RU2079307C1 - Antianemic agent - Google Patents

Abstract

FIELD: medicine, veterinary science. SUBSTANCE: antianemic agent has additionally iron-containing component - blood hemoglobin purified from hazard impurities and microorganisms and containing divalent iron from agriculture animals, beet juice after sublimation drying, ascorbic and/or citric acid and simple sugars taken at the following ratio, wt.-%: blood hemoglobin from agriculture animals, 20-40; sublimated beet juice, 30-70; ascorbic or citric acid, 10-40; and simple sugars (glucose, fructose, lactose), 20-60. Properties of antianemic agent: full absence of by-side effects, use of high doses for severe anemia treatment, high biological availability of iron hemoglobin (easily assimilated divalent chelate heme form), rapid and expressed curative and prophylaxis effect, additional source of essential amino acids. EFFECT: enhanced effectiveness, biological value, harmless. 6 tbl

Description

 The invention relates to medicine and veterinary medicine, namely, to the treatment and prevention of iron deficiency conditions in humans and animals.

 According to the WHO, every 4 people in the world have iron deficiency, that is, suffers from iron deficiency anemia. According to preliminary estimates, up to 60 million people in Russia are susceptible to this disease of varying severity. The development of this disease contributes to malnutrition (especially a sharp decrease in meat consumption of the main source of iron in the human body).

 For the prevention of iron-deficient compounds in humans and animals, preparations based on inorganic and organic iron salts are widely used [1]. They are used both for the enrichment of food products (USA, England, Sweden, Holland, etc.), and as medications.

 The most widely used in clinical practice for the treatment of anemia are drugs based on ferrous sulfate (feospan, conferon, tardiferron, actiferrin, ferrogramed and others), ferrous sulfites (ferrocal, ferroplex), as well as chloride (hemofer, aloe syrup with iron ) and iron lactase. The daily dose of iron preparations should be 4-5 mg of elemental iron per 1 kg of body weight, it is prescribed 1 hour before meals in 3 divided doses. Treatment is continued for at least 3 months with constant monitoring of the coefficient of transferrin saturation with iron (until its normalization is 30-60%). Currently, a large number of drugs are used, the effectiveness of which is determined not so much by the iron content as by the degree of its absorption in the intestine. The antianemic effect of many drugs is enhanced by a combination of iron with ascorbic acid (ferroplex, iron ascorbate, phytin (phytoferolactol), copper (hemostimulin), aloe and citric acid (ferraloe), with phosphorus (glycerophosphate), amino acids (for example, D, L-serine - actiferrin ). For better absorption, iron preparations should be prescribed in combination with reducing or acidifying agents (ascorbic acid, gastric juice, 1% hydrochloric acid) and enzymes (pepsin, pancreatin). In Russia for intravenous Fercoven (contains iron sugar and cobalt gluconate) is proposed for intramuscular administration, and colloidal compounds of iron sugar (ferrum-lek), iron dextrans (astrofen, imferon), ferbitol (with sorbitol) are used for intramuscular administration.

The main disadvantages of existing drugs based on inorganic and organic iron salts are:
low efficiency, which leads to the need to take significant doses of them, causing heartburn, lack of appetite, nausea, vomiting, belching, pain in the stomach, diarrhea;
poor tolerance (irritation of the small intestine, dyspepsia) in almost 10% of adult patients;
due to the binding of iron in the intestines of iron by inorganic hydrogen sulfide, which is a physiological stimulator of peristalsis, constipation occurs, insoluble iron sulfide is formed, staining stool black;
the need for additional use of ascorbic acid, other vitamins, gastric juice, hydrochloric acid to increase the digestibility of iron;
a drop in blood pressure, hyperemia of the face, neck, a feeling of constriction in the chest, back pain, headache, dizziness, the frequent occurrence of allergic reactions and even shock states of patients;
may cause darkening of the color of the teeth;
there is a high probability of acute poisoning in case of an overdose;
they are the cause (injections of iron dextran) of systemic lesions in the form of drug purpura, as well as local inflammatory and dystrophic changes (local lipomyodystrophy);
There are reports of carcinogenicity of certain drugs, for example, iron dextrans.

Also known is a drug of a similar purpose called "Hematogen" [2] Children's "Hematogen" is produced by stirring when heated to 122-125 ^o With sugar syrup, condensed milk and molasses to obtain a dense mass. Then it is cooled to 65-70 ^o C and black food albumin is added with stirring. "Hematogen" is prescribed as a therapeutic and nutritional drug for anemia, in the postoperative period, after infectious and other diseases.

 Despite the absence of obvious negative effects during its use, the Hematogen has a very weak therapeutic and prophylactic effect and therefore is considered as an auxiliary therapeutic and nutritional agent for anemia.

