DE2516922C3 - Disinfectants - Google Patents

Description

The well-known, widely used disinfectants based on antimicrobial aldehydes, such as Formaldehyde and glutaraldehyde have an unpleasant, pungent odor and are irritating to the mucous membranes. In addition, formaldehyde is relatively toxic, while glutaraldehyde is human Skin discolored brownish. The mode of action of the known aldehyde disinfectants is also the same does not meet the requirements. Formaldehyde is only effective in relatively high concentrations. Glutaraldehyde Only effective against bacteria in concentrations of 0.1% and above. For a fungicidal and The sporicidal effect and the killing of tubercle bacilli are much higher concentrations of this Aldehyde required. Glutaraldehyde is more effective against spores in an alkaline environment than in an acidic one Milieu, however, its resistance in the alkaline range decreases sharply. Glyoxal acts as a disinfectant practically only on the surface and does not have a prominent spectrum of activity.

Acrolein is a microbicide that is effective against bacteria, mold and algae therefore used to prevent slime formation in the paper industry. However, it is strong toxic and is therefore not suitable for use in the cosmetic field or for disinfecting rooms in food factories, dairies and commercial kitchens, for the preventive and acute treatment of Skin diseases caused by microorganisms or for the renovation of operating rooms.

In addition, acrolein polymerizes very easily or enters into addition reactions, so that a mixture with other substances made for disinfectants

= C-CHO

in which Ri, R2 and R3 are the same or different and a Hydrogen atom, a straight-chain or branched alkyl and / or alkenyl radical with 1 to 5 carbon atoms mean, where the total number of carbon atoms of the «^ -unsaturated aldehydes 6 to 12 amounts to

Preferably the total carbon number of the aldehydes is 8-10.

In contrast to known disinfectants, the disinfectants according to the invention have the basis of aldehydes has a much broader spectrum of activity with excellent effectiveness even in low use concentrations of z. B. < 0.1% active ingredient against bacteria, fungi, spores and viruses. The aldehydes used; own a remarkably pleasant to inconspicuously pleasant odor and excellent physiological tolerance. the The latter property is based in part on the fact that the aldol condensation, which leads to the invention used «^ -unsaturated aldehydes leads to a reaction that is widespread in living nature, so that the most of the aldehydes used according to the invention as naturally occurring antimicrobial agents can be designated. These unsaturated aldehydes are only sparingly soluble in water, they do dissolve but in organic solvents and can be caused by solubilizers or emulsifiers, anionic, Cationic or nonionic surfactants to disinfectants that can be diluted with water without difficulty be formulated. Another advantage of the "," - unsaturated aldehydes used according to the invention is their resistance in an alkaline environment and also their unchanged antimicrobial effectiveness after prolonged storage.

Due to these properties, the disinfectants according to the invention can be liquid, pasty or solid form and due to their stability in an alkaline medium z. B. also in liquid or solid Soap can be used. Because of their easy technical accessibility and their physiological compatibility they can be used in the field of cosmetics, cleaning and care of human skin Disinfection of rooms used in food factories, dairies, large kitchens and the like , also for preventive and acute treatment against caused by microorganisms

Skin diseases in living beings, for the renovation of operating rooms, air conditioning systems and for disinfecting instruments, also in the veterinary sector in the rehabilitation of hatcheries, fattening plants and in poultry or Mammalian stalls, i.e. in areas where Acrolein cannot be used because of its high toxicity.

Examples of the substituents Ri, R ₂ and Rj in the general formula are, in addition to hydrogen, straight-chain or branched alkyl radicals or alkenyl radicals having 1 to 5 carbon atoms, provided the total number of carbon atoms of the aldehydes used according to the invention is in the range from 6 to 12, with compounds having 8 to 10 total carbon atoms are preferred. Examples of such radicals are, in addition to hydrogen

Methyl, ethyl, n-propyl, isopropyl,
η-butyl, isobutyl, sec-butyl, n-pentyl,
2-pentyl, 3-pentyl, 2-methylbutyl,
3-methylbutyl, vinyl and the allyl radical

Preferred active ingredients are

2-methyl-pent-2-enal,

2-ethyl-hex-2-enal,

2-propyl-hept-2-enal,

2-isopropyl-5-methyl-hex-2-enal,

2-propyl-5-methyl-hex-2-enal,

2-isopropyl-hept-2-enal and

Mixtures of these ajS-unsaturated aldehydes.

