DE10256085A1 - Magnetic microbicides - Google Patents

Abstract

The present invention relates to magnetic microbicides and their use in sewage treatment plants and fermenters, for laundry disinfection and for the antimicrobial treatment of sales products, coolants and cooling lubricants and in neutral cleaners.

Description

The present invention relates to magnetic microbicides and their use in sewage treatment plants and Fermenters, for laundry disinfection and for the antimicrobial treatment of sales products, coolants and cooling lubricants as well as in neutral cleaners.

Microbicides (algicides, fungicides, Bactericides, virucides) are characterized by the fact that they contain microorganisms, dependent of their concentration, the exposure temperature and time, by damaging the Kill cell membranes or block vital metabolic processes, or the killing or destruction as well as inhibition or control the growth or reproduction of bacteria, fungi (including yeast and mold) and algae in dormant, immature stages of development and / or effect in the mature state and inactivate viruses.

The use of microbicides extends on a variety of different systems, fabrics and Products that can be attacked by microorganisms or meet hygienic requirements have to. For this reason, a variety of technologies and active ingredients developed to control the algae, bacteria and fungus population Service. Microbicides are e.g. B. as a preservative or disinfectant used against microorganisms.

The different mode of action of different microbicides enables a division into different groups, which can be treated together. An important group here are the biocides with a strong oxidizing effect, the so-called oxidizing biocides:
These include chlorine and bromine-releasing compounds, chlorine dioxide, ozone, permanganate and peroxides. These active substances have in common that they oxidatively change or destroy enzymes and information carriers of the microorganisms. The redox potential is a measure of their effectiveness.

Chlorine releasing compounds, e.g. B. gaseous Chlorine, inorganic and organic chlorine-releasing compounds (Chlorine bleach, chlorine lime, chloramines, chloroisocyanates) Hypochlorous in aqueous solution Acid, HOCL, the actual active ingredient. This preferentially oxidizes amino groups in cell molecules to chloramines. Because of the pH dependence the redox potential is an effective and economical application limited to pH values below 8. Reactions with chlorine are not very selective, making a number of undesirable By-products can arise especially chlorinated hydrocarbons. Still have chlorine-releasing Biocides, mainly because of the low cost, a wide range of applications, who is about Drinking water disinfection, treatment of water in swimming pools and process water extends in different areas.

The advantage of oxidative disinfection with chlorine dioxide is because that no Chlorinated hydrocarbons arise and contribute to better effectiveness pH values above 8 is given. The comparatively higher costs are disadvantageous. Chlorine dioxide cannot be stored, but must be stored before Dosing point are generated. Chlorine dioxide is also used as a disinfectant for drinking water authorized.

Disinfection with ozone is essentially limited to the treatment of drinking water and swimming pool water. ozone can also not be stored, but must be electrochemical generated at the dosing point. Because of the strong poisonous effect are also traces of drinking water treatment, such as with chlorine dioxide eliminate existing surpluses.

A second important group are the non-oxidizing biocides:
These include aldehydic agents, quaternary ammonium compounds, isothiazolone compounds and other microbicidal agents.

The activity of aldehydes as a biocide is based on responsiveness with amino groups. The preservative effect of formaldehyde (formalin) has long been known, but has its use as a biocide and disinfectants because of their potentially carcinogenic nature lost importance. On top of that are so-called multifunctional aldehydes, these are those with several aldehyde groups in one molecule, as a biocide effective. In addition to glyoxal and glutaraldehyde have recently high molecular weight Aldehyde compounds, not least because of their good degradability, gained in importance. Aldehydes have a broad spectrum of activity including Virus-effectiveness and sporicidal effect on formaldehyde and glutaraldehyde. aldehydes can however residues of blood and protein due to chemical reaction on objects to be disinfected fix so that this difficult to clean after disinfection.

The class of quaternary ammonium compounds has been used for a long time, especially in industrial cycles. The so-called Quats attack the cell membrane of microorganisms and have a good cleaning effect due to their surfactant properties. A quick and complete Degradation in biological clarification stages is proven. The strong foaming effect is disadvantageous.

For product preservation and as a biocide in process water have isothiazolone derivatives during a considerable amount in recent years Won market share. The reason is the generally low required application concentrations. The exact mechanism of action is not known. Isothiazolone derivatives are sufficient dilution slowly biodegraded, however, because of the considerable Toxicity too for higher water organisms in the Wastewater tax should always be exercised.

A large number of other microbicides was for developed different areas of application. Phenol derivatives for example, have good bactericidal activity but are not sporicidal. Across from they have almost all other disinfectant ingredients Preferred, relatively little due to dirt affected to become. They are therefore particularly suitable for disinfecting stools. Typical representatives are 2-biphenylol and p-chloro-m-cresol (4-chloro-3-methylphenol). But phenols are mainly because of their smell, their low Effectiveness against the poliovirus, its poor degradability, their high lipid solubility associated with a strong penetration through the skin as well as more toxic and mutagenic risks in almost all areas of application for microbicides and disinfectant on the retreat.

Alcohols are characterized by fast Efficacy out, but only at relatively high concentrations of approximately 40-80%.

Some of the substances mentioned are because of their toxicological or ecological concern largely disappeared from the market (acrolein, formaldehyde, chlorophenols, Heavy metal compounds). Others, however, continue to be used z. B. organic bromine and organic sulfur compounds.

However, the use of conventional microbicides is associated with not inconsiderable problems that have so far not been satisfactory solved could become.

common Microbicides act undirected, i.e. they have an effect both at the site of action (e.g. against harmful microorganisms in one Cooling circuit) as well afterwards against possibly useful microorganisms e.g. in a wastewater treatment plant, which among other things the ecological Raising concerns about many microbicides.

Another problem lies in the desired local efficacy: e.g. sufficient in the cooling water biocidal effectiveness guaranteed be without the Microflora in sewage treatment plants or receiving water is damaged becomes. Many active ingredients that have been used in the past are no longer used due to this problem.

Microbicides also act, depending on the concentration not only against microbial cells, e.g. Bacteria and fungi, but also against animal and human cells. This results in et al the toxicological potential of many microbicides.

In circulatory systems can also be against everyone a certain immunity of the aforementioned active substances occurs after some time. Therefor there are two main reasons.

1. Selection: In water-bearing Systems can Many types of microorganisms occur that are specific to certain biocides Active substances react differently sensitive. The elimination some types can be for others with higher resistance effect the expansion of their living space so that long term just a change the species composition is achieved.

2. Adaptation: microorganisms have favored due to their short generation change, a remarkable quality changed Adapt living conditions. So react e.g. some types of bacteria on cell poisons with increased Glycogen production and build up a protective cover in this way.

Such training less sensitive species and strains gradually leads to a limitation the effectiveness of biocides.

By optimizing the dosing intervals and occasional changes in the active ingredients can have such disadvantages can only be avoided incompletely.

The present invention lies hence the object of providing microbicides which have the disadvantages avoid the state of the art.

• a) mindestens eine mikrobizide Komponente und
• b) mindestens eine magnetische Komponente umfaßt, wobei Komponente a) und Komponente b) kovalent miteinander verknüpft sind.

This object is achieved according to the invention by providing a magnetic microbicide which

• a) at least one microbicidal component and
• b) comprises at least one magnetic component, component a) and component b) being covalently linked to one another.

• – alte, längst aus ökologischen und toxikologischen Gründen verbotene oder nur noch eingeschränkt verwendbare Biozide Wirkstoffe können (an eine magnetische Komponente gekoppelt) wieder eingesetzt werden,
• – vorhandene Biozide Wirkstoffe können aus den gleichen Gründen in höherer Konzentration eingesetzt werden,
• – die Wirkstoffe können zu ihren Wirkorten hin gesteuert werden, z.B. in Todenden oder Sprühschatten, wo sie in einem normalen Kreislauf, insb. in CIP-Anlagen (CIP: Cleaning in Place), sonst nicht hingelangt wären,
• – Produkte od. z.B. auch Abwässer können berechtigterweise als "Biozid-frei" deklariert werden mit entsprechenden ökologischen, toxikologischen und den daraus abgeleiteten Marketing-relevanten und somit ökonomischen Vorteilen,
• – das eingesetzte (magnetische = steuerbare) Biozid kann ggf. wiederverwendet werden,
• – aufgrund der beschriebenen ökologischen und toxikologischen Vorteile wird die Zulassung eines erfindungsgemäßen Mikrobizides gemäß der Biozidrichtlinie bzw. des Chemikaliengesetzes gegenüber herkömmlichen Bioziden erleichtert, woraus sich ein erleichterter Marktzugang ergibt.

The magnetic microbicide according to the invention has a number of advantages over conventional biocides:
The coupling of biocidal agents to magnetic components enables you to control biocides by simply applying a magnetic field. A magnetic field suitable for the separation of magnetic biocides according to the invention can, for example, have a strength in the range from 1 to 150 kA / m (at 30% by weight magnetic biocide in dispersion), preferably about 50 kA / m (at 30% by weight magnetic biocide in dispersion ). They can be separated so that they no longer burden the environment and humans, or direct them to the place of action that would otherwise not have been reached. Many of the limitations that were previously subject to the use of biocides are now lifted or are at least only valid to a limited extent:

• - Old biocidal active substances that have long been banned for ecological and toxicological reasons or can only be used to a limited extent can be reused (coupled to a magnetic component) the,
• - existing biocidal active substances can be used in higher concentrations for the same reasons,
• - The active ingredients can be controlled to their places of action, e.g. in the dead or in the shade, where they would otherwise not have gotten into a normal cycle, especially in CIP systems (CIP: Cleaning in Place),
• - Products or, for example, wastewater can legitimately be declared as "biocide-free" with corresponding ecological, toxicological and the marketing-relevant and therefore economic advantages derived from them,
• - The (magnetic = controllable) biocide used can be reused if necessary,
• - Due to the described ecological and toxicological advantages, the approval of a microbicide according to the biocide directive or the chemicals law is facilitated compared to conventional biocides, which results in easier market access.

