DE2349058A1 - Beta-hydroxy-carboxylic acid antimicrobials - contg. formaldehyde to increase antimicrobial activity - Google Patents

Abstract

Hydroxy-carboxylic acids of the formula : HO-CR1R2-CH2-COOH (I), (where R1 is 4-16C alkyl R2 is H or 1-15C alkyl; R1 + R2 =20C), are used in combination with formaldehyde as antimicrobial agents at pH values of is not >5. (I) is pref. used in an amt. of 0.005-20 (esp. 0.01-10)wt. % and the formaldehyde at 0.025-25 (esp. 0.05-10)wt. % of the antimicrobial agent contg. (I) and formaldehyde. The antimicrobial agents pref. also contain ethanol. The acidic compsns. contg. (I) and formaldehyde are useful as cleansing agents for dairies, breweries, food plants etc. and in veterinary applications such as stable disinfection. A partic. important application is in bottle disinfection in hospitals, etc.

Description

Düsseldorf, September 26, 1973 Henkel & Cie GmbH

Henkelstrasse 67 patent department

Z / s

Patent application D 4802

"Use of ^ -hydroxycarboxylic acids in combination with formaldehyde as an antimicrobial agent "

(Additional application to the patent (patent application

P 23 12 280.7 (D 4577))

The invention relates to the use of a synergistic combination of straight-chain or 3-position branched ^ -hydroxycarboxylic acids of medium to higher chain length with formaldehyde for combating bacteria and fungi in acidic pH ranges and is a further development of the patent. (Patent application P 23 12 280.7).

Subject of the patent (patent application P 23 12 280.7)

The use of 3-hydroxycarboxylic acids is the general one formula

^R 2

R ₁ -C- CH ₂ - COOH,

OH

in the FL represent an alkyl radical with ¹ J - 16 carbon atoms and R ₂ hydrogen or an alkyl radical with 1 - 15 carbon atoms, the sum of R ^ + Rp not exceeding 20 carbon atoms, as antimicrobial substances in acidic areas with pH- Values

5 09 8U / 0979

Henkel & Cie GmbH page 2 for patent application D 4 8O 2.

The preparation of the 3-hydroxycarboxylic acids to be used according to the invention can be carried out in a known manner according to the Synthesis of Refor / natsky from corresponding aldehydes or ketones and bromoacetic esters are carried out with subsequent saponification of the esters obtained. Corresponding information on the preparation of the compounds can be found, for example, in the publications by P.L. Breusch and P. Baykut, Chem. Ber. 90, 526 531 (1957), M. Skogh, Acta Chem. Scand. 6, 809-817 (1952) and F.L. Breusch and E. Ulusoy, Hoppe Seyler's Z. Physik. Chem. 286, 174-180 (1951). Another way to Production of the ^ -hydroxycarboxylic acids consists in the saponification of ß-hydroxycarboxylic acid nitriles Chain length. The g-hydroxycarboxylic acid nitriles to be used as starting materials in this saponification can particularly advantageous by reacting epoxides with hydrocyanic acid in the liquid phase and in the presence of strong bases and / or cyanide ion-forming compounds are obtained as catalysts.

As ^ -hydroxycarboxylic acids to be used according to the invention are therefore, for example, 3-hydroxyheptanoic acid, 3-hydroxyoctanoic acid, 3-hydroxynonanoic acid, 3-hydroxydecanoic acid, 3-hydroxyundecanoic acid, 3-hydroxydodecanoic acid, 3-hydroxytridecanoic acid, 3-hydroxytetradecanoic acid, 3-hydroxypentadecanoic acid, 3-hydroxyhexadecanoic acid, 3-hydroxyheptadecanoic acid, 3-hydroxyoctadecanoic acid, 3-hydroxynonadecanoic acid, 3-hydroxy-3-methyl-octanoic acid, 3-hydroxy-3-methyl-decanoic acid, 3-hydroxy-3-methyl-dodecanoic acid, 3-hydroxy-3-methyl-tetradecanoic acid, 3-hydroxy-3-methyl-hexadecanoic acid, 3-hydroxy-3-methyl-octadecanoic acid, 3-hydroxy-3-ethyl-tetradecanoic acid, 3-hydroxy-3-ethyl-penta-decanoic acid, 3-hydroxy-3-propyl-tetradecanoic acid, 3-hydroxy-3-butyl-tridecanoic acid, 3-hydroxy-3-pentyl-dodecanoic acid, 3-hydroxy-3-hexyl-undecaric acid, 3-hydroxy-3-heptyl-decanoic acid, 3-hydroxy-, 3-ethyl-hexadecanoic acid, 3-hydroxy-3-propyl-pentadecanoic acid, 3-hydroxy-3-butyl-tetradecanoic acid, 3-hydroxy-3-pentyl-tridecanoic acid, 3-hydroxy-3-hexyl-dodecanoic acid, 3-hydroxy-3-

