NO742940L - - Google Patents

Description

AGENT FOR COMBATING HARMFUL MICRO-ORGANISMS.

The present invention relates to means for combating

harmful microorganisms. The agents contain as active ingredient a compound of formula I

where X means halogen and

n an integer from 1-11.

The compounds of formula I, where X means chlorine or bromine and

I n means a whole number from 1-6, have proven to be particularly valuable.

The use of a number of alkylphenols for combating microorganisms, above all gram-positive bacteria, is already known (cf. K.H. Wallhauser and H. Schmidt, 11 Sterilisation, Desinfektion, Konservierung, Chemotherapie", Georg Thieme Verlag, 1967).

It was now surprisingly found that the alkylphenols used according to the invention, which compounds are partially known,

(cf. K.A. Thakar, Journal of the Indian Chemical Society 40, 539; 1963), and which, due to the special substitution, also has a high activity against gram-negative bacteria and fungi. The compounds preferably show a distinctly broad spectrum of action, but only weak toxicity. They can also be advantageously used as supplementary feed for promoting the growth of beneficial animals. A particular advantage of the compounds used according to the present invention is that, even at a relatively low concentration, they lead to a complete killing of the micro-organisms to be combated via a single inhibitory effect. With regard to application technology, it is of particular value that the compounds of formula I are colourless.

The compounds of formula I can be prepared by reduction of ketones of formula II

(

where X and n have the meanings given above.

The reduction of ketones can e.g. is carried out by means of the method according to Huang-Minlon (cf. Huang-Minlon, Journal of the American Chemical Society 68, 2487$ 1946), whereby the corresponding hydroazone is decomposed in an inert. solvent at a higher temperature using an inorganic base to hydrocarbon. Also with the Clemmensen reduction (cf. E. Clemmensen, Berichte der deutschen Chemischen Gesellschaft 46, 1837; 1913) one has a good method for producing alkylphenols from the corresponding ketones. The reduction is carried out here by heating ketones with amalgamated zinc and hydrochloric acid, and possibly in the presence of an organic solvent.

The ketones of formula II used as starting materials are known (cf. K.A. Thakar, Journal of the Indian Chemical Society 40, 539; 1963) or they are prepared using methods known per se, e.g. of the corresponding alkanecarboxylic acid phenyl esters by the Fries reaction (cf. Baltzly et al. Journal of the American Chemical Society 77, 2522, 1955 or G.A. Olah, Friedel-Crafts and Related Reactions 1964, page 499).

The compounds of formula I show good solubility in organic solvents. Their water-insoluble salts, and especially alkali and alkaline earth salts, are possibly effective, and then of particular importance where it may be relevant to use them in an aqueous medium and in soaps.

The use of the antimicrobial compounds of formula I

is possible on a broad basis, and especially for the protection of organic substrates against attack by harmful and pathogenic microorganisms. The mentioned antimicrobials are generally suitable as preservatives and disinfectants for technical products of any type. V_

Among the technical products, which can be preserved using

of the compounds with formula I, the following shall be mentioned as examples: Glue, binder, paint, texti1 aid or processing agent, color or printing pastes and similar formulations based on organic and inorganic dyes or pigments, and then also those containing casein or other organic compounds as additives. Also wall and ceiling paint, e.g. such as contain an egg-white color-

j binder, is protected from attack by harmful organisms by an addition of the compounds. The application to wood protection is also possible.

Also in the cellulose and paper industry, the compounds can be used as preservatives, among other things to prevent the well-known slime formation caused by microorganisms in equipment used for paper production.

The effect of the connections can also be utilized in connection

with preservative and disinfecting treatment of plastics. When using plasticizers, it is advantageous to add the antimicrobial to the plastic by loosening or disperse the additive in the plasticizer. It is appropriate to ensure the most even possible distribution in the plastic. Plastics with antimicrobial properties can find use as utility items of any type where a business against different germs is desired, such as e.g. bacteria and fungi. The compounds are used e.g. for foot mats, bathroom curtains, seating furniture, stair railings in swimming halls, wall coverings, etc. When incorporated in corresponding wax

and bone mass you get floor and furniture care products with a disinfecting effect.

