CH631869A5 - Storage-stable mixture which, upon dissolution in water, gives a solution with good antimicrobial activity - Google Patents

Description

631869

PATENT CLAIMS 1. A storable mixture which, when dissolved in water, gives a solution with a high antimicrobial activity, characterized by an aromatic acyloxycarboxylic acid content of the general formula

0

II

o C-R

!

in which R represents a lower alkyl radical optionally substituted by a hydroxyl, lower alkoxy, lower acyloxy, a carboxy group or a halogen atom or a phenyl group optionally substituted by hydroxyl groups, halogen atoms, lower alkyl or alkoxy groups, the carboxyl group in o- , m- or p-position to the acyloxy radical, or of their water-soluble alkali, alkaline earth or ammonium salts, in which up to four hydrogen atoms of the ammonium cation can be substituted by alkyl radicals and on H202 cleavers.

2. Mixture according to claim 1, characterized in that it additionally contains inert fillers.

3. Mixture according to claim 1, characterized in that the molar ratio of aromatic acyloxycarboxylic acid to H202 releaser is 1:10 to 10: 1.

4. Mixture according to claim 2, characterized in that it also contains a stabilizer for peracids.

5. Mixture according to claim 4, characterized in that it contains compounds for adjusting and / or stabilizing the pH to 4 to 12.

6. Mixture according to claim 5, characterized in that it also contains washing active substances.

7. Mixture according to claim 6, characterized in that it also contains corrosion inhibitors.

8. Mixture according to claim 7, characterized in that it contains water-binding agents.

9. Mixture according to claim 2, characterized in that it contains further antimicrobial active substances and odorous substances.

It is known that organic peracids have excellent antimicrobial activity, but their use is not easy.

Lower aliphatic monocarboxylic acids, such as peracetic and perpropionic acid, are able to form stable solutions if the peracid content of these solutions is high. Dilute ready-to-use solutions of these acids, e.g. for disinfection purposes, but are not stable over long periods of time and therefore cannot be put on the market. A disadvantage of the concentrated peracid solution is its extremely pungent smell, which makes it difficult and even questionable to use and use. In addition, spilling these concentrated solutions can cause burns, material damage or violent decomposition reactions.

Other percarbonates, e.g. ûieîerbenzoesâure, as such, are already volatile and therefore cannot be put on the market.

Stable percarboxylic acids, such as p-tert-butylperbenzoic acid and p-methoxyperbenzoic acid, are relatively sparingly soluble in water, so that the setting of a certain peracid content requires considerable time due to the slow dissolution rate.

In addition, organic peracids are generally not stable over long periods in the neutral and alkaline range.

It would therefore be very advantageous if a solid formulation could be prepared which, when used immediately, dissolved in water, gave a solution with a high content of percarboxylic acid and a good disinfectant effect. It would also be advantageous if this solution had an alkaline reaction since, in addition to the disinfectant effect, a cleaning effect favored by an alkaline medium is required for many purposes.

However, as mentioned above, organic peracids are not stable in an alkaline environment.

The mixtures according to the invention which can be stored and which result in a solution having a high antimicrobial activity when dissolved in water are characterized in the preceding patent claim 1.

When dissolved in water, these mixtures result in an alkaline solution with excellent antimicrobial activity, which is also effective against fungi, while organic peracids are otherwise unsatisfactory against fungi. The aromatic acylcarboxylic acids with a free COOH group (carboxy group) in the radical R have particularly good solubility.

During the dissolution of this mixture and also for some time after a clear solution has already formed, there is obviously a reaction between the acyloxycarboxylic acid and the H202 in such a way that free hydroxycarboxylic acid and percarboxylic acid are formed when the ester bond is broken down and in the alkaline solution for a long time a certain peracid content is maintained which cannot be maintained for a comparable period of time when dissolving peracid alone. It seems to be essential here that the ester cleavage does not proceed spontaneously, but requires a certain time and thus guarantees a high peracid content over a longer period. On the other hand, would the individual components resulting from the dissolution of the mixture according to the invention, i.e. combining the percarboxylic acid and the aromatic hydroxycarboxylic acid with one another, one would not obtain a stable product either in solid or in liquid form, in particular not in the pH range from 4 to 12 preferred for the solution according to the invention. The mixtures according to the invention and those of The solutions available therefore have properties that are not due to a combination of the individual components formed when the mixture is dissolved.

The mixtures according to the invention dissolve particularly quickly when water-soluble salts of aromatic acyloxycarboxylic acid are used.