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Henkel & Cie GmbH se »· 3 zurPo» »Bianm» wuned 4o02

heptyl-undecanoic acid, 3-hydroxy-3-ethyl-heptadecanoic acid, 3-hydroxy-3-propyl-hexadecanoic acid, 3-hydroxy-3-butylpentadecanoic acid, 3-hydroxy-3-pentyl-tetradecanoic acid, 3-hydroxy-3-hexyl tridecanoic acid » 3-hydroxy-3-heptyldodecanoic acid, 3" hydroxy-3-octyl-undecanoic acid, 3-hydroxy-3-ethyl-octadecanoic acid, 3-hydroxy-3-propyl-heptadecanoic acid, 3-hydroxy-3-butyl-hexadecanoic acid, 3-hydroxy-3-pentylpentadecanoic acid, 3-hydroxy-3-hexyl-tetradecanoic acid, 3-hydroxy-3-heptyl-tridecanoic acid, 3-hydroxy-3-octyldodecanoic acid, 3-hydroxy-3-ethyl-nonadecanoic acid, 3- Hydroxy-3-propyl-octadecanoic acid, 3-hydroxy-3-butyl-heptadecanoic acid, 3-hydroxy-3-pentylhexadecanoic acid, 3-hydroxy-3-hexyl-pentadecanoic acid, 3-hydroxy-3-heptyl-tetradecanoic acid, 3-hydroxy 3-octyl-tridecanoic acid, 3-hydroxy-3-nonyl-dodecanoic acid, 3-hydroxy-3-propyl-nonadecanoic acid, 3-hydroxy-3-butyloctadecanoic acid, 3-hydroxy-3-pentyl-heptadecanoic acid, 3-hydroxy-3- hexyl-hexadecanoic acid, 3-hydroxy-3-heptylpentadecanoic acid, 3-hydroxy-3-octyl-tetradecanoic acid, 3-hydroxy-3-nonyl-t ridecanoic acid, 3-hydroxy-3-butyl-nonadecanoic acid, 3-hydroxy-3-pentyl-octadecanoic acid, 3-hydroxy-3-hexylheptadecanoic acid, 3-hydroxy-3-heptyl-hexadeoanoic acid, 3-hydroxy-3-octylpentadecanoic acid ^> e, 3-hydroxy-3-nonyl-tetradecanoic acid, 3-hydroxy-3-decyl-trideqanoic acid should be mentioned. Among these are the g-hydroxycarboxylic acids in which, according to the aforementioned "structure R _{1 is} an alkyl radical with 6-10 carbon atoms and Rp is hydrogen, that is ^ -hydroxycarboxylic acids with a total number of carbon atoms of 9-13" such. B. 3-hydroxynonanoic acid, 3-hydroxydecanoic acid, 3-hydroxyundecanoic acid, 3-hydroxydodecanoic acid and 3-hydroxytridecanoic acid are characterized by particularly high antimicrobial activities. 3-Hydroxydecanoic acid is of particular importance.

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Henkel & Cie GmbH since · ty μγ Pat «ntonm» idun _e d ty8O2

Another object of the parent application is the synergistic increase in the antimicrobial effectiveness of the ^ -Hydroxycarboxylic acids in combination with ethanol. This effect allows in antimicrobial preparations and in preservative products that contain alcohol, a considerable reduction in the content of 8-hydroxycarboxylic acids without adversely affecting the effectiveness. On the other hand, in these preparations the antimicrobial effectiveness of the 3-hydroxycarboxylic acids increase the addition of ethanol in a remarkable way.

In the further development of the subject matter of the parent application, it has been found that particularly advantageous results are obtained in terms of antimicrobial effectiveness, if you combine the ß-hydroxycarboxylic acids used with formaldehyde.

The invention thus relates to the use of ^ -hydroxycarboxylic acids according to the patent. ... ... (patent application P 23 12 280.7), in which the β-hydroxycarboxylic acids are used in combination with formaldehyde.

