Water-soluble sodium-, calcium-, iron-polygalactouronate stimulating hemopoiesis

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention describes a water-soluble sodium-, calcium-, iron-polygalactouronate of the general formula (I): used as a stimulating agent of the hemopoiesis process. The compound is prepared by treatment of pectin with alkali NaOH solution at temperature 50-60°C and successive addition of aqueous solution of calcium and iron salts followed by precipitation with alcohol, centrifugation and drying. The compound can be used in using both a solid substance and as solutions for pharmaceutical aims.

EFFECT: valuable medicinal properties of agent.

3 cl, 2 tbl, 4 ex

 

The invention relates to the field of high-molecular natural compounds, namely to new polymetallic complexes polygalacturonic acid, possess valuable biological properties.

Known water-insoluble pectinate metals with antimicrobial properties (USSR Author's certificate No. 1776656 A1, class 08 In 37/06, 1992). The disadvantage of these compounds is the lack of solubility in water.

Known water-insoluble complexes of metal ions with polygalacturonic acid, having a biological effect on a living organism in oral introduction in solid form: increase the iron content in serum (Patent USSR No. 886750, class 08 In 37/06, 1981). The disadvantage of the proposed systems is the lack of water solubility, which limits the possibilities of their use in pharmacological practice.

The closest in technical essence and the achieved result of the present invention the solution are water-soluble, bi - and polymetallic complexes polygalacturonic acid using three metals trace elements Fe, Cu, Co, stimulating the blood circulation (Patent RF №2219187, class 08 In 37/06, And 61 R 7/00, a 61 K 31/732, 2003).

In this application seeks to obtain a new complex polygalacturonic acid containing macronutrients-Na, Ca and trace elements Fe, which will extend the range of biologically active substances with Antianemic properties.

The technical result - obtaining a new connection is a water - soluble sodium-, calcium-, ulasabileceklerini, stimulating the blood circulation and is suitable for use both in solid form and in the form of solutions for pharmaceutical purposes.

The problem is solved a new water-soluble polymetallic complex polygalacturonic acid of formula I with Antianemic properties.

The compounds of formula I get the same way (Patent RF №2220981, class a 61 K 31/732, 2004). At the first stage processing of pectin General formula II with alkali solution of NaOH at 50-60°get polygalacturonate Na. Then successively added aqueous solutions of salts of calcium and iron, and soluble complexes emit precipitation with alcohol, centrifugation and drying of the target product.

The new compounds of General formula I can be used for pharmaceutical purposes to promote hematopoietic function of the body, as illustrated in examples 3 and 4.

Obtaining compounds of General formula I is carried out as follows: to a solution of pectin in distilled water at paramasivan is at 50-60° With added for 1.0-1.5 hours a solution of caustic soda in water with the formation of polygalacturonate sodium, then add the solutions of salts of divalent metals calcium and iron, and after 20 min the precipitated target complex with ethanol, centrifuged and dried at 40-50°C.

Presents the results obtained when using citrus pectin brand "Classic C-401" production company "Herbstreith &Fox (Germany) with an average molecular mass Mn17600 determined by viscometry method.

The degree of polymerization (g) pectate sodium and presented in the application pectates divalent metals corresponds to the degree of polymerization source of pectin and is calculated by the formula

g=Mη/MG.K.where Mη- molecular mass source of pectin,

MGK- molecular mass balance of the galacturonic acid (176).

The molecular mass of the original pectin were determined by viscosimetry. Equation Kuhn-Mark establishes the dependence of average molecular weight from the characteristic viscosity

[η]=kMα;

where [η] - internal or characteristic viscosity; k and α are constants that depend on the polymer structure and its interaction with the solvent. For pectin by Glikman and Orlov equation Kuhn-Mark solvent - 1% NaCl solution) as follows (W is Luchina N.P., Abaev RS, Imuhamedov G.B. Pectin and the parameters of its receipt. Frunze: Ilim. 1987):

[η]=1.1·10-5·M1.22

The values n and m in the formula (I) was determined on the basis of calculations by the degree of substitution of Na metal 2: in the above examples, it is equal to 25%. According to this value when the degree of substitution of Na for CA, equal to 12.5%, and Fe, 12.5%, in each set of elementary units containing Na, CA and Fe, six elementary units containing Na (75%), have one link containing CA (12.5%), and one link containing Fe (12.5%). The total degree of substitution for CA and Fe is equal to 25%.

