WO2006117113A2 - Halomethylene alkanones and furanones for use as biofilm blocking substances - Google Patents

Abstract

The invention relates to the use of halomethylene alkanones and furanones as biofilm blocking substances in the industrial sector and in institutions. The invention also relates to methods for controlling processes based on microbial interaction using said biofilm blocking substances and to agents containing said biofilm blocking substances.

Description

 Halomethylene alkanones and furanones as biofilm blockers

The present invention relates to the use of halomethylene alkanones and furanones as biofilm blockers, and to methods of controlling processes based on microbial interaction using these biofilm blockers and agents containing these biofilm blockers in the industrial or institutional field.

Microorganisms communicate with each other via a variety of different signals. In particular, the communication and interaction mechanisms in bacteria are described in detail in the prior art.

In the documents WO 00/56154; EP 0881297; US 6287836; EP 0909820 and US Pat. No. 600,160 describe specific histidine kinases or proteins which are homologous thereto for the purpose of screening for antibacterial substances. The kinases are derived exclusively from gram-positive organisms.

In WO 01/49708, a peptide having at least 6 but less than 200 amino acids is used to block a response regulator. However, it does not block signaling molecules but activates the next proteins in the signal chain.

The development of mature biofilms in or with bacteria depends on the communication between bacterial cells via various extracellular signaling substances.

Depending on the cell number density of adherent bacteria, exceeding a minimum concentration of these messengers causes activation of biofilm formation as well as activation of further virulence genes. This phenomenon, called "quorum sensing," basically opens up the possibility of controlling biofilms without killing biofilm-borne germs.

To date, numerous signaling molecules have been identified in Gram-negative and Gram-positive bacteria [Miller, MB, Bassler, BL (2001) Quorum sensing in bactaha. Annu Rev Microbiol. 55, 165-199; Kleerebezem, M., Quadri, LE (2001) Peptides pheromone dependent regulation of antimicrobial peptide production in Gram-positive bacteria: a case of multicellular behavior. Peptides 22, 1579-1596].

The structure of these signaling molecules is well studied, especially in gram-negative organisms. The signal substances (pheromones) used by these organisms are often representatives of a group of different N-acyl-L-homoserine lactones (AHL), which are distinguished by the length of the N-acyl side group and by modifications of the C-3. Position (3-oxo or 3-hydroxy group) [Greenberg, EP (1997)] Quorum sensing in Gram-negative bacteria. ASM News 63, 371-377].

In gram-positive bacteria, the mechanisms are even less well known. Frequently, smaller peptides are described as signal molecules. [Kleerebezem, M., Quadri, L.E. (2001) Peptide pheromone-dependent regulation of antimicrobial peptide production in Gram-positive bacteria: a case of multicellular behavior. Peptides 22, 1579-1596].

However, the basic principle is similar. The respective signaling molecule is recognized and bound by specific, usually membrane-bound, cellular receptors (two-component systems).

In gram-negative bacteria, among others, function. specific histidine kinases as said receptors. These histidine kinases are components of so-called two-component systems. The second component is formed in each case by the so-called response regulator. When a signaling molecule binds to such a histidine kinase, it activates the response regulator. The activated response regulator then acts as an activator of various cellular processes [Chang C, Stewart, The two-component system. Regulation of various signaling pathways in prokaryotes and eukaryotes. Plant Physiol. 1998 Jul; 117 (3): 723-31.]

While there are a variety of such two-component systems with a wide variety of functions in all cells, biofilm formation by Gram-negative bacteria is mainly due to intracellular transcription activator proteins ("LuxR proteins") the LuxR-Classh on the one hand able to bind AHLs, on the other hand also to enter into interactions with control regions of DNA molecules. [Eberl L ₁ N-acyl homoserine lactone-mediated gene regulation in Gram-negative bacteria, Syst Appl Microbiol. 1999 Dec; 22 (4): 493-506 .; Michael B, Smith JN, Swift S, Heffron F, Ahmer BM. SdiA of Salmonella enterica is a LuxR homologous that detects mixed microbial communities. J Bacteriol. 2001 Oct; 183 (19): 5733-42; Gray KM, Garey JR., The Evolution of Bacterial Luxl and Lux Quorum Sensing Microbiology. 2001 Aug; 147 (Pt 8): 2379-87.].

It has recently become known that only the N-terminal part of the transcriptional activator protein (about 200 amino acids) is responsible for binding the AHL molecules. [Zhang RG, Pappas T, Brace JL, Miller PC, Oulmassov T, Molyneaux JM, Anderson JC, Bashkin JK, Winan's SC, A., Structure of a bacterial quorum-sensing transcription factor complexed with pheromone and DNA. Nature. 2002 Jun 27; 417 (6892): 971-4.].

Essentially, three different concepts for biofilm prevention or control are described in the prior art:

1. Cleavage of the messenger substances by enzymes, e.g. Lactonases.

Recently, several enzymes have been isolated from gram-positive bacilli that specifically cleave AHL molecules and thus can switch off these signaling pathways (quorum quenching) .These lactonases have been described several times [Dong YH, Wang LH, Xu JL, Zhang HB, Zhang XF, Zhang LH (2001) Quenching quorum-sensing-dependent bacterial infection by N-acyl homoserine lactonase, Nature 411, 813-817, WO 01/85664, WO 02/16623.

2. Blocking / binding of messengers themselves e.g. with antibodies.

Another way to prevent biofilms is the use of AHL-specific antibodies. After binding such an antibody to the messenger, it is no longer able to bind to its original receptor (= histidine kinase) [WO01 / 94543]. However, due to the high cost of antibody production, this method is at best practicable for medical purposes. 3. Blocking of the cellular receptors of messenger substances, for example by structurally analogous substances.

In particular, furanone and furanone derivatives are known as structurally analogous substances. [Manefield M, de Nys R ₁ Kumar N, Read R, Givskov M, Steinberg P, Kjelleberg., Evidence that halogenated furanones from Delisea pulchra inhibit acylated homoserine lactone (AHL) -mediated gene expression displacing the AHL signal from its receptor protein. Microbiology. 1999 Feb; 145 (Pt 2): 283-91; WO96 / 29392; WO01 / 68091; WO01 / 68090; WO01 / 76594].

Furanones are AHL analogues in their structure. They interrupt the signal transduction pathway by competitively displacing the AHL signaling substances and self-binding to the intracellular target molecule (intracellular transcriptional activator protein). The growth of the affected germs is not inhibited by the furanone exposure at low concentrations.

In addition to the use of furanones, the use of antibodies or antibody fragments is mentioned in individual cases. [Bryers, J.D., 2001, Gene therapy approach to biomaterials, abstracts of papers, 222nd ACS National Meeting]

Surprisingly, it has now been found that, on the one hand, halomethylene-alkanones of the general formula (I)

and on the other hand furanone of the general formula (II)

represent suitable biofilm blocker, which are even after incorporation into a marketable formulation to be able to effectively suppress biofilm formation.

The present invention therefore relates to the use of halomethylene alkanones of the general formula (I) and / or of furanones of the general formula (II) for controlling processes based on microbial interaction, in particular for controlling the formation and / or maturation of biofilms, particularly preferred biofilms in which Gram-negative bacteria are involved, in the industrial and / or institutional field, in particular in the field of industrial and / or institutional hygiene.

In the formulas (I) and (II), both the radicals R ₁ , R ₂ and R ₃ , which may be different or identical, and the radicals R a, R b, R _c and R d, which may also be different or identical, are independently selected from halogen, especially chlorine, bromine, fluorine or iodine, trifluoromethyl, hydrogen, alkyl, especially C _1-12 alkyl, cycloalkyl, in particular _C3 - ₈ cycloalkyl, alkenyl, in particular C ₂ - ₁₂ alkenyl, Alkynyl, in particular C _2-12 -alkynyl, heteroalkyl, alkoxy, in particular C _1-12 -alkoxy, alkylsulfanyl, in particular C _1-12 -alkylsulfanyl, alkylsulfonyl, in particular C _1-12 -alkylsulfonyl, alkylsulfoxidyl, in particular C _1-12 Alkylsulfoxidyl, alkanoyl, especially C _1-12 alkanoyl, acyl, alkoxycarbonyl, especially C _1-12 alkoxycarbonyl, alkylaminocarbonyl, especially C _1-12 - alkylaminocarbonyl, Alkylsulfanylcarbonyl, in particular C _1-12 -Alkylsulfanylcarbonyl, hydroxy, monoalkylamino, especially ( C _1-12 -A! Ky!) NH, di Alkylamäno, especially di- (C _1-12 alkyl) N, aryl, especially C _6-1 o-aryl, heteroaryl, heterocycloalkyl, arylalkyl, in particular