In principle, all microbicidal compounds which can be covalently coupled to a magnetic component b) can be used as the microbicidal component a). Microbicidal components a) which are suitable according to the invention are described, for example, in the following publications, to which reference is hereby made in full:
KH Wallhäuser, "Practice of Sterilization, Disinfection, Conservation", 5th revised edition, 1995 (ISBN 3134163055), Georg Thieme Verlag, Stuttgart, in particular Table 1.60 (p. 103-105), Table, 5.11 (p. 406) , Table 5.12 (p. 407), table 5.13, table 5.14, table 5.15 (p. 412-414), table 6.5, table 6.6 (p. 426), tables 6.7 and 6.8, page 434, 6 .4, 6.5, 6.6 and 6.8, Table 6.13 (p. 436) and Chapter 7 ("Antimicrobial agents", p. 465 ff.),
SS Block, "Disinfection, Sterilization, and Preservation", 5 ^th edition, 2000 (ISBN 0-683-30740-1), Lippincott Williams & Wilkens, Philadelphia, especially Tables 7.2, 8.1, 8.2, 9.5, 9.6, 9.7, 9.11 , 9.12, 9.13, 9.14, 10.3, 12.2-12.6, 13.1-13.4, 14.1, 14.2, 14.6, 14.7, 14.8, 14.17, 14.19-14.25, 15.1, 16.2, 17.2, 17.3, 18.1, 18.2, 19.1 and 20.2 as well 13 .1 and 20.1-20.4,
List of disinfection methods tested according to the "Guidelines for the Testing of Chemical Disinfectants" and found to be effective by the German Society for Hygiene and Microbiology, mhp-Verlag GmbH, Wiesbaden,
List of disinfectants and processes tested and recognized by the Federal Health Office, C.Heymanns Verlag Cologne,
Particularly suitable microbicidal components a) are selected from phenols, including their halogen derivatives, heterocyclic compounds, such as. B. isothiazolinones, benzothiazoles, imidazoles, benzimidazoles and derivatives of these compounds and other algicidal or fungicidal active ingredients, such as. B. guanidine, phthalimide or urea derivatives, as in the DE-C1-39 04 099 to which reference is hereby made in full.

wobei n, m und p gleich oder unterschiedlich sind und 1, 2 oder 3 betragen können, R und R' gleich oder unterschiedlich sein können und Wasserstoff, Alkyl-, Alkoxy-, Hydroxyalkyl-, Aryl-, Aralkyl- oder Alkaryl-bedeuten können.Phenols suitable as microbicidal components a) are in particular those of the general formula (I):

where n, m and p are the same or different and can be 1, 2 or 3, R and R 'can be the same or different and can be hydrogen, alkyl, alkoxy, hydroxyalkyl, aryl, aralkyl or alkaryl ,

Xylenols and o-phenylphenols are preferably used. A phenol derivative which can be used with particular preference in accordance with the invention is 4-hydroxybenzaldehyde. Other suitable phenolic compounds are, in particular, p-hydroxybenzoic acid esters, and further phenolates, as in US Pat DE-A-100 27 588 described. Preferred phenates are mono- or polysubstituted phenates with aliphatic and / or aromatic substituents. Examples of such derivatives which can be used according to the invention are o-phenylphenolate, halogenated phenolates, salts of cresols, salts of halogenated cresols and salts of resorcinols or mixtures thereof. Examples of salts of the cresols are salts of halogenated cresols, in particular salts of chlorinated cresols, salts of o-, m- and p-cresol, salts of isopropyl-o-cresol, salts of 4-isopropyl-m-cresol. An example of a salt of the resorcinols that can be used is a salt of 4-n-hexylresorcinol.

wiedergegeben werden, in der
Y eine (C1-C18)-Alkyl- oder (C3-C12)-Cycloalkylgruppe ist, die mit einer oder mehreren Hydroxy-, Halogen-, Cyano-, Alkylamino-, Dialkylamino-, Aryl-, Amä no-, Carboxy-, Carbalkoxy-, Alkoxy-, Aryloxy-, Alkylthio-, Arylt-hio-, Halogenalkoxy-, Cycloalkylamino-, Carbamoxy- oder Isothiazolonylgruppen substituiert sein kann, eine unsubstituierte oder mit Halogen substituierte (C2-C6)-Alkenyl- oder -Alkinylgruppe, eine (C7-C10)-Aralkyl-gruppe, die mit einem oder mehreren Halogenatomen oder einer oder mehreren (C1-C4)-Alkyl- oder (C1-C4)-Alkoxygruppen substituiert sein kann, oder eine Arylgruppe ist, die mit einer oder mehreren Halogenatomen, Nitro-, (C1-C4)-Alkyl-, (C1-C4)-Alkylacrylamino-, Carb(C1-C4)-alkoxy- oder Sulfamylgruppen substituiert sein kann, und
R und R1 jeweils unabhängig Wasserstoff, Halogen, eine (C1-C4)-Alkylgruppe, eine (C1-C4)-Cycloalkylgruppe sind oder miteinander unter Ausbildung einer Benzoisothiazolonylgruppe verbunden sind, wobei halogenfreie Isothiazolone und insbesondere N-Oktyl-Isothiazolon bevorzugt sind.The group of heterocyclic compounds which can be used according to the invention as microbicidal component a) bindings count e.g. B. the following active ingredients:
Methyl 2- (thiocyanomethylthio) benzothiazole, 2- (4-thiazolyl) -1-N-benzimidazole, 1-butyl- (carbamoyl) -2-benzimidazole-carbamic acid, N- (n-propyl) -N- (2,4 , 6-trichlorophenoxyethyl) -N'-imidazolylurea, 2-n-octyl-4-isothiazolin-3-one, 2-methyl-4-isothiazolin-3-one, 5-chloro-2-methyl-4-isothiazolin-3 -one, 2-cyclohexyl-4-isothiazolin-3-one, 2-dodecyl-4-isothiazolin-3-one and 2-benzyl-4-isothiazolin-3-one. Preferred heterocyclic compounds include those derived from the EP-B-0 443 821 are known. In particular, these are those which are represented by the formula (II)

are reproduced in the
Y is a (C1-C18) -alkyl or (C3-C12) -cycloalkyl group which is linked to one or more hydroxyl, halogen, cyano, alkylamino, dialkylamino, aryl, amino, carboxy, Carbalkoxy, alkoxy, aryloxy, alkylthio, arylt-hio, haloalkoxy, cycloalkylamino, carbamoxy or isothiazolonyl groups, an unsubstituted or halogen-substituted (C2-C6) alkenyl or alkynyl group, one (C7-C10) aralkyl group which may be substituted with one or more halogen atoms or one or more (C1-C4) alkyl or (C1-C4) alkoxy groups, or is an aryl group with one or more Halogen atoms, nitro, (C1-C4) alkyl, (C1-C4) alkyllacrylamino, carb (C1-C4) alkoxy or sulfamyl groups can be substituted, and
R and R1 are each independently hydrogen, halogen, a (C1-C4) alkyl group, a (C1-C4) cycloalkyl group or are linked together to form a benzoisothiazolonyl group, halogen-free isothiazolones and in particular N-octyl-isothiazolone being preferred.

Examples of the third group above Other algicidal or fungicidal active ingredients mentioned are: N-trichloromethylthio-phthalimide, N-dichlorofluoromethylthio-N ', N'-dimethyl-N-phenylschwefelsäurediamid, Dodecylguanidine acetate, N- (n-propyl) -N- (2,4,6-trichlorophenoxyethyl) -N'-imidazolylurea and 3- (3,4-dichlorophenyl) -1,1-dimethylurea.

in der R1 und R2 gleich oder verschieden sind und Wasserstoff, lineare oder verzweigte Alkyl- oder Alkenylreste mit 1 bis 6 Kohlenstoffatomen oder cyclische Alkylreste mit 5 bis 7 Kohlenstoffatomen oder R1 und R2 zusammengenommen -(CH2)n- bedeuten, wobei n 4 bis 6 ist, R3, R4, R5 und R6, die gleich oder verschieden sein können, Wasserstoff, Alkylreste mit 1 bis 4 Kohlenstoffatomen, Arylreste oder CCl₃ bedeuten oder R3 und R5 oder R4 und R6 zusammengenommen -(CH2)n bedeuten, wobei n 3 bis 5 ist, und R7 Wasserstoff, lineare oder verzweigte Alkylreste mit 1 bis 12 Kohlenstoffatomen oder cyclische Alkylreste mit 4 bis 8 Kohlenstoffatomen, Arylreste, substituierte Arylreste, Arylalkylreste oder Arylsulfonylreste bedeutet.Other compounds that can be used as microbicidal components a) are those in FIG DE-A-42 17 881 Biocides described by the applicant, in particular antimicrobial iodopropynyloxyethanol carbamate compounds, for example the 2- (3-iodo-2-propynyloxy) ethanol carbamates of the general formula (III):

in which R1 and R2 are the same or different and are hydrogen, linear or branched alkyl or alkenyl radicals having 1 to 6 carbon atoms or cyclic alkyl radicals having 5 to 7 carbon atoms or R1 and R2 taken together - (CH2) n-, where n is 4 to 6 R3, R4, R5 and R6, which may be the same or different, denote hydrogen, alkyl radicals having 1 to 4 carbon atoms, aryl radicals or CCl ₃ or R3 and R5 or R4 and R6 taken together - (CH2) n, where n is 3 to 5, and R7 is hydrogen, linear or branched alkyl radicals having 1 to 12 carbon atoms or cyclic alkyl radicals having 4 to 8 carbon atoms, aryl radicals, substituted aryl radicals, arylalkyl radicals or arylsulfonyl radicals.