 Of the known effective drugs used in the treatment and prevention of iron deficiency conditions, the composition of the components is closest to the declared food anti-anemic supplement "Hemostimulin" (VFS - 42-153-72), which is produced in Russia. This preparation is obtained from black food albumin (dried hemolized blood of cattle). It used a combination of blood proteins with a preparation of lactic iron and copper sulfate. To obtain "Hemostimulin" to 25 parts of albumin add 50 parts of lactic iron, 1 part of copper sulfate. 1 tablet of "Hemostimulin" contains edible blood 0.123 g, iron lactate 0.246 g, copper sulfate 0.005 g. The drug is taken 1 tablet 3 times a day with meals, washed down with diluted hydrochloric acid (10-15 drops per half glass of water). The course of treatment lasts 3-6 months or more.

This drug also has a number of significant disadvantages:
the need for additional daily intake of 1.5-2 glasses of 1% hydrochloric acid;
manifestation of side effects in the form of nausea, impaired activity of the gastrointestinal tract, etc.

 low effectiveness of the drug, which does not allow its use for the treatment of severe forms of anemia; significant inconvenience when using this form for the prevention of anemic conditions in everyday life.

 The invention is aimed at creating an anti-anemic agent that would have higher efficiency, biological value and harmlessness than known examples.

 For this purpose, an anti-anemic agent is used on the basis of hemoglobin from agricultural animals purified from harmful impurities and microorganisms, containing ferrous iron, as well as freeze-dried beet juice, ascorbic or citric acid and simple sugars in the following ratio of components, wt. blood hemoglobin of farm animals 20-40; freeze-dried beetroot juice 30-70; ascorbic or citric acid 10-40; simple sugars (glucose, fructose, lactose) 20-60.

 Hemoglobin from the blood of farm animals with a basic substance content of more than 80% (brand "B") was obtained by separating blood into plasma and red blood cells, performing hemolysis of the latter, purification from ballast substances by filtration, concentration using ultrafiltration, followed by sterilizing filtration of the target product, and if necessary, freeze-drying (spray) drying.

 This method provides the production of hemoglobin, which has important advantages over existing branded preparations of this protein, namely: the complete absence in the technology for its production of potentially harmful reagents (inorganic salts and organic solvents), microbiological purity, as well as maintaining the native structure of hemoglobin containing iron in a highly available divalent hemin form.

 The main indicators of hemoglobin are given in table 1.

 Hemoglobin, according to the degree of purification from other proteins, corresponds to branded hemoglobin preparations that are used in laboratory and scientific research. This is convincingly confirmed by the results of electrophoretic separation of hemoglobins produced by different manufacturers.

 In the table. 2 shows the expanded indicators of bovine hemoglobin brand "B", which was used in preliminary tests on piglets and in the clinic for patients.

 The data table. 2 indicate that the developed technology makes it possible to produce a product with fairly high quality indicators. This is especially true of the absence of heavy metal impurities (cadmium, mercury, lead) and arsenic in hemoglobin, as well as the microbiological purity of the product.

 These data additionally confirm the fact that the iron-containing component based on hemoglobin, which is part of the anti-anemic agent, makes it a valuable additional source of iron, other trace elements, as well as the most important essential amino acids. Moreover, in terms of amino acid content, the product far exceeds their presence in beef, as well as FAO norms for human needs. Hemoglobin contains 0.285 g% of iron, which is close to the theoretical 0.34% and makes it truly a natural source of iron, which is in the form of a hemin chelate available to the body.

 Hemoglobin, produced by foreign companies for analytical and laboratory studies, is not suitable for direct use as part of an anti-anemic agent. First of all, due to the high content of heavy metals and microbial contamination. In this regard, branded hemoglobin preparations require mandatory additional purification.

 In addition, most branded reactive hemoglobins are poorly and not completely soluble in distilled water. Hemoglobin NPF Mobitek dissolves quickly and completely in a minimum amount of water. Convincing evidence that the tetrameric hemoglobin molecule (M.V. 6400) easily dissociates into subunits is the electrophoretic separation of hemoglobins produced by Mobitek NPF under denaturing conditions in the presence of sodium dodecyl sulfate and mercaptoethanol, which confirms the “nativeness” of the hemoglobin supplement by , for example, with Reanal hemoglobin, which is partially denatured and, moreover, does not completely dissociate into subunits.

 As a positive fact, the absence of significant amounts of nucleic and fatty acids, as well as lipids in general, can be considered in hemoglobin. Insignificant amounts of total lipids make possible long-term storage of freeze-dried protein under ordinary temperature conditions with full preservation of the original properties.

 An anti-anemic agent is obtained by mixing blood hemoglobin, as well as freeze-dried beet juice, ascorbic or citric acid and simple sugars in the above ratios.

 The properties of the obtained funds are presented in table.3.

 Example 1. The use of an antianemic agent for the treatment and prevention of iron deficiency states of piglets.

 To study the biological value and effectiveness, an antianemic agent was used with the following ratio of its constituent components, wt. blood hemoglobin of agricultural animals (TU 2423-001-10837785-96) 25; freeze-dried beetroot juice (TU 10.0418-71-92) 33; ascorbic acid 10; citric acid 10; lactose (OST 49-63-85) 22.

 Beetroot juice is a dark brown powder, easily soluble in water, with a characteristic smell of beetroot. One part freeze-dried beetroot juice powder corresponds to thirty parts fresh beetroot.