Arylsulfonyl, in particular Cβ- _T o-arylsulfonyl, arylsulfoxidyl, in particular C _6-1 o-arylsulfoxidyl, arylcarbonyl, in particular Cβ-io-arylcarbonyl, aryloxycarbonyl, in particular C _6-1 o-aryloxycarbonyl, arylaminocarbonyl, in particular C _6-1 o- Arylaminocarbonyl, formyl and cyano, especially in particular fluorine, chlorine, bromine or iodine, Ci-12-alkyl, Ci _-I2 -alkoxy, C _2- i preferably from hydrogen, halogen, ₂ alkenyl, C ₂ i ₂ alkynyl, C _6- i ₄ - Aryl and Cβ-u-aryl-C- _M -alkyl,

wherein the alkyl, cycloalkyl, alkenyl, alkynyl, heteroalkyl, heterocycloalkyl, alkoxy, alkylsulfanyl, alkylsulfonyl, Alkylsulfoxidyl, alkanoyl, alkoxycarbonyl, alkanoyloxy, alkylaminocarbonyl, Alkylsulfanylcarbonyl-, (Ci. ₁₂ Alkyl) NH, di- (Ci-i ₂ alkyl) N, aryl, C ₆ -io-aryl-Ci-4-alkyl and heteroaryl radicals each independently of one another optionally also one or more times, in particular mono-, di- or tri-substituted, in particular by substituents selected from halogen, in particular chlorine, bromine or fluorine, trifluoromethyl, C ₁₂ -alkyl, C _3-8 -cycloalkyl, C ₂ -12 alkenyl, C _{2 -} i ₂ alkynyl, heteroalkyl, heterocycloalkyl, Ci- ₁₂ alkoxy, C _1-12 alkylsulfanyl, Ci- ₁₂ alkylsulfonyl, Ci- ₁₂ -Alkylsulfoxidyl, Ci- ₁₂ alkanoyl, Ci- ₁₂ alkoxycarbonyl, Ci_i ₂ - alkanoyloxy,

Hydroxy, (C _{1 -C 12 -alkyl} ) NH, di- (C ₁ -C 12 -alkyl) N, C ₆ -10-aryl, heteroaryl,

C _6- io arylsulfonyl, C ₆ -io-Arylsulfoxidyl, C _6- io-arylcarbonyl, C _6- io-aryloxycarbonyl, or C _6- io- arylaminocarbonyl, preferably by _d-6 alkyl, Ci _-6 alkoxy, halogen or hydroxy, and wherein the total number of substituents in the molecule is preferably up to 5, more preferably up to three, in particular one, two or three,

and X is halogen, in particular fluorine, chlorine, bromine or iodine, preferably bromine.

In a preferred embodiment, Ri and R _{2 are} independently selected

in particular from methyl, ethyl, i-propyl and n-propyl, especially from methyl and ethyl, R ₃ is hydrogen and X is bromine. Particularly preferred here is Ri ethyl and R _{2 is} methyl.

In another preferred embodiment, Ra is a halogen, in particular bromine, Rb C _1-12 alkyl, especially C _4- i ₀ alkyl, especially Rc is hydrogen or Ci _-4-heptyl n - alkyl, preferably hydrogen, and Rd Halogen, in particular bromine, particularly preferred here are Ra and Rd bromine, Rb n-heptyl and Rc hydrogen. In another preferred embodiment, Ra is Ci-1 ₂ alkyl, in particular C-MOalkyl, especially n-heptyl, Rb is halogen, in particular bromine, Rc is hydrogen or Ci _-4 - alkyl, preferably hydrogen, and Rd is halogen, in particular Bromine, particularly preferably Rb and Rd are bromine, Ra n-heptyl and Rc is hydrogen.

The alkyl group is preferably (C ₁ -C ₈ ) -alkyl, more preferably (C 1 -C ₂ ) -alkyl, in particular (C ₁ -C ₆ ) -alkyl. The alkyl group may be straight-chain or branched. The alkyl group may in particular be selected from methyl, ethyl, propyl, isopropyl, 1-butyl, 2-butyl, isobutyl and tert-butyl. The alkyl group can also be mono- or polysubstituted, in particular by radicals ("substituents") selected from the group consisting of alkyl, cycloalkyl, alkenyl, alkynyl, halo, haloalkyl, haloalkenyl, haloalkynyl, hydroxy, alkoxy, alkenyloxy, haloalkoxy, haloalkenyloxy , Nitro, amino, nitroalkyl, nitroalkenyl, nitroalkynyl, nitroheterocyclyl, alkylamino, dialkylamino, alkenylamino, alkynylamino, acyl, alkenoyl, alkynyl, acylamino, diacylamino, acyloxy, alkylsulfonyloxy, heterocyclyl, heterocycloxy, heterocycloamino, haloheterocyclyl, alkylsulfenyl, alkylcarbonyloxy, alkylthio, acylthio , Phosphorus-containing groups such as phosphono and phosphinyl, wherein, if the substituent carries an alkyl group, this preferably comprises up to 18, more preferably up to 12, in particular up to 6 carbon atoms.

The alkoxy group is preferably (dC-iβJ-alkoxy, more preferably _(Ci-Ci2) -alkoxy, in particular (Ci-CβJ alkoxy. The alkyl group of the alkoxy group may be straight or branched. The alkyl group may in particular may be selected from methyl, ethyl, propyl, isopropyl, 1-butyl, 2-butyl, isobutyl and tert-butyl The alkyl group may also be monosubstituted or polysubstituted, in particular by the abovementioned substituents.

When the alkenyl group is preferably (C ₂ -C ₈₎ alkenyl, more preferably (C ₂ -C ₂₎ alkenyl, in particular by (C ₂ -C ₆₎ alkenyl. The alkenyl radical may be straight-chain or branched. The alkenyl radical may in particular be selected from vinyl, allyl, 1-methylvinyl, butenyl, isobutyl, 3-methyl-2-butenyl, 1-pentenyl, cyclopentenyl, 1-methylcyclopentyl, 1-hexenyl, 3-hexenyl, cyclohexenyl , 1-Heptenyl, 3-heptenyl, 1-octenyl, cyclooctenyl, 1-nonenyl, 2-nonenyl, 3-nonenyl, 1-decenyl, 3-decenyl, 1, 3-butadienyl, 1, 4-pentadienyl, 1, 3 Cyclopentadienyl, 1, 3 Hexadienyl, 1,4-hexadienyl, 1,3-cyclohexadienyl, 1,4-cyclohexadienyl, 1,3-cycloheptadienyl, 1,3,5-cycloheptatrienyl andr 1, 3,5,7-cyclooctatetraenyl. The alkenyl group may also be mono- or polysubstituted, in particular by the abovementioned substituents.

The halogen is preferably fluorine, chlorine, bromine or iodine, more preferably bromine or fluorine.

The heteroatom is preferably oxygen, nitrogen or sulfur.

The acyl group may be an aliphatic acyl group ("alkanoyl group") or an acyl group containing a heterocyclic ring ("heterocyclic acyl group"). Preferably, it is a (Ci-Cie) alkanoyl group, more preferably a (Ci-Ci ₂₎ alkanoyl group, in particular a (Ci-Cβ) - alkanoyl. The alkyl radical of the alkanoyl group may be straight-chain or branched. The acyl group may also be mono- or polysubstituted, in particular by the abovementioned substituents. The acyl group may in particular be selected from carbamoyl, formyl, acetyl, propanoyl, butanoyl, 2-methylpropanoyl, pentanoyl, 2,2-dimethylpropanoyl, hexanoyl, heptanoyl, octanoyl, nonanoyl, decanoyl, methoxycarbonyl, ethoxycarbonyl, t-butoxycarbonyl, t-pentyloxycarbonyl , heptyloxycarbonyl, cyclopropanecarbonyl, cyclobutanecarbonyl, cyclopentanecarbonyl, cyclohexanecarbonyl, methanesulfonyl, ethanesulfonyl, methoxysulfonyl, ethoxysulfonyl, Heterocycloalkancarbonyl, Heterocyclyoalkanoyl, particularly Pyrrolidinylacetyl, Pyrrolidinylpropanoyl, Pyrrolidinylbutanoyl, Pyrrolidinylpentanoyl, Pyrrolidinylhexanoyl or Thiazolidinylacetyl, Heterocyclylalkenoyl, particularly Heterocyclylpropenoyl, Heterocyclylbutenoyl, Heterocyclylpentenoyl or Heterocyclylhexenoyl and Heterocyclylglyoxyloyl, in particular thiazolidinylglyoxyloyl or pyrrolidinylglyoxyloyl.

C _3-8 cycloalkyl in the present invention each independently for all cyclic alkyl radicals having 3 to 8 carbon atoms, preferably with 5 to 6 C-atoms, in particular cyclopentyl and cyclohexyl. C ₂ - ₁₂ -alkynyl according to the invention each independently for all linear and unbranched alkyl radicals having up to 12 carbon atoms, containing at least one triple bond, wherein said C ₂ - ₆ alkynyl radicals are preferred. C ₂ - ₆ -alkynyl according to the invention represents all linear and unbranched alkyl radicals having up to 6 C atoms which contain at least one triple bond, in particular ethynyl, propynyl, i-propynyl and all isomers of butynyl, pentynyl and hexynyl.

Heteroalkyl according to the invention in each case independently of one another for all saturated and mono- or polyunsaturated, linear or branched alkyl radicals which contain at least one, preferably exactly one heteroatom, in particular O, S or N, where the sum of C and hetero atoms up to 12, preferably up to 6.

Heterocycloalkyl according to the invention is in each case independently of one another for all cyclic alkyl radicals which contain at least one, preferably exactly one, heteroatom, in particular O, S or N, where the ring is from three to eight membered, preferably five to six membered. Examples of these are tetrahydrofuranyl, tetrahydrothiophenyl, pyrrolidinyl, 2-thiazolinyl, tetrahydrothiazolyl,

Tetrahydrooxazolyl, piperidinyl, piperazinyl, morpholinyl and thiomorpholinyl.