The compounds with formula I are advantageously used for preservative and disinfecting finishing of fibers and textiles, whereby the compounds can be applied to natural and artificial fibres,

so that they can Develop a permanent effect against harmful (also pathogenic) microorganisms, such as e.g. fungi and bacteria. The addition of the compounds can thereby take place before, at the same time or after a treatment of these textiles with other substances, e.g. color or print pastes, agents that provide flame resistance, agents that provide a softer grip and other finishing agents etc.

Textiles treated in this way also show protection against the appearance of sweat odors caused by microorganisms.

The application forms of the active substances with formula I may correspond

In the other formulations. The agents used to protect textiles must contain the active substances in finely divided form. For application, solutions, dispersions and emulsions of the active substances are thus used in particular. Aqueous dispersions can e.g. obtained from pastes or concentrates, and used as solutions or as an aerosol.

The aqueous solutions or dispersions may suitably contain surfactants, e.g. anionic compounds, such as soaps and other carboxylates (e.g. alkali salts of higher fatty acids), derivatives of sulphuroxyacids (e.g. sodium salt of dodecylbenzenesulphonic acid, water-soluble salts of the sulphurous acid monoesters of high molecular weight alcohols or their polyglycol ethers^ such as soluble salts of dodecyl alcohol sulfate or of dodecyl alcohol polyglycol ether sulfate), derivatives of phosphorus-oxygen acids (e.g. phosphates), derivatives with acidic (electrophilic) nitrogen in the hydrophilic group (e.g. disulfin salts), cationic surfactants, such as amines and their salts (e.g. lauryl-diethylenetriamine), onium compounds, amine oxides or non-ionic surfactants, such as polyhydroxy compounds, mono- or polysaccharide-based surfactants, higher molecular weight acetylene glycols, polyglycol ethers

(e.g. polyglycol ethers of higher fatty alcohols, polyglycol ethers of high-molecular-weight alkylated phenols). In addition, the dye solution may also contain other common auxiliary substances, such as water-soluble perborates, polyphosphates, carbonates, silicates, optical brighteners, softeners, acid-reactive salts, such as ammonium or zinc-silicon fluoride, or certain organic acids, such as oxalic acid, further finishing agents, such as those based on artificial resin or starch.

The textile materials can be impregnated with the help of hot or cold aqueous dyeing, bleaching, chroming or finishing baths with the active substances, whereby different textile finishing methods, such as e.g. The Foulard or extraction method may be appropriate.

Due to the better solubility in organic solvents, the active substances are also well suited for application from non-aqueous media. Thereby, the materials, which are to be finished or protected, easily impregnated with the solutions.

As organic solvents, e.g. trichlorethylene, methylene chloride, hydrocarbons, propylene glycol, methoxyethanol, ethoxyethanol, dimethylformamide, which may further have added dispersants (e.g. emulsifiers, such as sulphurised castor oil, fatty alcohol sulphates etc.) and/or other auxiliaries.

According to the present invention, the content of active substances can, depending on the intended use, be between 0.1 and 50 g, preferably between 1 and 30 g of active substance per liters of treatment liquid.

The active substances of formula I can be used alone or together with other known antimicrobial textile protection agents.

As textiles, which must be finished or protected, one has fibers of natural origin as well, such as cellulose-containing, e.g. cotton, or polypeptide-containing, such as e.g. wool or silk, or fiber materials of synthetic origin, such as on a polyamide, polyacrylonitrile or polyester basis, or mixtures of these fibres.

For the most part, the textile materials are sufficiently protected against fungal and bacterial attack by a content of 0.01 to 5%, preferably 0.1 to 3% active substance, calculated on the weight of the textile materials.

By combining the active substances with surface-active, and especially detergent-active substances, you get. one washing and cleaning agents with excellent antibacterial or antifungal effect.

