RU2316392C1 - Method for preparing hemosorbent - Google Patents

Abstract

FIELD: medicine, chemical technology.

SUBSTANCE: invention relates to a method for preparing sorbents of medicinal designation. Activated carbon is treated with methyltoluenesulfonate-N-cyclohexyl-N¹-(2-morpholinyl-4-ethyl)carbodiimide in the presence of melanin followed by incubation of modified carbon in the presence of glutathione. Invention provides enhancing anti-radical activity of hemosorbent.

EFFECT: improved preparing method.

1 tbl, 4 ex

Description

Technical field

The invention relates to biochemistry, in particular to methods for producing sorbents with a high level of affinity, and can be used in medicine in the processes of hemosorption, lymphosorption and plasma sorption.

State of the art

A known method of obtaining one of the forms of activated carbon from natural raw materials (V.V. Strelko, Applied Chemistry journal, No. 6, p. 1225-1230, 1984). The disadvantage of this method is that the sorbent does not have the ability to absorb active radicals, for example hydroxyl radicals.

A known method of producing activated carbon spherical granulation based on a modified nitrogen-containing polymer (Strelko VV, Applied Chemistry journal, No. 6, t.65, p.1257-1260, 1987). The disadvantage is that the sorbent has a low level of antiradical activity, exhibits the properties of anion exchange resin by the electrochemical mechanism.

The closest technical solution, selected as a prototype, is a method for producing hemosorbent, which consists in the fact that coal of spherical granulation is modified with a mixture of monochloracetic acid and carbodiimide followed by chemical bonding of glutathione (RF Patent No. 2026086, dated January 9, 1995). The known method does not allow to obtain hemosorbents with a high level of antiradical activity.

Disclosure of invention

The objective of the invention is to obtain a highly effective carbon hemosorbent having anti-radical activity, having active centers on the surface for absorption of hydroxyl radicals. Using the proposed method in medicine makes it possible to increase the effectiveness of measures for extracorporeal detoxification - hemosorption, lymphosorption and plasma sorption, to patients exposed to radiation, allergization and intoxication with chemical compounds of various nature, as well as tissue impression syndrome.

The technical result boils down to the fact that to increase the level of anti-radical activity of the carbon sorbent it is modified with a mixture of melanin and carbodiimide, followed by treatment with glutathione.

The essence of the method of producing hemosorbent, including the modification of activated carbon, characterized in that the processing of coal methyl-n-toluenesulfonate-N-cyclohexyl-N ¹ - (2-morpholinyl-4-ethyl) carbodiimide is carried out in the presence of melanin in solution in a mass ratio of 1: 2.3-1: 2.6 followed by treatment with glutathione.

Melanin, which is a long-chain polymer consisting of indoline-5,6-quinone structures, has antioxidant properties, and these properties are inherent in glutathione tripeptide. In the method for producing the sorbent, these components are immobilized on the surface with the formation of active centers, which gives the sorbent antiradical activity.

The implementation of the invention

The possibility of practical implementation of the method using the claimed features is illustrated by examples.

Example 1. To 1 g of activated carbon spherical granulation add 10 ml of phosphate buffer with a pH of 8.1, containing 0.6 g of melanin, then add 1.6 g of methyl-n-toluenesulfonate-N-cyclohexyl-N ¹ - (2- morpholinyl-4-ethyl) carbodiimide (1: 2.6 ratio) in 10 ml of isopropyl alcohol. The mixture is stirred at room temperature for 2 hours, after which the sorbent is washed three times with 50 ml of distilled water.

8 ml of distilled water containing 50 mg of glutathione are added to 1 g of modified coal. The mixture is incubated at 22 ° C for 12 hours, after which the sorbent is washed with distilled water. The concentration of active centers in the absorption of hydroxyl radicals is 37 mg per 1 g of sorbent. The multiplicity of radical inhibition in the Fenton reaction of 1.6.

Example 2. The method of producing the sorbent is carried out as in example 1, only for modification use 0.7 g of melanin and 1.6 g of methyl-n-toluenesulfonate-N-cyclohexyl-N ¹ - (2-morpholinyl-4-ethyl) carbodiimide (ratio 1: 2.3). The concentration of active centers in the absorption of hydroxyl radicals is 39 mg per 1 g of sorbent, the inhibition ratio of radicals in the Fenton reaction is 5.8.

Example 3. The method of producing the sorbent is carried out as in example 1, only for modification use 0.5 g of melanin and 1.6 g of methyl-n-toluenesulfonate-N-cyclohexyl-N ¹ - (2-morpholinyl-4-ethyl) carbodiimide (ratio 1: 3.2). The concentration of active centers in the absorption of hydroxyl radicals is 28 mg per 1 g of sorbent, and the ratio of inhibition of radicals in the Fenton reaction is 4.7.

Example 4. The method of producing the sorbent is carried out as in example 1, only for modification use 0.8 g of melanin and 1.6 g of methyl-n-toluenesulfonate-N-cyclohexyl-N ¹ - (2-morpholinyl-4-ethyl) carbodiimide (ratio 1: 2). The concentration of active centers in the absorption of hydroxyl radicals is 31 mg per 1 g of sorbent, and the ratio of radical inhibition in the Fenton reaction is 4.8.

The results are presented in the table.

Table The method of obtaining hemosorbent Monochloracetic acid The ratio of components upon receipt of hemosorbent The concentration of active centers, mg / g of sorbent The multiplicity of radical inhibition in the Fenton reaction The content of MDA in serum, nM / ml melanin carbodiimide ratio The initial concentration of 5.2 The known method (prototype) 0.4 - 1,6 - 24 3.2 2,5 Proposed Method 0.5 1,6 1: 3,2 28 4.7 2.2 0.6 1,6 1: 2.6 37 6.1 1,6 0.7 1,6 1: 2,3 39 6.8 1.4 0.8 1,6 1: 2 31 4.8 2,3

The table presents data on the assessment of the anti-radical activity of carbon sorbents when exposed to human serum in the process of enhancing lipid peroxidation. The antiradical effect of the sorbents was determined by the degree of decrease in the concentration of the lipid peroxidation product - malonic aldehyde (MDA) using the known method (O.K. Kolesnikova et al., Lab. Delo. No. 9, p. 540, 1984). Compared with the prototype, the sorbents obtained by the proposed method have more than 2 times greater anti-radical activity, the inhibition rate in the Fenton reaction is 6.8-6.1, in addition, sorbents reduce the level of lipid peroxidation in blood serum by 3.6 times. The data in the table show that the highest anti-radical activity are samples of activated carbon obtained by modifying the sorbent with a mixture of melanin and carbodiimide in a mass ratio of 1: 2.3-1: 2.6. With a decrease and increase in the concentration of melanin, the anti-radical activity of the sorbents does not increase.

Claims (1)

A method of producing a hemosorbent, including modifying activated carbon by treating it with methyl-toluenesulfonate-N-cyclohexyl-N ¹ - (2-morpholinyl-4-ethyl) carbodiimide and incubating the modified carbon in the presence of glutathione, characterized in that the processing of carbon is methyl-toluenesulfonate N-cyclohexyl-N ¹ - (2-morpholinyl-4-ethyl) carbodiimide is carried out in the presence of melanin in their mass ratio (2.3-2.6): 1, respectively.