Ci _-12 alkylsulphanyl is according to the invention are each independently, all saturated and unsaturated, linear and branched alkyl radicals having up to 12 carbon atoms, which are bonded via a sulfur atom, _{Ci-6-alkylsulfanyl} radicals are preferred. Ci-e-alkylsulfanyl according to the invention for all saturated and unsaturated, linear and branched alkyl radicals having up to 6 carbon atoms, which are bonded via a sulfur atom, in particular for methysulfanyl and ethylsulfanyl.

C _1-12 alkylsulfonyl stands according to the invention are each independently, all saturated and unsaturated, linear and branched alkyl radicals having up to 12 carbon atoms, which are bonded via an SO group, said _Ci-6 alkylsulfonyl radicals are preferred , d- alkylsulfonyl ₆ is according to the invention for all saturated and unsaturated, linear and branched alkyl radicals having up to 6 carbon atoms, which are bonded via an SO group, in particular for Methysulfonyl and ethylsulfonyl. C _1-12 -Alky Is u If oxidyl is according to the invention are each independently, all saturated and unsaturated, linear and branched alkyl radicals having up to 12 carbon atoms, which are bonded via a Sθ ₂ group, wherein Ci-β- Alkylsulfoxidyl radicals are preferred. C-ι- -Alkylsulfoxidyl ₆ is according to the invention for all saturated and unsaturated, linear and branched alkyl radicals having up to 6 carbon atoms which are bonded via an SO ₂ group, in particular for Methylsulfoxidyl and Ethylsulfoxidyl.

Ci- ₁₂ alkanoyl according to the invention are each independently, all saturated and unsaturated, linear and branched alkyl radicals having up to 12 carbon atoms, which are bonded via a carbonyl group, where _{Ci-6-alkanoyl} radicals are preferred. Ci ^ -Alkanoyl according to the invention for all saturated and unsaturated, linear and branched alkyl radicals having up to 6 carbon atoms, which are bonded via a carbonyl group, in particular for methycarbonyl and ethylcarbonyl.

Ci- ₁₂ -alkoxycarbonyl according to the invention are each independently, all saturated and unsaturated, linear and branched alkyl radicals having up to 12 carbon atoms, which are bonded via an oxycarbonyl group,

Residues are preferred. Ci. According to the invention, _6- alkoxycarbonyl stands for all saturated and unsaturated, linear and branched alkyl radicals having up to 6 C atoms which are bonded via an oxycarbonyl group, in particular for methoxycarbonyl and ethoxycarbonyl.

According to the invention, C ₁₂ -alkanoyloxy in each case independently of one another represents all saturated and unsaturated, linear and branched alkyl radicals having up to 12 C atoms which are bonded via a carbonyloxy group, preference being given to C 1-β-alkanoyloxy radicals. Ci _-6- alkanoyloxy is according to the invention for all saturated and unsaturated, linear and branched alkyl radicals having up to 6 carbon atoms, which are bonded via a carbonyloxy group, in particular methanoyloxy, ethanoyloxy, n-propanoyloxy and i-propanoyloxy.

C ₁₂ -alkylaminocarbonyl according to the invention in each case independently of one another represents an aminocarbonyl group which is monosubstituted or disubstituted by a saturated or unsaturated, linear or branched alkyl radical having up to 12 carbon atoms is, wherein one or two times by Ci- ₆ alkyl-substituted aminocarbonyl radicals, in particular monomethylaminocarbonyl, Diemethylaminocarbonyl, Monoethylaminocarbonyl and diethylaminocarbonyl, are preferred.

Ci- ₁₂ -Alkylsulfanylcarbonyl is according to the invention are each independently, all saturated and unsaturated, linear and branched alkyl radicals having up to 12 carbon atoms, which are bonded via a thiocarbonyl group, wherein Ci-β- Alkylsulfanylcarbonyl radicals are preferred. C _1-6 -alkylsulfanylcarbonyl according to the invention represents all saturated and unsaturated, linear and branched alkyl radicals having up to 6 C atoms which are bonded via a thiocarbonyl group, in particular methylthiocarbonyl and ethylthiocarbonyl.

According to the invention, (Ci-i ₂ -alkyl) NH is independently of each other all saturated and unsaturated, linear and branched alkyl radicals having up to 12 C atoms which are bonded via a hydrogenamino group, where (C _1-6 -alkyl) NH is preferred. (Ci _-6 alkyl) NH is according to the invention for all saturated and unsaturated, linear and branched alkyl radicals having up to 6 carbon atoms, which are bonded via a Hydrogenamino-group, in particular CH ₃ NH and C 2 H ₅ NH.

Di _(Ci-i2 alkyl) N according to the invention is in each case independently of one another for all saturated and unsaturated, linear and branched alkyl groups having up to 12 carbon atoms, which has a (Ci.i ₂ alkyl) amino group are bonded wherein di (Ci- ₆ alkyl) N is preferred. The two alkyl radicals here may be the same or different from each other. Di (Ci- ₆ alkyl) N stands according to the invention for all saturated and unsaturated, linear and branched alkyl groups having up to 6 carbon atoms, which are bonded via a (Ci _-6 alkyl) amino group, in particular (CH _{3) 2} N and (C ₂ Hs) ₂ N.

Cβ-io-aryl according to the invention is in particular phenyl and naphthyl, preferably phenyl.

In C ₆ -io-aryl-C _1-4 -alkyl, the alkyl radical may be saturated or unsaturated, branched or unbranched. Preferred radicals are benzyl, phenylethyl, naphthylmethyl and naphthylethyl. Heteroaryl is according to the invention, unless stated otherwise, for an at least one heteroatom selected from O, S and N containing aromatic radical having 5 to 10, preferably 5 or 6, ring members, in particular selected from furanyl, thienyl, thiophenyl, pyrrolyl, isopyrrolyl, pyrazolyl , Imidazolyl, oxazolyl, thiazolyl, isothiazolyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, triazinyl, benzofuranyl, benzothiophenyl, indolyl, quinolinyl, isoquinolinyl, benzimidazolyl, indazolyl, pyridofuranyl and pyridothienyl.

The aforementioned alkyl, cycloalkyl, alkenyl, alkynyl, heteroalkyl, heterocycloalkyl, alkoxy, alkylsulfanyl, alkylsulfonyl, alkylsulfoxide, alkanoyl, alkoxycarbonyl, alkanoyloxy, alkylaminocarbonyl, alkylsulfanylcarbonyl, (CM ₂ - alkyl) NH-, di _(Ci-i2 alkyl) N-, aryl, C _6- io-aryl-Ci-4-alkyl and heteroaryl radicals may each independently optionally also mono- or polysubstituted, in particular mono-, di- or tri-substituted, in particular by substituents selected from halogen, in particular chlorine, bromine or fluorine, trifluoromethyl, C ₁₂ -alkyl, C 8 -cycloalkyl, C ₂ -i ₂ -alkenyl, C _{2 -} i ₂ alkynyl, heteroalkyl, heterocycloalkyl, Ci _-I2 -Akoxy ₁ Ci- ₁₂ alkylsulfanyl, Ci.i ₂ alkylsulfonyl, Ci _-I2 - alkylsulfoxidyl, Ci- ₁₂ alkanoyl, Ci- ₁₂ alkoxycarbonyl, C _{1- 12} -Alkanoyloxy, C ₁ -I2 - alkylaminocarbonyl, Ci.i ₂ -alkylsulfanylcarbonyl, hydroxy, (Ci-i ₂ alkyl) NH, di- (Ci-l ₂ - alkyl) N, C ₆ - io-aryl, heteroaryl , Cβ-io-Aryl-C-C-alkyl, C _6- i o-arylsulfonyl, C _6- io- Arylsulfoxidyl, C ₆ -io arylcarbonyl, C _6- io-aryloxycarbonyl, or Cβ-io-arylaminocarbonyl, preferably by C _1-6 alkyl, _d-6 alkoxy, chlorine, bromine, Fluorine or hydroxy.

In a preferred embodiment, the total number of substituents on the residues in the sum over all residues in the molecule is not greater than 5, in particular it is not greater than 3 or is exactly 1, exactly 2 or exactly 3.

It may also be a fluorophilic compound in a preferred embodiment according to the invention. The term "fluorophilic" refers to affinity for alkyl groups bearing many fluorine atoms, such as perfluoroalkanes and perfluoroalkane polymers.

The halomethylene alkanones to be used according to the invention are preferably prepared by decarboxylation of compounds of the formula (III)

wherein Ri, R ₂ , R ₃ and X have the meanings given above, and wherein the decarboxylation is carried out in the presence of a weak base. In principle, all stereoisomers of the compounds of the formula (III) can be used as starting materials.

The weakly basic catalyst may be soluble or even insoluble in the reaction medium. Examples of basic catalysts which are insoluble in the reaction medium are basic resins, basic salts and basic polymers.

Examples of basic catalysts soluble in the reaction medium are triethylamine,

Pyridine, 1,4-diazabicyclo [2.2.2] octane (DABCO), 4- (dimethylamino) pyridine (DMAP) and

1, 8-diazabicyclo [5.4.0] undec-7-ene (DBU).