Examples of linear or branched alkyl radicals or alkenyl radicals with 1 to 6 carbon atoms, for which R1 and R2 are the methyl, ethyl, propyl, isopropyl, n-butyl, Isobutyl, sec.-butyl, tert.-butyl, pentyl, the hexyl radical and their branched isomers such as the vinyl, allyl, propenyl, butenyl, Pentenyl and hexenyl residues and the corresponding isomers of the alkenyls mentioned with 4, 5 and 6 carbon atoms.

Examples of cyclic alkyl radicals with 5 to 7 carbon atoms, for R1 and R2 are cyclopentane, cyclohexane and Cycloheptanrest. Compounds of the formula (III) are preferred in which both substituents R1 and R2 are hydrogen at the same time or at the same time are methyl radicals and those in which R1 and R2 is a substituent hydrogen while the other is methyl represents.

Examples of alkyl radicals with 1 to 4 carbon atoms, for the R3, R4, R5 and R6 are the methyl, ethyl, propyl, isopropyl and the n-butyl radical, isobutyl, sec-butyl and tert-butyl, where Methyl is preferred.

Examples of aryl residues for which R3, R4, R5 and R6 are the phenyl and the naphthyl radical.

Compounds of the general are preferred Formula (III) in which of the radicals R1 to R6 at least 4 radicals Mean hydrogen.

Examples of linear and branched alkyl radicals with 1 to 12 carbon atoms, for which R7 stands, are the methyl, Ethyl, propyl, isopropyl, n-butyl, isobutyl, sec.-butyl, tert.-butyl, Pentyl, hexyl, heptyl, octyl, nonyl, decyl, undecyl and the dodecyl radical and the branched isomers of alkyls having 5 to 12 carbon atoms.

Examples of cyclic alkyl radicals with 4 to 8 carbon atoms, for the R7 is the cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl and the cyclooctyl radical.

Examples of aryl and substituted aryl, for the R1 is the phenyl, naphthyl, tolyl, chlorophenyl, bromophenyl, Fluorophenyl, dichlorophenyl and the trichlorophenyl radical.

Examples of aralkyl and arylsulfonyl, for the R7 is the benzyl and p-toluenesulfonyl.

Compounds are preferred in which R7 is a lower alkyl radical having 1 to 4 carbon atoms, and is an aryl radical or aryl radical substituted with chlorine or bromine.

Examples of particularly preferred compounds are those in which R7 is propyl, butyl or phenyl.

The N-substituted 2- (3-iodo-2-propynyloxy) ethanol carbamates of the general formula (III) are prepared by methods known per se (Houben-Weyl, Methods of Org. Chemistry, Vol. 8, 5. 141- 144 (1952)) by reacting equimolar amounts of the alcohols with suitable, e.g. B. synthesized commercially available isocyanates, such as in the DE-A-32 16894 is described.

In addition, as as microbicidal components a) which in the DE-A-42 17 884 The biocides described by the applicant can be used, in particular antimicrobial aminopyridinium compounds of the formula (IV) which have an amino function in the para position of the pyridinium salt:

The following applies: R2 = C2-C14, aryl, aralkyl, alkenyl
R3 = H.

Examples of such antimicrobial active compounds are 1,10-di- (4-octylaminopyridinium) decane dihydrochloride, 4- (octylamino) benzyl pyridinium chloride or 4- (octylamino) dodecyl pyridinium bromide.

In addition, quaternary ammonium compounds [cationic surfactants (invert soaps) and amphoteric surfactants] can be used as microbicidal components a), as in US Pat DE-A-100 12 543 to which reference is hereby made in full. These belong to the class of surfactants. They are characterized by very good skin and material compatibility as well as odor neutrality. This subheading includes: B. benzalkonium chloride, cetrimonium bromide, cetylpyridinium chloride (hexadecylpyridinium chloride) and others. Quaternary ammonium compounds are organic ammonium compounds with quaternary nitrogen atoms.

Quaternary ammonium compounds are obtained by reacting tertiary amines with alkylating agents, such as. B. methyl chloride, benzyl chloride, dimethyl sulfate, dodecyl bromide, but also ethylene oxide. Depending on the tertiary amine used, a distinction is made between three groups, which are characterized by the following structural formulas Va), Vb) and Vc), in which R1 = CH3, R2 = C8-18 and X = halogen:

• a) Lineare Alkylammoniumverbindungen
• b) Imidazoliniumverbindungen
• c) Pyridinium-Verbindungen.

Here means:

• a) Linear alkyl ammonium compounds
• b) Imidazolinium compounds
• c) pyridinium compounds.

The alkylation of tertiary amines with a long alkyl radical and two methyl groups is particularly easy, also the quaternization of tertiary Amines with two long residues and one methyl group can be prepared using Methyl chloride can be carried out under mild conditions. Amines over three have long alkyl radicals or hydroxy-substituted alkyl radicals not very reactive and are preferably quaternized with dimethyl sulfate.

• – 0,1 bis 100 mol-% Vinylamin- oder Ethylenimin-Einheiten und
• – 0 bis 99,9 mol-% Einheiten mindestens eines Monomers aus der Gruppe, bestehend aus N-Vinylcarbonsäureamiden der Formel (VI)
  
  in der R1, R2 = N oder C1- bis C6-Alkyl bedeuten, Vinylformiat, Vinylacetat, Vinylpropionat, Vinylalkohol, C1- bis C6-Alkylvinylether, monoethylenisch ungesättigten C3- bis C8-Carbonsäuren, deren Ester, Nilrile, Amide und Anhydride, N-Vinylharnstoff, N-Imidazolen und N-Vinylimidazolinen und
• – 0 bis 5 mol-% Einheiten von Monomeren mit mindestens zwei ethylenisch ungesättigten Doppelbindungen, einpolymerisiert enthalten.

In addition, biocidal polymers can be used as the microbicidal component a) according to the invention, as in FIG DE-A-196 08 555 described. Suitable polymers are, for example, copolymers of diallyldimethylammonium chloride and sodium acrylate, which have bactericidal activity, copolymers of ethylene and dialkylaminoalkylacrylamides with biocidal activity, antimicrobially active polymers which contain vinylphosphonium and vinylsulfonium groups, and biocidally active copolymers of n-vinylpyrononononyl vinylamines. Suitable biocidal polymers are also polymers that

• - 0.1 to 100 mol% of vinylamine or ethyleneimine units and
• 0 to 99.9 mol% of units of at least one monomer from the group consisting of N-vinylcarboxamides of the formula (VI)
  
  in which R1, R2 = N or C1- to C6-alkyl, vinyl formate, vinyl acetate, vinyl propionate, vinyl alcohol, C1 to C6-alkyl vinyl ether, monoethylenically unsaturated C3 to C8 carboxylic acids, their esters, Nilrile, amides and anhydrides, N Vinyl urea, N-imidazoles and N-vinylimidazolines and
• - 0 to 5 mol% units of monomers with at least two ethylenically unsaturated double bonds, copolymerized.

Further microbicidal components a) according to the invention are, for example, biocidal halopropargyl compounds, in particular cyclodextrin inclusion complexes of such halopropargyl compounds, which are used in the DE-T2-697 09 659 to be discribed.

The magnetic component is b) preferably an optionally coated magnetic particle. Can be used according to the invention magnetic particles are particles of magnetic materials, z. B. magnetite, maghemite and iron to which component a) covalently is coupled. Polymer particles are also a magnetic component b) suitable with included magnetic particles, on the polymer surface of which Component a) is covalently bound. Below you can e.g. crosslinked magnetic polystyrene beads, polyvinyl alcohol beads or Introduce PMMA beads with polymerized functional groups, on which component a) is immobilized. The preferred according to the invention Particle size is 10 to 100 nm in diameter.

Magnetic particles and their production are, for example, in the DE-A-198 00 294 , the DE-A-195 28 029 as well as in the unpublished one on the filing date of the present application DE-102 35 302.6 described by the applicant, to which reference is hereby made in full.

