MEDICAL DISCLAIMER: Educational research guidelines only. Lyophilized peptides are investigational chemical compounds and are NOT approved for human consumption, diagnosis, or therapy. Consult a licensed physician before any research application.
Cortagen Dosage Chart, Schedule & Reconstitution Protocol
Quickstart Highlights
Cortagen is a Khavinson-class synthetic tetrapeptide with the sequence Ala-Glu-Asp-Gly (AED-G), developed at the Saint Petersburg Institute of Bioregulation and Gerontology as a short peptide bioregulator targeting the cerebral cortex. Like other Khavinson cytogens, it is hypothesized to act by penetrating the cell and nuclear membranes and binding regulatory regions of double-stranded DNA, modulating expression of tissue-specific genes governing neuronal survival, synaptic remodelling, and antioxidant defense (PMID: 12937682). Animal work indicates that Cortagen normalizes neurotransmitter balance, supports recovery after experimental peripheral nerve and cortical injury, and exhibits geroprotective effects in long-term rodent studies from the Anisimov and Khavinson groups (PMID: 16615542). Researchers study it for post-stroke recovery, polyneuropathy, age-associated cognitive decline, and as a model compound for the broader cytogen family of bioregulators.
Reconstitute: Add 3 mL bacteriostatic water → 6.67 mg/mL concentration.
Easy measuring: At 6.67 mg/mL, 1 unit = 0.01 mL = 0.0667 mg (67 mcg) on a U-100 insulin syringe.
Storage: Lyophilized frozen; reconstituted refrigerated; avoid repeated freeze–thaw.
Half-life: Plasma clearance of the tetrapeptide is rapid (minutes), but the proposed epigenetic mechanism of action means downstream transcriptional effects may persist for days to weeks per cycle.
Route: Intramuscular injection is the most common research route; intranasal and subcutaneous routes appear in some Russian protocols targeting cortical and peripheral nerve endpoints.
Status: Khavinson-licensed peptide bioregulator; not FDA or EMA approved. Evidence base outside Russia is limited to animal and translational work, with no large randomized controlled human trials.
Quick Protocol Navigation
Reconstitution Instruction & Mixing Step-by-Step
Lyophilized powder must be reconstituted carefully. Agitating peptide chains can shear disulfide bonds and render the peptide biologically inert.
Draw 3.0 mL bacteriostatic water with a sterile syringe.
Inject slowly down the vial wall; avoid foaming.
Gently swirl/roll until dissolved (do not shake).
Inject slowly; wait a few seconds before withdrawing the needle.
Do not aspirate for subcutaneous injections; inject slowly and steadily[9].
Interactive Cortagen Syringe Calculator
Currently visualizing the 20 mg vial reconstituted with 3 mL bacteriostatic water. Adjust the target dose to dynamically render syringe units.
Reconstitution Calculation: 20mg dry powder in 3mL water yields 6.67 mg/mL. To evaluate a 250mcg dose, pull to 3.8 units (4 syringe ticks).
U-100 Syringe Representation
3.8 Units (4 Ticks)
Educational reference visual. Assumes standard U-100 insulin syringe where 1.0 mL volume = 100 units.
Titration & Dose Escalation Schedules
| Week | Daily Dose (mcg) | Units (per injection) (mL) |
|---|---|---|
| Weeks 1–2 | 1000 mcg | 15 units (0.15 mL) |
| Weeks 3–4 | 2000 mcg | 30 units (0.30 mL) |
Administration guidelines: Refer to guidelines | 3 mL Reconstitution
Research Supplies Quantity Planner
Scientific mathematical planning of syringes, bacteriostatic water and dry vials needed for extended research blocks using the 20 mg vial.
Peptide Vials (Cortagen, 20 mg each):
- check4 weeks ≈ 3 vials (at average 1500 mcg/day = 42 mg total)
- check8 weeks ≈ 5 vials
Insulin Syringes (U-100):
- checkPer week: 7 syringes (1/day)
- check4 weeks: 28 syringes
- check8 weeks: 56 syringes
Bacteriostatic Water (10 mL bottles): Use 3.0 mL per vial for reconstitution.
- check4 weeks (3 vials): 9 mL → 1 × 10 mL bottle
- check8 weeks (5 vials): 15 mL → 2 × 10 mL bottles
Alcohol Swabs: One for the vial stopper + one for the injection site each day.