The aromatic acyloxycarboxylic acids or their salts and the H202-releasers contained in this mixture are not so reactive that they already react with each other in the solid state, but they are reactive enough to dissolve immediately in water or aqueous systems Highly effective percarboxylic acid and to convert to hydroxycarboxylic acid with long-term antimicrobial effects.

The ester bond is split by an alkali

2nd

5

10th

15

20th

25th

30th

35

40

45

50

55

60

65

favored milieu. The pH range 8 to 12, which is also optimal for a cleaning action of the mixture according to the invention, is particularly suitable.

The proportion of the components of the mixture with an alkaline reaction can, however, also be such that, after the ester has been split up, the alkaline components are consumed by neutralization of the percarboxylic acid and the hydroxycarboxylic acid, and a neutral solution is thus formed. In the present case, “neutral solution” means a solution with a pH of 4 to 8. This pH range is more advantageous for the stability of the organic peracids than an alkaline pH range.

In the aromatic acyloxycarboxylic acids used in accordance with the invention, R can in particular be methyl, ethyl, hydroxymethyl, acetoxymethyl, methoxymethyl, ethoxymethyl, 1-hydroxyethyl, 2-hydroxyethyl, 2-carboxyethyl, 3-carboxypropyl, 3- Carboxy-2-propyl, chloromethyl, phenyl, 2-methylphenyl, 3-methylphenyl, 4-methylphenyl, 2-tert-butylphenyl, 3-tert-butylphenyl, 4-tert-butylphenyl -, 2-methoxyphenyl, 3-methoxyphenyl, 4-methoxyphenyl, 2-ethoxyphenyl, 3-ethoxyphenyl, 4-ethoxyphenyl, 2-chlorophenyl, 3-chlorophenyl, 4-chlorophenyl, 2 -Hydroxyphenyl, 3-hydroxyphenyl and 4-hydroxyphenyl group. Suitable water-soluble salts of the aromatic acyloxycarboxylic acids are lithium, sodium, potassium, ammonium and magnesium salts, it being possible for ammonium cations 1, 2, 3 or even all 4 hydrogen atoms to be substituted by alkyl radicals. The sodium, potassium, ammonium and substituted ammonium salts are preferred.

Examples of aromatic acyloxycarboxylic acids which can be used according to the invention are

Acetyl-, propionyl-, benzoyl-, (4-methoxybenzoyl) -, (3-chlorobenzoyl) -, (4-tert-butylbenzoyl) - and (4-methyl-benzoyl) salicylic acid, 3-acetoxy-, 3- Propionyloxy-, 3-benzoyloxy-, 3- (4-methoxybenzoyloxy) -, 3- (3-chloro-benzoyloxyoxy) -, 3- (4-tert-butylbenzoyloxy) - and 3- (4-methylbenzoyloxy) benzoic acid as well 4-acetoxy-, 4-propionyloxy-, 4-benzoyloxy-, 4- (4-methoxybenzoyloxy) -, 4- (3-chlorobenzoyloxy) -, 4- (4-tert-butylbenzoyloxy) - and 4- ( 4-methylbenzoyloxy) benzoic acid,

where the acetyl, benzoyl, (4-methoxybenzoyl) and (4-tert-butylbenzoyl) salicylic acid are 3-acetoxy-, 3-benzoyloxy- and 3- (4-methoxy-benzoyloxy) -benzoic acid as well as the 4th Acetoxy, 4-propionyloxy, 4-benzoyloxy and 4- (4-methoxybenzoyloxy) benzoic acid are preferred.

Suitable H2O2 releasers for the purposes according to the invention are alkali perborates, alkali percarbonates, alkali perphosphates, alkali peroxides, alkali salts of Caro's acid, alkali salts of peroxydisulfuric acid and percarbamide, alkali in the present case meaning the salts of lithium, sodium, potassium and ammonium. The water-soluble salts of the aromatic acyloxycarboxylic acids contained in the mixtures according to the invention have high solubility and high dissolution rate in water, are easy to prepare and have a higher melting point than the acid on which they are based.

This high melting point is of particular importance for practical use. Otherwise, a clumping of the mixture, e.g. through exposure to sunlight or storage at a higher temperature. The sodium salt of benzoylsalicylic acid has e.g. B. a melting point of over 300 ° C. The salts of aromatic acyloxycarboxylic acids thus ideally meet the requirement for problem-free storage without clumping, which relate to the rapid and uniform dissolution

631 869

solution of the mixture according to the invention in water or aqueous systems would have a very disadvantageous effect.

