DD220902A1 - BACTERICIDAL AGENTS - Google Patents

Abstract

The invention relates to bactericidal agents which act equally against Gram-positive and Gram-negative bacteria. As active ingredient they contain a combination of 2-Hydroxybenzoylaminodiphenylethern of the general formula I and from Nitrodiphenylethern of the general formula II in the Gewichtsverhaeltnis 1: 9 to 9: 1.

Description

VEB GHEMIEKOMBIKAT BITTERPELD Bitterfeld, d. 30.11.1983

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Bactericidal agent

Area of application of the invention

The agents according to the invention can be used to combat gram-positive, tiger and gram-negative bacteria.

Characteristic of the known technical solutions

It is known to use diphenyl ethers of various structures to combat unwanted bacteria. In addition to halogenated hydroxydiphenyl ethers (DE-AS 1 793 664, DE-OS 2 800 105, US-PS 3 904 696, GB-PS 1 456 200 and GB-PS 1 300 232), nitrohydroxydiphenyl ethers and their O-substituents have also been described Derivatives (US Pat. No. 3,908,019, US Pat. No. 3,329,903) have been proposed for the same purpose. From DE-OS 1 492 is also known that o-Hydroxybenzoy! Have aminodiphenyl ether a bactericidal effect.

The disadvantage, however, is the fact that these active ingredients have gaps in the action either against Gram-positive or against Gram-negative bacteria and a sufficient effect is achieved only with high wall volumes.

"

- 2 -...-, · 2359

Object of the invention

The aim of the invention is to develop bactericidal agents which are equally effective against gram-positive and gram-negative bacteria and require only low levels of use.

Explanation of the essence of the invention

This object is inventively achieved in that the bactericidal agent in addition to conventional excipients aid and as an active ingredient a combination of ethers 2 ¹ '' · Hydroxybenzoylaminodipheny! Of the general formula I

CD

NH-CO- \ 0) OH

in the

R _{1 is} Cl or NO ₂ and

R ₂ , Ro, which may be the same or different,. «Mean H or Cl,

and from nitrodiphenyl ethers of the general formula II

O ₂ N-

in the -

R "H, CGCH ₃ , COCH ₂ Cl or COC ₂ H ₅ means

wherein the weight ratio of the active ingredients (I) χ (II) can be 1: 9 to 9: 1

Ee has surprisingly been found that relatively small additions of 4-bitro-2 '- (substituted) - hydroxy-diphenyl ethers au 2V'-hydroxy-benzoylamino ~ diphenyl ethers significantly improve their action against Gram-positive bacteria and that at the same time good activity against Gram-negative bacteria given is. At the same time, it has been found that relatively small additions of 2'-hydroxybenzoyl-diphenyl ethers to 4-nitro-2'-subst-hydroxy-diphenyi-ethers significantly improve their activity against gram-negative bacteria and, at the same time, provide very good efficacy against gram-positive bacteria is given · This synergism was unpredictable. .

The agents according to the invention can be used "in a variety of ways to combat undesired bacteria, for example * in conjunction with suitable detergents in antiseptic soaps and toiletries, for controlling slime formation in the paper industry and for storage preservation of products susceptible to bacterial decomposition Combination partner can vary between 10 j 90 and 90 s 10, but a mixing ratio of 1 s 1 has proved to be particularly advantageous.

Ouch fjihrung s example

The exemplary embodiment is intended to demonstrate the synergistic effect of the agents according to the invention.

a) A series of 2 ¹ • -hydroxy-benzoylaraino-diphenyl ethers is subjected to a flake test? In sterile Petri dishes are poured on horizontal surface 12 ml Hähragar. Thereafter, 0.1 ml of a bacterial suspension is uniformly spat out with a sterile glass spatula. Then a 2 × 2 cm filter paper, which has been impregnated with a defined concentrated solution of the substance to be tested, is applied after the solvent has evaporated. Is incubated at 37 ⁰ C. From each Bäkteriensuspension three parallel tests are carried out. The bacterial suspension is prepared as follows? Of a 16-hour broth culture (incubated at 37 ⁰ O) of the respective test bacteria strain are 0.1 ml

in 30 ml of sterile nutrient broth and then diluted 1: 2 with 0.9% saline. The test bacteria used are: Staphylococcus aureus SG511 and Escherichia coli. Evaluation takes place by measuring the zones of inhibition after 24 hours and after three days.

In the tables, the Roman numeral indicates the growth index, with the numeral V indicating the best effect. The Arabic numeral indicates the Hemmhofdurchmesser in millimeters, the larger diameter is synonymous with the better effect.