- checkPer week: 14 swabs (2/day)
- check4 weeks: 56 swabs → recommend 1 × 100-count box
- check8 weeks: 112 swabs → recommend 2 × 100-count boxes
Mechanism of Action (MOA)
Cortagen was designed as part of Khavinson's directed-synthesis program for short cytomedins, in which the amino acid composition of clinically used organ-extract polypeptides was analyzed and the most common di-, tri-, and tetrapeptide sequences were synthesized and screened for tissue-specific bioregulator activity. The parent preparation Cortexin had been used in Russian clinical neurology since the 1980s as a bovine cerebral cortex hydrolysate for stroke recovery, encephalopathy, and developmental disorders. Cortagen (Ala-Glu-Asp-Pro) emerged as a leading short-peptide candidate replicating much of Cortexin's central-nervous-system bioregulatory profile in defined form [1]. Khavinson's central mechanistic hypothesis is that short bioregulatory peptides cross plasma and nuclear membranes, penetrate the cell nucleus, and bind specific DNA sequences in gene promoter regions through electrostatic and steric complementarity, modulating local chromatin condensation and downstream transcription of tissue-specific gene programs [2]. For Cortagen, the targeted tissue is the cerebral cortex and the broader nervous system: experimental data show selective effects on neuronal gene expression including activation of interleukin-2 mRNA synthesis in immunocompetent cells of the brain and modulation of inflammatory and oxidative pathways under chronic ischemic stress [3]. In peripheral nerve injury models, Cortagen administration accelerates axonal regeneration, restores myelination markers, and supports functional recovery on motor and sensory testing, suggesting that its bioregulator activity extends to Schwann-cell and neuronal repair programs. Pharmacokinetically, Cortagen behaves like other Khavinson tetrapeptides: very short plasma half-life (under 5 minutes when given parenterally), but biological effects that persist for days to weeks after dosing, consistent with epigenetic modulation rather than receptor occupancy as the proximal mechanism. Administration is parenteral (subcutaneous or intramuscular injection) or oral; oral bioavailability of tetrapeptides is poor (probably under 5%), but Khavinson-school protocols nonetheless use oral capsules at higher milligram doses for outpatient bioregulator therapy, on the theoretical basis that even small fractions of intact peptide may reach systemic and nuclear targets. Standard research and clinical regimens use 100–400 mcg subcutaneously daily across 10–20 day courses, repeated 2–4 times yearly, mirroring the cycle-based bioregulator paradigm. Outpatient oral dosing is typically 1–3 mg/day across 20–30 day cycles. Effects on the cerebral cortex include reductions in markers of oxidative stress, normalization of EEG patterns in encephalopathy, and reported improvements in attention, memory, and emotional stability in observational Russian clinical use. Cortagen does not bind classical neurotransmitter receptors, does not activate the HPA axis, and is not metabolized to bioactive larger peptides; its effects are attributed solely to short-peptide gene-regulatory activity. Western mechanistic validation by ChIP-seq, ATAC-seq, or controlled human pharmacodynamic studies remains absent.
Clinical Trial Efficacy Highlights
- starKhavinson and colleagues reported that Cortagen at 1–10 ng/mL in cell culture activates interleukin-2 mRNA synthesis in lymphocytes and supports gene expression patterns characteristic of central-nervous-system bioregulation [1].
- starChalisova and colleagues showed in organotypic neural tissue culture that Cortagen at low nanomolar concentrations stimulates proliferation of cortical neurons and supports neurite outgrowth, providing preclinical evidence for a regenerative effect on cortex tissue.
- starAnisimov and Khavinson have documented that several short peptide bioregulators, including the AEDP/Cortagen family, support increased mean and maximum lifespan in rodent aging studies when administered cyclically over the animal's life course [4].
- starIn experimental cerebral ischemia models in rats, Cortagen reduced markers of oxidative stress, normalized EEG patterns, and improved performance on learning tasks compared to ischemic controls.
- starSibarov and collaborators demonstrated electrophysiologic effects of short Khavinson tetrapeptides on neuronal excitability and synaptic transmission, supporting a direct modulatory effect on cortical function beyond chronic gene-expression changes.
- starRussian observational use of Cortagen in patients with chronic cerebral ischemia, post-stroke encephalopathy, and age-related cognitive decline reports subjective improvements in memory, attention, and emotional stability, though randomized controlled trials are absent from the indexed literature.
- starPeripheral nerve injury experiments have shown that Cortagen accelerates axonal regeneration and functional recovery, suggesting bioregulator activity extends to Schwann cell biology and the peripheral nervous system.
- starCombination of Cortagen with other Khavinson peptides (Epitalon, Pinealon) is described in Russian gerontological protocols for complex bioregulator therapy in age-related cognitive disorders, though no controlled comparator data exist.
Side Effects & Tolerability Profile
Clinical subjects transiently report mild side effects. Slowly escalating the titration dose represents the single most effective intervention to limit side effects.
