RU-2861484-C1 - INFUSION AGENT FOR RESTORING CIRCULATING BLOOD VOLUME IN BLOOD LOSS IN ANIMALS

RU2861484C1RU 2861484 C1RU2861484 C1RU 2861484C1RU-2861484-C1

Abstract

FIELD: pharmaceuticals; veterinary medicine. SUBSTANCE: invention relates to an agent based on polymerised bovine haemoglobin for activating natural mechanisms for restoring circulating blood volume in acute blood loss, containing: polymerised bovine haemoglobin 0.1-0.3 g; dextrose – 0.01 g; sodium chloride – 0.08 g; ascorbic acid – 0.0042 g; potassium chloride – 0.002 g; calcium chloride – 0.002 g; sodium bicarbonate – 0.002 g; N-acetyl-L-cysteine – 0.0225 g; water for injection – up to 2 ml, where the ratio of components is given per 2 ml. EFFECT: activation of natural mechanisms for restoring circulating blood volume at low concentrations and doses of administration of the agent solution. 3 cl, 1 tbl, 1 ex

Inventors

KHOMYAKOVA Tatiana Ivanovna
ROZIEV RAKHIMDZHAN AKHMETDZHANOVICH
GONCHAROVA ANNA YAKOVLEVNA
KALASHNIKOVA Elena Evgenievna

Dates

Publication Date: 20260505
Application Date: 20251111

Claims (5)

1. A product based on polymerized bovine hemoglobin for activating natural mechanisms for restoring circulating blood volume in acute blood loss, containing:
polymerized bovine hemoglobin 0.1-0.3 g dextrose 0.01 g sodium chloride 0.08 g ascorbic acid 0.0042 g potassium chloride 0.002 g calcium chloride 0.002 g sodium bicarbonate 0.002 g N-acetyl-L-cysteine 0.0225 g water for injection up to 2 ml,
where the ratio of components is given per 2 ml.
2. The agent according to paragraph 1, wherein the agent is made in the form of a concentrate for the preparation of infusion solutions.
3. The agent according to item 1, wherein the volume of the agent is 1, 2, 5 or 10 ml.

Description

Field of technology to which the invention relates The invention relates to veterinary science, specifically to pharmacology, and concerns an infusion agent based on polymerized hemoglobin, which activates natural mechanisms for restoring circulating blood volume (CBV) in cases of blood loss in animals in cases of surgery or trauma. State of the art One of the main products of hemoglobin breakdown in the body is carbon monoxide (carbon monoxide CO), which under normal conditions is a colorless, odorless gas that is slightly lighter than air (molar mass 28.01 g/mol < 28.98 g/mol) [1,2]. CO is a product of the breakdown of hemoglobin and myoglobin, as well as other heme-containing proteins (cytochromes, cytochrome oxidase, catalase). In the human body, CO is a metabolite that participates in a number of vital processes. Endogenous CO is formed in the body during the action of the enzyme inducible heme oxygenase (HO-1) on heme [3]. CO production in the human body averages 16.4 μmol/h, reaching 500 μmol (12 ml) per day [4]. It has been established that hypoxic stimulation of HO-1 activity in the heart with subsequent increase in endogenous CO production leads to a decrease in coronary vascular tone and an increase in myocardial blood supply [5,6]. CO has been shown to have a protective effect on cardiomyocytes of isolated animal hearts under conditions of ischemia-reperfusion modeling [7]. Exogenous CO also reduced the severity of reperfusion injury in models of acute myocardial infarction in mice [8]. On the other hand, elevated levels of endogenous CO in the body upon inhalation are associated with a significant increase in the risk of developing cardiovascular diseases [9]. The phenomenon of CO-induced vasorelaxation was first described in 1984 by McGrath and Smith on the coronary arteries of rats [10]. It was soon established that this effect was not due to endothelial activity [11]. It was found that CO promotes relaxation of the tail artery, the thoracic aorta of the rabbit, the carotid arteries of the dog, the coronary mesenteric and femoral arteries of pigs and guinea pigs, the hepatic veins of the rat and many other blood vessels [12]. According to the literature, over the past decade, two types of methods for administering CO into the human body have been developed: direct and indirect administration of CO. Indirect administration of CO avoids toxicity compared to direct administration of CO. When developing methods for indirect administration of CO, developers are faced with such problems as lack of targeting and problems with controlling the dosage of CO. Alternative strategies are CO-releasing molecules (CORMs) [13], which are transition metal carbonyl complexes such as [ Mn2 (CO) 10 ] (CORM 1) and [ RuCl2 (CO) 3 ] 2 (CORM-2) and later synthesized water-soluble forms [Ru(CO) 3Cl (glycinate)] (CORM-3), as well as ALF492, CORM-A1, and ALF186 [13]. When these molecules are administered to the human body, CO is released from these compounds at a controlled rate under certain conditions and/or triggers. Such reactions are useful for achieving targets at the cellular level with a controlled release of CO. However, on the other hand, CORMs release toxic metal residues (i-CORMs) upon degradation. In order to improve the characteristics of CO precursor in CORMs, several new methods for the formation of CORMs have been developed, such as micellization, the use of peptides, vitamins, etc. [14], but to date, CORMs with sufficiently high efficiency and low toxicity when introduced into the body have not been obtained. Analogues of polymerized bovine hemoglobin are known and proposed as blood substitutes with oxygen-carrying properties. These include Gelenpol, Hemopur, and the blood substitute patented by RU2203087, which is derived from donor blood. Gelenpol (patent RU2132687) is a mixture of hemoglobin tetramers and oligomers of varying chain lengths. The oligomers are obtained by cross-linking hemoglobin tetramers with glutaraldehyde and modified with glutamic acid. Hemopur is derived from bovine erythrocyte hemoglobin (patents US5084558 and US6506725). Blood substitutes with oxygen transfer function are also known (patent RU2340354 and patent RU2361608). To replenish blood loss, it is proposed to use whole blood (patent RU2238680), autologous plasma (patents RU2409395, RU2704464), or autologous red blood cell (patent RU240995) from patients' blood collected before surgery. Patent RU2325924 proposes a method for treating patients with massive blood loss, which involves administering polymerized human hemoglobin obtained from donor blood in volumes no less than the volume of the circulating blood volume. Based on the mechanism of action of polymerized hemoglobin as an oxygen carrier, as well as the goal of increasing the hemoglobin concentration to circulating hemoglobin values above 5.0 g/L, the administered volume should be at least 5 liters. A key difference between the proposed drug and the drug in patent