to the olfactory epithelium in the upper part of the nasal cavity can be transported along the olfactory nerves directly to the olfactory bulb and further to the structures of the forebrain, bypassing the systemic circulation
• Trigeminal nerve pathway — the endings of the trigeminal nerve innervating the nasal mucosa constitute a second route of transport to the brain stem and further structures of the CNS

For a short cortical peptide such as Cortagen, the intranasal route is a logical research route: by partially bypassing first-pass metabolism and the blood-brain barrier, it allows the peptide to be delivered closer to central targets – the cerebral cortex and the neuron, to which Khavinson’s concept attributes its tissue specificity.

IMPORTANT DISTINCTION

Cortagen’s nose-to-brain transport remains level logical analogy to other short regulatory peptides administered intranasally — there is no published human Phase I study confirming intranasal bioavailability or CNS transport of this particular molecule. This is a significant difference from some related peptides (e.g. native Selank, which has a Russian registration in the form of a nasal solution, or the peptide Semax spray with documented intranasal work).

For Cortagen, intranasal bioavailability, transport kinetics, and the CNS exposure window remain for verification — data comes from models, no large RCTs. The kit format reflects the investigational route of administration and does not authorize the use of the reagent in humans.

Three distinctions are critical here and must not be merged into one.

First – data origin. The concept of tissue-specific peptide bioregulation is an original, consistently developed achievement Russian scientific school (St. Petersburg Institute of Bioregulation and Gerontology). It is characterized by limited independent replication outside its home centers and much of the literature in Russian. The data for Cortagen comes from cell and animal models – not large randomized clinical trials. This does not disqualify the concept, but sets a limit for interpretation: the observations are preliminary and require confirmation.

Second – Cortagen (RUO reagent) vs Cortexin (drug). These are two separate regulatory entities.

Cortexin is a registered medicinal product (neurological drug) in Russia and selected countries in the region. Cortagen in the reagent trade, it is a Research Use Only material – a chemical reagent for laboratory research, without registration as a drug in the EU, USA or other jurisdiction. Cortagen RUO reagent is not a replacement Cortexin and does not replace medical consultation or medicinal product.

Third – a set with an atomizer vs just a vial of lyophilisate. This product is a set (lyophilized vial + bacteriostatic water + glass atomizer) for self-preparation of a nasal solution; vial format (Cortagen 20 mg) is the freeze-dried product without water and applicator.

In both cases, the peptide occurs as a lyophilized product requiring reconstitution – the researcher selects the working concentration himself. The difference is that this kit adds water and an atomizer aimed at the research nasal route. The identity of the ordered material in both formats is determined by the sequence and MS mass in the batch COA.

Cortagen in this kit is used as a reagent in research work on the concept of peptide bioregulation of tissue-specific nervous tissue, prepared for the route of administration considered in peptide neuropharmacology. In vitro models (neuron cultures, tissue cultures of nervous tissue, models of oxidative stress, hypoxia and excitotoxicity) examine its impact on cell viability, neuroregeneration, differentiation and markers of oxidative damage and inflammation.

In vivo models (animal models used by bioregulation centers) examined the influence of peptides of this family on tissue parameters related to neuroprotection, regeneration and aging of nervous tissue. Specific research directions include:

• The concept of peptide tissue bioregulation — Cortagen as a model tissue-specific peptide for the cerebral cortex; research on the hypothesis of modulation of gene expression by short peptides in nerve cells
• Nose-to-brain transport studies — comparative pharmacokinetics of intranasal versus systemic administration for a short cortical peptide; characterization of the kinetics of transport through the olfactory epithelium and the trigeminal nerve pathway
• Neuroprotection models — assessment of the protective potential against oxidative stress, hypoxia and excitotoxicity in neuronal cultures
• Neuroregeneration and plasticity studies — the effect of the peptide on cell renewal parameters, sprout regrowth and neuroplasticity markers in culture models
• Experimental gerontology — bioregulatory peptides as tools for studying processes related to the aging of nervous tissue (Anisimov, Khavinson 2010)
• Independent and methodological verification — replication of observations of the bioregulation school in independent laboratories, including confirmation of the chemical identity and sequence of the tested material

Cortagen also remains a common reference within the broader category peptides on brain function studied in models of neuroactivity and cognitive functions.

SCIENTIFIC PERSPECTIVE

Because this is a self-preparation kit, the working concentration is not factory set – it results from the volume of bacteriostatic water that the researcher selects during reconstitution and the peptide content given in the COA. For protocols requiring different storage stability or concentrations, the format of the vial with the lyophilisate itself is also suitable (Cortagen 20 mg). Due to the sensitivity of short peptides to hydrolysis and deamidation in the aqueous phase, the stability of the working solution is worth monitoring by HPLC during long-term storage.

Cortagen nasal supplies a synthetic short regulatory peptide (traditionally linked to the tetrapeptide Ala-Glu-Asp-Pro, AEDP) from the family of tissue-specific bioregulators of the Vladimir Khavinson school (St. Petersburg Institute of Bioregulation and Gerontology), Endogenic line – as a kit for self-preparation of a nasal spray: a vial with lyophilisate, bacteriostatic water for reconstitution and a glass atomizer; the researcher reconstitutes the lyophilized product and fills the atomizer.

The peptide is attributed to the cerebral cortex and neuron, and the conceptual assumption is the modulation of neuronal cell gene expression by the short peptide – a hypothesis with four main themes: tissue-specific bioregulation of the neuron, modulation of neuroregeneration and neuronal protection, antioxidant/anti-inflammatory effects in neural tissue models, and modulation of cognitive function and neuroplasticity. The whole concept remains mainly developed by the Russian school of science and is characterized by limited independent replication – data comes from cellular and animal models, without large randomized clinical trials.

The intranasal format reflects the investigational route of administration and nose-to-brain transport (olfactory and trigeminal pathways), although the intranasal bioavailability of this molecule remains to be verified – it is a logical analogy to other short peptides, with no confirmed human intranasal precedent. Cortagen research reagent must be distinguished from the drug Cortexin, registered in Russia, and a set with an atomizer from the vial itself (Cortagen 20 mg).

HPLC purity ≥98%, MS confirmation (Q-TOF) with sequence verification, COA for each batch. Regulatory Status – Research Use Only; WADA status: not listed. The sequence of each batch requires confirmation with the COA.

1. Khavinson VKh (2002). Peptides and Aging. PubMed
2. Anisimov SV, Khavinson VKh, Anisimov VN (2004). Elucidation of the effect of brain cortex tetrapeptide Cortagen on gene expression in mouse heart by microarray. PubMed
3. Kozina, L. S. (2007). Effects of bioactive tetrapeptides on free-radical processes. PubMed
4. Anisimov VN, Khavinson VKh (2010). Peptide bioregulation of aging: results and prospects. PubMed
5. Khavinson VKh, Malinin VV (2001). Tissue-specific effects of peptides. PubMed