RU2098101C1 - Medicinal agent for asiderotic anemia treatment - Google Patents

Abstract

FIELD: medicine, therapy, pharmacology. SUBSTANCE: agent is an aqueous solution of iron-sorbitol complex and sucrose at the following ratio of components, %: ferbitol, 40-60; and sugar syrup, 40-60. EFFECT: enhanced effectiveness of agent. 2 dwg

Description

 The invention relates to medicine, in particular to pharmacology and therapy, and can be used to treat iron deficiency anemia (IDA) of various etiologies.

 For the treatment of patients suffering from IDA, iron-containing preparations are used both for parenteral administration and for oral administration. The method of parenteral iron therapy is limited by strict indications due to malabsorption in the gastrointestinal tract, intolerance to drugs when taken orally, severe forms of IDA [1,2] Parenteral drugs are complexes of iron with dextrin (ferrum-lek, inferon) or iron-sorbitol complexes (ectofer , ferbitol).

 There are a fairly large number of enteric forms of iron-containing preparations [3,4,5] They are mainly iron salts. The most common are foreign drugs, including sulfate forms of iron: ferroplex, conferon, tardiferon. Ferrocerone (orthocarboxybenzoylferrocel sodium salt) and aloe syrup with iron chloride are also used. Abroad, there are also iron preparations based on gluconate and fumarate.

Almost all available iron preparations for oral administration are poorly tolerated by patients [1,6,7]. They cause an upset gastrointestinal tract. Fe ²⁺ released in the intestinal mucosa denatures the protein of this membrane and, as a result, the mucose layer exfoliates from the stomach wall. Contact with stomach acids leads to inflammation. In this case, nausea, vomiting, diarrhea are possible. Their severity is stronger, the more will remain in the intestines of non-absorbed iron. When iron preparations are taken orally, constipation often occurs, since iron binds in the intestine hydrogen sulfide, which is a physiological stimulator of peristalsis [5] To increase the biocompatibility of drugs, iron salts are placed in shells that are hardly soluble in the gastric juice (ferrograduulite, Yugoslav feospan). Indeed, these drugs are fairly well tolerated by patients, but at the same time their therapeutic efficacy is questioned because of the possible insufficient absorption of iron from the tablets [5]
Due to adverse events, it is sometimes impossible to complete the course of treatment and achieve the desired results [8] Therefore, the search for new enteric treatment for IDA remains relevant.

 The objective of the invention is the creation of a drug for the treatment of IDA, which combines high therapeutic efficacy, good tolerance and low toxicity compared to existing drugs.

The developed product is an aqueous solution of the iron-sorbitol complex and sucrose in the following ratio of components: ferbitol 40-60% sugar syrup 60-40%
The specified composition of the drug allows to achieve the desired therapeutic effect in the absence of adverse reactions in patients.

Ferbitol [3] is a complex compound of iron with six-atom alcohol sorbitol, the so-called iron-sorbitol complex. To improve the taste, the iron-sorbitol complex is dissolved in sugar syrup. This allows you to improve the absorption of Fe ⁺⁺⁺ , which is part of the iron-sorbitol complex, in the intestine and, as a result, helps to increase therapeutic efficacy. In addition, the drug has low toxicity, due to the fact that iron is in the form of a complex. LD _{50 of the} claimed drug is more than 700 mg of iron / kg (ferbitol 160 mg / kg), which is 200 times the maximum daily dose.

 A drug is obtained by mixing components that do not enter into chemical interaction, so the process cannot be represented in the form of a diagram of chemical reactions.

The preparation is prepared as follows: a weighed portion of refined sugar weighing 209 g is placed in a flask, 118 cm ^{3 of} water for injection are added and heated to boiling with constant stirring. To the resulting solution, with constant stirring, add 250 cm ³ ferbitol. It is cooled to room temperature, filtered and poured into 20 cm ³ into vials from a drone. Get 500 cm ³ preparation containing: Ferbitol 250 cm ³ sugar syrup 25 cm ³ . 1 ml of the drug contains 25 mg of elemental iron.

When conducting a clinical study of the drug in medical institutions designated by the Pharmacological Committee of the Ministry of Health of Russia, it was found:
the drug has a pronounced therapeutic effect in patients with a diagnosis of iron deficiency anemia: it helps to restore hemoglobin, increase the number of red blood cells, serum iron, transferrin saturation coefficient and normalize the total iron binding capacity of blood serum;
the drug is easily (well) tolerated by patients, does not give side effects, and therefore its tolerance is estimated at 5 points (the highest positive rating).

 The restoration of hemoglobin level begins 2 weeks after the start of the course of treatment (with Ferbitol after 4 weeks), which is associated with the best effect of iron absorption in the gastrointestinal tract due to the presence of sugar syrup in its composition. The full course of treatment is 4-6 weeks, in some cases up to 8 weeks, depending on the severity of anemia.