It had been shown that the ß-hydroxycarboxylic acids in certain areas of application of disinfection technology, z. B. surface disinfection, could not yet fully satisfy, since to achieve the desired effects high application concentrations were required. Formaldehyde, whose antimicrobial effectiveness is well known, only had to be used in concentrations to achieve satisfactory results for reasons the odor nuisance were no longer justifiable.

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Henkel & Cie GmbH Salt « 5 ^for patent application D 48O2

Surprisingly, it has now been found that the combination of the β-hydroxycarboxylic acids with pormaLdehyde results in a synergistic increase in the effectiveness in a manner which allows the disinfection problems in question to be dealt with satisfactorily. The combination according to the invention makes it possible, with a good disinfecting effect, to lower the active ingredient concentration overall and also of ^ -hydroxycarboxylic acids and formaldehyde to such an extent that the antimicrobial agents can be used without problems.

The combination according to the invention of 3-hydroxycarboxylic acids with formaldehyde can be used in a wide variety of acidic cleaning agents in the industrial sector, e.g. B. in acidic cleaning agents for dairies, breweries, food companies, in acidic surface disinfectants, in disinfectants in the veterinary sector, e.g. B. in stable disinfectants, be incorporated. The combination of ^ -hydroxycarboxylic acids with formaldehyde is of particular importance in the field of surface disinfection in hospitals and similar institutions.

When used in antimicrobial cleaning agents, the 3-hydroxycarboxylic acids are used in an amount of 0.005 20, preferably 0.01-10 percent by weight and formaldehyde in an amount of 0.025-25, preferably 0.05-10 percent by weight, based on the total detergent used.

A use of ethanol in the antimicrobial cleaning agents in addition to ^ -hydroxycarboxylic acids and formaldehyde is possible and may lead to a further increase in effectiveness.

The following examples are intended to explain the subject matter of the invention in more detail without, however, restricting it thereto.

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3. 12 71 HD

Henkel & Cie GmbH S.It 6 XUrPattnionmessageD 48O2

Examples

The antimicrobial effectiveness of 3-hydroxycarboxylic acids, of formaldehyde, as well as the combination of ß-Hydroxycarbcnsäuren with formaldehyde was determined with the aid of the suspension test. The methodology of this test procedure is the guidelines for testing chemical disinfectants, published by the German Society for Hygiene and Microbiology (1959). According to these guidelines, 0.1 ml of the germ suspensions listed below were made Bacteria pipetted into test tubes at a temperature of 18-21 ° C.

■ 7

1. Staphylococcus aureus 5 x 10 germs / ml

2. Escherichia coli Ί χ ίθ germs / ml

To this end, 10 ml of the various dilution quantities of the substances to be tested were added to acidic aqueous solutions of various pH values. The concentrations of the ^ -hydroxycarboxylic acids to be used according to the invention were in each case 25, 50, 100 ppm. of formaldehyde 1 and 2 %. After exposure times of 1, 2 1/2, 5, 10, 20, 30, 40 and 60 minutes, one loop of material was removed from each test tube and inoculated into 10 ml nutrient broth containing 0.1 % histidine to eliminate the bacteriostatic after-effects . The inoculated culture media were incubated at 37 ⁰ C. After 6 days, the cultures were assessed macroscopically for growth and in this way the killing times were determined, which are compiled in Table 1 below. The tests were carried out with the following substances:

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Henkel & Cie GmbH Sett · J «ir Pateolanm-irdune D 4802

A) 3-hydroxyheptanoic acid

B) 3-hydroxynonanoic acid

C) 3-hydroxydecanoic acid

D) 3-hydroxyundecanoic acid

E) 3-hydroxytridecanoic acid

F) 3-hydroxypentadecanoic acid

G) 3-hydroxynonadecanoic acid

H) 3-hydroxy-3-methyl-decanoic acid I) 3-hydroxy-3-propyl-tridecanoic acid K) 3-hydroxy-3-octyl-tridecanoic acid L) formaldehyde

Table 1

Killing times in different concentration % Germ 1 ι pH ranges in minutes PH ₄ substance ppm. PH ₃ PH ₁ Germ 2 60 1 ppm. 60 60 \ ^pH 3 40 L. 2 ppm. -ι 40 40 60 120 L. 50 ppm. λ . 60 120 40 120 A. 100 ppm .. 30th 60 60 60 A. 50 ppm. 20th 40 30th 40 AH 50 ppm. η 10 30th 30th 60 AH 50 ppm. -ι 30th 60 20th 30th B. 100 ppm. 20th 60 30th 20th B. 50 ppm. 20th 30th 20th 10 B H 50 ppm. η 10 20th 10 30th B i 50 ppm. η 10 20th 10 10 C. 100 ppm. ^J VJl 10 10 10 C. 50 ppm. ^J VJl 10 5 10 C j 50 2.5 5 VJl VJl C ■ 100 1 Ul 5 5 C - 100 1 2 2.5 ■ c - , 5 1 ν 1 % ν 2 % ι- L y ι % h L Y 2 % »· L ν 1 % l · L ν 2 % ν 1 % l 2 55 ι- L h L ν L l · L