Magnetic colloids, which mainly consist of magnetite (Fe ₃ O ₄ ), iron oxide (Fe ₂ O ₃ ) or iron oxyhydroxide (FeOOH) and have a particle size of 5-100 nm and among other things as a contrast agent in NMR diagnostics, as information storage media, seals - or use damping agents are generally known. As a rule, iron (III) and iron (II) salt solutions with varying molar ratios (2: 1, 0.5: 1 to 4: 1) by adding bases or by applying heat to corresponding colloidal magnetic dispersions ("magnetic colloids"). In order to prevent agglomeration of the magnetic colloids, particularly caused by the Van der Waals forces, surface-active substances are added to them, which are generally referred to as "surfactants", "emulsifiers", "stabilizers", "complexing agents", "surfactants" or "dispersants" are known, which practically prevents settling of the colloid in aqueous dispersion. Such stabilized colloidal dispersions are also known under the name "ferrofluids". They are also offered commercially today (Ferrofluidics Corp., USA, Advanced Magnetics, USA, Taibo Co., Japan, Liquids Research Ltd, Wales, BASF, Germany, Schering AG, Germany). The stabilizers used are either cationic or anionic in nature or non-ionic. Suitable compounds for this are e.g. For example: alkylaryl polyether sulfates, lauryl sulfonate, alkylaryl polyether sulfonates, phosphate esters, alcohol ether sulfates, citrates, oleic acid, alkyl naphthalene sulfonates, polystyrene sulfonic acid or petrolium sulfonates as cationic surfactants, or polyphenol oxyoloxychloride as well Another class of substances that have proven themselves as colloid stabilizers are: polysaccharides and synthetic polymers such as polyvinyl alcohol, polyoxyethylene or proteins.

The particle sizes using the aforementioned preparation ways magnetic colloids shown hang on the concentration of the base, the type of base, the temperature as well as the salt ratio and the ion concentration.

The magnetic colloids can Obtaining a likewise according to the invention suitable embodiment component b) with various functional polymer substrates (Matrix) can be coated, which are capable of component a) to bind covalently. Matrices that are suitable for such purposes are z. B. poly- and oligosaccharides, polysaccharide derivatives, such as hyaluronates, alginates, dextran, agarose, dextrin, starch, heparin, hydroxyethyl cellulose, further synthetic polymers such as polyvinyl alcohol, polyacrylic acid and Derivatives thereof, polyurethanes, polyoxyethylene, polylactide, polyglycolide, Polycyanoacrylates, polyhydroxyethyl methacrylate and copolymers of these substances. Proteins such as z. B. gelatin, casein, collagen, albumin, fibrinogen or polyamic acids in Question.

For encapsulating the magnetic Colloids with the polymers can generally be used in such processes which the magnetic colloids completely encapsulate and appropriately isolated nano- or microparticulate magnetic particles result.

Advantageously, the general come for this known processes such as suspension crosslinking, emulsion polymerization, Suspension polymerization or precipitation process ("solvent evaporation process") from organic Application phase. The differentiation between emulsion and suspension The following consistently refers to the different particle sizes: emulsion for particle sizes <1 µm and suspension for those> 1 um.

In the suspension crosslinking process becomes an aqueous polymer solution, in which is the magnetic colloid dispersed in one with water immiscible phase (organic phase) suspended and then with a suitable bi- or trifunctional crosslinker. water-soluble Polymers for this Processes preferably come into question, e.g. B. serum albumin, Proteoglycans, glycoproteins, polyvinyl alcohol, cellulose, agarose, Dextran, alginates, hyaluronates, starch, polyhydroxyethyl methacrylate. As organic phase, oils are suitable like paraffin oils, Vegetable oils, Silicone oils, cottonseed or organic solvents such as chloroform, butanol, heptanol, toluene, benzene, ethyl acetate, hexane, Heptane, octane and mixtures thereof.

The direction of the droplet size during the suspension process the for analytical purposes preferred small particle sizes of 0.5-5 to shift, the dispersion phase is usually 0.3-15 % By weight of stabilizers, preferably from the group of polyoxyethylene adducts, Polyoxyäthylensorbitolester, Polyäthylenpropylenoxid block copolymers, Alkylphenoxypolyät-hoxyäthanole, Fettalkoholglycoläther-organophosphate, Sorbitan fatty acid ester, Polyoxyäthylenalkohole, PolyoxyC äthylensorbitanfettsäureester, or belong to polyoxyethylene acids added. The volume ratios vary from organic phase to polymer / magnetic colloid phase between 10: 1 and 60: 1, that of the polymer phase to the colloid phase usually between 1: 0.5 and 1: 4, preferably between 1: 1 and 1: 3, where the polymer / magnetic colloid ratio determined by the amount of solids in the colloid becomes. This is generally between 1 and 10% by weight of the magnetic solid content in the polymer advantageously 10 to 60% by weight.

Suitable crosslinkers for the polymer matrix are di- and trifunctional substances that work with the functional Groups of the matrix (e.g. hydroxyl, carboxyl, amino groups) react can.

Suitable crosslinking agents are, for example, N, N'-methylenebisacrylamide, polyethylene glycol diacrylate and polyethylene glycol dimethacrylate, which are each derived from polyethylene glycols with a molecular weight of 120 to 8500, preferably 400 to 2000, trimethylolpropane triacrylate, trimethylolpropane trimethacrylate, ethylene glycol diacrylate diacrylate, diacrylate diacrylate, diacrylate, Dimethacrylates of block copolymers of ethylene oxide and propylene oxide, two or three diesterified with acrylic acid or methacrylic acid, polyhydric alcohols such as glycerol or pentaerythritol, triallylamine, tetraallylethylenediamine, divinylbenzene, diallyl phthalate, Polyethylenglykoldivinylether of polyethylene glycols having a molecular weight of from 126 to 4000, trimethylolpropane diallyl ether, butanediol divinyl ether, pentaerythritol triallyl ether and / or divinylethyleneurea.

Water-soluble crosslinking agents are preferably used a, e.g. B. 1,1,1, -Tris (hydroxymethyl) propane triacrylate, 3- (acryloyloxy) -2-hydroxypropyl methacrylate, allyl methacrylate, Acrylsäuevinylester N, N'-methylenebisacrylamide, Polyethylene glycol diacrylates and polyethylene glycol dimethacrylates, which depend on addition products of 2 to 400 moles of ethylene oxide Derive 1 mole of a diol or polyol, vinyl ether from addition products from 2 to 400 moles of ethylene oxide to 1 mole of a diol or polyol, Ethylene glycol diacrylate, ethylene glycol dimethacrylate or triacrylates and trimethacrylates of addition products of 6 to 20 moles of ethylene oxide one mole of glycerin, pentaerythritol triallyl ether and / or divinyl urea.

Connections are also used as crosslinkers suitable, the at least one polymerizable ethylenically unsaturated group and contain at least one further functional group. The functional Group of these crosslinkers must be in be able to react with the functional groups of the matrix. Suitable functional groups (of the crosslinking agent) are e.g. B. hydroxyl, Amino, epoxy, isocyanate, ester, amide and aziridino groups.

Such crosslinkers also come Compounds considered that have at least two of the aforementioned functional Wear groups that react with the functional groups of the matrix can. examples for such crosslinkers are ethylene glycol, diethylene glycol, triethylene glycol, Tetraethylene glycol, polyethylene glycol, glycerin, polyglycerin, propylene glycol Diethanolamine, triethanolamine, polypropylene glycol, block copolymers from ethylene oxide and propylene oxide, sorbitan fatty acid esters, ethoxylated sorbitan fatty acid esters, trimethylolpropane, Pentaerythritol, polyvinyl alcohol, sorbitol, polyglycidyl ethers such as ethylene glycol diglycidyl ether, polyethylene glycol diglycidyl ether, Glycerol diglycidyl ether, glycerol polyglycidyl ether, diglycerol polyglycidyl ether, Polyglycerol polyglycidyl ether, sorbitol polyglycidyl ether, pentaerythritol polyglycidyl ether, Propylene glycol diglycidyl ether and polypropylene glycol diglycidyl ether, Polyaziridine compounds such as 2,2-bishydroxymethylbutanoltris [3- (I-aziridinyl) propionate], 1,6-hexamethylene-diethyleneurea, diphenylmethane-bis-4,4'-N, N'-diethyleneurea, Halogenepoxy compounds such as epichlorohydrin and a-methylfluorohydrin, Polyisocyanates such as 2,4-tolylene diisocyanate and hexamethylene diisocyanate, Alkylene carbonates such as 1,3-dioxolan-2-one and 4-methyl-1,3-dioxolan-2-one, polyquaternary Amines such as condensation products of dimethylamine with epichlorohydrin, Homopolymers and copolymers of diallyldimethylammonium chloride as well as homo- and copolymers of dimethylaminoethyl (meth) acrylate, optionally with, for example Methyl chloride are quaternized.

Other suitable crosslinkers are polyvalent metal ions capable of ionic crosslinks train. examples for such crosslinkers are magnesium, calcium, barium and aluminum ions. This Crosslinkers are used, for example, as hydroxides, carbonates or hydrogen carbonates the aqueous polymerizable solution added.

Other suitable crosslinkers are multifunctional bases that are also capable of ionic To form crosslinks, for example polyamines or their quaternized ones Salts. examples for Polyamines are ethylene diamine, diethylene triamine, triethylene tetramine, Tetraethylene pentamine, pentaethylene hexamine and polyethyleneimines as well Polyvinylamines with molecular weights of up to 4000000 each.

The aforementioned crosslinkers can be used individually or used in mixtures.

The amount of crosslinker used in is determined primarily by the fineness of the magnetic colloid is in the Rule 0.5-10 mol%, based on the polymer content. Consistently higher levels of networking are required to diffuse out in the case of very fine colloids to prevent from the matrix.