The organic peracid that forms during dissolution has excellent, very rapidly occurring antimicrobial activity. This immediate germicidal effect of peracid is very important for the practical application of the mixtures according to the invention as disinfectants, since under the conditions of practice the organic peracids are not long-lasting, but gradually under the catalytic influence of metal ions, enzymes or other catalytically active Substances break down into oxygen and into the underlying carboxylic acid.

Of particular importance for the practical application of the mixtures according to the invention is that the second component of the ester cleavage, i.e. the aromatic hydroxycarboxylic acid itself has antimicrobial activity. Their mode of action is not comparable to that of percarboxylic acid, which leads to rapid germ killing. However, the aromatic hydroxycarboxylic acid outperforms the percarboxylic acid in its long-term effect.

The quantitative ratio of aromatic acyloxycarboxylic acid to H202 releaser can be varied within wide limits in the mixtures according to the invention. A molar weight ratio of 1:10 to 10: 1 can be used. This ratio is preferably 1: 4 to 4: 1.

The mixture according to the invention can also contain organic and inorganic salts for adjusting and stabilizing the pH of the solution prepared from the mixture. Such salts are e.g. Alkali phosphates, alkali pyrophosphates, alkali polyphosphates, alkali tripolyphosphates, alkali carbonates, alkali bicarbonates, alkali borates, alkali acetates, alkali citrates, alkali lactates and alkali tartrates. These inorganic and / or organic salts can be present in the mixtures according to the invention in an amount of 1 to 90% by weight and preferably 5 to 80% by weight.

Wash-active substances can also be added which increase the wetting ability and the cleaning action of the solution prepared from them, e.g. anionic active detergents, namely alkyl sulfates such as coconut fatty alkyl sulfates and tallow fatty alkyl sulfates; Alkyl sulfonates such as lauryl sulfonate; Alkylarylsulfonates, such as alkylbenzenesulfonates, the alkyl radicals of which contain 8 to 14 carbon atoms; Soaps made from natural or synthetic fatty acids; Alkyl ether sulfates; Alkyl phenol ether sulfates and alkyl sulfosuccinates such as lauryl alcohol sulfosuccinate.

Nonionic detergent active substances, namely alkylphenol polyglycol ethers, such as nonylphenol polyglycol ether; Fat alcohol polyglycol ether; Fatty acid polyglycol esters, polyoxypropylene glycols (Pluronics); Amine oxides, such as dodecyldi-methylamine oxides and betaines, such as carboxy, sulfate or sulfonate betaine.

The proportion by weight of these substances in the mixture according to the invention can be 0.5 to 80% by weight and preferably 1 to 50% by weight.

It can also contain substances which increase the stability of the organic peracid formed during the hydrolysis, e.g. Chelating agents such as ethylenediaminetetraacetic acid and alkali salts thereof, nitrilotriacetic acid and its alkali metal salts, alkali metal salts of metaphosphoric acid, alkali salts of poly-phosphoric acid, water-soluble salts of higher molecular weight poly-carboxylic acids, alkylphosphonic acids, Dialkylphosphon acids such as methylenediphosphonic acid, polyphosphonic acids, urea, pyridine-2,3-dicarboxylic acid or pyridine-2,6-dicarboxylic acid.

Some of these substances also have the task of carrying out heavy metal ions which can give rise to colored complexes with the aromatic hydroxycarboxylic acids

3rd

5

10th

15

20th

25th

30th

35

40

45

50

55

60

65

631 869

To bind complex formation, while others soften the water by binding the alkaline earth metal ions causing the water hardness. The substances mentioned can be present in the mixture according to the invention in an amount of 0.5 to 80% by weight and preferably 2 to 20% by weight.

Inert fillers can also be added, e.g. Alkali sulfates, alkali chlorides, alkali silicates, carboxymethyl cellulose and water-soluble salts of aromatic sulfonic acids, such as benzene, toluene, xylene and cumolsulfonic acid. These substances, which can also have the task of binding water in order to prevent the mixture from clumping together with atmospheric moisture, liberated crystal water or other H20 sources, can be present in an amount of 0.5 to 80% by weight and preferably 2 to 50 % By weight can be used in the mixture.