Preferably, the decarboxylation is carried out using triethylamine or DBU or mixtures of these bases with other bases. Most preferably, the reaction is carried out in the presence of triethylamine.

The decarboxylation can be carried out with a mild base in the presence or absence of a solvent. The solvent may be any solvent. Preferred solvents according to the invention are alkyl acetates, aromatic hydrocarbons, chlorinated alkanes, tetrahydrofuran,

Diethyl ether and dioxane.

The solvent is particularly preferably an alkyl acetate or a chlorinated alkane, in particular dichloromethane, dichloroethane or

Trichloroethane.

The reaction is preferably carried out at mild temperatures. The cyclization step is preferably carried out at temperatures between -20 and 150 ⁰ C. The reaction time is preferably between 2 and 12 hours. The Reaction conditions are adjusted depending on the respective substrates and the desired reaction rate.

The brominated keto acids according to formula (III) can be obtained by bromination of the corresponding 4-oxo-2-alkene acids.

Microorganisms whose quorum sensing is disrupted are preferably selected from Aeromonas hydrophila, Aeromonas salmonicida, Agrobacterium tumefaciens, Burkholderia cepacia, Chromobacteum violaceum, Enterobacter agglomerans, Erwinia carotovora, Erwinia chrysanthemi, Escherichia coli, Nitrosomona europaea, Obesumbacterium proteus, Pantoea stewartii, Pseudomonas aeruginosa , Pseudomonas aureofaciens, Pseudomonas fluorescens, Pseudomonas syringae, Ralstonia solanacearum, Rhizobium etli, Rhizobium leguminosarum, Rhodobacter sphaeroides, Salmonella enterica, Serratia liquefaciens, Vibrio anguillarum, Vibrio fish, Xenorhabdus nematophilus, Yersinia enterolytica, Yersinia pestis, Yersinia pseudotuberculosis, Yersinia ruckeri.

Gram-positive bacteria are also suitable microorganisms according to the invention.

Most significant are germs that are particularly involved in biofilm formation in aqueous solutions. These are primarily germs from the large pseudomonad group (especially P. aeruginosa as bes. Target bacterium), Burkholderia cepacia, Serratia, Rhizobium, E. coli. Other important biofilm germs are Aquabacterium, Xanthomonas.

In most cases, the bacterial communication systems do not control morphological changes of individual cells, but influence the pathogenicity of the respective organisms. Some of the most significant features of these communication systems are listed below by way of example:

Control of the expression of the bioluminescent genes (eg Photobacterium fischeri)

Production of the β-lactam antibiotic carbapenem (Erwinia carotovora) and AB production in Pseudomonas aureofaciens

Conjugative plasmid transfer (tral / traR from Agrobacterium tumefaciens), Starvation response (eg Pseudomonas)

• Bacterial locomotion (swrl / swrR from Serratia liquefaciens) and P. aeruginosa

• Development of differentiated biofilms (P aeruginosa, B. cepacia)

Production of various virulence factors (cell-associated virulence factors in P. aeruginosa, for example extracellular factors such as proteases (LasB elastase, alkaline protease and LasA protease), hemolysins (rhamnolipid and phosoholipase) and toxins (exotoxin A and exoenzyme S)

• Interspecific cell-cell communication ("cross-talk" between different bacterial species). Between P. cepacia and P. aeruginosa

According to the invention, the microbial interaction is selected from the formation and / or maturation of biofilms, multicellular swarming, the concerted formation of antibiotic resistance, the concerted synthesis of antibiotics, the concerted synthesis of pigments, the concerted production of extracellular enzymes, especially hydrolytic enzymes, and the concerted production of virulence factors, preferably the formation and / or maturation of biofilms.

Another object of the invention is the use of the compounds according to the invention for the control of processes based on microbial interaction, in particular for controlling the formation and / or maturation of biofilms, more preferably of biofilms in which Gram-negative bacteria are involved.

Advantageously, in contrast to antibiotics, the compounds according to the invention do not kill off the bacteria, but only inhibit their communication system so that no mature, slimy biofilm is formed. It is particularly advantageous that the microorganisms can not form any resistance to these compounds, which are structural analogues to the AHL molecules they themselves use, since otherwise they would severely impair their own communication system.

The compounds according to the invention can be used in pure form or as active constituents of mixtures. In the majority of cases, the mixtures intended for practical use contain a total of from 0 to about 99, preferably 90 to 10 wt .-% further commonly used ingredients, which are selected according to the intended use and the intended use.

For liquid preparations, for example, come as a solvent with water miscible organic solvents into consideration, for example, ethanol, isopropanol and ethylene glycol, propylene glycol, ethylethylene glycol, propylene glycol 20 and water-immiscible solvents such as white spirit, benzene, toluene, Essigsäureethy-Iester or dimethylene chloride.

Therefore, the use according to the invention is preferably carried out in sterilizing, disinfecting, impregnating, preserving, washing, dishwashing or cleaning agents, cooling, cooling lubricant or corrosion protection agents (technical application solutions) which can be used in the institutional and / or industrial field, in the field water purification / water treatment and agents for finishing or treating surfaces, foodstuffs, filter media, adhesives, building materials, building aids, ceramics, plastics, metals, textiles, furs, paper, hides, polymers, leather or packaging. In particular, the application in this case in the pharmaceutical, food, brewery, dairy, medical technology, paint, wood, textile, cosmetics, leather, tobacco, fur, rope, paper, pulp , Plastics, fuel, oil, rubber, automotive, polymer, steel or mechanical engineering industry.

Another object of the present invention are accordingly compositions, preparations and materials - hereinafter also simply called "agent" - containing substances of the invention and / or coated or equipped with substances of the invention.

The agents according to the invention are in particular selected from institutional and / or industrial sterilization, disinfection, impregnation, preservation, corrosion protection, washing, dishwashing or cleaning agents, cooling or cooling lubricants and water treatment agents containing substances according to the invention. According to the invention, the agents may further be, for example, filter media, adhesives, building materials, building aids, textiles, furs, paper, hides, leather, ceramics, plastics, polymers, packaging or metals, as well as means for finishing or treating surfaces, foods , Filter media, adhesives, building materials, building aids, ceramics, plastics, metals, textiles, furs, paper, hides, polymers, leather or packaging. The surfaces are, in particular, surfaces of devices and apparatuses in the industrial and / or institutional sector as well as surfaces of automobiles.

In a further preferred embodiment according to the invention, the use for biofilm control in medical devices, instruments and apparatus, in particular in catheters and endoscopes. The present invention therefore also relates to medical devices, instruments and apparatus obtainable by appropriate treatment, in particular catheters and endoscopes.

The substances according to the invention can be present in the agents according to the invention and / or the agents according to the invention can be coated with them and / or be equipped with them, it being possible for the substances according to the invention to be covalently or noncovalently bound to the agents.

In a particular embodiment of the invention, the effect according to the invention is achieved here by a surface modification of the apparatuses, machines and / or devices, wherein surface modification means that the substances according to the invention are fixed to the surface of the corresponding apparatuses, machines and / or devices, wherein any type of bond, in particular covalent bond, is conceivable.

The compounds of the invention are useful for inhibiting microbial growth wherever this growth is undesirable, e.g. In aqueous systems in a variety of industrial applications such as papermaking. A number of important industries are severely affected by the activity of these bacteria, algae and fungi on the raw materials used, on various aspects of their manufacturing activities or on the final products produced. These industries include the paint, wood, textile, cosmetics, leather, tobacco, fur, rope, paper, pulp, plastics, fuel, oil, rubber and machinery industries.

Important applications of the compounds of this invention include: preventing bacterial contamination of air conditioners, inhibiting the growth of bacteria and fungi in adhesives, latex emulsions and potting compounds; Wood preservatives; Bohrölkonservierung; Controlling slime-producing bacteria and fungi in pulp and paper mills and cooling water; as a spray or dipping treatment for textiles and leather to prevent mold growth; Protection of processing equipment from slime deposits in the production of cane and beet sugar; Preventing the accumulation and deposition of microorganisms in fume scrubber systems and industrial fresh water supply systems; Combating contamination with and deposition of microorganisms in oil drilling fluids and sludges and in secondary oil treatment processes; Inhibition of bacterial and fungal growth in paper coating processes that could affect the quality of the paper coating; Combating bacterial and fungal growth and deposition in the manufacture of various specialty paperboard, e.g. B. solid board and chipboard; Prevention of cell juice discoloration of freshly beaten wood of various kinds; Control of bacterial and fungal growth in clay and pigment sludges of various types, which are prepared for later use, for example in paper coating and paint production and are subject to degradation by microorganisms during storage and transport; as an institutional and / or industrial hard surface disinfectant for preventing growth of bacteria and fungi on walls, floors, etc., and in swimming pools for preventing algae growth.

Particularly important is the control of bacteria and fungi in water systems of pulp and paper mills, the aqueous dispersions of the fibers for Paper production included. The uncontrolled accumulation of mucus by the accumulation of bacteria and fungi leads to poor quality production, reduced production due to breaks and higher cleaning frequency, increased consumption of raw materials and higher maintenance costs. The problem of slime deposits in the paper industry is exacerbated by the widespread use of closed white water systems.