Analogous to the networking procedure in Suspension, suspension polymerization also offers the possibility of encapsulate the magnetic colloids in a defined manner. This will a water soluble Vinyl monomer in an organic immiscible with the monomer Phase suspended and then radically polymerized with the addition of suitable stabilizers.

Procedures of this kind are from the Literature known (see Paine et al, Macromolecules, 23, 3104, 1990, Tuncel et al., J. Appl. Polym. Sci., 50, 303, 5 1993, Takahashi et al., J Polymer Sci., Part A: Polymer Chem., 34, 175-182, 1996).

Water-soluble monomers come as monomers such as B. vinyl pyrrolidone, acrylamide, 2-hydroxyethyl methacrylate, hydroxyethyl acrylate, Acrylic acid, methacrylic acid as well as mixtures thereof in question. The dispersion phases correspond consistently the organic specified in the suspension crosslinking, not phases miscible with water. Coming as suspension stabilizers usually the same stabilizers for use as in the aforementioned Crosslinking process.

Within this process engineering has opted for the encapsulation especially as 2-hydroxyethyl methacrylate proven advantageous because the polymer due to its chemical Structure is highly functional. For encapsulation with this polymer have become stabilizers in the form of synthetic polymer systems such. B. polymethyl methacrylate, Polymethyl methacrylate, polystyrene, containing methacryloyl end groups, Polystyrene derivatives or polybutadiene derivatives are particularly advantageous proved.

The quantitative ratios of polymer to magnetic colloid are analogous to those in the aforementioned networking process.

Another method of encapsulation the magnetic colloid is derived from the known manufacturing processes from polymer particles with the help of emulsion polymerization, such as them for Styrene, methyl methacrylate and glycidyl methacrylate has been described (see Woods et al., J. Paint Techn., 40, 541-548, 1968, Smigol et al, Angew. Makromol. Chem., 195, 151-164, 1992, Okubo and Shiozaki, 35 Polymer Int., 30, 469 ^ 74), 1993).

This will advantageously either by adding anionic surfactants such as polyacrylic acid or dodecylbenzyl sulfonate, nonionic surfactants such as alkylphenyl polyethylene glycols or polyethylene glycol trimethylnonyl ether combined Add anionic and non-ionic surfactants or under emulsifier-free conditions carried out, the latter procedure optionally in the presence of sodium chloride can be done.

Based on this process technology could be shown that by Addition of stabilized lipophilic or semi-lipophilic surfactants Magnetic colloids for emulsion polymerization approach these in the polymer particles forming are encapsulated. Suitable surface active Substances are those that have an HLB value (hydrophilic-lipophilic balance, see Griffin, J. Soc. Cosmetic Chemists, 5, 249-255, 1954) by 1-12.

Examples of these are: polyethylene propylene oxide block copolymers, Alkylphenoxypolyethoxyethanols, polyoxyethylene alcohols, Polyoxyäthylensorbitanfettsäurester, Sorbitan.

Have the following reaction approaches proved to be suitable: monomer concentration 0.7-5.2 mol / liter, Initiator concentration 1-10 mmol / liter, stabilizer concentration 0.1-80 mmol / liter; the sodium chloride concentration can be optional up to 20 mmol / liter.

These approaches provide magnetic particles with particle sizes between 0.4 and 8 µm.

For the production of the magnetic particles after the solvent evaporation process, which is a special method within the precipitation technology represents, one usually starts from a two-phase system, the from a water-immiscible organic polymer phase and an aqueous dispersant. The lipophilic polymer phase, in which the Magnetic colloid is dispersed under defined stirring conditions in the aqueous phase suspended.

Through contact with the aqueous phase does that fall Polymers with evaporation of the solvent in Form of isolated particles. Experience has shown that with the help of the stirring speed as well as by adding surfactants Substances for both the organic and the dispersion phase the particle sizes in the range can be varied from 1-250 µm.

Alternatively, the organic polymer phase also with the help of a spray device enter into the hydrophilic phase. Spray systems and processes of these Are state of the art (see Iwata and McGinity, J. Microencapsulation, 9, 201-214, 1992; Thoma and Schlütermann, Pharmacy, 47, 115-119, 1991).

Polymers that are suitable for such Suitable manufacturing processes are basically those polymers that in organic solvents, but not in an aqueous environment soluble are. Examples of this are: polystyrene, poly (lactide coglycolide), polymethacrylate, polyamides, Polyester, polyvinyl ether, Polyvinyl acetals, polyvinyl ketones, polyvinyl halides, polyvinyl esters or polycarbonates. Suitable solvents for this Polymers are e.g. E.g .: dimethylformamide, dimethyl sulfoxide, trifluoroacetic acid, trifluoroethanol, Phosphorsäu-retrisdimethylamid, Dioxane, tetrahydrofuran, esters, pyridine, halogenated hydrocarbons as well as aromatic, halogenated and non-halogenated compounds.

The volume ratios of the aqueous phase to the organic polymer phase, which is usually 1-10 wt .-% polymer contains is in about 10-30: 1.

The reverse procedure, a in an aqueous medium soluble Polymer by dispersing in a lipophilic phase (preferably oils or chlorinated hydrocarbons) and subsequent addition of an organic, water-miscible non-solvent (e.g. acetone, methanol, ethanol) failing leads in analogy for the above-mentioned procedure also for defined colloid encapsulations.

Suitable polymer systems in question come, 1-10% aqueous solutions are for example polyvinyl alcohol, polyacrylic acid, polysaccharides, polysaccharide derivatives, Polyhydroxyäthylmethacrylat or proteins.

The coupling of the microbicidal component a) to the optionally polymer-coated magnetic colloids according to known methods depending on the skilled person from the desired coupling partners chosen and can be varied.

For a covalent connection of active ingredients to metal oxide particles preferably silanes with one to three reactive end groups and at least one usually about used a hydrocarbon spacer further functionality.

Examples include: aminopropyltrimethoxysilane, acetoxypropyltrimethoxysilane, N, N, N-trimethylaminopropyltrimethoxysilane, N- (3-acryloxy-2-hydroxypropyl) -3-aminopropyltriethoxysilane, (3-acryloxypropyl) dimethylmethoxysoxypropyl, (3-acryloxiloxane), (3-acryloxiloxane) (3-acryloxypropyl) trimethoxy silane, 3- (N-allylamino) propyltrimethoxysilane, 4- (m-aminophenoxy) propyltrimethoxysilane, aminophenyltrimethoxysilane, aminoalkyltrimethoxysilane, haloalkyltrimethoxysilane, glycidoxypropyltrimethoxysilane, 3-isocyanlopropysiloxysilane, 3-isocyanatopropyloxiloxysilane, 3-isocyanato

The fine precipitated in alkaline magnetic particles are in aqueous or in aqueous / organic Media such as Water / ethanol, water / ethylene glycol, water / glycerin or water / THF with a silane or a mixture of different Coated with silanes. The particle surface functionalized in this way becomes for the immobilization of active substances or of those bound to spacers Active ingredients used. The covalent bond between the active ingredient and particles that prevent the active ingredient from bleeding out by reaction of functional groups on the particle surface the active ingredient guaranteed. All known organic reactions are available a covalent and hydrolysis resistant Form a bond. Substitution, addition, Oxidation, reduction, rearrangement and condensation reactions as well as radical implementations. Exemplary of a covalent Attachment of a phenol to a magnetic particle surface therefor the reaction of with 3-chloropropyltrimethoxysilane coated magnetite particles, which reacted with 4-aminophenol become.

Polymerization reactions can also be used be carried out with appropriately functionalized particles, being the surface of the magnetic particle is the starting point of the polymerization forms to drug sites or multiple reactive polymer attachment sites to tie.

One can advantageously in one first step the surfaces functionalize magnetic particles so that they are used for covalent attachment of microbicidal components a) or of spacers with at least two functional groups, both with the particle surface as can also react covalently with microbicidal components and so produce a magnetic component b) and then in one second step a microbicidal component a) covalently to the magnetic Bind component b). For the functionalization of magnetic surfaces Compounds suitable for particles are selected, for example, from Polymers, polyethylene glycol, polypropylene glycol, polyvinyl alcohol, Copolymers of maleic anhydride, Polyamines, polyacrylates and their copolymers, polystyrene and their copolymers, fatty alcohols and unsaturated fatty acids.

It is particularly advantageous here the coupling of a large number of active ingredients in succession, the leads to potentiation of drug efficiency. Are particularly preferred living polymerizations on the particle surface, which is a realization of defined polymer lengths and also enable block copolymers. A shortcut of hydrophilic and hydrophobic chain blocks is possible that Avoid direct adhesion of the hydrophobic blocks to the particle surface.

Multi-stage reactions are also possible, which first involves coupling a spacer, functional polymer and / or enable multiple binding partners, with a subsequent one Linking / activation of drug molecules to the same.

For the immobilization of microbicides Components a) on polymeric supports come as coupling media to the above-mentioned such agents in question, which are in the preparation of affinity resins proven have such. B. cyanogen bromide, carbodiimides, hexamethylene diisocyanate, Tosyl chloride, tresyl chloride, 2-fluoro-1-methyl-pyridinium-toluene-4-sulfonate, Epichlohydrin, N-hydroxysuccinimide, Chlorocarbonate, isonitrile, hydrazide, glutaraldehyde, 1,1'-carbonyldiimidazole, 1,4-butanediol di-glycidyl ether.