The preparation of these "Jj-unsaturated aldehydes is known and takes place, for example, after the aldol condensation described in Houben-Weyl, Vol. 7/1, pages 82-83. For the production of z. B. 2-Ethylhex-2-enal is allowed to flow together 100 cm ^{3 of} 3% sodium hydroxide solution and 500 g of n-butyraldehyde with stirring within 15 to 30 minutes in such a way that the reaction temperature is 60 to 70.degree. It is then refluxed for 4 hours. The alkaline-aqueous layer is then separated off, the oily layer is washed neutral several times with a little water and fractionated in vacuo. A special aldol condensation via Schiff's base according to Angew is more expedient. Chemie Vol. 75, p. 978 (1963), according to which aldehydes of the formula

R ₃ -CH ₂ -CHO
with carbonyl compounds of the formula

C = O

in which R 1 and R _{2 are} alkyl groups, are condensed with elimination of water to form the abovementioned «, ^ - unsaturated aldehydes. Examples of readily available carbonyl compounds for such an aldol condensation are formaldehyde, acetaldehyde, propionaldehyde, n-butyraldehyde, i-butyraldehyde, n-valeraldehyde, i-valeraldehyde, 2-methylbutyraldehyde, caproaldehyde, onanthaldehyde, caprylaldehyde, acetone, methyl ethyl ketone, methylpropyl ketone, and methylpropyl ketone. The α-unsaturated aldehydes or aldehyde mixtures obtained by the aldol condensation do not need to be worked up further for their use in the disinfectants according to the invention. So z. B. an aldol condensation between several compounds of the general formula

R ₃ CH ₂ CHO
and several compounds of the general formula

C = O

R ₂

are made, and the mixture obtained by this aldol condensation of various «^ -unsaturated Aldehydes of the general formula

C = C-CHO

can be used without further separation. Mixtures of "^ -unsaturated aldehydes are particularly suitable, obtained by aldol condensation of mixtures of n- and i-valeraldehyde.

The active ingredients according to the invention can be used in without impairing their antimicrobial effect Combination with antioxidants, anti-corrosion agents and detergents can be used. They can also be used together with other disinfectants, e.g. B. with antimicrobial agents Aldehydes, alcohols or carboxylic acids, furthermore with correspondingly effective amphoteric surfactants, quaternary Ammonium compounds or substituted phenols are used.

j5 The use concentration of the invention Aldehydes depend on the specific purpose and the effectiveness of the aldehydes used. she is generally in a range from 0.001 to 1 and preferably from 0.05 to 0.5% by weight, based on all of the disinfectant.

example 1

A disinfectant was prepared with the following composition:

2-ethyl-hex-2-enal

Isopropyl alcohol

Triethylene glycol

Anionic surfactant

(Alkyl sulfonate)

as an emulsifier

water

10 parts by weight
5 parts by weight
5 parts by weight

30 parts by weight
50 parts by weight

The disinfectant obtained consisted of a clear, colorless, pleasant-smelling liquid that in a concentration of 1 to 5% was particularly suitable for disinfecting instruments.

Example 2

From equimolar amounts of n- and i-valeraldehyde

bo an aldehyde mixture was prepared in a known manner by aldol condensation with 1 η sodium hydroxide solution at 90 to 10O ⁰ C within 5 hours, which consisted of the following components:

t, -, 2-isopropyl-5-methyl-hex-2-enal
2-propyl-hept-2-enal
2-isopropyl-hept-2-enal
2-propyl-5-methyl-hex-2-enal.

From this mixture, a disinfectant was prepared according to Example 1, which as a clear, colorless, pleasant smelling liquid in a concentration of 1 to 5% for disinfecting instruments was suitable.

Example 3

A hand disinfectant was made with the following composition:

2-isopropyl-5-methylhex-2-enal
Sorbitol solution as
Humectants
Ethanol

Isopropyl alcohol
Isopropyl myristate
Distilled water

0.2 parts by weight

0.5 parts by weight
80 parts by weight
10 parts by weight
1 part by weight
8.3 parts by weight

Comparative experiments

In the following comparative tests the bactericidal, fungicidal and sporicidal effectiveness as well as the effectiveness against tuberculosis according to the guidelines for the testing of chemical disinfectants, published by the German Society for Hygiene and Microbiology, 3rd edition, with a Standard preparation of the following composition examined:

Aldehyde to be investigated

Isopropyl alcohol

Triethylene glycol

Anionic surfactant (alkyl

sulfonate)

as an emulsifier

Distilled water

10 wt. O / o
5% by weight
5% by weight

20% by weight
60% by weight

The pH of these compositions with the respective aldehyde was between 4 and 6. Als Comparative aldehyde, both formaldehyde and glutaraldehyde were used.