Another important area in which control of bacterial and fungal growth is critical is the clay and pigment sludges. These sludges consist of different clays, e.g. Kaolin, and pigments, e.g. For example, calcium carbonate and titanium dioxide. They are usually manufactured in a location different from that of final use, e.g. As in the paper coating and paint production, is removed and then stored for later transport to the final consumption. The high quality standards for the paper and paint end products in which the slurry is used require that the clay or pigment slurry have a very low microorganism content so that it can be used for paper coating or paint production.

Another important area for controlling microbial growth is cooling systems, such as those with recirculating cooling towers. These systems expose a large amount of water to the atmosphere for a considerable time under conditions that do not include adequate ventilation and exposure to sunlight to combat microbial growth, particularly bacterial and fungal growth. Many cooling towers also use a fill of beads of synthetic polymer or other materials to increase the heat exchange surface area. This construction aggravates the problem of microbial growth as it provides the ideal physical environment for the proliferation of troublesome microbes. Unfilled, these microorganisms thrive and produce colonies sufficient to block the heat exchange surfaces with a biofilm and clog the components of the water transport device used to operate the refrigeration system. The compounds of the invention provide excellent control of microbial growth in these systems. The compounds according to the invention are particularly suitable for controlling the harmful effects of microorganisms in water or aqueous media. Systems using circulating water or circulating aqueous media become infected with microorganisms and significantly impair their effectiveness as microorganism deposits accumulate in the system. The deposits called slimes coat the walls of containers and other vessels, any machinery and processing equipment used, and create obstructions in pipes and valves. The formation of slime promotes the corrosion of metal surfaces and facilitates the rotting of wooden towers. The slimes also cause discoloration and other defects in all manufactured products and force costly business interruptions. The control of microorganisms in aqueous media is particularly important if there are dispersed particles or fines therein, e.g. B. dispersed cellulose fibers and dispersed fillers and pigments in papermaking.

For the preparation of ready-to-use disinfectants and preservatives, liquid concentrates and solid products, preferably in powder or granule form, containing the substances according to the invention can be provided.

The agents according to the invention can be used in every conceivable institutional and / or industrial area, for example in hospitals, hotels, schools, swimming pools, baths, cisterns, public transport, public buildings, public sanitary facilities, saunas, sports facilities or in doctor's or massage practices , in commercial and industrial plants, in particular for cleaning hard surfaces, such as, for example, floors, tiles, tiles and plastics.

Furthermore, the compounds according to the invention can be used in the preservation of technical products still to be processed, such as glazes, adhesives and adhesives, drilling and cutting oils or products of the paper, paperboard or leather processing industry and for the preservation of industrial and industrial water.

The application can be done for example by spraying, brushing, brushing, knife coating, dipping or pressure or vacuum impregnation. The compounds according to the invention of the formula (I) or (II) are preferably used in a concentration in the range from 1 ppm to 1000 ppm, in particular 20 to 500 ppm, particularly preferably 20 to 50 ppm.

The equipment of the surfaces, filter media, adhesives, building materials, construction auxiliaries, ceramics, plastics, metals, textiles, furs, papers, hides, polymers, leather parts or packaging with the substances according to the invention is carried out in a manner known to those skilled in the art, for example by immersion in a suitably concentrated Solution of a composition according to the invention or by spraying with such a solution. Thus, for example, works of art on paper, parchment, wood and / or canvas can be protected from infestation by microorganisms, in particular mold, or be freed from this. The equipment of the filter media, building materials or auxiliary building materials, for example, by applying or by mechanical incorporation of the substances of the invention or a suitably concentrated solution of the substances according to the invention on or in the filter media, building materials or building aids. The substances according to the invention can thus be incorporated mechanically into the relevant materials prior to their use, e.g. be incorporated by stirring, or alternatively they can already be incorporated during the preparation of the materials in this.

Building and construction aids

In a preferred embodiment, the building materials or building aids of the invention are selected from adhesives, sealants, fillers and paints, plastics, paints, paints, plaster, mortar, screed, concrete, insulating materials and primers. Particularly preferred building materials or building aids are jointing compounds (eg silicone-containing

Joint sealants), wallpaper paste, plaster, carpet fixer, silicone adhesive, tile adhesive.

Sealants and in particular jointing compounds typically contain organic polymers and, in many cases, mineral or organic fillers and other additives. Suitable polymers are, for example, thermoplastic elastomers, as described in DE 3602526, preferably polyurethanes and acrylates. Suitable polymers are also mentioned in the published patent applications DE 3726547, DE 4029504 and DE 4009095 as well as in DE 19704553 and DE 4233077, to which reference is hereby made in their entirety.

The sealing compounds according to the invention (sealants or sealant mixtures) preferably contain 0.001-3.0% by weight of substances according to the invention of the formula (I) and / or (II). Particularly preferred amounts are between 0.01 and 1, 0 wt .-%.

According to the invention, the equipment of the sealants according to the invention can be carried out both in the uncured or under 60 ⁰ C cured state. In the context of the invention, sealants are materials according to DIN EN 26927, in particular those which cure plastically or elastically as sealants. The sealants of the invention may contain all additives typical of the corresponding sealants, such as typical thickeners, reinforcing fillers, crosslinkers, crosslinking catalysts, pigments, adhesives or other bulk extenders. The application or introduction of the nonionic surfactants can by dispersing in the expert known manner, for example by the use of dispersing, kneader, planetary mixer, etc., with the exclusion of moisture and oxygen both in the finished and in parts of these sealants or together with a or more components of the sealants.

Even the treatment of already cured, crosslinked sealing compound surfaces can be carried out by applying solutions or suspensions of the substance used according to the invention, by transporting the active substance by swelling or diffusion into the sealing compound.

Sealants which can be used according to the invention can be produced both on silicone, urethane and on acrylic base or about on MS polymer basis. Urethane-based sealants are disclosed, for example, in Ullmann's Encyclopedia of Industrial Chemistry (8th Edition 2003, Chapter 4) and US 4,417,042. Silicone sealants are the expert known, for example. from EP 0,118,030 A, EP 0,316,591 A, EP 0327847 _A1 EP 0553143 A, DE 195 49 425 A and US 4,417,042. Examples of acrylic sealants are disclosed inter alia in WO 01/09249 or US 5,077,360. Examples of MS polymer-based sealants are disclosed, for example, in EP 0 824 574, US 3,971,751, US 4,960,844, US 3,979,344, US 3,632,557, DE 4029504, EP 601 021 or EP 370 464.

In particular, systems crosslinking at room temperature, as described, for example, in EP 0 327 847 or US Pat. No. 5,077,360, are preferred. These may be single-component or multicomponent systems, it being possible for catalyst and crosslinker to be present separately in the multicomponent systems (for example disclosed in US Pat. Nos. 4,891,400 and 5,502,144), or other so-called silicone RVT 2K systems, in particular platinum-free systems ,

Particular preference is given to so-called one-component systems which contain all ingredients for the construction of a sealant, are stored with the conclusion of atmospheric moisture and / or atmospheric oxygen and cure on site under reaction with atmospheric oxygen and / or atmospheric moisture. Particularly preferred are the so-called silicone neutral systems, in which the reaction of crosslinking agents with the water of the ambient air does not lead to corrosive, acidic, basic or odor-intensive cleavage products. Examples of such systems are disclosed in DE 195 49 425, US 4,417,042 or EP 0 327 847.

The sealants and especially jointing compounds may contain aqueous or organic solvents. Suitable organic solvents are hydrocarbons such as cyclohexane, toluene or else xylene or petroleum ether. Other solvents include ketones such as methyl butyl ketone or chlorinated hydrocarbons.

Furthermore, the sealants may contain other rubbery polymers. Here are relatively low molecular weight, commercially available types of polyisobutylene, polyisoprene or polybutadiene styrene in question. The concomitant use of degraded natural rubber or neoprene rubber is possible. Here, even at room temperature still flowable types can be used, which are often referred to as "liquid rubber". The sealing compounds of the invention can be used to connect or seal the most diverse materials. This is intended primarily for use on concrete, glass, plaster and / or enamel, as well as ceramics and porcelain. But also the joining or sealing of moldings or profiles made of aluminum, steel, zinc or even of plastics such as PVC or polyurethanes or acrylic resins is possible. Finally, the sealing of wood or wood materials with a variety of other materials is mentioned.

The stability of jointing compounds is usually achieved by the addition of finely divided solids - also called fillers. These can be distinguished in such organic and inorganic type. As inorganic fillers, for example silicic acid / silica (coated or uncoated), chalk-coated or uncoated, and / or zeolites may be preferred. The latter can also act as a desiccant. As organic filler is e.g. PVC powder into consideration. The fillers generally contribute significantly to the sealant having a necessary internal hold after application such that leakage or debound of the sealant from vertical joints is prevented. The cited additives or fillers can be classified into pigments and thixotropic fillers, also abbreviated as thixotropic agents.