The couplings of the are also suitable Microbicides about so-called spacer molecules, hetero-bifunctional, reactive compounds that work with both functional groups of the matrix (carboxyl, hydroxyl, sulfhydryl, Amino groups) as well as a chemical bond with the microbicide can enter into. Examples therefor are: succinimidyl-4- (N-maleümidomethyl) cyclohexane-1-carboxylate, 4-succinimidyloxycarbonyl-α- (2-pyridyldithio) toluene, Succinimidyl 4- (p-maleimidophenyl) butyrate, N-γ-Maleimidobutyryloxysuccinimidester, 3- (2-pyridyldithio) propionyl hydrazide, sulfosuccinimidyl 2- (p-azidosalicylamido) ethyl 1,3'dithiopropionate (cf. Ullmann's encyclopedia der Technische Chemie, 4th ed., vol. 10, and G.T. Hermanson, "Bioconjugate Techniques", Academic Press, San Diego, 1996). Such spacer molecules in particular enable couplings of proteins on particle surfaces.

If desired, the magnetic according to the invention Microbicides in addition free, d. H. microbicides not coupled to magnetic components Compounds are added, the z. B. as a preservative should remain in an end product. Due to the fact that the magnetic biocide in very high doses or with very effective (toxic) microbicidal agents Components a) can be used, since it is essentially Completely can be regained, the need in practice Free microbicide to be added only rarely, or the concentrations free microbicide to be added because of the thorough Disinfection of the product should be very low.

The magnetic microbicides according to the invention are suitable for inhibiting microbial growth wherever this occurs Growth undesirable is, e.g. B. in aqueous Systems in a number of industrial applications, such as papermaking.

A number of important industries are affected by the activity of these bacteria, algae and fungi on the raw materials used, on various aspects of their manufacturing activities, or on those produced End products severely affected. These industries include the paint, wood, textile, cosmetic, leather, tobacco, fur, rope, paper, pulp, plastic, fuel, oil, rubber and machine industries.

For important applications of the magnetic according to the invention Microbicides include: Inhibiting the growth of bacteria and fungi in aqueous Paints, adhesives, latex emulsions and potting compounds; Wood preservatives; Bohrölkonservierung; fight slime-producing bacteria and fungi in pulp and paper mills and Cooling water; as spray or diving treatment for Textiles and leather for preventing mold growth; as Component in anti-decay colors to prevent the attachment of putrefactive organisms; Protection of Paint films, especially exterior paints, before the attack by fungi, which occurs during the weathering of the paint film occurs; Protection of processing equipment from slime deposits in the production of cane and beet sugar; Prevention of Enrichment and deposition of microorganisms in exhaust air scrubber systems and in industrial fresh water supply systems; Fighting the Contamination with and deposition of microorganisms in oil drilling fluids and sludges as well as in secondary oil treatment processes; Inhibition of bacterial and fungal growth in paper coating processes, that's the quality affect the paper coating could; fight of bacterial and fungal growth and deposits during production various special cardboards, e.g. B. Solid cardboard and chipboard; prevention cell stain discoloration of freshly cut wood of various types; Combat Bacteria and fungal growth in clay and pigment sludges differ Kind for later Use, for example, in paper coating and paint manufacturing be produced and dismantled during storage and transport subject to microorganisms; as a disinfectant for hard surfaces to prevent the growth of bacteria and fungi on walls, floors, etc. as well as in swimming pools to prevent algae growth.

The fight against Bacteria and fungi in water systems from pulp and paper mills aqueous Dispersions of fibers for paper manufacture included. The uncontrolled Enrichment of mucus through the accumulation of bacteria and fungi leads to low quality production, reduced production due to of breaks and higher Cleaning frequency, increased consumption of raw materials and higher maintenance costs. The problem of slime deposits is in the paper industry through the widespread use of closed white water systems worse.

Another important area in the fight of bacterial and fungal growth is crucial, the clay and pigment slurries. These muds consist of different shades, e.g. B. kaolin, and pigments, e.g. B. calcium carbonate and titanium dioxide. They are usually on manufactured in a location different from that of the final use, e.g. B. in paper coating and paint manufacturing is removed and then for later Transport stored to the final place of consumption. The high quality standards for the paper and paint end products, in which the mud is used require that the clay or Pigment sludge has a very small amount of microorganisms, so that it can be used for paper coating or paint production can be.

Another important area for fight microbial growth are cooling systems like those with circulation cooling towers. This Systems put a big one Amount of water considerable long of the atmosphere out under conditions that do not have adequate ventilation and do not involve sufficient exposure to sunlight, that microbial growth, especially bacterial and fungal growth would be fought. Lots Put cooling towers also a filling from beads made of synthetic polymer or other materials to the To enlarge heat exchange surface. This Construction exacerbates the problem of microbial growth as it the ideal physical environment for the growth of troublesome microbes provides. blank Fight these microorganisms thrive and create colonies sufficient for that the heat exchange surfaces with blocked a biofilm and the components of the water transport device, to operate the cooling system used to be clogged. The magnetic according to the invention Microbicides are an excellent way to combat microbial growth ready in these systems.

The magnetic microbicides according to the invention are particularly suitable for combating the harmful Effects of microorganisms in water or aqueous media. Systems that circulating water or circulating aqueous media infected with microorganisms and significant in their effectiveness impaired when microorganism deposits accumulate in the system. The deposits called slime cover the walls of containers and other vessels, any used Machinery and processing equipment and create blockages in pipes and valves. The slime formation promotes the corrosion of metal surfaces and eases the rotting of wooden towers. Generate the slimes also discoloration and other shortcomings in all manufactured products and enforce costly business interruptions. The fight of microorganisms in aqueous Media is especially important when dispersed in these particles or fines, e.g. B. dispersed cellulose fibers and dispersed fillers and pigments in papermaking, and dispersed pigments in paint manufacturing.

The microbicides according to the invention can be used in pure form or as microbicidal constituents of Ge Mixing are used, for example as components of sterilization, disinfection, impregnation or preservatives.

Included in the majority of cases the for the practical application of certain mixtures was still 0 to about 99, preferably 90 to 10% by weight of other commonly used constituents, depending on the intended form of application and the application selected become. For liquid Preparations, for example, come as water-miscible solvents organic solvents into consideration, for example ethanol, isopropanol and ethylene glycol, Propylene glycol, ethyl ethylene glycol, propyl propylene glycol 20 as well water-immiscible solvents such as white spirit, benzene, toluene, ethyl acetate or dimethylene chloride.

If in addition to the antimicrobial effect an additional Cleaning effect desired is, can mixtures according to the invention also contain surfactants, especially nonionic surfactants. examples for Suitable surfactants are C8-C18 alkyl glucosides with about 1 to 10 glucose units in the molecule, Addition products of 4 to 40, preferably 4 to 20, moles of ethylene oxide to one mole of fatty alcohol, alkylcyclohexanol, alkylphenol, fatty acid, fatty acid amide or alkanesulfonamide. Addition products are of particular interest from 5 to 16 moles of ethylene oxide on coconut oil or tallow fatty alcohols Oleyl alcohol, a mixture of oleyl alcohol and cetyl alcohol as well on mono-, di- or trialkylphenols and on monoalkylcyclohexanols with 6 to 14 carbon atoms in the alkyl radicals. Even mixed ones Addition products of ethylene oxide and propylene oxide to the above Compounds with an active hydrogen atom are suitable. The alkoxylation products mentioned can also be end-capped be, for example, by ether or acetal groups.

In the mixtures according to the invention can also builder substances to be available; alkali salts, for example, are suitable as such gluconic acid, in particular sodium gluconate, the alkali salts of nitrilotriacetic acid, ethylenediaminetetraacetic acid, hydroxyethane diphosphonic acid, phosphonobutane tricarboxylic acid, lactic acid, citric acid or Tartaric acid. Furthermore come as framework substances the water soluble Salts of higher molecular weight polycarboxylic into consideration, such as polymers of maleic acid, itaconic acid, fumaric acid and Citraconic. Also copolymers of these acids with each other or with other polymerizable monomers, such as B. ethylene, propylene, acrylic acid, Vinyl acetate, isobutylene, acrylamide and styrene can be used. In the mixtures according to the invention can also cleaning boosters like fatty acid mono- and diethanolamides, for example coconut fatty acid monoethanolamide and coconut fatty acid diethanolamide, and addition products of up to 4 moles of ethylene oxide or propylene oxide of fatty alcohols with 8 to 12 carbon atoms and free fatty alcohols with 8 to 12 carbon atoms and cleaning boosters Cellulose base can be incorporated.

It can also be used for more Areas of application may be advantageous if the mixtures according to the invention additionally contain other antimicrobial substances. In the mixtures according to the invention can also insecticides such as B. pyrethroids (permethrin, cypermethrin, Decamethrin and fenvalerate) and / or lindane, endosulfan, dieldrin be incorporated.

The quantities of the possible to assemble of the agents according to the invention used components generally depend on commercial and pricing and are in principle not inventive.

For the manufacture of ready-to-use preservatives can also liquid Concentrates also solid products, preferably in powder or granule form are provided which are the antimicrobial active according to the invention Mixtures included.

Leave the magnetic microbicides through the simple application of a magnetic field, even in a fixed one Separate the phase from the antimicrobial mixtures.

