CS264785B1 - Di(8-hydroxyquinolino silver nitrate - Google Patents

Abstract

The solution concerns di / 8-hydroxy-quinolino / silver nitrate prepared by reaction from silver nitrate and 8-hydroxyquinoline. The substance obtained has a strong antipseudomonad effect and has been effective even in cases where the use of antibiotics or other chemotherapeutic agents has failed. It can be used in human and veterinary medicine, cosmetics, agriculture and the food industry as an effective disinfectant or drug.

Description

This novel compound was prepared by the reaction of silver nitrate with 8-hydroxyquinoline and is useful as a bactericidal agent in human and veterinary medicine, cosmetics, agriculture and food.

The preparation of di (8-hydroxyquinolino) silver nitrate CggH2OgNgAg having a molecular weight of 460.2 is explained in more detail in the following examples.

He did

While stirring at 50-55 ° C, 290.3 wt. parts of 8-hydroxyquinoline p.a. in 800 wt. Then, after gently cooling, a solution of chemically pure silver nitrate prepared from 169.89 parts by weight and 1100 parts by weight of distilled water was added to the reaction vessel.

During the metering of the silver disulphate solution, finely dispersed di (8-hydroxyquinolino) silver nitrate is formed in the reaction vessel.

After the addition of the silver nitrate solution was complete, it was stirred for a further 15 minutes. After standing for 16 hours, the resulting di (8-hydroxyquinolino) silver nitrate was filtered off and washed twice with distilled water. Freeze-dried at 45 to 50 ° C.

Yield: 387 wt. parts of silver di (8-hydroxyquinolino) nitrate having a melting point of 194-199 ° C.

Elementary analysis

Theory

Found

Example 2

C H

46.98 3.07

47.12 3.25

. Ag

9.13 23.44

9.23 24.16

The production process was carried out in the same manner except that the weight ratio of silver nitrate to 8-hydroxyquinoline was adjusted (e.g. in a ratio of 1: 1.3 or 1: 2.3 or 1: 3). In all cases, a complex compound of the same composition, ie silver (8-hydroxyquinolino) nitrate, was formed, which must be protected from light, so-called brown bottles.

Characteristics

Mass spectrum of the di (8-hydroxyquinolino) silver nitrate complex obtained by the desorption (direct) chemical isolation (DCI) technique, reaction gas - methane:

M / Z REL.INT. » M / Z REIi.INT.% 46.0 0,728 3 148.0 1,595 7 48.0 2,921 2 158.0 1,383 9 49.0 0,499 2 159.0 0,535 5 55.0 1,025 3 160.0 2,524 5 56.0 0,293 8 161.0 0,453 4

57.0 1,462 9 162.0 0,657 2 59.0 0.297 0 172.0 1,679 4 63.0 0.285 9 173.0 1,226 0 64.0 0.260 6 174.0 29,106 5 69.0 0.535 5 175.0 3,649 5 89.0 0,613 0 176.0 0,796 2 90.0 0.475 5 186.0 5,989 4 91.0 0.417 0 187.0 0,897 3 116.0 0.328 6 188.0 1,003 2 117.0 2,793 2 190.0 0,268 5 118.0 4,230 9 200.0 0.475 5 119.0 0.412 3 202.0 0,977 9 130.0 1,995 4 214.0 0,379 1 131.0 0.338 0 290.0 0,271 7 132.0 0,617 7 144.0 0,827 8 145.0 17,402 6 146.0 100,000 0 147.0 11,203 0 Dlslčnan di (8-hydroxyquinoline) silver o molecular weight 460.2 of the sum formula ^C 18 ^H 14 ^N ° 5 3 ^Ag - The structure of this the substance was extra verified by the method of nuclear magnetic reso- nance (NMR) a using infrared spectroscopy. Spectrum antimicrobial Effectiveness of di (8-hydroxyquinolino) silver nitrate authors

tested on mirkoroganism strains isolated from patients from the catchment area of the Mělník District Hospital. It was a cross-section of strains circulating in the human population causing serious infections. A standard methodology for determining minimum inhibitory concentrations in a test tube was used (Urbášková et al .: Investigation for Antimicrobial Therapy, 1985).