Suitable thixotropic agents are the known thixotropic agents such as bentones, kaolins or organic compounds such as hydrogenated castor oil or derivatives thereof with polyfunctional amines or the reaction products of stearic acid or ricinoleic acid with ethylenediamine. Particularly advantageous is the co-use of silica, in particular of silica from pyrolysis has been found. In addition, suitable thixotropic agents are essentially swellable polymer powders. Examples of these are polyacrylonitrile, polyurethane, polyvinyl chloride, polyacrylic acid esters, polyvinyl alcohols, polyvinyl acetates and the corresponding copolymers. Particularly good results can be obtained with finely divided polyvinyl chloride powder. In addition to the thixotropic agents, it is also possible to use additional adhesion promoters, such as, for example, mercaptoalkylsilane. Here it has proven to be expedient to use a Monomercaptoalkyltrialkoxysilan. Commercially available is, for example, the mercaptopropylthmethoxysilane. The properties of a jointing compound can be further improved if further components are added to the plastic powder used as thixotropic agent. These are substances that fall under the category of plasticizers used for plastics or swelling agents and swelling aids.

It come z. As plasticizers, in particular for the sealing compounds based on urethane or acrylic from the class of phthalic acid into consideration. Examples of applicable compounds from this class of substances are dioctyl phthalate, dibutyl phthalate and benzyl butyl phthalate. Further suitable classes of substances are chloroparaffins, alkylsulfonic acid esters of, for example, phenols or cresols, and fatty acid esters.

For the silicone sealants are as plasticizers silicone oils, more preferably polydimethylsiloxanes, and hydrocarbons and / or mixtures thereof, of which especially hydrocarbons or mixtures thereof having a boiling point of greater than 200 ⁰ C, in particular greater 230 ⁰ C, well suited.

Suitable source aids are those low molecular weight organic substances which are miscible with the polymer powder and the plasticizer. Such source aids can be found in the relevant plastic and polymer manuals for the expert. Preferred swelling aids for polyvinyl chloride powder are esters, ketones, aliphatic hydrocarbons, aromatic hydrocarbons and aromatic hydrocarbons with alkyl substituents.

Pigments and dyes used are the substances known for these uses, such as titanium dioxide, iron oxides and carbon black.

To improve the storage stability known stabilizers such as benzoyl chloride, acetyl chloride, Toluolsulfonsäuremethylester, carbodiimides and / or polycarbodiimides are added to the sealants. As particularly good stabilizers, olefins having 8 to 20 carbon atoms have been found. In addition to the stabilizing effect, these can also fulfill the tasks of plasticizers or swelling agents. Preference is given to olefins having 8 to 18 carbon atoms, in particular if the double bond is arranged in the 1, 2 position. Best results are obtained when the molecular structure of these stabilizers is linear.

A further preferred embodiment of the present invention is wallpaper adhesive containing preferably 0.000001 to 3 wt .-% of the inventive compounds of the formula (I) and / or (II). The wallpaper adhesives may be wallpaper pastes of aqueous solutions of hydrocolloids such as methylcellulose, methylhydroxypropylcellulose or water-soluble starch derivatives or aqueous dispersions of film-forming high molecular weight such as polyvinyl acetate, in particular in combination with the already mentioned cellulose and starch derivatives.

As filter media, all known types can be used, as long as they are suitable for use in water or air filter systems, in particular for air conditioners or humidifiers. In particular, filter materials of cellulose, glass fibers, PVC fibers, polyester fibers, polyamide fibers, in particular nylon fibers, nonwovens, sintered materials and membrane filters can be mentioned.

Cleaning and disinfecting agents

The cleaning and / or disinfecting agent according to the invention, which contains the biofilm blockers according to the invention, is biocide-free in a preferred embodiment, but may optionally also contain biocides.

The cleaning agent may in particular be liquid, gelatinous or pasty-aqueous and may contain, for example, customary cleaning agent constituents. These ingredients include in particular surfactants, but also builders, acids, alkalis, hydrotropes, solvents, thickeners, abrasives and other auxiliaries and additives such as dyes, perfumes, corrosion inhibitors or skin care products.

The optionally used surfactants are preferably selected from the group of anionic surfactants, nonionic surfactants and / or amphoteric surfactants. In this case, preference is given to using anionic and / or nonionic surfactants. If used, anionic surfactants are preferably used in amounts of from 0.1 to 15% by weight, nonionic surfactants preferably in amounts of from 0.1 to 10% by weight. and amphoteric surfactants are preferably used in amounts of 0.1 to 4 wt .-%, each based on the total composition. In a less preferred embodiment, it is also possible to use cationic surfactants, in particular in amounts of up to 2% by weight, based on the total composition. In a preferred embodiment, however, the cleaning agent is free of these due to the biocidal effect emanating from cationic surfactants.

The anionic surfactants which can be used according to the invention include in particular aliphatic sulfates such as fatty alcohol sulfates, fatty alcohol ether sulfates, monoglyceride sulfates and aliphatic sulfonates such as alkanesulfonates, .alpha.-olefinsulfonates, ether sulfonates, n-alkyl ether sulfonates, sulfonated fatty acids, ester sulfonates and lignosulfonates. Also useful in the present invention are alkylbenzenesulfonates, fatty acid salts (soaps), fatty acid cyanamides, sulfosuccinates (sulfosuccinic acid mono- and dialkyl esters), sulfosuccinamates, sulfosuccinamides, carboxylic acid amide ether sulfates, alkyl polyglycol ether carboxylates, fatty acid isethionates, acylaminoalkanesulfonates (fatty acid taurides, N-acyltaurides), fatty acid sarcosinates, ether carboxylic acids, and alkyl (Ether) phosphates and α-sulfo fatty acid salts, acyl glutamates, Monoglyceriddisulfate and alkyl ethers of Glycerindisulfats, and finally their mixtures.

In the context of the present invention are fatty acids or fatty alcohols or their derivatives - unless otherwise stated - representative of branched or unbranched carboxylic acids or alcohols or their derivatives having preferably 6 to 22 carbon atoms, in particular 8 to 20 carbon atoms, particularly preferably 10 bis 18 carbon atoms, most preferably 12 to 16 carbon atoms, for example 12 to 14 carbon atoms. The fatty acids / alcohols or their derivatives with an even number of carbon atoms are particularly preferred on account of their vegetable base as based on renewable raw materials for ecological reasons, but without limiting the teaching of the invention to them. In particular, the oxo alcohols obtainable, for example, by Roelen's oxo synthesis or derivatives thereof having preferably 7 to 19 carbon atoms, in particular 9 to 19 carbon atoms, are particularly preferred to 17 carbon atoms, especially 11 to 15 carbon atoms, for example 9 to 11, 12 to 15 or 13 to 15 carbon atoms, can be used accordingly.

They are in the form of their alkali metal and alkaline earth metal salts, in particular sodium, potassium and magnesium salts, as well as ammonium and mono-, di-, tri- or tetraalkylammonium salts and in the case of the sulfonates also in the form of their corresponding acid, for example dodecylbenzenesulfonic acid, used. Due to their production, the alkyl ether sulfates always contain residual contents of non-alkoxylated fatty alcohol sulfates, especially at low degrees of ethoxylation. Furthermore, the compositions according to the invention may also comprise soaps, ie alkali or ammonium salts of saturated or unsaturated C ₆ -C ₂₂ -fatty acids.

The anionic surfactants are preferably selected from the group comprising fatty alcohol sulfates in amounts of up to 5 wt .-%, alkylbenzenesulfonates in amounts of up to 7.5 wt .-% and soaps in amounts of up to 2 wt .-%, each based on the overall composition, as well as mixtures thereof.

Suitable nonionic surfactants are, for example, C 6 -C 18 -alkyl alcohol polyglycol ethers, alkyl polyglycosides and nitrogen-containing surfactants or mixtures thereof, in particular the first two.

Cβ-Ciβ-Alkylalkoholpolypropylenglykol / polyethylene glycol ethers can be represented by the formula

R ¹ O- (CH ₂ CH (CH ₃ ) O) _P (CH ₂ CH ₂ O) ₆ -H

in which R ^{1 is} a linear or branched, aliphatic alkyl and / or alkenyl radical having 8 to 18 carbon atoms, p is 0 or numbers from 1 to 3 and e is numbers from 1 to 20. They are obtained by addition of propylene oxide and / or ethylene oxide to alkyl alcohols, preferably to fatty alcohols. Furthermore, end-capped C ₈ -C ₈ -alkyl alcohol polyglycol ethers can also be used, ie alkyl alcohol polyalkylene glycol ethers according to the above formula in which the free OH group has been etherified. Inventive cleaners may contain alkyl alcohol polyglycol ethers in amounts of 0.1 to 4 wt .-%, based on the total composition.