Comparative experiment 1

It became the limit concentration for killing Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa and Proteus OX 19 determined over a period of 30 minutes, the following in the The values listed in Table 1 were obtained.

Table 1 Limit Bactericidal effectiveness concentration
% Aldehyde used 0.025 0.050 2-isopropyl-5-methyl-hex-2-enal Unpurified n- / i-valeraldehyde 0.050 Aldol condensation product 0.100 Glutaraldehyde 0.100 2-propyl-hept-2-enal 1,000 2-ethyl-hex-2-enal formaldehyde

These values show that all active ingredients according to the invention are considerably better than formaldehyde, and the the first two active ingredients according to the invention were better or just as effective as glutaraldehyde. Compared to glutaraldehyde, all disinfectants according to the invention have the advantage of being pleasant or just a slight odor. Furthermore, like glutaraldehyde, they are not unstable or lead to discoloration of the skin.

Comparative experiment 2

To determine the fungicidal effectiveness, the limit concentration for the killing of Trichophyton was used mentagrophytes, Microsporum gypseum and Candida albicans in a period of r <30 minutes found. The values obtained are listed in Table 2 below.

Table 2

Fungicidal effectiveness

Disinfectants
with a detention

Limit concentration

2-isopropyl-5-methyl-hex-2-enal 0.005

2-propyl-hept-2-enal 0.01

Glutaraldehyde 0.2

Formaldehyde 0.5

These values show the considerably better fungicidal effectiveness of the aldehydes used according to the invention.

Comparative experiment 3

To determine the sporicidal effectiveness, j-, which is responsible for killing B. subtilis within 3 hours required concentration determined. The following values were obtained:

Table 3
^{4 (1} Sporicidal Effectiveness

Disinfectants
with a content of

Mortification
after 3 hours

2-isopropyl-5-methyl-hex-2-enal 0.05%

2-propyl-hept-2-enal 0.1%

i-Zn-Valeraldehyd-Aldol-Kond.prod. 0.1%

2-ethyl-hex-2-enal 0.2%

Glutaraldehyde 2%

Formaldehyde 2%

These values show the very good sporicidal effectiveness of the disinfectants according to the invention compared to those with a content of known aldehydes.

Comparative experiment 4

To prove that the aldehydes used according to the invention are also better than acrolein and Crotonaldehyde, the next member of the homologous series, were comparative experiments with these two aldehydes carried out.

Since acrolein polymerizes very easily or undergoes addition reactions, it was a mixture with others Substances that are required for disinfectants for application reasons are not possible. That Acrolein was therefore in the form of a 10% aqueous

Solution examined. The crotonaldehyde, on the other hand, was incorporated into an aldehyde formulation according to the invention. According to comparative experiments 1, 2 and 3

The limit concentrations determined for bactericidal, fungicidal and sporicidal effects are shown in Table 4 compiled.

Table 4
Limit concentration Bactericidal
effect Fungicides
effect Sporicides
effect 0.05
> 0.25 <0.05
> 0.25 Sl
> 4 Acrolein in
water
Crotonaldehyde
in aldehyde
formulation

These values show that acrolein drops sharply when one considers the effects of crotonaldehyde. With deviating composition of the test solution provides excellent physiological compatibility, in its effect approximately the good antimicrobial effect of the invention used in accordance with the invention Corresponds to aldehydes, see Tables 1.2 according to the aldehydes used with 6 to 12 carbon and 3, but is highly toxic. The antimicrobial atom is therefore surprising.

Comparative experiment 5

Various disinfectants against mycobacterium were used to determine the TB effectiveness smegmatis investigated. In the table below is the

percentage concentration of active ingredient and the corresponding killing time indicated.

Table 5
TB effectiveness

Disinfectants
with a content of

Killing time in minutes
30th

120

2-propyl-hept-2-enal

2-isopropyl-5-methyl-hex-2-enal 2-ethyl-hex-2-enal

Glutaraldehyde

formaldehyde

0.2 0.1

= £ 0.025
0.2
2

i £ 0.025

> 0.5 0.5

That not only those in Tables 1 to 3 and 5 The test series were standardized under

investigated Λ, / 9-unsaturated aldehydes with 8 or 10 conditions. For this purpose the aldehydes,

Carbon atoms, beneficial antimicrobial effects, which are for the most part limited water solubility, in one

substances are shown in Tables 6 to 9. Brought into chemically identical environment by emulsifying

Table 6 shows the constitution of the investigated aldehydes with the following composition:
de specified.

