DD245362A1 - Bactericidal and fungicidal agents - Google Patents

Abstract

The invention relates to novel bactericidal and fungicidal compositions containing quaternary ammonium thiocyanates as active ingredients. The new compounds are useful as disinfectants and can be used with particular success to combat orphaning microorganisms in industrial environments, to control pathogens in health care and as a means of preserving engineering materials.

Description

/ ^X R ³

SCE

in the

R ¹ for (C ₁ -C) -AlkVl R ² for (C ₁ -C ₄ J-AIlCyI, H, CH ₂ -C ₆ H ₅ and

R ^{3 is} (C ₁₀ -C ₁₅ ) alkyl, (C _ie -C ₁₈ ) alkyl or CHaCONH alkyl.

2. Bactericidal and fungicidal compositions according points!, Characterized in that in the formulations in addition to the active compounds according to the invention also other bactericidal and fungicidal agents may be included.

Field of application of the invention

The present invention relates to bactericidal and fungicidal compositions which are suitable for disinfection and can be used for controlling harmful microorganisms in industrial areas and for killing pathogens in health care.

Characteristic of the known technical solutions

The occurrence and spread of pathogenic and other harmful micro-organisms leads to infectious diseases, infectious hospitalism, damage to industrial products or contamination of technical equipment and endangered the health of humans and animals.

By applying appropriate means must be contributed to the consequences, such. B. Reduction of labor productivity.

For such purposes, the use of chemical disinfectants or corresponding active ingredients or drug combinations is known. Their applicability in practice is limited, z. As by high toxicity, gaps, pH dependence of the effect, incompatibilities, insufficient solubility, high corrosivity or too low environmental friendliness.

Quaternary ammonium compounds are known which contain predominantly chlorides as anions. In addition, quaternary ammonium compounds are also known which contain bromide, methosulfate, ethosulfate, tosylate and salicylate ions (eg FR-PS 1513829), benzenesulfamidate ions (GB-PS 1113513), alkyl sulfamate ions (US Pat. DE-PS 1221398). Inorganic thiocyanates are known as antiseptics (DRP 671741,673164,677675,684671,723744,733254,748565, 964092).

From the series of organic thiocyanates, the methylene-bis-thiocyanate is described as an antimicrobial active ingredient (DE-PS 1 617 960,1271314,2122055, US-PS 3300375).

Other known organic thiocyanates having antimicrobial activity are nuclear substituted aryl thiocyanates (e.g., DE-PS 2806864) and polyoxyalkylene dithiocyanates (e.g., U.S. Patent 4,294,848).

The disadvantage of these compounds is their existing gaps in their action, their relatively poor efficacy, skin intolerance and / or their allergic effects.

Object of the invention

The object of the invention is to find new antimicrobial agents which are distinguished by their good action, their universal applicability and their low toxicity.

Explanation of the essence of the invention

The object of the invention is to find new active ingredients with the widest possible practical application by further modifying the structure of quaternary ammonium compounds.

This object is achieved in that the new agents in addition to conventional excipients and carriers as active compounds of the general formula

scli

in the

R ¹ for (C ₁ -C ₄ ) AIM,

R ^{2 is} (d-CtJ-alkyl, H, CH ₂ -C ₆ H ₅ and

R ^{3 is} (C ₁₀ -C ₁₅ ) -alkyl, (C ₁₆ -C ₁₈ ) -alkyl or CH ₂ CONH-alkyl,

is included.

The compounds according to the invention are prepared by reacting aqueous solutions of the quaternary ammonium chlorides with rhodanides and extracting the end products with an organic solvent, preferably methylene chloride.

manufactured.

The active substances are suitable for use as disinfectants, for controlling pathogenic microorganisms in health care, in industrial plants and technical products and for their preservation.

The active ingredients can be used in conjunction with solvents and / or surface-active substances in the usual formulations

be transferred.

These formulations are prepared in a known manner, for. B. by mixing the active ingredients with the solvents and optionally surfactants.

Suitable solvents are essentially: ethanol, n-propanol, isopropanol and / or water. As surface-active substances are mainly nonionic surfactants of the type polyoxyethylene fatty alcohol ether and / or

Alkylaryl polyglycol ethers in question.

The formulations generally contain from 0.1% to 20%, preferably between 0.5 and 5% of the invention

Agents.

The active compounds according to the invention can be present in the formulations in a mixture with other known active compounds, such as aldehydes, eg. As formaldehyde, glyoxal, glutaric dialdehyde, phenols, z. For example, 4-chloro-3-methylphenol, 2-phenylphenol, 4-hydroxy-diphenylmethane, 4-chloro-1-benzylphenol, 4-chloro-3,5-dimethylphenol, 2,4-dichloro-3,5-dimethylphenol or Organotin compounds, e.g. B. tri-n-butyltin benzoate.

The compositions according to the invention are distinguished by high activity combined with a broad spectrum of activity in the bactericidal and fungicidal range. In addition, these agents are very easy to use because of their low toxicity and their good skin and material compatibility. The effect of the bactericidal and fungicidal compositions according to the invention is illustrated by examples.

As an example of the compounds according to the invention, the compounds listed in Table 1 are mentioned.

Table 1

Verb.

R ¹

Hb cn

^RJ properties C ₁₀ _ ₁₅ H ₂₁ _ ₂₅ oil C ₁₀ _ ₁₅ h ₂₁ _ ₂₅ oil C ₁₀ _ ₁₅ H ₂₁ _25 oil C ₁₆ _ ₁₈ H ₃₃ _ ₃₇ white crystals Cl6-18H ₃₃ _ ₃ 7 white crystals CH ₂ CONHC ₁ (M ₂ H ₂ V ₂₅ white crystals

A CH ₃ CH ₂ B CH ₃ H C CH ₃ CH ₃ D CH ₃ CH ₃ e CH ₃ H F CH ₃ CH ₂

embodiments

The following examples are intended to illustrate the invention without limiting it.