 The experiment was conducted under the conditions of a vivarium of the All-Russian Research Institute of Physiology, Biochemistry and Nutrition of Farm Animals (Borovsk) on 29 suckling pigs from their birth to 56 days (7 weeks). Piglets of the experimental group (14 goals) received, in addition to the diet, the proposed product according to the scheme shown in Table 4.

 As the data in Table 5 show, anemia in piglets who did not receive the drug begins to develop immediately after birth and reaches a climax by about three weeks of age. It is a known fact that there is a direct proportional dependence of the severity of anemia on a decrease in blood levels of hemoglobin, red blood cells, and hematocrit.

 In the experimental group, all studied hematological parameters were significantly higher than those in the control. But, if the content of hemoglobin and iron in the blood plasma of experimental piglets reached a physiological level by the age of seven days, then the indicators of erythrocytes and hematocrit were below normal (the lower limit of the norm for hemoglobin is 8.8 g% of erythrocytes 4.6 million / mm hematocrit 33% and plasma iron 70-75 mcg% These data indicate the presence of a latent form of anemia in the piglets of the experimental group.In subsequent experiments, it seems necessary to increase the dose of hemoglobin supplementation by 20-30% Still high hemoglobin and pla barley iron indicates that the body of piglets is able to maintain the level of oxygen consumption unchanged.

 It should be noted the increased total protein in the blood of experimental animals. This indicator is largely associated with biosynthetic processes. By the 56th day, the live weight of the experimental piglets reached 16 ± 0.6 kg (in the control 12.4 ± 0.4 kg). In this case, the average daily gain in live weight in the experimental group was 66 g more than in the control. These results confirm the position that the proposed tool is, on the one hand, a source of essential amino acids, and on the other hand, due to the "cooperative" effect, it increases the absorption of nutrients in the diet as a whole.

 In this regard, it is important to note a significant increase in gammaglobulins in the blood, which indicates an increase in the resistance of the organism of piglets. Associated with this is the higher safety of piglets in the experimental group. It should also be noted the complete absence of negative side effects when feeding them funds.

 Example 2. The use of antianemic drugs for the treatment and prevention of iron deficiency in patients in a clinic.

 For clinical trials, an antianemic agent was made with the following ratio of components, wt. blood hemoglobin of farm animals 30; sublimated beetroot juice 30; ascorbic acid 10; citric acid 10; lactose 20.

 Tests of the drug were conducted at the Medical Radiological Research Center of the Russian Academy of Medical Sciences (Obninsk) for 25 patients with severe iron deficiency syndrome (20 women and 5 men) aged 36 to 54 years. They were given tablets containing 063 g of hemoglobin 3 times a day for 3 weeks.

 Evaluation of the effectiveness of the drug was carried out according to clinical signs, the state of blood parameters, the content of serum albumin, the total iron-binding speed of blood serum (OZHSS). The results of the study are given in table.6.

 From the data given in Table 6, it can be seen that in all groups of patients there is a significant increase (P <0.05) in the hemoglobin content, the number of red blood cells and serum iron with a simultaneous decrease in OGSS (P <0.01).

 Since the main contingent of patients was women, it should be borne in mind that an increase in iron metabolism during the experiment was observed in them against the background of continuing menstruation.

 Additional consumption by patients during the experiment daily of about 2.6 mg of iron also improved their overall well-being (82%), increased physical performance (73%) and appetite (62%). It should be noted the good tolerability of the drug in no case was recorded adverse side effects. This confirms the absence in it of allergenic macromolecular compounds, low molecular weight potentially toxic substances, as well as the microbiological purity of the product. All this in general determines the safety of the proposed anti-anemic agent.

 Thus, the study of the biological value and harmlessness of the hemoglobin-based antanemic agent under clinical conditions has confirmed its high effectiveness in the treatment and prevention of anemic conditions in humans and farm animals.

 The above examples showed the high efficiency of the proposed anti-anemic agent for the treatment and prevention of iron deficiency conditions and allow us to conclude its advantages over foreign and domestic drugs, namely: the complete absence of side effects, which allows the use of high doses of the drug in severe forms of anemia; high bioavailability of hemoglobin iron (easily digestible divalent chelate heme form); quick and pronounced therapeutic and prophylactic effect; drugs are an additional source of essential amino acids.

 Based on the above unique properties of hemoglobin-based agents, it can be concluded that it is promising for the treatment and prevention of iron deficiency anemia in medical and veterinary practice.

Claims (1)

 Antianemic agent, comprising a complex of components, one of which is iron-containing, characterized in that the iron-containing component is hemoglobin of farm animal blood purified from harmful impurities and microorganisms, containing iron in divalent form, as well as freeze-dried beetroot juice, ascorbic or citric acid and simple sugars in the following ratio, wt. Blood hemoglobin of farm animals 20 40
Freeze-dried Beetroot Juice 30 70
Ascorbic or citric acid 10 -40
Simple sugar glucose, fructose 20 60.

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