Table I

Effect of 2 "-hydroxybenzoylaminodiphenyl ethers against Gram-positive and Gram-negative bacteria (Staphylococcus aureus and Escherichia coli, respectively). /

Active diphenyl ether substance no. , 4-nitro-4 ^t - (2 ^ll hydrogencarbonates droxybenzoyl) amino Concentration ^ (mol / 1) Efficacy Staphylococcus richia aureus coli 6 0 I i 0 0 1 2-chloro-4-nitro-4 · - (2 * V-hydroxybenzoyl) -amino 0.01 0.001 V • II OVJ! I i 0 0 - 2 * 4 ^ Ni-tro-3 ¹ - (2 "-hydroxybenzoyl) -amino 0.01 0.001 V II 9. 0 I i 0 o 3 2-chloro-4-nitro-3 ^l - (2 '' - hydroxybenzoyl) - 0.01 0.001 V III OCD II 0 0 4 2 ^L , 4-dichloro-4 · - (2 "-hydroxybenzoyl) - 0.01 0.001 V III 5 0 I i 0 0 5 0.01 0.001 V II

amino-

It can be seen that the effect of the 2 '' -hydroxy-berizoylamino-dL-phenyl ethers is restricted on one side to gram-positive bacteria and that in conventional concentrations the activity decreases greatly.

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b) The bactericidal action of 4-nitro-2 ^l - (substituted) - hydroxy ~ diphenyl ethers was tested analogously to Example a).

Table II . ';

Effect of 4-nitro-2 '- (sub8t.) - hydro: x: ydiphenyl ethers against gram-positive and gram-negative bacteria (Staphylococcus aureue or Escherichia coli)

Active agent Diphenyl ether, Concentration Efficacy (raol / 1) Staphylococcus Eusebius richia. aureus coli 0.01 0.001 I 0 IO V 8 II 0 6 4-hydrogen-2'-hydroxy- 0.01 0.001 IO IO V 12 III 0 .7 4-nitro-2'-acetyl- 0.01 0.001 I 0 I 0 V 10 j III 0 8th 4-Hitro-2'-propionyl-oxy- ' 4-Hitro-2 ^l -chloro-acetyl-0.01 oxy-0.001 I 0 IO V 7 ,, \ II 0 9

It can be seen that the bactericidal action of this class of compounds is limited to Gram-negative bacteria and that also here the activity at low concentrations decreases.

c) Analog. Example a) the agents according to the invention were tested for their bactericidal activity against gram-positive or gram-negative bacteria,

Table III

Effect of the agents according to the invention against Gram-positive and Gram-negative bacteria (Staphylococcus aureus or Escherichia coli).

Combination of active ingredients No. 6 * Weight ratio : 1 Concentration (mol / 1) Efficacy Staphylococcus acacia richia aureus coli 18 12 V v 13 8 3 + 6 1 s 1 0.01 0.001 V v 18 V v 6; 3, - 3 + 7 9 it 0.01 0.001 V v 12 7 V v 19 13 2 + 7 1 : 8th 0.01 0.001 V v 9 4 V v 19 12 2 + 9 2 : 1 0.01 0.001 V v 14 9 V v 14 10 4 + 6 1 : 1 0.01 0.001 V v 11 6 V v 13 p .5 + 6 1 : 6 0.01 0.001 V Y 14 10 V v 12 e 3 + 4 0.01 0.001 V v

From the example it is clear that the compositions according to the invention show a very good action against both Gram-positive and Gram-negative bacteria even in low concentration ranges which are favorable for practical use.

(I)

Ο-

R2 Ri

^ NH-CO

OH ^r

in the

R.,

Ql or KOp and "... ·

which can be the same or different,

β Η or Cl, and from Nitrodiphenylethern of the general formula II

(H)

OR

R ₁ = H, COCH ₃ , COCH ₂ Cl or COC ₂ H ₅ ,

wherein the weight ratio of the active ingredients (I): (II) "1s 9 to 9: 1 may be.

Pormel I

NH-CO- (O,

R2 R3

OH

H ₁ =

Cl or NO,

.- /. ^e

(same or different): H or Cl

Pormel II

O ₂ N

R: H, COCH ₃ , GOCHgCl or

Claims (1)

Inventory of benefits Bactericidal agents for the simultaneous control of gram-positive and gram-negative bacteria, characterized in that they contain, in addition to customary auxiliaries and excipients, "as active ingredient a combination of 2'-hydroxybenaoylaminodiphenyl ethers of the general formula I