UA116810U - MALEILATED HALOTANINE WITH ANTIMicrobial PROPERTIES - Google Patents

Abstract

Maleileated halothane with antimicrobial properties. Modification of halotanine is carried out by acylation with maleic anhydride of its structure at a ratio of halothane: maleic anhydride 1: 4.

Description

The utility model belongs to the biotechnology and pharmaceutical industry, relates to derivatives of maleylated halotannins that exhibit antibacterial properties, and can be used to expand the spectrum of antibacterial agents by modification for further use in the development of pharmaceuticals.

The unreasonableness of the regimen of antibiotic therapy has not only severe individual consequences for the patient, but also contributes to the further spread of the infectious agent within the hospital.

The search and development of antimicrobial drugs remains an urgent task of modern medicine and pharmacy. At the same time, the effectiveness of existing antibacterial agents on the pharmaceutical market decreases in proportion to the increase in the volume of their use, which is due to the spread of resistant strains. We have proposed a substance with antibacterial properties - maleylated halotannin (MG).

The method of synthesizing phosphorylated halotannin for the treatment of skin and mucous membranes for cosmetology and pharmacy is known. Modified halotannin has moderate antibacterial properties and its effect is associated with the release of halotannin in the skin or mucous membranes Application for

US Patent 05 2008/0095866 A1, dated 04/24/2008)|. The disadvantage of the prototype is the use of complex and environmentally hazardous synthesis of phosphorylated derivatives from toxic chloroderivatives of phosphoric acid. In addition, the obtained substance was poorly soluble in water, unstable to oxidation, and the antibacterial effect was manifested only in high doses that exceeded 1 95.

The useful model is based on the task of modifying halotannin derivatives - maleylated halotannin (MG).

The task is solved by combinatorial synthesis of the maleylated complex ether halotannin derivative with a ratio of tannin: maleic anhydride from 1:1, 1:2 to 1:4. Unmodified halotannin did not show antibacterial activity against the tested microorganisms. Maleylated halotannin with a ratio of maleic anhydride: halotannin less than 1:1 did not show antibacterial activity, with a ratio of more than 1:4, maleic anhydride did not dissolve in the solution, which indicated the absence of available acceptor groups for attack by maleic anhydride. Due to the fact that only a part of phenolic hydroxyls is adilated, the formation of a large amount is observed

Of the combinatorial derivatives of the halotannin molecule, there are more than 10,000 substances. These substances not only interact with the target, but are also able to form supramolecular complexes with each other with the induction of porin-like structures in the membrane of microorganisms. Such a complexation reaction takes place only in the case when only a part of the phenolic groups available for modification are substituted. This useful model offers highly soluble MG with degree

C5 chemical modification 1:4 with antibacterial properties. The obtained products can be used in pharmacy for the development of highly effective antimicrobial agents that can be used in the treatment of purulent-inflammatory diseases.

Example 1.

The synthesis of MG is carried out as follows: 1.0 g of halotannin is dissolved in 40 ml of distilled water (1-70-80 C), 1.0-4.0 g of maleic anhydride is added, the solution is stirred until the latter is completely dissolved. Upon cooling to -5700, a precipitate of MG falls out, which was recrystallized in a similar way from distilled water.

Example 2.

The study of the antibacterial properties of the obtained complex was carried out by the method of serial dilutions. The antimicrobial properties of MG with 1:1 and 1:2 modification were also studied. Data given in examples and tables.

The standard strains 5iarpuiosossiv ashgei5 ATSS 25923, Euspegispia soii ATOS 25922, Vasyiv5 zibiyv ATOSS 6633, Rgoieiv myYidag iv ATOS 4636, Rzeidotopazh aegidiposa ATOS 27853, which are regulated by the WHO for the study of the antimicrobial effect of the drugs and archeivosiv epuisiv 1/3 clinical strains, were used in the experiment: , EusPegisnia soii 1/254-1, Rheidotopav aegidiposa 2/116-1. To determine the antibacterial action of the test substance, microorganisms were grown on nutrient agar at 1-37 "b. The term of cultivation of microorganisms was 24 hours.

The minimum inhibitory concentration (MIC) was set according to the lowest concentration of the substance under study that inhibited the visible growth of the culture. To determine the minimum bactericidal concentration (MEC), dosed inoculations were performed on a solid nutrient medium (Muller-Hinton agar) of the culture liquid from all test tubes in which the growth of the microorganism was not observed. According to MBuK, the lowest concentration that caused the death of at least 99.995 bacteria was considered. The results were recorded after 24-48 hours. The data are given in the table.

Table

Antibacterial activity of maleylated halotannin derivative 111111 | MIC | ММБцК МБЧК МБЧК 5. asheiv ATSS 25923 125.0 31.25 31.25

E. soybean ATSS 25922 31.25 31.25 31.25

R. upidagizATSS 4636 125.0 250.0 125.0 250.0 125.0

R. aegidiposa ATSS 27853 125.0 250.0 125.0 250.0 125.0

V. zibiyz ATSS 6633 125.0 250.0 125.0 125.0 5. ashtvyv 1/239-1 125.0 250.0 125.0 250.0 125.0

E. soybean 1/254-1 125.0 250.0 125.0 250.0 125.0

R. aegidiposis 2/116-1 250.0 500.0 125.0 250.0 125.0

As a result of the study of antimicrobial activity, it was established that partially maleylated halotannin in modification 1.4 was active in terms of antimicrobial properties.

Claims (1)

USEFUL MODEL FORMULA Maleylated halotannin with antimicrobial properties, which differs in that halotannin is modified by acylation of its structure with maleic anhydride at a halotannin:maleic anhydride ratio of 1:4.