RU2278677C2 - Agent for erythropoiesis stimulation and elimination of iron deficiency - Google Patents

Abstract

FIELD: medicine, pharmacology.

SUBSTANCE: agent for stimulation of erythropoiesis and elimination of iron deficiency comprises hemoglobin obtained from animal blood containing methemoglobin additionally. The ratio of hemoglobin and methemoglobin in the agent = (25-75)-(75-25) wt.-%. The agent shows the expressed heme-stimulating effect. The agent can be used in producing medicinal agents and biologically active supplements.

EFFECT: valuable medicinal properties of agent.

4 dwg

Description

The invention relates to medicine and can be used in pharmacology, the food industry in the manufacture of drugs and dietary supplements.

A wide range of drugs is known that solve the problem of stimulating erythropoiesis and eliminating iron deficiency. So, for these purposes, it is proposed to use products containing germinated grain / RF patent 2132135 /, extracts of the tripartite series / RF patent 2206998 /, narrow-leaf fireweed / RF patent 2206997 /, licorice root / RF patent 2206996 /, ginseng / RF patent 2197868 /, as well as iron-containing mineral water / RF patent 2116038 /. The disadvantage of all these known means is their low efficiency.

Known agent that affects hematopoiesis obtained from the blood of deer / RF patent 2017493, A 61 K 35/14, 1994 /. Since deer live only in a certain, limited territory of the globe, the source of the preparation is limited by the scope of this territory. In addition, since blood must be taken during the period of greatest physiological activity, the time and duration of obtaining raw materials is limited. The drug itself is lysed blood, partially purified from large fragments, by filtration, however, low-molecular substances contained in the blood, including undesirable ones for consumers, remain in the well-known product. These include toxins, hormones, bile pigments, cholesterol, various inorganic substances, etc. All these substances can be contained in excess in the blood of deer also because this species of animals does not have a gall bladder, namely with bile, mainly the listed substances are excreted. Finally, the most important multicomponent drug is extremely difficult to standardize.

It is known that intravenous administration of hemoglobin stimulates erythropoiesis. However, for intravenous administration, the hemoglobin preparation must be completely purified from phospholipids and endotoxins, in addition, hemoglobin must be stabilized in the form of a tetramer, since when introduced into the blood, native hemoglobin dissociates with the formation of dimers that have a nephrotoxic effect. To obtain injectable forms, sterilization conditions must be observed when hemoglobin is excreted, and, in addition, sterilization of the drug at the final stage of isolation is necessary.

The closest in essence to the proposed is the tool proposed in US patent 5631219, A 61 K 038/16, 1997, where it is proposed to use especially pure hemoglobin, which is injected or orally, to stimulate erythropoiesis. This tool is selected for the prototype. However, obtaining hemoglobin is a labor-intensive process, in addition, in the process of isolation, part of the hemoglobin is oxidized and passes into methemoglobin. To prevent this process, the production of hemoglobin should be carried out under conditions of strict temperature at a temperature of 4 ° C, as well as deoxygenation with nitrogen.

It is known that the protoporphyrin complex (i.e., the non-protein part of hemoglobin), which contains iron in the trivalent (oxide) form — hemin, also has the ability to stimulate erythropoiesis when administered intravenously. However, the isolation of hemin requires effort, and in addition, its injectable form requires sterility.

The problem solved by the invention is to obtain a drug to stimulate erythropoiesis, not inferior in effectiveness to the prototype, but much cheaper than the latter, which could be used to eliminate iron deficiency.

To solve this problem, a tool is proposed to stimulate erythropoiesis and eliminate iron deficiency, including hemoglobin obtained from animal blood. A distinctive feature of the claimed drug is that it additionally contains methemoglobin in a ratio of 25-75: 75-25% wt. respectively.

The introduction of methemoglobin into the preparation can significantly reduce technological costs for the separation of hemoglobin and methemoglobin. Moreover, it unexpectedly turned out that the effectiveness of a hemoglobin-containing preparation in the metaphor practically does not decrease with respect to pure hemoglobin.

The drug is prepared as follows. The blood of animals is washed from whey proteins with 0.9-1.0% sodium chloride solution. The red blood cells are then lysed with four volumes of distilled water. The stroma of red blood cells is removed by filtration through porous membranes. The resulting solution was lyophized or dried by evaporation of moisture. Isolation of the product is carried out at room temperature in an air atmosphere.

The drug is administered orally. The intake rate for the purpose of enhancing erythropoiesis is from 100 mg to 1 g. A similar norm is also used to eliminate iron deficiency.

To prove the achievement of the claimed result, the following information obtained as a result of an experiment in mice can be given. To obtain erythropenia in mice, a platinum preparation was used. Two preparations were used in the experiments: one with a hemoglobin content of 40% and methemoglobin of 60%, and the second with a content of hemoglobin of 60% and methemoglobin of 40%, which showed identical results.

The drawings show materials on monitoring the state of red blood in animals after prescribing carboplatin preparations that were simultaneously exposed to the proposed drug (the chemotherapeutic drug and the proposed drug were administered simultaneously for 5 days; point “O” in the drawings indicates the level of the indicator in intact healthy animals before administration of cytostatic and proposed funds). Figure 1 shows the content of red blood cells in mice at different times, where 1 is a graph of the change in red blood cells after a five-day course of administration of carboplatin and the claimed funds, 2 is a graph of the change in red blood cells after a five-day course of administration of carboplatin. Figure 2 shows the hemoglobin content in the blood of mice at different times, where 3 is a graph of the change in hemoglobin content after a five-day course of administration of carboplatin and the claimed funds, 4 is a graph of the change in hemoglobin content after a five-day course of administration of carboplatin. Figure 3 presents the change in blood hematocrit in mice at different times, where 5 is a graph of hematocrit changes after a five-day course of carboplatin administration and the claimed funds, 6 is a graph of hematocrit changes after a five-day course of carboplatin administration. Figure 4 presents the change in the content of reticulocytes in the blood of mice at different times, where 7 is a graph of changes in reticulocytes after a five-day course of administration of carboplatin and the claimed funds, 8 is a graph of changes in reticulocytes after a five-day course of administration of carboplatin.

The introduction of the claimed funds in a five-day course during the formation of anemia under the action of cytostatics. As the results of studies showed, the introduction of the claimed drug simultaneously with the cytostatic carboplatin had, as a consequence, the development of mild anemia with a decrease in the number of red blood cells, hematocrit and hemoglobin level. It should be noted that the degree of anemia in the control group (carboplatin without the claimed drug) for the listed signs was expressed to a greater extent and amounted to moderate severity (Fig.1-3).

The number of reticulocytes decreased significantly towards the end of carboplatin administration and remained at a low level (14000 ± 1916) for another 5 days, and the level of decrease in the number of reticulocytes did not differ at all in the group with the introduction of the proposed drug. However, in the subsequent periods of observation, the rate of recovery of the number of reticulocytes in the group of mice treated with the previously claimed tool exceeded that in the control (reaching 388000 ± 55564 versus 214000 ± 22992 in the control by 20 days after the administration of cytostatic, figure 4).

Claims (1)

Means for stimulating erythropoiesis and eliminating iron deficiency, including hemoglobin obtained from animal blood, characterized in that it additionally contains methemoglobin in a ratio of 25 ÷ 75: 75 ÷ 25% wt. respectively.

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