Therefore, n=75:25=3,

m=g:(n+1)=100:(3+1)=25 (for g=100).

The invention is illustrated by examples 1-4 obtain polymetallic complexes polygalacturonic acid and study of their biological activity. Sodium, calciumreactor described in example 2, was synthesized for comparison of biological properties with the inventive sodium-, calcium-, rulesofrelationship.

Example 1. Obtaining sodium-, calcium-, ulasabileceklerini:

a) obtaining polygalacturonate sodium

10 g of pectin contribute to the flask, and with stirring, add 375 ml of water. Pectin is evenly distributed throughout the volume, lumps are not formed. With a bath temperature of 50-60°to a solution of pectin add a solution of alkali 1.275 g NaOH in 25 ml water is small, p is rceme under continuous stirring for 2 hours, controlling the pH to 7.0-7.5. Once the total volume was adjusted with water to 500 ml. of the resulting solution (volume 500 ml) contains 11 g of polygalacturonate sodium (determined experimentally).

b) receiving sodium-, calcium-, ulasabileceklerini

400 ml of a solution containing 8.8 g of polygalacturonate sodium, transferred into a flask, add ferric sulfate solution (0.44 g FeSO4·7H2In 178 ml of water), then add a solution of calcium chloride (0.18 g CaCl2in 178 ml of water). Previously all three solution heated to 55°C. After 20 minutes to a transparent solution was added 1500 ml of ethanol, the precipitate was separated by centrifugation, washed with 200 ml of ethanol, dried at 40-50°in an oven and ground to a homogeneous powder. The release of Na, Ca, Fe - polygalacturonate formula I is 6.1, Content: Na 7.21%, Ca 1.05%, Fe 1.46%. The degree of substitution of Na for Ca is equal to 12.5%, Na Fe - 12.5%; g=100, n=3, m=25.

Target product - sodium-, calcium-, ulasabileceklerini powder, yellowish-brown, odorless, slimy taste. Soluble in water at 50-60°education solutions with concentrations up to 1.5%, optically active: [α]D20=+327.27° (0.15; H2O). IR range (νcm-1): 954 square (SN), 1015, 1101 (C-O, C-C), 1149 cf. (C-C-C), 1334 SL. (OO), 1633 (C=O).

Example 2. Obtaining sodium, cancionaguante:

a) polygalacturonate sodium obtained according to paragraph (a) of example 1.

b) receiving sodium, cancionaguante

100 ml of a solution containing 2.2 g of polygalacturonate sodium, transferred into a flask, add a solution of calcium chloride (0.09 g CaCl2in 100 ml of water). Both pre-solution is heated to 55°C. After 20 minutes to a transparent solution was added 400 ml of ethanol, the precipitate was separated by centrifugation, washed with 50 ml of ethanol, dried at 40-50°in an oven and ground to a homogeneous powder. The output of sodium, cancionaguante formula I is 1.67, Content: Na 6.60%, Sa 1.90%. The degree of substitution of Na for CA is equal to 25%;

g=100, n=3, m=25.

The resulting product is sodium, calciumreactor - white powder, without odor, slimy taste. Soluble in water at 50-60°education solutions with concentrations up to 1.5%, optically active: [α]D20=+307.25° (0.15; N2About). IR range (νcm-1): 954 square (SN), 1015, 1101 (C-O, C-C), 1149 cf. (C-C-C), 1333 CL. (C-PA), 1634 (C=O).

Example 3. The influence of sodium-, calcium-, ulasabileceklerini on hematopoietic function in young rats.