Corrosion inhibitors, perfumes and other antimicrobial agents can also be added. Suitable corrosion inhibitors are benzotriazole, alkali phosphates, alkali hexametaphosphates, alkali nitrates, alkyl phosphates, amine oxides, ammonium soaps, sodium silicate, sodium benzoate, sodium fluoride and alkyl sulfamidocarboxylic acid. The amount of the corrosion inhibitors can be 0.5 to 30% by weight, preferably 1 to 30% by weight 20% by weight.

Suitable additional antimicrobial agents are carboxylic acids, such as benzoic acid, salicylic acid and sorbic acid, phenols, such as 2,6-dimethyl-4-bromophenol and o-phenylphenol.

The solutions prepared from the mixtures according to the invention are suitable for disinfecting and cleaning instruments, devices, articles of daily use,

Wall and floor as well as other surfaces in the hospital area, in medical practice, in the veterinary field, in the household, in industrial and public work areas as well as in the sanitary area.

The mixtures can be in the form of powders, granules, tablets or other shaped solids. The mixtures and the aqueous solutions made from them are practically odorless. Another advantage is that the solutions are harmless in terms of taste, physiology and toxicology.

The antimicrobial activity of the solutions obtainable from the mixtures according to the invention can be seen from the attached tables 1 to 6 (corresponding to examples 1 to 6). The bacteriological tests were carried out in accordance with the guidelines for testing chemical disinfectants (DGHM).

The tables illustrate:

the wide range of antimicrobial effects, also against fungi

25 the long duration of action (usually a shelf life of around 1 day is required for a disinfectant solution) and the excellent resilience due to protein (serum).

Table 1 Example 1

Composition:

1.8 g acetylsalicylic acid 3.0 g sodium perborate ad 200 g H20 perm.

t = 30 minutes

Suspension, bacteria

Suspension, mushrooms

Germ carrier grenade batiste

Staphylococcus aureus

area

Concentrate

Staphyl. Klebsi-

Pyo-

Proteus

Tricho

Candida Asper

Bacillus

Myco

PVC

Wood-

PVC

occurred aureus ella genes vulgaris phyton albicans gillus subtilis bacte

paint

pneu-

menta niger

rium

mon.

grophytes

smegma-tis

5

30th

5

2Vz

15

5

15> 30

lh

> 120

> 6h

4h

10th

2 Vi

2Vz

2 / z

15

2 Vi

2Vz> 30

lh

> 120

> 6h

lh

25th

2 Vi

2Vz

2Vz

2 Vi

2 Vi

2 / z> 30

lh

> 120

lh

lh

+ 20%

serum

25th

2 / z

2 Vi

2Vz

2 Vi

50

2 Vi

2 V2

2 Vi

2Vz

80

2 Vi

2 Vi

2 Vi

2 / z

t = 18

Hours

10th

5

2 Vi

2 Vi

2 Vi

25th

5

2Vz

2 / z

2Vz

50

2 Vi

2 / z

2 / z

2 / z

MIC

5

5

10th

5

.5

10 25

Escherichia coli wood varnish

631869

Table 2 Example 2

Composition:

2.4 g benzoylsalicylic acid 3.0 g Na perborate ad 200 g H20 perm.

t = 30 minutes

Suspension, bacteria

Suspension, mushrooms

Germ carrier

Staphylococcus

area

Ash

Grenades batist aureus

richia coli

Concentrate

Staphyl.

Klebsi

Pyo

Proteus

Tricho

Candida Asper

Bacillus

Myco

PVC

Wood-

PVC

Wood-

tration aureus ella genes vulgaris phyton albicans gillus subtilis bacte

paint

paint

pneu-

mon.

menta-

grophy-tes niger

rium smegma-

tis

5

2 Vi

5

> 30

> 30

2 Vi

5

> 30

6h

> 120

> 6 "

> 6h

10th

2 Vi

2 Vi

2 Vi

5

2 Vi

2 Vi

30th

3h

> 120

> 6h

6h

25th

2 Vi

2 Vi

2 Vi

5

2 Vi

2 Vi

2 Vi lh

15

> 6h

lh

+ 20% serum

25th

2Vi

2 V2

2 Vi

2 Vi

50

2 Vi

2 Vi

2 Vi

2 Vi

80

2 V2

2 Vi

2 Vi

2 Vi

t = 18 hours

10th

> 30

2 Vi

5

5

25th

2 Vi

2 Vi

2! A

2 Vi

50

2 Vi

2 Vi

2 Vi

2 Vi

MIC

5

5

5

5

5

25th

25th

Table 3 Example 3

Composition:

1.8 g 4-acetoxy-benzoic acid 3.0 g Na perborate ad 200 g H2O

t = 30 minutes

concentration

Staphylococcus aureus

Klebsiella pneumoniae

Pyogenes

Proteus vulgaris

5 10

Composition:

30 '2Vi'

2W 2W

2.1 g 4- (methoxymethylcarbonyloxy) benzoic acid 3.0 g Na perborate ad 200 g H2O

5 '

2 W

2W VA '

concentration

5 10 25

Staphylococcus aureus

5 '

2Vi 2 Vi '

Klebsiella pneumoniae

> 30 '

> 30 '

> 30 '

Pyogenes

> 30 '> 30'> 30 '

Proteus vulgaris

> 30 '> 30'> 30 '

631869 6

Table 4 Example 4

Composition: 3.0 g of 2- (4-methoxybenzoyloxy) benzoic acid Na salt

3.2 g Na percarbonate t = 30 minutes ad 100 g H20

Suspension bacteria

Concentrated-Staphylo- Klebsi- Pyo-kick coccus ella genes aureus pneu-mon.

Suspension mushrooms germ carrier

Grenades batiste

Proteus Tricho- Candida Asper- Bacillus Myco-vulgaris phyton albicans gillus subtilis bacte-menta- niger rium grophytes smegmatis

Staphylococcus surface Ash-aureus richia coli

PVC wood PVC wood lacquer lacquer.

0.1

30 '

> 30 '

> 30 '

> 30 '

15 '

> 30 '

> 30 '

0.25

15 '

15 '

> 30 '

2 Vi '

15 '

> 30 '

> 30 '

0.5

2 Vi '

15 '

> 30 '

2 Vi '

15 '

> 30 '

> 30 '

1

2 Vi '

2Vz '

> 30 '

2 Vi '

5 '

30 '

> 30 '

2.5

2Vz '

2 W

15 '

2 Vi '

2Vz

5 '

> 30 '

> 6h

> 6h

> 6b

> 6h

5

2 Vi '

2W

5 '

2Vi '

2 Vi '

2Vz '

> 30 '

> 6h

> 6h

> 6 "

> 6h

10th

2 Vi '

2W

2Vz '

2Vi '

2Vz '

2Vi '

30 '> 6h

> 6h

> 6h

2h

> 6h

25th

2Vz '

2 Vi '

2W 2h lh lh

2h

2h

MIC

5

5

5

1

1

10th

10th

Table 5 Example 5

Composition: 3.0 g 2- (4-methoxybenzoyloxy) benzoic acid Na salt 3.2 g Na percarbonate ad 100 g H20

Suspension bacteria

Concentration Staphylococcus Klebsiella Pyogenes Proteus vulgaris aureus pneumoniae t = 30 minutes, 20% serum

1> 30 '> 30'> 30 '> 30'

2.5 2Vi '> 30'> 30 '5'

5 2Vi '2 * 4' 5 '5'

10 2 Vi '2lA' 5 '5'

t = 24 hours

1 15 '> 30'> 30 '> 30'

2.5 15 '> 30'> 30 '> 30'

5 5 '30'> 30 '15'

10 5 '5' 15 '5'

MIC

Table 6 Example 6

Composition: 2.5 g sorbic acid (2-carboxy-phenyl) ester Na salt

3.0 g Na perborate t = 30 minutes ad 200 gH20

Suspension bacteria suspension fungi germ carrier Staphylococcus surface ash-

Grenades Batist aureus richia coli

Konzen- Staphylo- Klebsi- Pyo- Proteus Tricho- Candida Asper- Bacillus Myco- PVC Holz- PVC Holztrat coccus ella genes vulgaris phyton albicans gillus subtilis bacte- Lack Lack aureus pneu- mentaniger rium mon. grophytes smegmatis

5

30 '2 Vi'

5 '

2 Vi '

2Vz '

2Vz '

> 30 '

> 6h

> 120 '

> 6h

4h

10th

2 Vi '2 Vi'

2 Vi '

2Vz '

2Vz '

2Vz '

> 30 '

> 6h

> 120 '

4h

2h

25th

2 Vi '2 Vi' 20% serum

2 Vi '

2Vz '

IVz '

2Vz '

2VS

15 '

30 '

lh lh

5

5 '5'

> 30 '

15 '

10th

2 Vi '2 Vi'

5 '

2Vz '

25th

2 Vi '2 Vi'

2 Vi '

2Vi '

MIC

5 5

25th

25th

5

25th

25th

s