RU2308287C2 - Hemostatic preparation - Google Patents

Abstract

FIELD: medicine, experimental medicine.

SUBSTANCE: for the purpose to stop hemorrhages it is necessary to introduce fibrin-monomer for a rabbit at the dosages ranged 0.5-5 mg/kg animal body weight. In case of intravenous injection at the dosages ranged 0.5-5 mg/kg animal body weight fibrin-monomer is of immediate hemostatic action and has no influence upon basic hemostatic parameters.

EFFECT: higher efficiency.

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Description

The invention relates to medicine and can be used to stop bleeding.

Blood proteins are known that have hemostatic activity and are used to stop bleeding, including those serving as replacement therapy for hemorrhagic diathesis against a background of deficiency of certain coagulation factors (factors VIIa, VIII, IX, XIII, fibrinogen). Details of these proteins at the present level are set forth in the monograph by D.A. Zubairova "Molecular basis of blood coagulation and thrombosis", Kazan, FEN, 2000.

We found that the blood protein fibrin monomer has hemostatic activity under intravenous conditions.

To stop bleeding, the formation of a fibrin clot is necessary - a strong mesh structure of polymer fibrin. The formation of a fibrin clot looks like a cascade of reactions. The main final step is the formation of fibrin from fibrinogen. Under the action of thrombin, fibrinogen turns into monomeric fibrin, which spontaneously polymerizes, forming a three-dimensional network - the basis of a blood clot. In the literature, fibrin monomer is considered as a passive material from which a complete fibrin polymer is built. We found that fibrin monomer, when administered intravenously, has a pronounced and persistent hemostatic effect. This is evidenced by a series of experiments, during which it was established that with the intravenous administration of various doses of the drug, the time for stopping bleeding decreases.

At the moment, the clinic uses drugs whose action is aimed at reducing bleeding time. Ethamsylate has a hemostatic effect and is widely used in clinical practice. The initial hemostatic effect with intravenous administration develops after 1-2 hours, maximum after 12 hours or more, which completely eliminates the use of this drug in extreme situations.

The genetically engineered drug "Novoseven" is also used, but the use of this product is limited due to its high cost - 1.2 mg (single dose) costs an average of 1,500 euros.

Protein fibrin monomer has an instant hemostatic effect and the cost of its manufacture is relatively low.

Specific examples of the hemostatic effect of fibrin monomer.

Example No. 1.

The effect of the hemostatic effect of the Fibrin monomer was studied in laboratory conditions on a 4 kg Chinchilla rabbit. Laparotomy was performed using a longitudinal section along the white line of the abdomen. Intestine was taken out into the wound, limiting it with napkins moistened with warm saline and the front surface of the liver. Using a special device-limiter, a superficial liver wound of about 1.5 cm square and a depth of about 0.1 cm was applied with a sharp razor. The bleeding stopping time required for comparison was measured. As a control, we stopped the bleeding by tightly pressing a tampon from a gauze napkin to the wound surface. A solution of the drug was administered intravenously at a dose of 3 mg / kg of animal weight.

The bleeding stopped 3, 15, 30, 60, 90, and 120 minutes after the drug was administered for 240, 165, 165, 180, 340, 360 seconds, respectively, with a control of 480 seconds.

Example No. 2.

The influence of the hemostatic effect of the Fibrin monomer was studied in laboratory conditions on a 3.8 kg chinchilla rabbit. Laparotomy was performed using a longitudinal section along the white line of the abdomen. Intestine was taken out into the wound, limiting it with napkins moistened with warm saline and the front surface of the liver. Using a special device-limiter, a superficial liver wound of about 1.5 cm square and a depth of about 0.1 cm was applied with a sharp razor. The bleeding stopping time required for comparison was measured. As a control, we stopped the bleeding by tightly pressing a tampon from a gauze napkin to the wound surface. A solution of the drug was administered intravenously at a dose of 0.5 mg / kg of animal weight.

The bleeding stopped 3, 15, 30, 60, 90, and 120 minutes after drug administration occurred in 285, 195, 210, 300, 360, 480 seconds, respectively, with a control of 510 seconds.

Example No. 3.

The influence of the hemostatic effect of the Fibrin monomer was studied in laboratory conditions on a 3.9 Chinchilla rabbit. Laparotomy was performed using a longitudinal section along the white line of the abdomen. Intestine was taken out into the wound, limiting it with napkins moistened with warm saline and the front surface of the liver. Using a special device-limiter, a superficial razor of the liver of about 1.5 cm square and a depth of about 0.1 cm was applied with a sharp razor. The bleeding stopping time required for comparison was measured. As a control, we stopped the bleeding by tightly pressing a tampon from a gauze napkin to the wound surface. The drug solution was administered intravenously at a dose of 1 mg / kg of animal weight.

The bleeding stopped 3, 15, 30, 60, 90, and 120 minutes after drug administration occurred for 225, 225, 225, 270, 360, 420 seconds, respectively, with a control of 420 seconds.

Example No. 4.

The influence of the hemostatic effect of the Fibrin monomer was studied in laboratory conditions on a 3.8 kg chinchilla rabbit. Laparotomy was performed using a longitudinal section along the white line of the abdomen. Intestine was taken out into the wound, limiting it with napkins moistened with warm saline and the front surface of the liver. Using a special device-limiter, a superficial liver wound of about 1.5 cm square and a depth of about 0.1 cm was applied with a sharp razor. The bleeding stopping time required for comparison was measured. As a control, we stopped the bleeding by tightly pressing a tampon from a gauze napkin to the wound surface. A solution of the drug was administered intravenously at a dose of 5 mg / kg of animal weight.

The bleeding stopped 3, 15, 30, 60, 90 and 120 minutes after the drug was administered in 140, 100, 100, 170, 180, 270 seconds, respectively, with a control of 255 seconds.

Example No. 5.

For comparison, we conducted an experiment with an assessment of the hemostatic effect of the known preparation of dicinone, produced in a concentration of 12.5%, the volume of the ampoule is 2 ml. The experiments were conducted in laboratory conditions on a chinchilla rabbit weighing 3.5 kg. Laparotomy was performed using a longitudinal section along the white line of the abdomen. Intestine was taken out into the wound, limiting it with napkins moistened with warm saline and the front surface of the liver. Using a special device-limiter, a superficial razor of the liver of about 1.5 cm square and a depth of about 0.1 cm was applied with a sharp razor. The bleeding stopping time required for comparison was measured. As a control, we stopped the bleeding by tightly pressing a tampon from a gauze napkin to the wound surface. A solution of the drug in a dose of 0.2 ml was intravenously administered.

Stopping bleeding after 3, 15, 30, 60, 90 and 120 minutes after drug administration occurred in 521, 510, 503, 495, 486, 498 seconds, respectively, with a control of 505 seconds.

Thus, in its activity, the fibrin monomer exceeds the effect of dicinone widely used in our country.

Claims (1)

The use of fibrin monomer to stop bleeding in an experiment when administered intravenously in doses of 0.5 to 5 mg / kg of animal weight.