USE OF SULFASALAZINE AS AN INHIBITOR OF THE FORMATION OF ADVANCED GLYCATION END PRODUCTS

Abstract

The invention relates to the field of healthcare, namely, to the treatment of socially significant diseases, such as complications of diabetes mellitus, atherosclerosis, rheumatoid arthritis, osteoarthritis, neurodegenerative diseases including Alzheimer's and Parkinson's diseases, cataract, age-related diseases, etc. The essence of the invention is the use of sulfasalazine (international non-proprietary name; synonyms: Salazosulfapyridine, Azopyrine, Asulfidine, Salazopyridin, Salazopyrin, Salazosulfapyridine, Salicylazosulfapyridin, Salisulf, Sulfasalazyn, Sulphasalazine) of the general formula I as an inhibitor of the formation of advanced glycation end-products:

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Claims

1. The use of Sulfasalazine (international non-proprietary name; synonyms: Salazosulfapyridine, Azopyrine, Asulfidine, Salazopyridin, Salazopyrin, Salazosulfapyridine, Salicylazosulfapyridin, Salisulf, Sulfasalazyn, Sulphasalazine) of general formula I for a new purpose: ##STR00004##

Description

EXAMPLE OF THE CLAIMED TECHNICAL SOLUTION IMPLEMENTATION

EXAMPLE

Determination of Antiglycation Activity

[0019] The glycation reaction is reproduced according to the method of A. Jedsadayanmata ([14] A. Jedsadayanmata, Naresuan University Journal, 2005, 13(2): 35-41). The reaction mixture contains solutions of bovine serum albumin (1 mg/ml) and glucose (500 mM) in phosphate buffer (pH=7.4). To prevent bacterial growth, sodium azide in a final concentration of 0.02% is added to the buffer solution. All substances are dissolved in dimethyl sulfoxide (DMSO). 30 μl of sulfasalazine solution in various concentrations is added to the experimental samples; DMSO is added to the control samples in the same volume. All experimental samples are incubated for 24 hours at 60° C. At the end of the incubation period, specific fluorescence of glycated bovine serum albumin (BSA) is determined using an F-7000 spectrofluorimeter (Hitachi, Japan) at an excitation wavelength of 370 nm and an emission wavelength of 440 nm. As a comparison substance, a known glycation inhibitor aminoguanidine is used (Table 1) ([15] P. J. Thornalley, Archives of Biochemistry and Biophysics, 2003, 419: 31-40).

[0020] Statistical processing of the results is carried out using the non-parametric Mann-Whitney test, the Microsoft Excel 2007 table editor and the GraphPad Prism 5.0 software. The calculation of the IC.sub.50 indicator is carried out by the method of regression analysis (Table 2).

TABLE-US-00001 TABLE 1 The effect of sulfasalazine and aminoguanidine on BSA glycation at various concentrations Drug concentration (mol) Drug name 10.sup.−3 3*10.sup.−4 10.sup.−4 3*10.sup.−5 10.sup.−5 — The average concentration of AGEs in the sample at a given concentration of the drug (Δ %, M ± m) Sulfasalazine 98.94 ± 0.20* 97.53 ± 0.43* 81.60 ± 7.18* 65.37 ± 2.25* 43.42 ± 4.21* Aminoguanidine 58.08 ± 0.72* 50.25 ± 1.08* 38.75 ± 1.52* 19.14 ± 2.24*  3.53 ± 2.31* Note: *the data are reliable in relation to the positive control (Mann-Whitney test, p < 0.05).

TABLE-US-00002 TABLE 2 IC.sub.50 values for BSA glycation Substance IC.sub.50, μM Sulfasalazine I 23.90 Aminoguanidine 765.00

[0021] The analysis of the data shown in Table 1 and Table 2 allows us to conclude that sulfasalazine exhibits a high level of antiglycation activity (Table 1), which allows us to determine the dependence of its effect on concentration and calculate the IC.sub.50 index (Table 2).

[0022] Thus, the results obtained by the applicant demonstrate that the activity of sulfasalazine significantly exceeds that of aminoguanidine, which allows us to consider it as an effective inhibitor of the formation of glycation end-products. At the same time, unlike aminoguanidine, sulfasalazine is an approved drug that has proven its high effectiveness and safety during many years of trials and clinical use.

[0023] Based on the foregoing, we can conclude that the claimed technical solution allows to create new highly effective and safe drags for the prevention and treatment of micro- and macrovascular complications of diabetes, atherosclerosis, neurodegenerative diseases, cataract, and age-related diseases, thereby improving the quality of life of patients.

[0024] The claimed technical solution meets the criterion of “novelty” imposed on inventions, as the prior study has not detected any technical solutions with the claimed combination of distinctive features that achieve the claimed results.

[0025] The claimed technical solution meets the criterion of “inventive step” imposed on inventions, as it is not obvious to a specialist in this field of science and technology.

[0026] The claimed technical solution meets the criterion of “industrial applicability”, as it can be implemented at any specialized enterprise using standard equipment, well-known domestic materials and technologies.