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23A9058

Henkel & Cie GmbH s "" 8 "in the patent notice d ^ 802

Killing times in under + 1 % different 1 1 pH ranges in minutes PH /, substance concentration + 2 % No PH ₂₁ Germ 2 60 PH ₃ 30th PH ₃ 20th D. 50 ppm. 10 20th 20th 20th D. 100 ppm. + 1 % 5 10 10 10 D. 50 ppm. + 2 % 5 10 5 60 D. 50 ppm. 2.5 30th 5 30th E. 50 ppm. 20th 30th 30th 20th E. 100 ppm. + 1 % 10 10 20th 10 E ■ 50 ppm. + 2 % 5 10 10 60 E ■ 50 ppm. 5 60 5 20th P. 50 ppm. 20th 30th 30th 20th P. 100 ppm. + 1 % 10 20th 10 10 P ■ 50 ppm. + 2 * 10 10 10 60 F ι 50 ppm. 10 60 5 30th G 50 ppm. 20th 30th 30th 20th G 100 ppm. + 1 Jf 20th 20th 20th 10 G H 50 ppm .. + 2 JS 10 10 10 30th G H 50 ppm. 10 20th 5 10 H 50 ppm. 10 10 10 10 H 100 ppm. 1 % 5 10 10 10 H H 50 ppm. 2% UI 5 5 60 H H 50 ppm. 2.5 30th 5 20th J ■ 50 ppm. 30th 20th 30th 20th J 100 ppm. f 1 % 10 10 10 10 ' J H 50 ppm + f 2% 10 10 10 60 J H 50 ppm + 5 60 5 30th K 50 ppm. 30th 20th 30th 30th K 100 ppm. 20th 20th 10 10 K ^ 50 ppm. 10 20th 10 K i 50 ppm. 10 10 f L f L f L * ■ L h L h L h L h L l · L H L - L ^k L ■ L ■ L

The pH values are adjusted with hydrochloric acid citrate powder

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Henkel & CiO GmbH Salt 9 iur Potentanmeldiiiia I> 4 8O2

In the following experiment, the germicidal effect of the individual components and the combinations in surface disinfection on Staphylococcus aureus was investigated. Lacquered wooden boards (6x6 cm) and PVC floor covering (6x6 cm) served as test areas. To contaminate the surfaces, mixtures of germ suspensions were used, which were prepared by washing away cultures of 3 different strains of Staphylococcus aureus for 16 hours from glass dishes with 5 nil broth. 3 drops of the germ suspension (germ density 13 × 10 germs / ml) were pipetted onto each test area and distributed evenly with a glass spatula. After the surfaces had dried, they were disinfected by thorough wetting with the active ingredient solutions given in Table 2. After 1, 2, 1 and 6 hours of exposure, a quarter of each of the treated areas was thoroughly rubbed with a moistened cotton swab to remove the germs. The swab was streaked on Bouillonagar, of 0 _s l% histidine contained in order to eliminate the bacteriostatic aftereffect. The evaluation was carried out after 72 hours of incubation at 37 ° C. The "killing times or the respective reduction in the number of germs on the surface after a certain time can be found in Table 2 below.

In the table, the characters have the following meanings:

+++ = 250 germs per plate and above * + = 50-25O germs + = 10-50 germs

Numbers = number of germs

= no germs could be detected,

- 10 -

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Henkel & Cie GmbH

Since «10 * ur Potantanmalduna D * IÖO2

Table 2

Germicidal effect on the surface (wood, PVC)
Test germ: Staphylococcus aureus. Initial bacterial count 13 χ IO / ml. concentration
in % PH value Wood (hours)
12 4 6 PVC (hours)
12 4 6 " substance 0.05
0.025 3 J £ + £ £ + ++ "+ J _- J _- J _- J, J_ J_ J.
TtT Tt T T L. 0.05
0.025 4th ι LJ. .1 .1, 1 Y_J_ J, J-
TTT TTT TT TT r ι ι, J _- J ι J _-
TTT ΤΊ T T C.
C + L 0, 05
0.025 3 £ +++ ++ + D.
D + L 0.05
0.025 4th +++ +++ ⁺ ₊₊₊ ++ ++ ++ + 10
+++ +++ ++ + 0.05 + 0.05
0.025 + 0.05
0.05 + 0.025
0.025 + 0.025 3 ++ + 5 1
++ ++ 10 5
+++ ++ + 10 ++ 2 - 2
+ + 101
++ + + 10 0.05 + 0.05
0.025 + 0.05
0.05 + 0.025
0.025 + 0.025 +++ ++ 7 5
+++ ++ 10 5 ++ + 10 -
+++ 51
++ + + 10 0.05
0.025 3 ++ + + 7 0.05
0.025 4th +++ ++ + + ++ ++ + 10 0.05 + 0.05
0.025 + 0.05
0.05 + 0.025
0.025 + 0.025 3 + 10
++ + 8 2
++ + 8 -
++ ++ + 10 + 3
++ + + 5
+ 10 5
YY-YY-Q
TT TT ö 0.05 + 0.05
0.025 + 0.05
0.05 + 0.025
0.025 + 0.025 4th + 10 2 1
Il IIIC
TT TT T 'O
++ + 9 4
+++ ++ + + + + 11
+ + 52
+++ ++ + 10

- 11 -

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Since·

a: ur Potantonni «! dunc D

uO2

Germicidal effect on the surface (wood, PVC)
Test germ: Staphylococcus aureus. Initial bacterial count 13 χ 10 / ml. concentration
in % PH value Wood (hours)
12 4 6 PVC (hours)
12 4 6 substance 0.05
0, 025 3 VZ VZ Z ++ VZ +++ ++ I E. 0.05
0.025 4th VZ VZ Z Z VZZ ₊ S + 0.0.5 + 0.05
0.025 + 0.05
0.05 + 0.025
0.025 + 0.025 3 ++ + 10 2 ++ + 8 4
+++ + + 7
+++ 43 0.05 + 0.05
0.025 + 0.05
0.05 + 0.025
0.025 + 0.025 4th ++ ++ + 8
++ + 10 5
• 1 - ++ +++ + + ++ ++ 9 3
++ ++ + 5

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509814/0979

Henkel & Cie GmbH seii.l2 ", rPat" ntanm "i <iviigd 4802

The following are acidic antimicrobial agent compositions. The funds generally arrive in 0.25-2% concentration, preferably 0.5% concentration for use.

Antimicrobial acidic detergent for the beverage industry

Phosphoric acid (8O / Sig) 50 parts by weight Nonylphenol * 9 ethylene oxide Nitrilotriacetic acid II " Substance C 2.5 Formaldehyde solution 35 pounds 15 " water 24.5 Antimicrobial acidic detergent for industry

Phosphoric acid 80% 35 parts by weight

Sulfuric acid 752ig 35 "

Nonylphenol + 9 ethylene oxide 4 "

Corrosion inhibitor 1 "

Substance D 2.5 "

Formaldehyde solution 35% ± g 17.5 "

Water 5 "

Surface disinfectants for hospitals

Nonylphenol + 9 ethylene oxide 4 parts by weight

Phosphoric acid 80 $ ig 5 "

Formaldehyde solution 35 ^ ig 20 "

Substance D 2.5 "

Water 68.5 "■

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Henkel & Cie GmbH SaIIe 13 ar Pal.ntanmeldung D ty8

Surface disinfectants for hospitals

Nonylphenol + 9 ethylene oxide 4 parts by weight

Phosphoric acid 80% 5 "

Formaldehyde solution 17.5 "

Substance C 2.5 "

Ethanol 6 "

Water 65 "

5098U / 0979

Claims (3)

Henkel & CIe GmbH S.lt · l4 IUr Pat «mtonm« ldune D 4802 patent claims 1. Use of 3-hydroxycarboxylic acids according to Patent (patent application P 23 12 280.7), characterized in that the $ -hydroxycarboxylic acids are used in combination with formaldehyde v / earth. 2. The use of beta-hydroxycarboxylic acids according to claim 1, characterized in that the beta-hydroxycarboxylic acids in an amount of 0.005 - 20, preferably 0.01 10 weight percent, and formaldehyde in an amount of 0.025 - ² 5, preferably O ₉ O5 - 10 Percentage by weight, based on the antimicrobial agents containing them, are used. 3. Use of ^ -hydroxycarboxylic acids according to claim 1 and 2 in further combination with ethanol. V- " 509814/0979