Preferred nonionic surfactants are also alkyl polyglycosides (APG) of the formula R ² O [G] _x , in which R ^{2 is} a linear or branched, saturated or unsaturated alkyl radical having 8 to 22 carbon atoms, [G] is a glycosidically linked sugar moiety and x is a number from 1 to 10 are. The index number x indicates the degree of oligomerization (DP degree), ie the distribution of monoglycerides and oligoglycosides. While x in a given compound always has to be an integer, and above all can assume the values x = 1 to 6, the value x for a given alkyl glycoside is an analytically determined arithmetic variable, which usually represents a fractional number. Preferably, alkyl glycosides having a mean degree of oligomerization x of

1.1 to 3.0 used. From an application point of view, those alkyl glycosides are preferred whose degree of oligomerization is less than 1.7, and in particular between

1.2 and 1, 6 lies. The glycosidic sugar used is preferably xylose, but especially glucose. The alkyl or alkenyl radical R ² can be derived from primary alcohols having 8 to 18, preferably 8 to 14 carbon atoms. Typical examples are caproic alcohol, caprylic alcohol, capric alcohol and undecyl alcohol, and technical mixtures thereof, such as those obtained in the course of the hydrogenation of technical fatty acid methyl esters or in the course of the hydrogenation of aldehydes from Roelene's oxosynthesis. Preferably, however, the alkyl or alkenyl radical R ² is derived from lauryl alcohol, myristyl alcohol, cetyl alcohol, palmoleyl alcohol, stearyl alcohol, isostearyl alcohol or oleyl alcohol. Also to be mentioned are elaidyl alcohol, petroselinyl alcohol, arachidyl alcohol, gadoleyl alcohol, behenyl alcohol, erucyl alcohol and technical mixtures thereof.

Alkyl polyglycosides can be contained in cleaners according to the invention in amounts of from 0.1 to 6% by weight, based on the total composition.

Further nonionic surfactants may contain nitrogen-containing surfactants, for example fatty acid polyhydroxyamides, for example glucamides, and ethoxylates of alkylamines, vicinal diols and / or carboxylic acid amides which have alkyl groups with 10 to 22 C atoms, preferably 12 to 18 C atoms. The degree of ethoxylation of this Compounds are generally between 1 and 20, preferably between 3 and 10. Preferred are ethanolamide derivatives of alkanoic acids having 8 to 22 carbon atoms, preferably 12 to 16 carbon atoms. Particularly suitable compounds include the Lauhnsäure-, Myristinsäure- and Palmitinsäuremonoethanolamide.

Amphoteric surfactants (amphoteric surfactants, zwitterionic surfactants) which can be used in the present invention include, but are not limited to: Betaines, amine oxides, alkylamido alkylamines, alkyl-substituted amino acids and acylated amino acids. Preferred amphoteric surfactants are, for example, betaines of the formula

(R ³⁾ (R ⁴⁾ (R ⁵⁾ N ⁺ CH ₂ COO-,

in which R ^{3 is} an optionally interrupted by hetero atoms or heteroatom groups alkyl radical having 8 to 25, preferably 10 to 21 carbon atoms and R ⁴ and R ^{5 are} identical or different alkyl radicals having 1 to 3 carbon atoms, in particular Cio-Ciβ-alkyl-dimethylcarboxymethylbetain and Cn -C- ₁₇ -alkylamidopropyl-dimethylcarboxymethylbetaine.

If cationic surfactants are included in the composition, these are preferably the quaternary ammonium compounds of the formula

(R ⁶ ) (R ⁷ ) (R ⁸ ) (R ⁹ ) N ⁺ X-,

in which R ⁶ to R ^{9 are} four identical or different, in particular two long and two short-chain, alkyl radicals and X- for an anion, in particular a halide ion, for example, didecyl-dimethyl-ammonium chloride, alkyl-benzyl-didecyl ammonium chloride and their mixtures. Preferably, however, the detergent composition is free of cationic surfactants.

When selecting the appropriate surfactants, it must be ensured that, if enzymes are additionally present in the cleaning agent, they are then compatible with the enzymes used. Preferably, the enzyme activity is lowered by not more than 50% during a typical 15 minute median exposure time, more preferably not more than 30%. Thus experiments have shown that this is known as denaturing Sodium dodecyl sulfate (SDS) lowers the activity of the corolase already in a concentration of 1% within 15 minutes to less than 30%, while the activity of the xylanase already decreases with only 0.1% SDS to less than 40%, so that this surfactant for the use in cleaning agents according to the invention is not preferred. If this or a similarly acting surfactant still be used, it is preferable to ensure a spatial separation during storage, for example by encapsulation of the enzymes or by the use of a multi-chamber bottle, so that enzymes and surfactants together until immediately before or during use get in touch. By contrast, alkyl polyglycosides are well suited for use in enzyme-containing compositions according to this invention. Thus, the activity of corolase even with 3% APG 600 remains well over 50%, the xylanase even experiences an increase in activity (more than 150% activity with 0.1% surfactant) with the addition of APG 600 and always shows 3% APG still over 80% activity on.

Furthermore, the agents according to the invention may contain builders. Examples of suitable builders are alkali metal gluconates, citrates, nitrilotriacetates, carbonates and bicarbonates, especially sodium gluconate, citrate and nitrilotriacetate, and sodium and potassium carbonate and bicarbonate, and also alkali metal and alkaline earth metal hydroxides, in particular sodium and potassium hydroxide, ammonia and amines , in particular mono- and triethanolamine, or mixtures thereof. These include the salts of glutaric acid, succinic acid, adipic acid, tartaric acid and benzene hexacarboxylic acid and phosphonates and phosphates. The agents may contain builders in amounts, based on the composition, of from 0.1 to 5% by weight.

Furthermore, the agents according to the invention may contain acids and / or alkalis. These serve on the one hand as pH regulators, on the other hand, however, the acids can also contribute to the removal of limescale from the surfaces to be cleaned. In accordance with the invention can be used acids may be inorganic mineral acids, for example hydrochloric acid, and / or C ₁ - ₆ - mono-, di-, tri- or polycarboxylic acids or hydroxy carboxylic acids such as formic acid, acetic acid, lactic acid, citric acid, gluconic acid, glutaric acid , Succinic acid, adipic acid, tartaric acid or else malic acid, as well as other organic acids such as salicylic acid or amidosulfonic acid. However, the citric acid is particularly preferably used; also mixtures of several Acids can be used. Acids can be present in the inventive detergent in amounts of up to 6 wt .-%, based on the total composition.

The optionally usable bases include alkanolamines, for example mono- or diethanolamine, and ammonium or alkali metal hydroxides, especially sodium hydroxide. The cleaning agent according to the invention may contain bases in amounts of up to 2.5% by weight, based on the total composition.

The agent according to the invention can furthermore contain one or more thickeners for viscosity regulation. Suitable thickeners are natural and synthetic polymers and inorganic thickeners. The polymers which can be used include polysaccharides or heteropolysaccharides and other organic natural thickeners, including the polysaccharide gums such as gum arabic, agar, alginates, carrageenans and their salts, guar, guar gum, tragacanth, gellan, Ramzan, dextran or xanthan and their derivatives, eg propoxylated Guar, and their mixtures, as well as pectins, polyoses, carob seed flour, starch, dextrins, gelatin, casein. Furthermore, organic modified natural substances such as carboxymethyl cellulose and cellulose ethers, hydroxyethyl and propyl cellulose and the like or cellulose acetate and core flour ethers can be used. Homogeneous and copolymeric polycarboxylates, especially polyacrylic and polymethacrylic compounds, as well as vinyl polymers, polycarboxylic acids, polyethers, polyimines or else polyamides can serve as organic fully synthetic thickeners. The inorganic thickeners which can be used include polysilicic acids, clay minerals such as montmorillonites, zeolites, silicic acid and various nanoparticulate inorganic compounds such as nanoparticulate metal oxides, oxide hydrates, hydroxides, carbonates and phosphates and silicates having an average particle size of from 1 to 200 nm, based on the Particle diameter in the longitudinal direction, ie in the direction of the largest expansion of the particles. These nanoparticulate substances can optionally be treated in one further embodiment of the invention with one or more surface modifiers. The surface modification is carried out in a manner known to those skilled in the art with mono- and polybasic

or hydroxycarboxylic acids, functional silanes of the type (OR) _4-11 SiR _n (R = org. radicals having functional groups such as hydroxy, carboxy, Ester, amine, epoxy, etc.), quaternary ammonium compounds or amino acids and other substances usable for this purpose.

In addition to the previously mentioned thickening agents, the cleaning agent according to the invention may contain electrolyte salts. These can also contribute to an increase in viscosity. Electrolyte salts in the context of the present invention are salts which decompose into their ionic constituents in the aqueous agent according to the invention. Preference is given to the salts, in particular alkali metal and / or alkaline earth metal salts, of an inorganic acid, preferably of an inorganic acid from the group comprising the hydrohalic acids, nitric acid and sulfuric acid, in particular the chlorides and sulfates. Within the scope of the teaching according to the invention, an electrolyte salt can also be used in the form of its corresponding acid / base pair, for example hydrochloric acid and sodium hydroxide instead of sodium chloride.

In the composition according to the invention, it is possible to use organic and / or inorganic thickeners in amounts of up to 2% by weight, based on the total composition.

The agent according to the invention may advantageously additionally contain one or more water-soluble organic solvents, usually in an amount of up to 6% by weight, based on the total composition. The solvent is used in the context of the teaching of the invention as needed in particular as a hydrotrope, viscosity regulator and / or cold stabilizer. It acts solubilizing in particular for surfactants and electrolyte as well as perfume and dye and thus contributes to their incorporation, prevents the formation of liquid-crystalline phases and has a share in the formation of clear products. The viscosity of the agent according to the invention decreases with increasing amount of solvent. However, too much solvent can cause excessive viscosity drop. Finally, as the amount of solvent increases, the clouding and clearing point of the composition according to the invention decreases.

