Neovasculgen^® (Lyophilisate) Instructions for Use

Marketing Authorization Holder

Nextgen LLC (Russia)

Manufactured By

FSBI Hematology Research Center Of Roszdrav (Russia)

Contact Information

Human Stem Cell Institute JSC (Russia)

ATC Code

V03AX (Other therapeutic agents)

Dosage Form

Neovasculgen®

Lyophilizate for preparation of solution for intramuscular injection 1.2 mg: fl. 1 pc.

Dosage Form, Packaging, and Composition

Lyophilizate for preparation of solution for intramuscular injection in the form of a white powder.

Excipients: dextrose monohydrate – 60 mg, sodium hydrogen phosphate dodecahydrate – 3.94 mg, sodium dihydrogen phosphate dihydrate – 0.16 mg.

Vials (1) – cardboard packs.

Clinical-Pharmacological Group

Stimulator of endothelial cell proliferation, promoting revascularization in occlusive peripheral artery disease

Pharmacotherapeutic Group

Tissue repair stimulant

Pharmacological Action

The drug Neovasculgen^® is a highly purified supercoiled form of the plasmid pCMV-VEGF165, encoding the vascular endothelial growth factor (VEGF) under the control of a promoter (DNA regulatory region).

The recombinant plasmid DNA consists of the following components: a fragment of the regulatory region (22 nucleotide pairs) that determines gene transcription, the VEGF minigene, the expression of which synthesizes the VEGF isoform consisting of 165 amino acids, a splicing signal, a polyadenylation signal and the SV40 transcription terminator, which ensure the synthesis of mature gene RNA, and auxiliary regions necessary for the efficient biosynthesis of plasmid DNA in the cells of the producer strain Escherichia coli.

When molecules of this plasmid penetrate into mammalian cells, VEGF is produced, which stimulates endothelial cells, leading to the growth of blood vessels (vascularization) in the area of administration.

Endothelial cells are involved in such diverse processes as vasoconstriction and vasodilation, antigen presentation, and also serve as very important elements of all blood vessels – both capillaries and veins or arteries.

Thus, by stimulating endothelial cells, VEGF plays a central role in the process of angiogenesis.

There are two different but structurally similar VEGF receptors located on the surface of vascular endothelial cells.

These receptors, known as VEGF receptor type 1 (Flt-1) and VEGF receptor type 2 (KDR/Flk-1), are receptor tyrosine kinases that undergo phosphorylation after binding to the VEGF ligand.

Activation of these receptors leads to the initiation of numerous intracellular post-receptor signaling cascades that trigger angiogenesis.

The penetration of the plasmid into cells is a spontaneous process, and plasmid DNA cannot multiply in mammalian cells. The molecular weight of the plasmid is 2817091.85 g/mol. Size – 4559 base pairs. A feature of supercoiled circular DNA is its sensitivity to the breakage of one of the 9116 phosphodiester chemical bonds. A DNA molecule with a single broken bond loses its supercoiling, turning into a relaxed circular form (related compound).

In experiments, Neovasculgen^® stimulated the proliferation of human endothelial cells, comparable to recombinant vascular endothelial growth factor, and also Neovasculgen^® significantly stimulated the growth of mouse blood vessels.

The drug was created as a therapeutic agent to reduce the frequency of amputation and mortality in the population of patients with chronic limb ischemia, especially in patients who cannot undergo standard revascularization for occlusive peripheral artery disease.

Pharmacokinetics

No data available.

Indications

• As part of complex therapy for revascularization in ischemia of the lower extremities of atherosclerotic origin (stage IIa-III according to A.V. Pokrovsky-Fontaine).

ICD codes

Dosage Regimen

The drug is administered intramuscularly, twice, at a dose of 1.2 mg with an interval of 14 days, if possible, in a place as close as possible to the ischemic area.

The drug, diluted according to the instructions, after standard skin treatment, observing the rules of asepsis, is administered fractionally through several injections so that the entire muscle mass of the affected segment is infiltrated with the solution.

Adverse Reactions

Possible allergic reactions.

Contraindications

• Children under 18 years of age;
• Hypersensitivity to the components of the drug.

Use in Pregnancy and Lactation

The drug is contraindicated during pregnancy and lactation.

Pediatric Use

Use in children and adolescents under 18 years of age is contraindicated.

Special Precautions

Before use, add 1.2 ml of water for injections to the contents of the vial.

It is necessary to wait for the complete dissolution of the drug (within 5-10 minutes).

Before administration to the patient, the solution must be at room temperature.

Treatment with the drug should be carried out under the supervision of surgeons in outpatient or inpatient settings.

Effect on the ability to drive vehicles and mechanisms

Caution should be exercised, as there are no data on the effect of the drug on the ability to drive vehicles and mechanisms.

Overdose

No data available.

Drug Interactions

No data available.

Storage Conditions

The drug should be stored in a light-protected place at a temperature from 2°C (35.6°F) to 8°C (46.4°F).

Shelf Life

Shelf life – 2 years.

Dispensing Status

The drug is dispensed by prescription.

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.