FI60098C - LARRINGSBESTAENDIG BLANDNING SOM VID LOESNING I VATTEN GER UPPHOV TILL EN LOESNING MED EFFEKTIV ANTIMIKROBISK NETKAN - Google Patents

Description

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Patent aieddelat (51) Ky.ik.VcL3 A 01 N 37/10 // A 01 N 37/16 FINLAND — FINLAND (21) Patent Kakamus - Patantamekninf 7735 31 (22) HakamltpiM - Arattknlnpdai 22.11.77 ^ (23) Alkupllvl —Glltfghetsdag 22.11.77 (41) Tullut Julkisakai - Bllvlt offantllg lU. 07.78

Patent and Registration Office ....... .. . . . tl, _. ,. (44) Date of departure and date of issue. -. .

Patent and registration authorities in the United Kingdom of Great Britain and Northern Ireland published on 31.08.8l (32) (33) (31) Pyy ^ Ytty atuolkaua - Baglrd prloritat 13.01.77

Federal Republic of Germany-Förbundsrepubliken Tyskland (DE) P 2701133.2 (71) Schiilke & Mayr GmbH, Robert-Koch-Str. 2, D-2000 Norderstedt,

Federal Republic of Germany-Förbundsrepubliken Tyskland (DE) (72) Heinz Eggensperger, Hamburg, Wolfgang Emil August Beilfuss, Hamburg-Hummelsbuttel, Helmut Heinrich Nolte, Tangstedt,

Norbert Weigand, Norderstedt, Federal Republic of Germany-Förbunds-republiken Tyskland (DE) (7 ^) Berggren Oy Ab (5U) A storable mixture which, when dissolved in water, effectively forms a solution having an antimicrobial effect -Lagringsbeständig blandning, som vid lös hov account en lösning med effektiv antimikrobisk verkan

It is known that organic peracids have an excellent antimicrobial effect, but their use is not without problems.

However, small molecule aliphatic monocarboxylic acids, such as peracetic acid and perpropionic acid, are able to form stable solutions if the peracid content of these solutions is high. However, dilute, ready-to-use solutions of these acids, e.g. solutions for disinfection, do not keep for a long time and therefore cannot be supplied commercially. One of the downsides of concentrated peracid solutions is their extremely pungent odor, which makes them difficult to handle and use, making it even dangerous. In addition, corrosion, material damage, or severe decomposition reactions may occur upon spillage of these concentrated solutions.

Other percarboxylic acids, such as perbenzoic acid, are already volatile as such and cannot therefore be marketed. Preserved percarboxylic acids, such as p-tert-butylperbenzoic acid and p-methoxyperbenzoic acid, are relatively difficult to dissolve in water, so adjusting a certain concentration of perbenzoic acid requires considerable time due to the low dissolution rate.

60098

In addition, organic peracids generally do not persist for long periods in a neutral or alkaline environment.

Therefore, it would be advantageous if a solid mixture could be prepared which, before immediate use, dissolved in water, forms a solution with a high percarboxylic acid content and a good disinfecting effect. It would also be advantageous if this solution reacted initially, because in addition to the disinfecting effect for many uses, the cleaning effect promoted by the alkaline environment is desirable.

DE-A-807 122 discloses an antibacterial agent which is prepared by melting non-toxic esters of p-oxybenzoic acid together with sodium perborate or sodium percarbonate. Such a mixture, when dissolved in water, has a better disinfecting effect than p-oxybenzoic acid alone. However, thawing the components leads to side reactions in which undesired by-products of the disinfectant are formed. In addition, melting an inorganic family compound with an organic material is not a completely safe operation.

However, as mentioned above, organic peracids do not persist in an alkaline environment.