Aldehyde standard formulation

10Gew.- ⁰ / o aldehyde

5% by weight isopropanol,

5% by weight triethylene glycol,
20% by weight sodium lauryl alkyl sulfonate,

93% ig, Bayer,
60% by weight of distilled water.

The bacteriostatic and fungistatic effectiveness was determined with the aid of the dilution test according to the guidelines for testing chemical disinfectants of the DGHM. The MIC values the aldehyde formulations are given in Table 7.

Table 8 shows the bactericidal and fungicidal effects of the aldehyde formulations.

The determination was carried out in the suspension test according to the guidelines of the DGHM.

The sporicidal and TB activity was demonstrated on germ carriers determined Bohemian garnets were used as germ carriers for B. subtilis and batiste lobes for M. smegmatis. The experiment was also carried out according to the guidelines of the DGHM. The values obtained are given in Table 9.

Table 6

R ¹

10

Compilation of the Λ, / ί-unsaturated aldehydes C = C - CHO

R ² R ¹

Molecular formula aldehyde

R '

QH ₈ O 2,4-hexadienal CH ₃ -CH = CH- C ₆ H ₁₀ O 2-methyl-pentene-2-al CH ₃ -CH ₂ - C ₆ H ₁₀ O trans-hexen-2-al CH ₃ -CH ₂ -CH ₂ - C ₈ H ₁₄ O 2-n-penlyl-aciolein H QH ₁₄ O 2-ethyl-hexen-2-al CH ₃ -CH ₂ -CH ₂ - CHj Q ₀ H ₁₈ O 2-isopropyl-5-methyl-
hexen-2-al \
pll PLJ
L. rl L rl?
/
CH ₃ CioH _1B 0 2-propyl-hepten-2-al CH ₃ - (CH ₂ J ₂ -CH ₂

C ₁₀ H ₁₈ O 2-isopentyl-3-methyl- CH ₃ -

butene-2-al

H H H H H

H - H

CH ₃

C ₁₂ H ₂₂ O 2-n-Butyl-octene-2-al CH ₃ - (CH ₂ J ₃ -CH _{2 -H}

Table 7

MIC values of α, / J-unsaturated aldehydes, data in% active ingredient

R ¹

CH ₃ -

CHj- (CH ₂ Ij-CH ₂ -

CH ₃ -CH ₂ -

CH ₅

CH-

/ CH ₃

CH ₃ -CH ₂ -CH ₂ -CH,

CH-CH ₂ -CH ₂ -

CH ₃ CH ₃ - (CH ₂ I ₂ -CH, -

aldehyde Staph. E.
aureus 1
I. ProL Trich. Cand.
vulgaris mentagr. albicans Conc. Staph.
aureus E. coli Ps. Aeru- ProL
ginosa vulgaris > 30 Trich.
mentagr. 0.05
0.1
0.05
0.05
0.0125
0.025 Asperg,
Niger 0.05
0.05
0.05
0.025>
0.05> 0.05 0.001
0.05 0.005
0.1 0.5
0.25 > 30 > 30 30th
> 30 2 '/ 2
15th
> 30 30th
> 30 0.005
0.01 0.5
0.25
0.1 2 '/ 2
15th
> 30 5
> 30 5
> 30 15th
> 30 > 30 2,4-hexadienal
2-methyl-pentene-2-al
trans-hexen-2-al
2-ethyl-hexen-2-al
2-isopropyl-5-methyl-hexen-2-al
2-propyl-hepten-2-al . coli Ps. Aeru-
ginosa Germicidal effect of e ^ S-unsaturated aldehydes. Concentration data in% active ingredient;
Killing times in minutes 0.5
0.25 > 30 > 30 30th
> 30 2 '/ 2
> 30 > 30 Microsp.
gyps. Table 8 0.05
0.1
0.05
0.1
0.1
0.1 0.05
> 0, l
0.05
0.1
> 0, l
> 0, l aldehyde 0.25
0.1 > 30 5
> 30 30th
> 30 30th
> 30 Cand.
albicans 2,4-hexadienal 30th
> 30 > 30 2-methyl-pentene
2-al > 30 > 30 trans-hexen-2-al 15th
> 30 > 30 2-n-pentyl
acrolein > 30

12th

continuation

aldehyde

Conc.

Staph. aureus

E. coli

Ps.aeruginosa

Prot.
vulgaris

Trich.
mentagr.