The washing and cleaning agents can be available in different forms,

e.g. liquid, cavernous, solid, flocculent or granular form. The compounds of formula I can be incorporated into both anionic compounds, such as soaps and other carboxylates (e.g. alkali salts of higher fatty acids), derivatives of sulphur-

IN

In oxygen acids (e.g. sodium salt of dodecylbenzenesulfonic acid, water-soluble salts of the sulfuric acid monoesters of the high molecular weight alcohols or their polyglycol ethers, such as soluble salts of dodecyl alcohol sulfate or of dodecyl alcohol polyglycol ether sulfate), derivatives of phosphorous oxygen acids (e.g. phosphates ), derivatives with acidic (electrophilic) nitrogen, the hydrophilic group, (e.g. disulfine salts) as also in cationic surfactants, such as amines and their salts (e.g. lauryl-diethylenetriamine), onium compounds, amine oxides or non-ionic surfactants , such as polyhydroxy compounds, surfactants on a mono- or polysaccharide basis, high molecular weight acetylene glycols, polyglycol ethers (e.g. polyglycol ethers, higher fatty alcohols, polyglycol ethers of high molecular weight alkylated phenols), or mixtures of different surfactants. Thereby their antimicrobial activity is in full effect. The active substance content in washing and cleaning agents, calculated on the weight of these agents, is usually 0.01 to 5%, mostly 0.1 to 3.%. Aqueous preparations of such washing and cleaning agents, which contain compounds of formula :i, can e.g. used for antimicrobial finishing of textile materials, as the active substance can be applied substantively to the textile material. They are also suitable as antimicrobial cleaning agents in the food and beverage industry, e.g. breweries, dairies and slaughterhouses.

Furthermore, the compounds can also be incorporated into cosmetic preparations, such as e.g. essential oils, bath salts, brilliantines, salves, face water, hair dyes, hair oil, hair lotion, skin cream, skin oils, K61n-water perfume, powder, make-up, depilatories, tanning agents, dental care agents, etc., whereby these agents are given additional antimicrobial action. Thereby, it is usually sufficient, calculated on the total weight of the agent, with an active substance content of 0.01 to 5%, preferably from 0.1 to 3%.

For disinfection and preservation purposes, the compounds of formula I can also be used in combination with known antimicrobial agents. These include, for example:

Halogens and halogen compounds with active halogen

e.g. sodium hypochlorite, calcium hypochlorite, chloral lime,

in sodium p-toluenesulfochloramide, p-toluenesulfodichloramide, N-chlorosuccinimide, 1,3-dichloro-5,5-dimethyl-bydantoin, trichloroisocyanuric acid, potassium dichloroisocyanurate, iodine, iodine trichloride, complex compounds of iodine and iodine trichloride with surfactants, such as polyvinylpyrrolidone , alkylphenoxy polyglycols, polyoxypropylene glycols, alkylaminoethanesulfonic acids and sulfonates, alkylarylsulfonates and quaternary ammonium compounds.

Boron compounds

e.g. boric acid and borax.

Organometallic compounds

e.g. bis-tributyltin oxide, triphenyltin hydroxide, tributyltin salicylate, tributyltin chloride, phenylmercury perborate and phenylmercury acetate.

Alcohols

e.g. hexyl alcohol, trichloroisobutyl alcohol, 1,2-propylene glycol, triethylene glycol, benzyl alcohol, 4-chlorobenzyl alcohol, 2,4- and 3,4-dichlorobenzyl alcohol, 2-phenylethyl alcohol, 2-(4-chlorophenyl)-ethyl alcohol, ethylene glycol monophenyl ether, menthol, linalool and 2-bromo-2-nitro-propanediol-1,3.

Aldehydes

e.g. formaldehyde, paraformaldehyde, glutaraldehyde, benzaldehyde, 4-chlorobenzaldehyde, 2,4- and 3,4-dichlorobenzaldehyde, cinnamaldehyde, salicylaldehyde, 3,5-dibromosalicylaldehyde, 4-hydroxybenzaldehyde, anisaldehyde and vanillin.

Carboxylic acids and derivatives

e.g. trichloroacetic acid, monobromoacetic acid glycol ester, Na and Ca propionate, caprylic acid, undecylenic acid, Zn undecylenate, sorbic acid, K and Ca sorbate, lactic acid, malonic acid, aconitic acid, citric acid, benzoic acid, 4-chlorobenzoic acid, benzoic acid benzyl ester, salicylic acid, 4-chloro-salicylic acid-n-butylamide, salicylanilide, 3,4',5-tribromosalicylanilide, 3,3<1>,4<1>,5-tetra-chlorosalicylanilide, 4-hydroxybenzoic acid, 4-hydroxybenzoic acid ethyl ester , gallic acid, mandelic acids, phenylpropiolic acid, phenoxy-

acetic acid, dehydroacetic acid, vanillin propyl ester.