It has now surprisingly been found that a mixture containing as main components an aromatic oxycarboxylic acid derivative and a H 2 Cl 2 cleaving agent and which, when dissolved in water, effectively forms a microbicidal solution characterized in that the mixture is characterized by an aromatic

O

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O - C-R

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wherein R represents a lower alkyl residue optionally substituted by hydroxy, lower alkoxy, lower acyloxy, carboxy or halogen atom, or a phenyl group optionally substituted by hydroxy groups, halogen atoms, lower alkyl or alkoxy groups, whereby the carboxyl group may be in the -, m- or p-position to the acyloxy residue. or its water-soluble alkali metal, alkaline earth metal or ammonium salts, in which up to 4 of the hydrogen atoms of the airanonium cation may be replaced by alkyl radicals.

When dissolved in water, the mixture according to the invention forms an alkaline-reactive solution which has an excellent antimicrobial effect, also being effective against fungi, whereas organic peracids, on the other hand, do not otherwise have a satisfactory fungicidal effect. In addition, the solubility of aromatic acyloxycarbonyl acids in which the residue R has a free COOH group (carboxy group) is particularly good.

60098 When this mixture dissolves and also some time after a clear solution has already formed, the reaction between acyloxycarboxylic acid and H 2 O 2 apparently takes place so that upon cleavage of the ester bond, free hydroxycarboxylic acid and percarboxylic acid are formed and the alkaline solution retains a certain peracidity for a long time. alone would not maintain a similar length of time. What seems to be essential here is that the cleavage of the ester does not take place spontaneously, but requires a certain time and thus the peracid content is kept high for a relatively long time. If, on the other hand, the individual components are formed when the mixture according to the invention dissolves, i.e. percarboxylic acid and aromatic hydroxycarboxylic acid, if combined, would not give a product that is stable in storage in solid or liquid form, especially in the preferred solution pH range of 4-12 according to the invention. The mixtures according to the invention and the solutions obtained therefrom thus have properties which are not present in the combination of the individual components formed when the mixture is dissolved.

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

The aromatic acyloxycarboxylic acids or their salts contained in this mixture and the H 2 O 2 cleavage compound are not so reactive as to react already solid, but are sufficiently reactive to react rapidly with water or an aqueous system to rapidly dissolve into highly effective microbic acid and hydroxycarboxylic acid and hydroxycarboxylic acid. the effect is long-lasting.

The cleavage of the ester bond is promoted by an alkaline environment. A particularly suitable pH range is between 8 and 12, which is also optimal for the cleaning effect of the mixture according to the invention.

However, the proportion of alkali-reactive components in the mixture can also be dimensioned so that after cleavage of the ester, the alkaline components can be disposed of by neutralizing percarboxylic acid and hydroxycarboxylic acid to form a neutral solution, "neutral solution" here means a solution having a pH of 4-8. From the point of view of the preservation of organic peracids, this pH range is more preferable than the alkaline pH range.

5 60098

In the aromatic acyloxycarboxylic acids used according to the invention, R may in particular be methyl, ethyl, hydroxymethyl, acetoxymethyl, methoxymethyl, ethoxymethyl, 1-hydroxyethyl, 2-hydroxyethyl, 2-carboxyethyl, 3-carboxypropyl, -Carboxy-2-oxa-propyl, chloromethyl, phenyl, 2-methyl-phenyl, 3-methyl-phenyl, 4-methylphenyl, 2-tert-butylphenyl, 3-tert-butyl- 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. Suitable water-soluble salts of aromatic acyloxycarboxylic acids are the lithium, sodium, potassium, ammonium and magnesium salts, in which case 1, 2, 3 or also all 4 hydrogen atoms of the ammonium cation can be replaced by alkyl radicals. Sodium, potassium, ammonium and substituted ammonium salts are preferred.