Example 1. Patient M., 27 years old, was admitted with complaints of weakness, dizziness, taste perversion. Blood test: hemoglobin 84 g / l, reticulocytes 15% erythrocytes 3.1 • 10 ¹² / l, color index - 0.74, hematocrit 0.34. Tachycardia 90 strokes in 1 min. Diagnosis: iron deficiency anemia, drug allergy, pregnancy 20 weeks.

 The claimed drug was treated for 4 weeks, 1 teaspoon 3 times a day.

 After a course of treatment, the hemoglobin level increased by 16 units. the content of reticulocytes decreased slightly (up to 10%). There was a complete normalization of the number of red blood cells and color index. The patient took the drug without a negative attitude towards him. Nausea, vomiting, bowel dysfunction and other complaints were not.

 The harmlessness of the drug is indicated by the absence of influence on the state of the fetus, ESR, leukocyte formula, transaminase activity, general urine analysis.

Example 2. Patient P. 24 years old, was admitted with complaints of dizziness, weakness, palpitations. Blood test: hemoglobin 88 g / l, reticulocytes 13% erythrocytes 3.0 • 10 ¹² / l, color indicator - 0.88, hematocrit 0.34. Tachycardia 92 strokes in 1 min, pallor. Diagnosis: iron deficiency anemia, chronic hypoacid gastritis.

 After a course of treatment with the claimed agent for 6 weeks, the hemoglobin level increased to 112 g / l, the indicators of red blood and iron metabolism returned to normal. No side effects were noted, the patient took the drug without a negative attitude towards him.

 The harmlessness of the drug is evidenced by the lack of effect on the gastrointestinal tract (no exacerbation of gastritis was detected), ESR, leukocyte formula, transaminase activity, urinalysis.

 The results of a clinical study of the drug are presented in FIGS. 1 and 2. It should be noted that in terms of its medicinal qualities and ability to increase hemoglobin, the proposed drug is not inferior to conferone and ferroplex and surpasses ferbitol, which is clearly shown in FIG. 1, where is the proposed drug, ------ conferon, -.-.-. ferbitol.

 As can be seen from the dynamics of hemostatic indicators, in patients as a result of the treatment with the claimed agent, there is a significant increase in hemoglobin level, an increase in the number of red blood cells, as well as a significant decrease in reticulocytes, which is clearly shown in Fig. 2, where 1 proposed drug, 2 ferroplex.

 An analysis of the data shows that the drug is quite effective in the treatment of IDA, in addition to good tolerance, all patients noted a significant improvement in overall health.

 Specific examples of the proposed drug.

Example 1. A weighed portion of refined sugar weighing 122 g is placed in a flask, 95 cm ^{3 of} water for injection are added and heated to boiling with constant stirring. 300 cm ^{3 of} ferbitol are added to the resulting solution with constant stirring. It is cooled to room temperature, filtered and poured into 20 cm ³ into vials from a drone. Get 500 cm ^{3 the} drug in the following ratio, wt. Ferbitol - 60, sugar syrup 40%
Example 2. A weighed portion of refined sugar weighing 251 g is placed in a flask, add 141 cm ^{3 of} water for injection and heated to boiling with constant stirring. 200 cm ^{3 of} ferbitol are added to the resulting solution with constant stirring. It is cooled to room temperature, filtered and poured into 20 cm ³ into vials from a drone. Get 500 cm ^{3 the} drug in the following ratio, wt. ferbitol - 40, sugar syrup 60.

Sources of information
1. Idelson L.M. Hypochromic anemia. M. "Medicine", 1989.

 2. Modern hematology and oncology (Ed. By V.F. Fairbanks). M. "Medicine", 1987.

 3. Mashkovsky M.D. Medicines Part II. M. "Medicine", 1988.

 4. Lepakhin V. K. Belousov Yu.B. Moiseev V.S. Clinical pharmacology with an international nomenclature of drugs. "Medicine", 1988.

 5. Satoskar R.S. Bakuarkar S.D. Pharmacology and pharmacotherapy. Part I. - M. "Medicine", 1986.

 6. Carone D. Orlando Z. Vigna C. et al. Ferric chondroitin 6 -sulfate (condrofer): a new potent antianaemic agent with a favored pharmacocinetic profile // Drugs Expll. Clin. Rer. Suppl. 1, 1988, XIV, p. 1-14.

 7. Tokarev Yu.N. Settarova D.A. The mechanism of action and clinical manifestations of iron overload in hereditary hemachromatosis // Hematology and transfusiology. 1987, N 2, p. 52-57.

 Brock C. Curry H. Charles H. Advirse effects of iron supplementation: a conparative trial of wax-matrix iron preparation and conventional ferrous sulfate tablets // Clin. Hur. 1985, v. 7, No. 5, p. 568-573.

Claims (1)

 A medicine for treating iron deficiency anemia containing ferbitol and a solvent, characterized in that it contains sugar syrup as a solvent in the following ratio of components, wt. Ferbitol 40 60
Sugar syrup 40 60 °

Images