Phenols

e.g. phenol, mono- and polychlorophenols, cresols, 4-chloro-3-, methylphenol, 4-chloro-3,5-dimethylphenol, thymol, 4-chloro-thymol, 4-t-amylphenol, saligenin, 4-n-hexylresorcin, carvacrol, 2-phenylphenol, 2-benzyl-4-chlorophenol, 2,2<1->dihydroxy-5,5'-dichloro-diphenylmethane, 2,2<1->dihydroxy-3,3',5,5< 1>,6,6'-Hexachloro-diphenylmethane, 2,2'-dihydroxy-5,5<1->dichloro-diphenylsulfide, 2,2<1->dihydroxy-3,3',5,5<1- >tetrachlorodiphenylsulfide, 2-hydroxy-2',4,4<1->trichlorodiphenyl ether and dibromosalicyl.

Quinones

e.g. 2,5-dimethylquinone, 2,3,5,6-tetrachloro-benzoquinone, 1,4-2,3-dichloro-1,4-dinaphthoquinone.

Carbonic acid derivatives

e.g. pyrocarbonic acid diethyl ester, tetramethylthiouram disulfide, 3,4,4'-trichloro-N,N'-diphenylurea, 3-trifluoromethyl-4,4<1->dichloro-N,N'-diphenylurea, N-3-trifluoromethylphenyl-N' -2-ethylhexyl-urea, 1,6-bis-(4'-chlorophenyl-di-guanidino)-hexane, dodecylmethyl-guanidine acetate, ammonium rhodanide, 4,4'-diamidino-α,α-diphenoxy-hexane.

Amines

e.g. dodecylpropylenediamine, dodecyldiethylenetriamine, diaminobenzene dihydroiodide.

Quaternary ammonium compounds

e.g. alkyl-dimethyl-benzyl-ammonium chloride, alkyl-dimethyl-ethyl-benzyl-ammonium chloride, dodecyl-dimethyl-3,4-dichlorobenzyl-ammonium chloride , dodecyl-di-(2-hydroxyethyl)-benzyl-ammonium chloride, dodecyl-di-(2 -hydroxyethyl)-benzyl-ammonium-pentachloro-phenolate, dodecyl-di(2-hydroxyethyl)-benzyl-ammonium-4-methyl-benzoate, dodecyl-dimethyl-phenoxyethyl-ammonium bromide, 4-diiso-butyl-phenoxyethoxyethyl-dimethyl-benzyl -ammonium chloride, 4-di-isobutyl-cresoxyethoxyethyl-dimethyl-benzyl-ammonium chloride, dimethyl-dodecyl-ammonium chloride, cetyl-trimethylammonium bromide, dodecyl-pyridinium chloride, cetyl-pyridinium chloride, dodecyl-

j isoquinolinium chloride, decamethylene-bis-4-aminoquinaldinium di-chloride, a-(p-tolyl)-dodecyl-trimethyl-ammonium methosulphate,

(dodecanoyl-N-methyl-aminoethyl)-(phenylcarbamoyl-methyl)-dimethyl-ammonium chloride.

Quaternary phosphonium compounds

e.g. dodecyl-triphenyl-phosphonium bromide.

Amphoteric compounds

e.g. dodecyl-di-(aminoethyl)-glycine.

Heterocyclic compounds

e.g. 2-mercaptopyridine-N-oxide, Na and Zn salt of 2-mercaptopyridine-N-oxide, 2,2'-dithiopyridine-1,1'-di-N-oxide, 8-hydroxyquinoline, 5-chloro -8-hydroxyquinoline, 5-chloro-7-iodo-8-hydroxy-quinoline, 5,7-dichloro-8-hydroxyquinoline, 5,7-dichloro-8-hydroxy-quinaldine, bis-2-methyl-4-amino -quinolyl urea hydrochloride, 2-mercaptobenzthiazole, 2-(2'-hydroxy-3 ' , 5 1 -dichlorophenyl)-5-chlorobenzimidazole, 2-aminoacridine hydrochloride, 5,6-dichlorobenzoxa-zolor-1-dodecyl -2-iminoimidazoline hydrochloride, 6-chloro-benz-isothiazole.