Examples of aromatic acyloxycarboxylic acids useful in the present invention include acetyl, propionyl, benzoyl, (4-methoxybenzoyl), (3-chlorobenzoyl), 4-tert-butylbenzoyl) and (4-methylbenzoyl) salicylic acid. , 3-acetoxy-, 3-propionyloxy-, 3-benzoyloxy-, 3- (4-methoxy-benzoyloxy) -, 3- (3-chloro-benzoyloxy) -, 3- (4-tert-butyl-benzoyloxy) - and 3- (4-Methyl-benzoyloxy) -benzoic acid and 4-acetoxy-, 4-propionyloxy-, 4-benzoyloxy-, 4- (4-methoxy-benzoyloxy) -, 4- (3-chloro-benzoyloxy) -, 4- (4- tert-butyl-benzoyloxy) and 4- (4-methyl-benzoyloxy) -benzoic acid, with acetyl, benzoyl, (4-methoxybenzoyl) and (4-tert-butylbenzoyl) salicylic acid, 3-acetoxy- , 3-benzoyloxy and 3- (4-methoxybenzyloxy) benzoic acid, and 4-acetoxy, 4-propionyloxy, 4-benzoyloxy and 4- (4-methoxybenzyloxy) benzoic acid.

Suitable cleavable compounds for the purposes of the invention are alkali metal perborates, alkali percarbonates, alkali perphosphates, alkali peroxides, alkali salts of caro acid, alkali salts of peroxydisulphuric acid and percarbamide, in which case alkali means lithium, sodium, potassium and ammonium salts. The water-soluble salts of the aromatic acyloxycarboxylic acids contained in the mixtures according to the invention 60098 have good solubility and dissolution rate in water, can be prepared in a simple manner and have a higher melting point than the acids from which they are derived.

This high melting point is of particular importance in practical applications. Otherwise, agglomeration of the mixture could occur during storage, e.g. due to solar radiation or storage at higher than normal temperatures. The melting point of the sodium salt of benzoylsalicylic acid is, for example, above 300 ° C. Thus, the salts of aromatic acyloxycarboxylic acids ideally meet the requirement of trouble-free storage without causing agglomeration, which would have a very detrimental effect on the rapid and uniform dissolution of the mixture according to the invention in water or aqueous systems.

The organic peracid formed on dissolution has an excellent, very rapid onset of antimicrobial action. This immediate-action spore-killing effect of peracid is very important when practicing the compositions of the invention as a disinfectant, since under practical conditions organic peracids do not persist for a long time but gradually decompose into oxygen and carboxylic acid due to the catalytic action of metal ions, enzymes or other catalytic substances. are from.

Of particular importance for the practical application of the compositions according to the invention is further provided that the second component formed during the cleavage of the ester, i.e. the aromatic hydroxycarboxylic acid itself has an antimicrobial effect. Its mode of action cannot be compared to that of percarboxylic acid, which causes rapid destruction of the spore. However, the long-term effect of aromatic hydroxycarboxylic acid is better than that of percarboxylic acid.

The ratio of the amounts of aromatic acyloxycarboxylic acid to i 2 Cl 2 cleavage compound contained in the compositions of the invention can be varied within wide limits. The molar weight ratio used can thus be between 1:10 and 10: 1. Mainly this ratio is between 1: 4-4: 1.

7 60098

In order to adjust and stabilize the pH of the solution prepared from the mixture, the mixture according to the invention may also contain organic and inorganic salts. Such salts include, for example, alkali metal phosphates, alkali pyrophosphates, alkali polyphosphates, alkali metal tripolyphosphates, alkali carbonates, alkali metal carbonates, alkali borates, alkali acetate, alkali citrates, alkali lactates and alkali tartrates. The mixtures according to the invention may contain from 1 to 90% by weight and mainly from 5 to 80% by weight of these inorganic and / or organic salts.

Detergents may also be added to the compositions to enhance the wetting and cleaning performance of the solution prepared therefrom, e.g., anionic detergents, namely, alkyl sulfates such as coconut oil alkyl sulfates and tallow alkyl sulfates; alkyl sulfonates such as lauryl sulfonate; alkylarylsulfonates such as alkylbenzenesulfonates having 8 to 14 carbon atoms in the alkyl radicals; soaps made from natural fatty acids or synthetic fatty acids; alkyl ether sulfates; alkylphenol ether sulfates and alkyl sulfosuccinates such as lauryl alcohol sulfosuccinate, nonionic detergents, namely alkylphenol polyglycol ethers such as nonylphenol polyglycol ether; fatty alcohol; fatty acid polyglycol esters, polyoxypropylene glycols (Pluronics); amino oxides such as dodecyldimethylamino oxides and betaines such as carboxy, sulfate or sulfonate betaines.