The antimicrobial active according to the invention Mixtures can as a disinfectant and preservative in many areas are used, for example in households and in trade such as B. hospitals, Schools, baths, public Transportation, commercial operations and industrial facilities.

The mixtures according to the invention can also in the preservation of technical products still to be processed such as glazes, emulsion and emulsion paints, adhesives and pastes, Drilling and cutting oils or products from the paper, cardboard or leather processing industry as well as for the conservation of industrial and industrial water application Find.

The application can be done by spraying, brushing, Brushing, knife coating, dipping or pressure or vacuum impregnation respectively.

The following examples explain the Invention without, however, restricting it to:

example 1

The permanent immobilization of biocides on magnetic particles could be achieved through covalent attachment. Different coupling reagents were used for this, firstly ensure firm adhesion to iron oxide hydroxide surfaces and secondly have a functional group ("anchor") that enables a covalent and hydrolysis-stable connection of the biocide to the particle surface. Aminomethoxysilanes were used to implement the concept. After surface coating of freshly precipitated magnetite particles, the free primary amino group is coupled to the biocide (4-hydroxybenzaldehyde via the aldehyde group), so that a biocidal phenolic group has been immobilized.

To stabilize the bound In biocides, the imino groups formed became a secondary amine reduced. The covalent bond will detach and thus an occurrence of unbound biocides in the supernatant largely prevented.

The antimicrobial effectiveness of Powder produced was by series of inhibitions based on the DGHM method (changed) examined. (J. Gebel, H.-P. Werner, A. Kirsch-Altena, K. Bansemir: Standard methods of the DGHM for testing chemical disinfection process, as of September 1, 2001, mhp Verlag GmbH, Wiesbaden (ISBN 3-88681-042-9): Determination of the bacteriostatic and fungistatic effect as well as suitable neutralizing agents)

1) Preparation of an aminosilane-modified ferrofluid

Iron (III) chloride is in 240 ml deionized water dissolved. Iron (II) chloride is deionized in a separate beaker in 80 ml Water and 4 ml conc. hydrochloric acid solved. The combined iron salt solutions will with vigorous stirring carefully placed in 750 ml of 25% ammonia.

The rainfall is (no longer than 30 min) sedimented on a magnet and the ammoniacal solution decanted. The precipitate is washed three times with deionized water washed, the wash water being decanted off again. After that you take up the iron oxide particles in 450 ml of deionized water, and adjust the suspension to about pH 4 with 2 M hydrochloric acid, stir for 15 min, decanted, washes twice with deionized water, decanted again, adds 900 ml of deionized water add and stir strongly by.

II) Modification with aminosilane

Concentrated to the suspension. Add ammonia until an alkaline environment (approx. PH = 9) is established. The dispersion is stirred vigorously with 1800 ml of ethanol and added to the silane under reflux for 4 hours touched and over Stirred at RT overnight.

The dispersion is left (no longer than 30 min) over sit with a magnet and decant the clear overhang solution from. The particles are then washed three times with water and washed once with ethanol (do not sediment for more than 30 min to let).

A small sample of the magnetite paste is in a vacuum at 60 ° C dried and their C, H, N content determined. The rest of the paste is processed wet.

II) Implementation of aminosilane-modified Magnetite particles with 4-hydroxy-benzaldehyde

In an apparatus consisting of a 2 l flask with water separator, reflux condenser and KPG stirring the moist modified magnetite paste and 1000 ml of toluene. Under stir the suspension is carefully heated first to 80 ° C and further up to 112 ° C. First the alcohol distills off, so the first 100ml directly can be distilled off until the temperature over 100 ° C increased is. After the alcohol has been separated off, 4-hydroxybenzaldehyde and p-toluenesulfonic acid are added, top up toluene if necessary. Then boil on the water separator for so long (strong mixing required) until no more water separates (at least 4 h). The reaction solution is decanted and the particles intensely 6 times with 300 ml of ethanol washed.

III) Reduction of the imino bond

The hydroxybenzimino magnetite is dispersed in a 500 ml round bottom flask in 150 ml ethanol using a KPG stirrer. With stirring the dispersion is cooled to 0 ° C. in an ice bath. Then sodium borohydride is added. After 1 hour the ice bath is removed and stirring is continued overnight. After that becomes the surplus of sodium borohydride destroyed with 0.5M hydrochloric acid. After 15 min the dispersion sedimented and decanted.

The precipitation becomes intense five times washed with 200 ml of 0.01 M sodium hydroxide solution and then with Washed water neutral. Then you fill the wet precipitate to 200ml with water, stir for 1 h, sediment, takes a water sample that tests for 4-hydroxybenzaldehyde is (VTA) and dries the precipitate at 50 ° C in a vacuum.

IV) Testing the antimicrobial activity

The antimicrobial effectiveness of Powder produced was by series of inhibitions based on the DGHM method (see Appendix 3) examined. In the inhibition series test, the bacteriostatic effectiveness of a test substance against defined Test germs examined. The ones to be checked Active ingredients or formulated products are in certain concentrations prepared together with test specimens in nutrient solutions and that active ingredient concentration determined that the germ growth still suppressed.

Staphylococcus was used as the test germ aureus (ATCC 6538) uses [ATCC: American Type Culture Collection]. The bacterial test germ to be used was selected according to its specific growth requirements defined culture conditions, i.e. in the present Case, Caso medium was used. The germs were cultivated at 37 ° C. for 24 hours, then transferred to fresh medium and cultivated again 24 h. 5 ml of medium were placed in sterile flasks submitted. and mixed well with the coupled active ingredient so that, as far as not stated otherwise, contain 0.5% coupled active ingredient per formulation was. Subsequently the pH of the batch was checked and with 1 M sterile HCl adjusted to that of the culture medium used. To Add 50 μl Germ suspension per batch, the test batches were then under the for incubated the test germs suitable culture conditions: o.g. Bacteria for 24 h 37 ° C.

Since the approaches of a through the ferrofluids severe cloudiness could not be read directly according to DGHM regulation. Therefore, the magnetic particles were incubated after 24 h 30 or 37 ° C separated from the medium with a strong magnet and the bacterial count of the supernatant determined by plating.

Results:

1) Testing the antimicrobial activity

Testsubstanz: Kontrolle (Magnetit-Partikel mit „Anker" ohne die gekoppelte biozide Gruppe);
LAO-BG-7846-059

Tab 1: Hemmreihe in Anlehnung an DGHM-Methode; Testsubstanz: Aminosilan-Magnetit mit 4-Hydroxybenzaldehyd; LAO-BG-7846-066 und Kontrolle (Magnetit-Partikel mit „Anker" ohne die gekoppelte biozide Gruppe; LAO-BG-7846-059)

Abb. 1: Hemmreihe in Anlehnung an DGHM-Methode; Testsubstanz: Aminosilan-Magnetit mit 4-Hydroxybenzaldehyd; LAO-BG-7846-066 und Kontrolle (Magnetit-Partikel mit Aminosilan-„Anker" ohne die gekoppelte biozide Gruppe; LAO-BG-7846-059) An antimicrobial activity of the surface-fixed biocide (aminosilane magnetite with 4-hydroxybenzaldehyde; LAO-BG-7846-066) was shown against the bacterial test germ Staphylococcus aureus (Tab. 1 / 1 ). With this coupled biocide it was also possible to show a concentration-dependent activity against the test germ. The magnetite particle with aminosilane “anchor” without the coupled biocidal group served as a control.
Method: series of inhibitions based on the DGHM method
Test germ: Staphylococcus aureus
Test time: 24 h
Test substance: aminosilane magnetite with 4-hydroxybenzaldehyde; LAO-BG-7846-066

Test substance: control (magnetite particles with "anchor" without the coupled biocidal group);
LAO-BG-7846-059

Tab. 1: Inhibition series based on the DGHM method; Test substance: aminosilane magnetite with 4-hydroxybenzaldehyde; LAO-BG-7846-066 and control (magnetite particles with "anchor" without the coupled biocidal group; LAO-BG-7846-059)

Fig. 1: Inhibitor series based on the DGHM method; Test substance: aminosilane magnetite with 4-hydroxybenzaldehyde; LAO-BG-7846-066 and control (magnetite particles with aminosilane "anchor" without the coupled biocidal group; LAO-BG-7846-059)

II) Evidence of microbiological activity of the surface-fixed biocide

Through further work it was shown that the surface fixed described Biocide (aminosilane magnetite with 4-hydroxybenzaldehyde; LAO-BG-7846-066) for the below Point 1 described microbiological activity is responsible and not free, uncoupled biocide in the supernatant.

Tab. 2: Hemmreihe in Anlehnung an DGHM-Methode; Testsubstanz: Aminosilan-Magnetit mit 4-Hydroxybenzaldehyd; LAO-BG-7846-066; Bestimmung freien Biozids mittels HPLC For this purpose, the active ingredient, as described, was used against the test germ Staphylococcus aureus in an inhibitory series test based on the DGHM method and the inhibition of growth (in log steps) was determined. In order to rule out that free, uncoupled biocide is responsible for the microbiological activity, before and after the inhibitor series test (values "0" and "24" in Tab. 2), phenolic biocide possibly freely present in the supernatant was determined analytically by HPLC (see Tab. 2).