The use of compounds of formula I for combating microorganisms, and in particular bacteria and fungi, and for protecting organic materials and objects against attack by microorganisms is multifaceted. Thus, the connections can be incorporated directly into materials to be protected, e.g.

in synthetic resin-based material, such as polyamides and polyvinyl chloride in the paper treatment dye solution, in printing ink thickeners of starch or cellulose derivatives, in varnishes and paint colors, such as e.g. contains casein, in cellulose,

in the viscose spinning pulp, in paper, in mucus or oil of animal origin, in permanent smoothing agents based on polyvinyl alcohol, in cosmetic articles, in ointments or powders. Furthermore, the compounds can also be added to preparations of inorganic or organic pigments in the paint industry, plasticizers, etc.

Thus, one can also use the compounds of formula I in form

in their organic solutions, e.g. as so-called "spray"

or as dry cleaning agents or for the impregnation of wood, "whereby as organic solvents, solvents that are not soluble in water are preferably used, and in particular petrol fractions, but also water-miscible solvents, such as lower alcohols, e.g. methanol or ethanol or ethylene glycol monomethyl ether or -monoethyl ether One part of the new compounds can also be used in aqueous solution.

Furthermore, the compounds can be used together with wetting or dispersing agents, in the form of their aqueous dispersions, e.g. for the protection of substances that have a tendency to rot, as well as for the protection of leather, paper, etc.

Active substance solutions or dispersions, which can be used for the protection of these materials, advantageously have an active substance content of at least 0.005 g/litre, e.g. 0.01 to 5 and preferably 0.1 to 3 g/litre.

The compounds of formula I also exhibit an excellent growth-promoting effect on livestock, e.g. pigs, poultry, as well as ruminants such as sheep, cows etc.

The active substances can be administered in the form of solutions, emulsions, suspensions, powders, tablets, large pills, capsules, and then orally, abomasally or by means of injections directly to the animals, and then as a single dose, as well as repeatedly. The active substances or the mixtures containing the active substances can also be added to the food or drink, or they can also occur in the so-called pre-mixtures.

Due to the broad spectrum of microbicidal action, the compounds of formula I can also be used in veterinary medicine to combat pathogenic microorganisms on the animal's skin, and especially on the skin, in the intestinal and urogenital system. For combating pathogenic microorganisms in veterinary medicine and/or for achieving a growth-promoting effect in livestock, the compounds according to the present invention can

i is combined with the following substances:

1. Antibiotics:

Penicillin and their derivatives

Cephalosporin.and their derivatives

chloramphenicol

Tetracycline (eg, chlortetracycline, oxytetracycline)

Rifamycin and their derivatives (e.g. rifampin)

Lincomycin

Bacitracin and their salts

Pyrrolnitrin

Myxin'

Streptomycin

Nigericin

Parvulin

Spiramycin

Neomycin

Thiopeptin

Tylosin.

2. Sulfonamides:

N'-(3,4-dimethyl-5-isoxazolyl)-sulfanilamide

N<1->2-pyrazinylsulfanilamide 2.4-dimethoxy-6-sulfamylamido-1,3-diazine

N'-(4-methyl-2-pyrimidyl)-sulfanilamide

3. Nitrofurans:

3-(5-nitrofurfurylideneamino)-2-oxazolidinone 5-morpholinomethyl-3-(5-nitrofurfurylideneamino)-2-oxazolidine. 3-amino-6-[2-(nitro-2-furyl)vinyl]-pyridazine 1,5-di-(5'-nitro-2'-furyl)penta-1,4-dien-one (3)-2" -amidino-hydrazone hydrochloride 4. Diaminopyrimidine: 2,4-diamino-5-(3,4,5-trimethoxybenzyl)-pyrimidine

2,4-diamino-5-(3,4-dimethoxybenzyl)-pyrimidine

2,4-diamino-5-(p-chlorophenyl)-6-ethylpyrimidine

i 5.Hydroxyquinolines:

5,7-dichloro-8-hydroxyquinaldine

5-chloro-7-iod-8-hydroxyquinoline.