All strains were known to be qualitatively susceptible to antibiotics.

In tab. 1 compares the biological activity of 8-hydroxyquinoline, i.e. the starting material and the authors of the prepared di (8-hydroxyquinoline) silver nitrate. The efficiency limits for 8-dihydroxyquinoline are about 1.5% aqueous solution and for di (8-hydroxyquinolino) silver nitrate about 0.01%.

A concentration of 0.04% inhibits the growth of gram negative rods of species: Pseudomonas aeruginosa, Enterobacter cloacae, Klebsiella pneumoniae, Proteus hauseri, Proteus rettgeri, Proteus mirabilis and Escherichia coli. See tab. 2. Serratia marcescens was inhibited by a concentration of 0.08%. In some microorganisms, a concentration of 0.01% is sufficient to inhibit.

At the same time, all strains tested had high resistance to antibiotics commonly used to treat them.

A good effect was achieved in gram positive cocci of Staphylocoocus pyogenes and Streptococcus pyogenes. A concentration of 0.01% was effective.

In tab. 3 are the results of the activity of silver di (8-hydroxyquinolino) nitrate in 50 strains of the genus Pseudomonas. In three patients, these microorganisms caused fatal sepsis. The strains were insensitive to ampicillin, carbenicillin, cephalotin, cotrimoxazole, furadantine, chloramphenicol, kanamycin, streptomycin, tetracycline, and 3 strains were insensitive to gentamycin and colistin.

All strains were inhibited at 0.01%, 15 strains (35%) at 0.008% and 5 strains (10%) at 0.004%. See tab. 3.

The broad spectrum of silver nitrate di (8-hydroxyquinolino) nitrate and its stability in solution makes it particularly suitable for use as a disinfectant with a special focus on pseudomonads. It can be used successfully in the entire health care sector, in veterinary medicine, agriculture and the food industry.

The high antipseudomonad activity of silver (8-hydroxyquinolino) nitrate shown by the inventors can be used to prepare medicaments for topical application to the skin and cavities of humans. The treatment of pyogenic infections, pressure sores, infected burns and otitis indicates a range of possible uses. The use of this chemotherapeutic agent in the treatment of intestinal infections is also contemplated

Table 1

Comparison of biological activity of 8-hydroxyquinoline and silver nitrate di (8-hydroxyquinoline)

Test strain Concentration in percent

5,2 2,5 Pseudomonas 1,2 0.6 0.3 0.08 0.04 0.02 8-hydroxyquinoline 0.01 0.008 0.004 0,002 aeruginosa Enterobaoter + + + + + + + + + + cloacae + + + + + + + + + + Escherichia coli - Pseudomonas + + Nitrate + di / 8 · + + + -hydroxyquinoline / + + silver + + aeruginosa Enterobacter - + + + cloacae - - - - - - - + + + Escherichia coli - - - _ _ _ + + +

Explanation: - inhibition of bacterial strain growth + normal bacterial strain growth

Table 2

The basic potency range of di (8-hydroxyquinolino) silver nitrate per gram neg. sticks and gram pos coca

Test strain Concentration in percent

0,1 0,08 0.04 0.02 0.01 0.008 0.004 Pseudomonas aeruginosa - - - - + + Enterobacter cloacae - - - + + + Klebsiella pneumonia - - - - + + Próteus hauseri - - + + + + Próteus rettgeri - - - - + + Proteus mirabilis - + + + + Serratia marcescens - + + + + + Escherichia coli - - - + Staphylococcus pyogen. - - - + + Streptococcus pyogenes - - - - + + Explanation: - inhibiting growth bacterial strain + normal growth bacterial strain

Table 3

Susceptibility of 50 strains of Pseudomonas species to di (8-hydroxyquinolino) nitrate silver

Substance concentration Inhibition of growth Percentage of activity

0.020% 50 strains 100 Ϊ

264785 ·

Table 3 continued

Concentration of the substance Growth inhibition Percentage of efficacy 0.010% 50 strains 100% 0.008% 15 strains 35% 0.004% 5 strains 10% Subject OF THE INVENTION

Di (8-hydroxyquinolino) silver nitrate of the formula

Claims (1)

Di (8-hydroxyquinolino) silver nitrate of the formula