Tab. 2: Inhibitor series based on the DGHM method; Test substance: aminosilane magnetite with 4-hydroxybenzaldehyde; LAO-BG-7846-066; Determination of free biocides using HPLC

The experiment shown in Tab. 2 shows that only very small amounts of free phenol (180 ppm) existed before attempting. After 24 h as the inhibitory factor of As growth was determined, phenol (<10 ppm) was no longer analytical using HPLC detectable. These concentrations are both more than a factor 10 below the minimum inhibitory concentration of (free) Phenol against Staphylococcus aureus (≥ 2000 ppm with an exposure time from 24 h; see Wallhäusers).

Tab. 3: V1: Hemmreihe in Anlehnung an DGHM-Methode; Testsubstanz: Aminosilan-Magnetit mit 4-Hydroxybenzaldehyd; LAO-BG-7846-066 und Kontrolle (Magnetit-Partikel mit Aminosilan-„Anker" ohne die gekoppelte biozide Gruppe; LAO-BG-7846-059); V2: Wiederholung mit Keim- und Partikel-freien Überständen aus V1 In order to rule out that a small residual amount of free phenol is responsible for the activity of the surface-fixed biocide (aminosilane magnetite with 4-hydroxybenzaldehyde; LAO-BG-7846-066) against the test germ Staphylococcus aureus, another inhibition test with the coupled biocide was carried out carried out. After 24 h the coupled biocide was separated from the supernatant by a magnet and test germs remaining in the supernatant by centrifugation and pasteurization (30th min, 60 ° C) removed or killed. This germ-free supernatant from experiment 1 (V1) was inoculated again with the test germ and a second inhibition test (V2) was carried out (see Table 3).

Tab. 3: V1: series of inhibitions based on the DGHM method; Test substance: aminosilane magnetite with 4-hydroxybenzaldehyde; LAO-BG-7846-066 and control (magnetite particles with aminosilane "anchor" without the coupled biocidal group; LAO-BG-7846-059); V2: Repetition with germ-free and particle-free supernatants from V1

The shown in Tab. 2 and 3 Experiments demonstrate that the microbiological described here Effectiveness clearly on the surface fixed described Biocide (aminosilane magnetite with 4-hydroxybenzaldehyde; LAO-BG-7846-066).

III) Evidence of the "recyclability" of the active ingredient by testing the antimicrobial activity

In further work it was shown that the surface fixed described Biocide (aminosilane magnetite with 4-hydroxybenzaldehyde; LAO-BG-7846-066) is "recyclable".

V2: Testsubstanz: Aminosilan-Magnetit mit 4-Hydroxybenzaldehyd; LAO-BG-7846-066 aus V1
(Keimzahl Staphylococcus aureus Kontrolle ohne Wirkstoff: 1 × 10⁹ KBE/ml)

Tab. 4: V1: Hemmreihe in Anlehnung an DGHM-Methode; Testsubstanz: Aminosilan-Magnetit mit 4-Hydroxybenzaldehyd; LAO-BG-7846-066 V2: Wiederholung des Hemmreihenversuchs mit zurückgewonnenen Partikeln aus V1 KBE = Kolonie-bildende EinheitenFor this purpose, the active ingredient, as described, was used against the test germ Staphylococcus aureus in an inhibitory series test based on the DGHM method (V1). The magnetic active ingredient was recovered by separation using a permanent magnet, washed (cf. implementation point III) and used again in an inhibitor series test based on the DGHM method (V2).
Method: series of inhibitions based on the DGHM method
Test germ: Staphylococcus aureus
Test time: 24 hours each
V1: test substance: aminosilane magnetite with 4-hydroxybenzaldehyde; LAO-BG-7846-066
(Number of bacteria Staphylococcus aureus control without active ingredient: 1 × 10 ⁹ CFU / ml)

V2: Test substance: aminosilane magnetite with 4-hydroxybenzaldehyde; LAO-BG-7846-066 from V1
(Number of bacteria Staphylococcus aureus control without active ingredient: 1 × 10 ⁹ CFU / ml)

Tab. 4: V1: series of inhibitions based on the DGHM method; Test substance: aminosilane magnetite with 4-hydroxybenzaldehyde; LAO-BG-7846-066 V2: Repetition of the inhibition series test with recovered particles from V1 KBE = colony-forming units

Example 2

Separation magnetic Particles using magnetic filters (on a laboratory scale)

A magnetic filter is a 30 cm long glass tube with a diameter of 1.5 cm, which is filled with a magnetizable material that is permeable to liquid substances. in the 8 g steel wool (PerfectA; steel wool for industry, handicraft, household; no .: 2, medium) is used in particular. The steel wool is introduced into the glass tube to a length of 25 cm and then magnetized by applying a magnetic field with a permanent magnet (neodymium iron boron, from IBS Magnet, Berlin, model NeoDelta magnet ND 7550).

With such a filter, magnetic Particles with a magnetic core larger than 20 nm are separated. The filter is ideal for magnetic particles with a size of 20-10,000 nm. Particles larger than 10 microns can alone held because of their size so that the advantage of magnetic separation alone eliminated.

The separation looks experimental as follows that a suspension is placed on the magnetic filter and the liquid independent or with the help of negative or positive pressure from the magnetic Filter promoted becomes. The particles separated in the filter can be removed after removing the permanent magnet rinsed from the steel wool become. Particles larger than 10 microns heavier to not washed down by the steel wool, so that further fractionation of the particles take place with this method can.

For the separation of magnetic particles become larger than 10 μm Magnetic filters used on the use of steel wool dispense. Here the magnetic particles are directly on enriched with a permanent magnet and then the Particles mechanically removed from the magnet. Experimentally looks the procedure so that permanent magnets (filter rods) in one flowing Suspension or by means of permanent magnets (filter plates), which is a big one have magnetic range on the vessel wall of a flowing suspension separate the particles.

Claims (13)

A magnetic microbicide comprising a) at least a microbicidal component and b) at least one magnetic Component, component a) and component b) being covalent to one another connected are. Magnetic microbicide according to claim 1, wherein the Component a) selected is among phenols, including their halogen derivatives, heterocyclic compounds, such as. B. Isothiazolinones, benzothiazoles, imidazoles, benzimidazoles and Derivatives of these compounds, guanidine, phthalimide, urea derivatives, Iodopropynyloxyethanol carbamate compounds, aminopyridinium compounds, quaternary Ammonium compounds, biocidal polymers and cyclodextrin inclusion complexes biocidal halopropargyl compounds. Magnetic microbicide according to one of claims 1 or 2, component a) being selected from phenols. Magnetic microbicide according to one of claims 1 to 3, wherein component a) is 4-hydroxybenzaldehyde. Magnetic microbicide according to one of claims 1 to 4, component b) being selected from particles magnetic materials, in particular. Magnetite, maghemite and iron as well as under polymer particles with included magnetic particles, especially under cross-linked magnetic polystyrene beads, polyacrylamide beads, Polyacrylate beads, polyvinyl alcohol beads or PMMA beads. Process for making one in the previous claims described magnetic microbicide, characterized in that at least a microbicidal component a) and at least one magnetic component b) covalently linked. A method according to claim 6, characterized in that he for the covalent linkage from components a) to components b), in particular to metal oxide particles, Silanes used, preferably silanes with one, two or three reactive End groups and at least one usually via a hydrocarbon spacer bound further functionality. Process according to Claim 6 or 7, characterized in that silanes are used which are selected from aminopropyltrimethoxysilane, acetoxypropyltrimethoxysilane, N, N, N-trimethylaminopropyltrimethoxysilane, N- (3-acryloxy-2-hydroxypropyl) -3-aminopropyltriethoxysilane, ( 3-acryloxypropyl) dimethylmethoxysilane, (3-acryloxypropyl) methyldichlorosilane, (3-acryloxypropyl) trimethoxysilane, 3- (N-allylamino) propyltrimethoxysilane, 4- (m-aminophenoxy) propyltrimethoxysilane, aminophenyltrimethilanoxysimethoxysilane Haloalkyltrimethoxysilane, glycidoxypropyltrimethoxysilane, 3-isocyanatopropyldimethylchlorosilane, 3-isocyanatopropyltriethoxysilane and hydroxymethyltriethoxysilane. A method according to claim 6, characterized in that he in a first step the surfaces of magnetic particles so functional that it for the covalent attachment of microbicidal components a) or of Spacers with at least two functional groups, both with the particle surface as can also react covalently with microbicidal components and so creates a magnetic component b) and one in a second Step a microbicidal component a) covalently to the magnetic Component b) binds. A method according to claim 9, characterized in that he the functionalization of the surfaces of magnetic particles with the aid of compounds selected from polymers, polyethylene glycol, Polypropylene glycol, polyvinyl alcohol, copolymers of maleic anhydride, Polyamines, polyacrylates and their copolymers, polystyrene and their copolymers, fatty alcohols and unsaturated fatty acids. Microbicidal agents, especially sterilization, Disinfectant, impregnation or preservative, containing magnetic microbicides as in claims 1 to 5 defined. Use of magnetic microbicides, as in the claims Defined 1 to 5, for killing or destruction of bacteria, fungi or algae and / or to inhibit or combat the Growth or multiplication of bacteria, fungi or algae and the inactivation of viruses in the field of paint, wood, textile, Cosmetics, leather, tobacco, fur, rope, paper, pulp, plastic, Fuel, oil, Rubber and machine industry, in detergents and cleaning agents as well as for the disinfection of cooling and cooling lubricants. Use of magnetic microbicides according to claim 12 in CIP systems.