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

The mixtures may further contain substances which improve the stability of the organic peracid formed in the course of the hydrolysis, e.g. complexing agents such as ethylenediaminetetraacetic acid and its alkali salts, nitrilotriacetic acid and its alkali salts, methylenediphosphonic acid, polyphosphonic acids, urea, pyridine-2,3-dicarboxylic acid or pyridine-2,6-dicarboxylic acid.

At the same time, some of these substances have the task of binding complexes to form heavy metal ions, which can form colored complexes with aromatic hydroxycarboxylic acids, while others soften water by binding alkaline earth metal ions that increase water hardness. The mixture according to the invention may contain from 0.5 to 80% by weight and in particular from 2 to 20% by weight of said substances.

Neutral fillers can also be added to the mixtures, e.g. alkali sulphates, alkali chlorides, alkali silicates, carboxymethylcellulose and water-soluble salts of aromatic sulphonic acids such as benzene, toluene, xylene and cumenesulphonic acid. These substances, which may also have the function of binding water to prevent agglomeration of the mixture, which may be caused by air humidity, liberated crystal water or other sources of I 2 O, can be used in the mixture in an amount of 0.5 to 80% by weight and mainly 2 to 50% by weight.

Corrosion inhibitors and fragrances can be further added. Suitable corrosion inhibitors include benzotriazole, alkali metal phosphates, alkali hexametaphosphates, alkali nitrates, alkyl phosphates, amine oxides, ammonium soaps, sodium silicate, sodium benzoate, sodium fluoride and alkyl sulfamidocarbon. The amount of corrosion inhibitor may be 0.5-30% by weight, mainly 1-20% by weight.

The solutions prepared from the mixtures according to the invention are suitable for disinfection and cleaning of instruments, devices, utensils, wall and floor and other hospital surfaces, in the medical practice, in the veterinary field, in the household, in industrial plants and public workshops and in the sanitary field.

The compositions may be in the form of powders, granules, tablets or other solid forms. The mixtures and the aqueous solutions prepared therefrom are practically odorless. An additional advantage is that the solutions are physiologically and toxicologically harmless in terms of taste.

The antimicrobial activity of the solutions obtained from the mixtures according to the invention is shown in the accompanying Tables 1 and 2. Bacteriological studies were carried out in accordance with the guidelines for test methods for chemical disinfectants (DGHM).

60098

The tables illustrate:

Wide antimicrobial range, including against fungi, long duration of action (shelf life of the disinfectant solution is usually required to be about 1 day), and excellent potency despite the addition of protein (serum).

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Claims (5)

A storage resistant mixture which contains as its main components an aromatic oxycarboxylic acid derivative and a splitting agent which, when dissolved in water, gives rise to a solution of effective antimicrobial action, characterized in that the aromatic oxycarboxylic acid derivative is an aromatic acrylic acid derivative. wherein R represents a lower alkyl residue optionally substituted with a hydroxy, lower alkoxy, lower acyloxy or carboxy group or with a halogen atom or a phenyl group optionally substituted by hydroxy groups, halogen atoms , lower alkyl or alkoxy groups, wherein the carboxyl group may be in the oxy-, m- or β-position, or its water-soluble alkali, alkaline earth metal or ammonium salts, where at most 4 of the hydrogen atoms of the ammonium cation can be substituted with alkyl residues. Mixture according to claim 1, characterized in that the weight ratio of the aromatic acyloxycarboxylic acid to the H Mixture according to claim 2, characterized in that it additionally contains stabilizer for peracid.