6. Hydroxyquinoline carboxylic acids and hydroxynaphthyridine acids: 1-ethyl-1,4-dihydro-7-methyl-4-oxo~1,8-naphthyridine-3-carboxylic acid Oxolinic acid.

7. Quinoxaline di- N-oxides:

Quinoxaline-1,4-di-N-oxide. 3-(1,4-dioxo-2-quinoxalinemethylene)-carbamic acid methyl ester. 8. Halogenated - hydroxydiphenyl ether:

2-Hydroxy-2',4,4'-trichloro-diphenyl ether.

9. Nitrohydroxydiphenyl ether

10. Optionally halogenated salicylic acid anilides

11. Triarylmethylimidazoles:

Di-(phenyl)-2-chlorophenyl-imidazolyl (1)-methane.

12. Vitamins

13. 3- hydroxy- 2- methyl- 4- pyrone

14. 2- mercaptoimidazole

15. Ethoxylated alcohols:

As R-0 (choch;,0) H

Z z n

16. 2-bromo-5-nitrothiazole

17. Guanidine

18. N-substituted aminoacetic acids

19. (3-nitropropionic acid

20. Phenylcyclopropylamine

21. 2-(4-thiazolyl)-benzimidazole

22. Piperazine and its salts

23. Benzdiazepinone derivatives

24. Dihydroxydiphenyl sulfides

25. 4., 5- dihydroxy- 2, 4, 6- octatrienedicarboxylic acids

26. 2- formyl- 4- chlorophenoxyacetic acids

27. Straight-chain aliphatic alcohols

28. 2-chloro-10-(3-dimethylaminopropyl)-phenothiazine

29. Acetoxybenzoic acid

30. Auxins: 3,5-di-sec.butyl-a,(3,6-trihydroxy-l-cyclopentenevaleric acid 3,5-di-sec.butyl-6-hydroxy-(3-oxo-l-cyclopentenevaleric acid.

' EXAMPLE 1

128.6 g of 3-chlorophenol is dissolved in 400 ml of benzene and 79.1 g of anhydrous pyridine. 92.5 g of propionic acid chloride are then added dropwise at 5 - 10°C with stirring over the course of 25 minutes. The temperature of the reaction mixture is allowed to rise to 25°C, the separated pyridine hydrochloride is filtered off, the benzene solution is washed with water and this, after drying over sodium sulfate in a water jet vacuum, is concentrated completely. The remaining propionic acid 3-chlorophenyl ester (175.4 g) is heated to 75 - 80°C and 267 g of anhydrous aluminum chloride are added over the course of 30 minutes. The reaction melts are heated for a further 5 hours to 100°C and then poured with stirring into 4 l of ice water. The crystalline product is filtered off, washed with water and dried in a vacuum. 160.1 g of 2-hydroxy-4-chloro-propiophenone with a melting point of 50 - 52°C is obtained.

A mixture of 158.0 g of 2-hydroxy-4-chloro-propiophenone, 255 g of hydrazine hydrate, 286 g of potassium hydroxide and 700 ml of diethylene glycol is refluxed for 3 hours. The excess hydrazine hydrate is distilled off and the reaction solution is then heated for 2 1/2 hours at 195 - 205°C. The mixture is now stirred in 4 l of ice water, acidified with concentrated hydrochloric acid and extracted with chloroform. The chloroform solution is dried over sodium sulfate and then evaporated. From the remaining oil, the compound with the formula is isolated

with high vacuum distillation. The yield amounts to 122.5 g. Boiling point 61 - 65°/0.04 mm Hg.

According to the method according to example 1 or according to a further method mentioned above, the compounds according to formula I listed in the following table A can be prepared.

Determination of the minimal inhibitory concentration (MIC)

against bacteria and fungi:

With the compounds of formula I, a 1.5%<!>ig stock solution is prepared in methylcellosolve and this is then diluted so that the incorporation of 0.3 ml of the stock solutions and their dilutions in 15 ml of warm nutrient agar gives a concentration range of 300 , 100, 30, 10, 3.1, etc. ppm. active substance in agar. The still warm mixtures are poured onto plates and inoculated after solidification with the following test organisms:

Gram-positive bacteria:

Staphylococcus aureus

Sarcina ureae

Streptococcus faecalis

Streptococcus agalactiae A

Corynebacterium diphteroides

Bacillus subtilis

Mycobacterium phlei

Gram-negative bacteria:

Escherichia coli

Salmonella pullorum

Salmonella cholerae-suis

Bordetella bronchiseptica

Pasteurella multocida

Proteus vulgaris

Justice of Proteus

Pseudomonas fluorescens

Pseudomonas aeroginosa

Mushrooms:

Trichophyton gypseum

Trichophyton gallinae

Trichophyton verrucosum

Candida albicans

Candida krusci

Aspergillus niger

Aspergillus flavus

Penicillium funiculosum

Penicillium expansum

Trichoderma viride

Fusarium oxysporum

Chaetonium globosum

Alternaria tenuis

Paecilomyces varioti

Stachybotrys atra

After an incubation time of 48 hours at 37°C (bacteria) or After 5 days at 28°C (fungi), the minimum limit concentration (ppm) of the active substance is determined, at which the growth of the host organisms is inhibited.

As MIC, one detects values for the compounds of formula I which are clearly below the initial concentration of 300 ppm.

Determination of the microbicidal effect

A. In order to determine whether the active substances in the previous experiment killed the applied test germs (biocidal effect) or exclusively inhibited their growth (biostatic effect), sterile filter-

In paper discs with a diameter of 20 mm, and after a contact time

in 30 minutes the germs are covered with the help of these rondels. sterile, respectively active substance f with "Tween 80", blocked agar. The contact time is again 30 minutes. In the event that no growth of the coated germs can be observed on secondary agar plates, the germs on the first plate are killed with the help of the active substance, i.e. the active substance beyond the "relevant concentrations" has a biocidal effect on the exposed germs.

To confirm the above provision, the following additional test is carried out:

B. Solutions are prepared with the active substances of formula I

with the following composition:

5% active substance

5% Na-N-cocos-(3-aminopropionate

20% permutite water

70% ethyl cellosolve (ethylene glycol monoethyl ether).

Aliquots of these solutions are transferred with sterile, distilled water to emulsions with 1000 ppm, 500 ppm, 250 ppm and 125 ppm active substance content.

Samples of 9.9 ml of the emulsion are inoculated with 0.1 ml of germ suspensions (approx. 10 7 germs/ml).

Test organisms:

Staphylococcus aureus

Strephylococcus faecalis

Bacillus subtilis Proteus vulgaris

After an impact time of one minute, an oil is brought off

the inoculated emulsion in 10 ml of sterile "Brain-Heart-Infusion-Broth", after which the incubation time is 24 hours at 37° and then the "Brain-Heart-Infusion-Broth" is judged by drying (germ growth).

The proven compounds of formula I show a biocidal effect

in the previous attempts.

Claims (12)

1. Means for combating harmful microorganisms, containing as active ingredient a compound of formula I where X means halogen and n an integer from 1-11. 2. Agent according to claim 1, characterized in that it contains as active substance a compound of formula I, where X means chlorine or bromine and n means a number from 1-6. 3. Agent according to claim 2, characterized in that it contains as active substance a compound with formula 4. Agent according to claim 2, characterized in that it contains a compound of formula as active ingredient 5. Means according to claim 2, characterized in that the active substance contains a compound with formula 6. Means according to claim 2, characterized in that the active substance contains a compound with formula 7. Agent according to claim 2, characterized in that it contains a compound of formula as active substance 8. Agent according to claim 1, characterized in that, in addition to an active substance of formula I, as a solid or liquid carrier it also contains at least one of the following additives: soaps, surfactants, foaming agents, emulsifying agents, dispersing agents j or wetting agents, water, organic solvents, light protective agents, optical brighteners, fungicidal substances and bactericidal substances. 9. Means for combating pathogenic microorganisms in veterinary medicine, characterized in that they contain as active substance at least one of the active substances defined in claims 1-7 with formula I. 10. Use of compounds of formula I where X means halogen and n means a lame number from 1 - 11, as an active substance for combating harmful microorganisms. 11. Use of compounds of formula I according to claim 1, for combating pathogenic microorganisms in veterinary medicine. 12. Method for protecting organic materials against the harmful effects of microorganisms, characterized by incorporating at least one bond of formula I where X means halogen and n means an integer from 1-11, to the materials to be protected or brings it on their surface.