Technical Field

The invention is related to a composition comprising the immune plasma extracellular vesicles developed against the COVID-19 viral infection and metabolites which are the cellular elements, vitamins, minerals, fatty acids, nucleic acids, DNA and RNA fragments, proteins, and/or enzymes.

State of Art (Prior Art)

COVID-19 (SARS-CoV-2), which is known to be a viral respiratory tract illness that emerged first in the Wuhan province of China, belongs to the coronavirus family which was witnessed before with SARS and MERS, infecting through droplets. Fever, cough, and malaise were considered as the most prominent symptoms of COVID-19, which took a hold of the world. Several medication studies were made to cure Covid- 19. However, the said medications have been found to be insufficient in treating the disease and preventing the infection of the virus. In addition, the medications that are used create cellular and tissular toxicity with low biocompatibility. Besides, they cause high production costs.

Brief Description and Objects of the Invention

The main object of the invention is to obtain a pharmaceutical composition with high biocompatibility that does not contain toxic substances that will harm cells and tissues.

The object of the invention is to prepare a pharmaceutical composition that is more effective, easily applicable, and affordable than the readily available medications for both preventing the COVID-19 virus infection and decreasing cellular inflammation.

Another object of the invention is to remedy the cellular and tissular damage in the damaged organs, alleviate the damage-induced inflammation (burning), eliminate the virus- and inflammation-induced vasocontraction, and provide tissue hemostasis.

Another object of the invention is to prepare a composition to be used in the preparation of the medication to be used in the treatment of patients with CO VID-19 characterized by severe acute respiratory failure (pneumonia).

Description of the Figures Describing the Invention

Figure 1: Extracellular vesicle characterization. Electron microscope image showing morphological features and size measurements of the immune plasma exosomes.

Detailed Description of the Invention

The invention is related to a pharmaceutical composition that comprises a therapeutically effective amount of extracellular vesicle obtained from the immune plasma of a patient who had suffered from COVID-19 and recovered as the active substance, and at least one pharmaceutically acceptable excipient.

Extracellular vesicles (EVs) are the saccules synthesized by cells that are used as ‘cell free’ therapy without cells. They play a role in repairing the damage that occurs in the cells, tissues, organs, or organisms or inter-cellular communication. In the convalescent plasma, the body’s immune response against the pathogen and a protective co-factor are present. The advantage of using EVs and not just the plasma is to get rid of cellular waste and other useless components in the plasma. The exosome goes directly to the damaged area and enters the cell, both preventing the entry of the virus into the cell, and taking part in repair mechanisms.

In the invention, the convalescent plasma is the immune plasma of the patient who had suffered from COVID-19 and recovered. The composition of the invention is used for the treatment of patients with COVID-19 characterized by severe acute respiratory failure (pneumonia). The composition of the invention comprises a therapeutically effective amount of extracellular vesicle and at least one pharmaceutically acceptable excipient. The pharmaceutically acceptable excipient may be PEG (polyethylene glycol), DEX (Dextran), sucrose. Here, the effective amount is 107-1012 particles in 0,l-20mL saline per application. The composition of the invention is administered by inhalation or topically and contains dextran as an excipient.

The exosome is isolated from the blood plasma obtained from the patient who had suffered from Covid- 19 and whose antibody test came as positive. For the isolation of immune plasma exosomes used within the scope of the invention, isolation is performed with the isolation method with a double-phase liquid system.

Extracellular Vesicle Isolation:

The prepared plasma is mixed with the isolation solution in 50mL falcons by inverting 20 times at a ratio of 1 : 1 and centrifuged at 1,000 x g for 10 minutes to achieve phase separation. The upper phase, which corresponds to approximately 90% of the total volume is discarded and the lower phase, where small extracellular vesicles are accumulated is collected and stored at -80 degrees until use.

As seen in Figure 1, the isolated extracellular vesicles are observed as spherical and in the size range of 50-200 nm, as they should be.

As a result of the analysis performed by determining the protein content of the extracellular vesicles obtained from convalescent immune plasmas, and as a result of the analysis performed using the ontology program of the KEGG gene bank, 64 proteins related to COVID-19 were detected in these extracellular vesicles and these proteins act against the COVID-19 virus and inflammation in the body in the immune system.

Table 1. List of proteins that are present in the exosomes obtained from the convalescent immune plasma as a result of the analysis performed with the KEGG Ontology data bank and that are related to “Coronavirus disease - COVID-19”