On the young (age 1-5 days) experiment was carried out according to the following scheme: the tested solutions was given to lactating females, then, when rats age 1-1 .5 months, females were odarivali, and the rats continued to drink fluids. In the daily experience at ayvali the number of drunken solution, conducted surveillance of the condition of the animals, weekly researched weight and took the blood from the tip of the tail for analysis. In the blood was determined by the concentration of hemoglobin (grams per liter) hemiglobincyanide method, the number of erythrocytes (in millions per microliter) in the camera gariaev and expected content of hemoglobin in a single red blood cell. Received digital material were processed statistically using the program Origin 6.0, data were compared by t-criterion of student. Average daily gain was determined using the regression analysis in the program Origin 6.0.

Declared a new connection - sodium-, calcium-, ulasabileceklerini (1% solution) was investigated for biological activity: growth, development and hematological indices of young rats. For comparison, take a solution of sodium-, iron-, cobalt-, meliponiculture (PG Na, Fe, Co, Cu)were synthesized according to the method described in the Patent of Russian Federation №2219187, class 08 In 37/06, And 61 R 7/00, a 61 K 31/732, 2003, and a solution of sodium, cancionaguante, synthesized according to example 2. The results are shown in table 1.

As can be seen from the table, complex with calcium - sodium-, calciumreactor (PG Na, Sa) did not cause significant changes in the investigated parameters in the blood picture and average daily gain. In contrast to complex with calcium, metal complex with cal is receiving and iron - sodium-, calcium-, ulasabileceklerini (PG Na, CA, Fe) caused a significant increase in hemoglobin and hemoglobin in a single red blood cell. The data hematological indices exceeded the corresponding figures for the group receiving politicalcompass PG Na, Fe, Co, Cu. For PG Na, CA, Fe concentration of hemoglobin in comparison with the control group of rats was higher by 61%, as compared to older females by 35%. Compared to the same examples described in the patent of Russian Federation №2219187, class 08 In 37/06, And 61 R 7/00, a 61 K 31/732, 2003, the effect of GHGs CA, Fe concentration of hemoglobin was significantly higher as compared to polymetallurgical PG Na, Fe, Co, Cu (increase compared with the control 12.8%), and sodium, rulesofrelationship (increase compared with control at 9.9%). Installed the new compound - sodium-, calcium-, ulasabileceklerini in the investigated concentrations did not show toxic effects on experimental animals and is of low toxicity (LD50intraperitoneal injection of 1100 mg/kg).

Example 4. The influence of sodium-, calcium-, ulasabileceklerini on hematological parameters in mice.

Analogously to example 3 male mice for drinking has introduced a 1% solution of sodium-, calcium-, ulasabileceklerini or sodium-, iron-, cobalt-, meliponiculture (PA is UNT of the Russian Federation No. 2219187, CL 08 In 37/06, And 61 R 7/00, a 61 K 31/732, 2003). For test solutions pre-diluted with distilled water in the ratio 1:1 or 1:3. Prior to the experiment and during the experiment, every 10 days in animals examined hematological parameters: hemoglobin, number of erythrocytes, hemoglobin in a single red blood cell. The results are shown in table 2. The greatest effect was observed at 20-25 day from the start of consumption of the solution, so the table shows data for the period of the experiment.

As can be seen from table 2, when the same concentrations of substances in giving to drink fluids PG Na, Ca, Fe exhibits a higher effect on the studied blood parameters (hemoglobin concentration, the number of red blood cells)than previously developed politicalcompass PG Na, Fe, Co, Cu.

Thus, a new connection - sodium-, calcium-, ulasabileceklerini is highly promising Antianemic agent. As part of the claimed compounds includes such valuable nutrient metals such as calcium and iron, the resulting material can have a wide range of use in medical practice.

1. Water-soluble sodium-, calcium-, ulasabileceklerini General formula I

2. Water-soluble sodium-, calcium-, ulasabileceklerini according to claim 1 as a stimulator of the process of hematopoiesis.



 

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7 cl, 2 dwg, 8 tbl

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9 cl, 6 ex

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EFFECT: improved preparing method, valuable medicinal properties of agent.

9 cl, 6 ex

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