Microsp.
gyps.

Cand. albicans

2-ethyl-hexene- 0.1 2 '/ 2 5 5 2 '/ 2 2V2 2 ¹ ii 2 '/ 2 2-al 0.05 15th > 30 > 30 15th > 30 > 30 > 30 0.025 > 30 > 30 2-isopentyl-3- 0.25 5 > 30 30th 2V2 30th 15th 5 methyl-butene-2-al 0.1 30th > 30 2V2 30th 15th 15th 0.05 > 30 30th > 30 30th 30th 2-isopropyl-5- 0.1 2 '/ 2 2 ¹ ii 15th 2 ¹ ii 2V2 2 '/ 2 2 '/ 2 mythyl-hexen-2-al 0.05 2 '/ 2 5 30th 2V2 2V2 2 '/ 2 2 '/ 2 0.025 2 '/ 2 15th > 30 2V2 2V2 2 '/ 2 2V2 0.01 5 30th 15th 2V2 2 '/ 2 5 0.005 > 30 > 30 > 30 5 15th 30th 2-propyl heptene 0.1 2 ¹ ii 5 30th 2 '/ 2 2 '/ 2 2V2 Vh 2-al 0.05 2 '/ 2 5 > 30 2 '/ 2 2 '/ 2 2V2 2 ¹ /: 0.025 2 ¹ ii > 30 5 2 '/ 2 5 5 0.01 30th > 30 15th 30th 30th 0.005 > 30 > 30 > J0 > 30 2-n-butyl-octene 0.25 5 30th 30th 5 15th 15th 15th 2-al 0.1 5 > 30 > 30 15th 15th 30th 15th 0.05 15th > 30 30th 30th 15th

Table 9

Germicidal effect of ^ -unsaturated aldehydes against B. subtilis and Mycobact. smegmatis. Concentration data in% active ingredient. Killing times in minutes (M. smegm.) Or hours (B. subt.)

aldehyde

Conc.

B. subL

Conc.

M.

smegm.

2,4-hexadienal

2-methyl-pentene-2-al trans-hexene-2-al 2-n-pentyl-acrolein

2-ethyl-hexen-2-al

2-isopentyl-3-methyl-buten-2-al 2-isopropyl-5-niethyi-hexen-2-al

2-propyl-hepten-2-al

4th 4th 1 > 120 2 5 1 > 6 1 60 4th > 6 0.5 120 4th > 6 0.25 120 4th 6th 0.3 30th 2 > 6 0.2 30th 0.1 120 1 1 0.05 > 120 0.5 3 0.25 120 0.25 4th 0.25 1 r
IJ 0.1 > 6 0.1 15th 0.5 > 6 0.05 15th 1 2 0.025 30th 0.5 3 0.25 3 0.1 3 0.25 15th 0.05 3 0.1 30th 0.025 4th 0.05 30th 1 3 0.025 30th 0.5 4th 0.01 > 120 0.25 4th 0.1 4th 0.05 4th 0.025 > 6

2-n-butyl-octene-2-al

> 120

Claims (5)

Patent claims: 1. Disinfectants, labeled by a content of one or more <x, ^ -unsaturated aldehydes of the general formula C = C-CHO in which Ri, R2 and R3 are the same or different and a hydrogen atom, a straight-chain or branched alkyl and / or alkenyl radical with 1 to 5 Mean carbon atoms, where the total number of carbon atoms of the «jS-unsaturated aldehydes 6 to 12 is 2. Disinfectant according to claim 1, characterized in that the total carbon number of the Aldehydes is 8-10. 3. Disinfectant according to claim 1 and 2, characterized in that it is used as an aldehyde Contains 2-ethyl-hex-2-enal 4. Disinfectant according to claim 1 and 2, characterized in that it is used as an aldehyde Contains 2-isopropyl-5-methyl-hex-2-enal 5. Disinfectant according to claim 1 and 2, characterized in that it is used as an aldehyde Contains 2-propyl-hept-2-enal. application-related reasons is not required or only succeeds with considerable research effort The invention has set itself the task of a Group of novel disinfectants available to provide a pleasant or at least non-annoying odor, good physiological tolerance and a broad spectrum of antimicrobial activity even at lower concentrations of e.g. 0.1% Active ingredient against bacteria, fungi, yeast, algae, Spores, mycobacteria and viruses are effective, even in an alkaline environment, are stable and, in particular, are color-fast and do not become ineffective even after prolonged storage.
These disinfectants contain one or more unsaturated aldehydes of the general formula