- warningCortagen is generally well tolerated in Russian observational use; the most common reported effects are mild injection-site discomfort with subcutaneous administration and occasional transient headache.
- warningNo serious adverse events have been documented in the indexed literature, but the absence of large randomized safety trials means the side-effect profile is poorly characterized by Western standards.
- warningGastrointestinal upset (nausea, loose stools) is occasionally reported with oral administration, particularly at higher milligram doses, and typically resolves on dose reduction.
- warningNo tolerance, dependence, or withdrawal phenomena have been reported, consistent with the proposed epigenetic rather than receptor-occupancy mechanism.
- warningHypersensitivity reactions are rare; allergic skin reactions to peptide preparations should prompt discontinuation.
- warningNo HPA axis activation, hormonal disturbance, or significant metabolic effects have been reported with research-typical doses.
- warningReproductive, pregnancy, and lactation safety data are absent; use during these periods is not advised.
- warningDrug-drug interaction data are not available; theoretical concerns about combination with immunomodulators are unstudied.
Subcutaneous Injection Technique
Most research peptides require subcutaneous injection into fatty tissue. Never inject directly into a blood vessel or deep muscle tissue unless clinically detailed.
1. Site Selection
Common locations include the abdomen (2 inches from navel), outer upper arms, or thighs.
2. Sanitization
Thoroughly clean the selected site, stopper and vial top using 70% isopropyl alcohol prep swabs.
3. Angle & Push
Pinch the skin and insert the needle at a 45 to 90-degree angle. Depress plunger smoothly.
4. Site Rotation
Rotate injection sites continuously to avoid lipodystrophy or tissue scarring.
Frequently Asked Questions
What is the typical Cortagen dosage?expand_more
Research and Russian observational protocols typically use 100–400 mcg subcutaneously daily for 10–20 day courses, repeated 2–4 times per year. Oral capsule formulations use 1–3 mg/day across 20–30 day cycles. There is no established Western clinical reference dose.
How is Cortagen administered?expand_more
Cortagen is administered subcutaneously (most common in research), intramuscularly, or orally as a capsule. Subcutaneous injection achieves higher systemic exposure but oral capsules are used in outpatient Russian bioregulator practice despite low absolute bioavailability.
Can Cortagen be stacked?expand_more
Cortagen is frequently combined with other Khavinson bioregulators (Epitalon, Pinealon, Cerebrolysin) in Russian neurogerontology protocols. Combination evidence is observational rather than randomized; mechanistic overlap between Cortagen and other cerebral cortex bioregulators is significant.
What are the side effects of Cortagen?expand_more
Reported side effects are mild and infrequent: occasional injection-site discomfort, transient headache, and rare gastrointestinal upset with oral use. No serious adverse events are documented in the indexed literature, but Western-standard safety trials are lacking.
Is Cortagen FDA approved?expand_more
No. Cortagen is registered in Russia as a peptide bioregulator under dietary-supplement and bioregulator legislation rather than as a pharmaceutical, and has no FDA, EMA, or MHRA approval. In the United States and EU it is sold strictly as a research chemical.
Academic References & Study Citations
Khavinson VK, Malinin VV. Gerontological aspects of genome peptide regulation. Karger Publishers, Basel; 2005. View Scientific Paper →
Khavinson VK, Popovich IG. Short peptides regulate gene expression. Bull Exp Biol Med. 2017;162(3):288-292. View Scientific Paper →
Khavinson VK, Lin'kova NS, Tarnovskaya SI. Short peptides regulate gene expression. Mol Biol (Mosk). 2016;50(2):350-356. View Scientific Paper →
Anisimov VN, Khavinson VK. Peptide bioregulation of aging: results and prospects. Biogerontology. 2010;11(2):139-49. View Scientific Paper →
Khavinson VK, Kvetnoy IM, Popovich IG, Anisimov VN. Mechanisms of biological activity of short peptides: cell-tissue specificity. Bull Exp Biol Med. 2020;168(3):378-381. View Scientific Paper →
Lin'kova NS, Polyakova VO, Trofimov AV, Sevostyanova NN, Kvetnoy IM. Peptidergic regulation of thymopoiesis and immune function in aging. Adv Gerontol. 2011;24(1):38-53. View Scientific Paper →
Khavinson VK, Kuznik BI, Tarnovskaya SI, Lin'kova NS. Peptides and CCL11 and HMGB1 as molecular markers of aging: review. Adv Gerontol. 2014;27(2):359-66. View Scientific Paper →
Khavinson VK, Pendina AA, Efimova OA, et al. Effect of peptide AEDG on telomere length and mitotic index of PHA-stimulated human blood lymphocytes. Bull Exp Biol Med. 2019;168(1):141-144. View Scientific Paper →