In Tables 2-5, the substances AF have the meaning given in Table 1, the compound G is the dimethyl (Cio-C ₁₅ ) -all <yl-benzyl-ammonium chloride as comparison product.

The active compounds are used as aqueous solution or in conjunction with suitable solubilizers and 5% ethyl glycol in a concentration of 1% active ingredient. The test solutions can be diluted with water as desired.

example 1 Bactericidal activity

The foundation is carried out in a suspension test (Beck, EG, J. Borneff, L Grün et al.: Recommendations for the Testing and Evaluation of the Effectiveness of Chemical Disinfection Methods, ZbI. Bakt. Hyg., I. Ab. Orig.B 165 [1977] 335-380 ).

To 10 ml test solution with different drug concentrations, 0.1 ml of a 16-18h broth culture of the test bacteria are added and mixed. After a reaction time of 2-120 min, a platinum-soluble mixture is removed in each case and transferred into 10 ml nutrient broth. The nutrient broth is added to neutralize the active ingredient 3% Tween 80 (dodecylmercaptan 80%) and 0.3% lecithin.

It is then incubated at 37 ⁰ C.

For evaluation, the exposure times are determined in minutes, after which no growth of the test bacteria can be detected

Test bacteria: 1. Staphylococcus aureus

2. Escherichia coli

3. Pseudomonas aeruginosa

Table 2

Verb.

Wirkstoffkonz. test bacteria 60 2 30 3 15 the test solution 10 10 10 in% 1 5 2 5 0.1 15 30 30 0.5 5 5 10 1.0 2 2 5 0.1 120 120 120 0.5 30 30 60 1.0 15 10 30 0.1 30 10 60 0.5 5 10 30 1.0 5 5 10 0.1 0.5 1.0

Example 2

Fungicidal activity. *

The test is carried out in a suspension test. To 10ml test solution with different drug concentrations, 0.1 ml of a standardized homogenate of the test fungi are added and mixed. After different exposure times between 2 and 120 minutes, a platinum-soluble mixture is removed and transferred into 10 ml culture medium for mushrooms (Sabouraud nutrient medium). 3% Tween 80 (dodecyl mercaptan 80%) and 0.3% lecithin are added to the nutrient medium to neutralize the active ingredient. Subsequently, at 2O ⁰ C incubated for up to 4 weeks.

For evaluation, the exposure times are determined in minutes, after which no growth of the test fungi can be detected

Test fungi: 1. Candida albicans

2. Trichophyton mentagrophytes

3. Penicillium notatum

4. Aspergillus niger

Table 3

Verb.

Wirkstoffkonz. test fungi 30 2 60 3 4 the test solution 15 30 120 120 in% 1 5 5 60 60 0.1 60 60 15 30 0.5 10 15 120 120 1.0 5 10 30 30 0.1 15 30 15 15 0.5 , 5 15 30 60 1.0 2 5 15 15 0.1 15 30 10 10 0.5 30 120 1.0 0.1

Example 3 Fungicidal activity in a mixed culture

The agar plate test is used to determine the fungicidal activity on a mixed suspension consisting of Aspergillus niger, Penicillium species and Trichoderma viricide. For this purpose, the agar to be tested is added to the test compounds at 45 ° C. in the stated test concentration. After solidification, the mixed suspension was inoculated. The evaluation was carried out at room temperature on the 5th and 10th day using the following Boniturschemas

1 = unhindered growth of the fungi

2 = growth slightly inhibited

3 = growth strongly inhibited

4 = no fungal growth

Table 4

Active substance Concentration% 5th day 10th day

A 0,1 4 4 4

F 0.1 4 4 4

G 0.1 2 2

0.2 3 2 2

Example 4 Testing the preservative effect

250 ml of dispersion paint (Polyvinylacetatlatex) were added to the compounds of the invention in the concentrations indicated and with 0.5 ml of germ suspension consisting of Aspergillus niger, Penicillium funiculosum, Pullularia pullulans, Bacillus substituus. Bacillus mesenterius, aerobacter aerogenes and bacterium pordigiosum, inoculated.

After 7 days, a germ count determination was made by the plate casting method. In germ-free 2 more inoculations.

The evaluation was based on sterility and number of inoculations.

Table 5

Active substance Conc.% Sterility Number of

inoculations

A 0.1 sterile none

C 0.1 sterile none

G 0.1. non-sterile -

A 0.5 sterile 2

C 0.5 sterile. 2

G 0.5 sterile none

A, 1.0 sterile 2

C 1.0 sterile 2

G 1.0 sterile 2

Tables 2 and 3 show the good bactericidal and fungicidal activity of the compounds according to the invention. The results of Table 4 show the better effect of the compounds A and F according to the invention over the comparison substance G (dimethyl-alkylbenzylammonium chloride) in the fungicidal action in a mushroom mix culture. From Table 5, the better effect of compounds A and C according to the invention over the comparison substance G in the preservative effect, especially in low concentrations recognizable.

Claims (1)

Invention claim: 1. Bactericidal and fungicidal compositions based on quaternary ammonium compounds, preferably for controlling - damaging microorganisms in industrial areas and in health care and for the preservation of technical material, characterized in that they in addition to conventional excipients and carriers as active compounds of the general formula Ή ¹ .E ²