Suitable solvents are, for example, saturated or unsaturated, preferably saturated, branched or unbranched C 20 -hydrocarbons, prefers

with at least one hydroxy group and optionally one or more ether functions COC, ie the carbon atom chain interrupting oxygen atoms. Preferred solvents are, however, the - optionally etherified on one side with a Ci ₆ alkanol - C ₂ - ₆ - alkylene glycols and poly-C ₂ - ₃ -alkylene with an average of 1 to 9 identical or different, preferably identical, alkylene glycol per molecule, for example ethylene glycol , Propylene glycol, butylene glycol, diethylene glycol, dimethoxy diglycol, dipropylene glycol, propylene glycol butyl ether, propylene glycol propyl ether,

Dipropylene glycol monomethyl ether and PEG. Further preferred solvents are the C ₆ -alcohols, such as methanol, ethanol, n-propanol, isopropanol, n-butanol, t-butanol, etc., more preferably ethanol and / or isopropanol is used.

As solubilizers, in addition to the solvents described above, for example, alkanolamines and alkylbenzenesulfonates having 1 to 3 carbon atoms in the alkyl radical, e.g. XyIoI or Cumolsulfonat be used. Other useful hydrotropes are e.g. Octyl sulfate or butyl glucoside. The agent of the invention may contain up to 4% by weight of these hydrotropes in amounts of, based on the total composition.

In one embodiment, the agents of the invention may contain abrasives. The abrasive component used may be solid water-soluble and water-insoluble, preferably inorganic compounds and mixtures thereof. These include, for example, alkali metal carbonates, alkali metal bicarbonates and alkali metal sulfates, alkali metal borates, alkali metal phosphates, silicon dioxide, crystalline or amorphous alkali metal silicates and phyllosilicates, finely crystalline sodium aluminum silicates and calcium carbonate. The advantage of water-soluble Abrasivkomponenten consists in a virtually residue-free flushability of the agent. In addition to these inorganic substances, it is also possible to use abrasives obtained from animate nature, for example ground nut shells or woods, as well as abrasion-resistant plastics, for example polyethylene beads, or even ceramic or glass beads. The cleaning agent according to the invention may contain abrasives in amounts of up to 2% by weight, based on the total composition. In addition to the abovementioned components, the compositions according to the invention may contain one or more other auxiliaries and additives, such as are customary, above all, in hard surface cleaners. These include in particular UV stabilizers, corrosion inhibitors, cleaning enhancers, antistatic agents, preservatives (eg 2-bromo-2-nitropropane-1, 3-diol or an isothiazolinone Bromnitropropandiol preparation), perfume, dyes, pearlescing agents (for example, glycol distearate) and opacifiers or also skin protection agents, as described for example in EP 522 506. The amount of such additives is usually not more than 12 wt .-% in the detergent. The lower limit of the use depends on the nature of the additive and can be up to 0.001 wt .-% and below, for example, in the case of dyes. The amount of auxiliaries is preferably between 0.01 and 7% by weight, in particular 0.1 and 4% by weight.

Dyes which may be used are all dyes customarily used in detergents. Even with the fragrances all common perfumes can be used. Preference is given to fruity scents, such as citrus, pine (spruce) and mint and floral scents. Preservatives have a biocidal effect, so that it is desirable to use only low concentrations, but preferably no preservatives, in detergents according to the invention.

It is advantageous if the agent contains no complexing agents; the addition of a bleaching agent to the cleaning agent according to the invention is not required.

The pH of the compositions according to the invention is preferably between 1 and 7.5, particularly preferably between 2 and 5, in particular between 2.5 and 4.5. In the case of multiphase agents, the pH of the composition means the pH of the temporary emulsion formed after shaking; in the case of compositions offered in multi-chambered bottles, the pH of the composition is that of the common intended dosage of the components stored in the various chambers components obtained solution. Thus, it is meant in each case the pH of the ready-to-use cleaning solution. If it is a liquid agent, this preferably has a viscosity of up to 1000 mPas. By contrast, gelatinous or pasty cleaning agents can have viscosities of up to 150,000 mPas. The viscosity measurements are made at 2O ⁰ C in a Brookfield viscometer LVDV II with a rotor frequency of 20 U / min (spindle no. 31, conc. 100%).

The cleaning agent may contain one or more propellants (INCI propellants), usually in an amount of from 1 to 80% by weight, preferably from 1 to 5% by weight, in particular from 2 to 10% by weight, particularly preferably 2.5 to 8% by weight, most preferably 3 to 6% by weight.

Propellants are inventively usually propellants, especially liquefied or compressed gases. The choice depends on the product to be sprayed and the field of application. When using compressed gases such as nitrogen, carbon dioxide or nitrous oxide, which are generally insoluble in the liquid detergent, the operating pressure decreases with each valve actuation. Detergent-soluble or even solvent-acting liquefied gases (liquefied gases) as propellants offer the advantage of constant operating pressure and uniform distribution because the propellant vaporizes in the air, taking up more than a hundred times that volume.

According to INCI suitable propellants are accordingly: butanes, carbon dioxides, dimethyl carbonates, dimethyl ether, ethanes, Hydrochlorofluorocarbon 22, hydrochlorofluorocarbon 142b, hydrofluorocarbon 152a, hydrofluorocarbon 134a, hydrofluorocarbon 227ea, isobutanes, isopentanes, nitrogen, nitrous oxides, pentanes, propanes.

Chlorofluorocarbons (chlorofluorocarbons, CFCs) as propellant are, however, preferably largely and in particular completely dispensed with because of their harmful effect on the ozone shield of the atmosphere, which protects against hard UV radiation, the so-called ozone layer.

Preferred blowing agents are liquefied gases. Liquefied gases are gases that can be converted from the gaseous to the liquid state at usually already low pressures and 20 ^° C. In particular, under liquefied gases, however, the - in oil refineries hydrocarbons propane, propene, butane, butene, isobutane (2-methylpropane), isobutene (2-methylpropene, isobutylene) and mixtures thereof are understood as by-products in the distillation and cracking of crude oil and in the natural gas treatment in the gasoline separation.

The cleaning agent particularly preferably contains propane, butane and / or isobutane, in particular propane and butane, as one or more propellants, more preferably propane, butane and isobutane.

A cleaning agent according to the invention may further contain enzymes, in particular selected from polysaccharidases, proteases and nucleases, which are suitable for biofilm degradation.

The polysaccharidase may in particular be a β-glucanase, cellulase, hemicellulase, arabinase, xylanase, amylase, dextranase, glucosidase, galactosidase, pectinase, chitinase, lysozyme, alginate lyase or any mixtures thereof. The protease may in particular be subtilisin, thermolysin, pepsin, a carboxypeptidase, an acid protease, a serine proteinase or mixtures thereof. The nucleases may be any DNAse or RNAse.

The enzymes which can additionally be used in the enzyme preparations for the purposes of this invention can be obtained by conventional biochemical methods from the corresponding organisms. But they are also commercially available, for example from the companies Novozymes, Genencor International, Sigma, AB Enzymes or ASA enzymes. The enzyme preparations may also be of technical quality and consist of several different enzyme activities. The presence of side activities, some of which are not further characterized, can also have a favorable influence on the hydrolysis of the complex biofilm polymers.

The hygienic effect of the cleaning agent according to the invention can optionally be enhanced by the addition of germ-inhibiting agents. Suitable germ-inhibiting agents here are in particular isothiazoline mixtures, sodium benzoate and / or salicylic acid. Further examples are substances with specific activity against Gram-positive bacteria such as 2,4 _I 4'-trichloro-2 ^I -hydroxydiphenyl ether, chlorhexidine (1,6-di- (4-chlorophenyl-biguanido) -hexane) or TCC (3 , 4,4'-trichlorocarbanilide). Also, numerous fragrances and essential oils have antimicrobial properties. Typical examples are the active ingredients eugenol, menthol and thymol in clove, mint and thyme oil. An interesting natural germ inhibitor is the terpene alcohol farnesol (3,7,11-trimethyl-2,6,10-dodecatrien-1-ol), which is present in lime blossom oil and has a lily-of-the-valley odor. Glycerol monolaurate has also proven itself as a bacteriostat. The amount of these antimicrobial agents depends strongly on the efficacy of the particular compound and may be up to 5% by weight.

Also suitable as preservatives are e.g. Benzoic acid or benzoate, salicylic acid or salicylate, sorbic acid or sorbate, formic acid or formate, propionic acid or propionate, formaldehyde, glutaraldehyde, o-phenylphenol, pHB esters (for example butyl-4-hydroxybenzoate, methyl-4-hydroxybenzoate) hydroxybenzoates, ethyl 4-hydroxybenzoates, propyl 4-hydroxybenzoates), 10-undecylenic acid, hexetidine, Bronidox, bronopol, trichlorocarbanilide, p-chloro-m-cresol, triclosan, imidazolidinylurea, 2-phenoxyethanol, dimethyldimethylolhydantoin , Benzyl alcohol, dibromocyananobutane, isothiazolinone mixtures, 2-chloroacetamide, chlorhexidine gluconate, diazolidinyl urea, benzalkonium chloride, 1,2-benzisothiozolone, benzyl alcohol monochemical, 2- (2-hydroxypropyl) aminomethanol, methylene bisthiocyanate, (thiocyanomethylthio) benzothiazole, dithio-2,2 ' bis (benzmethylamide), silver chloride supported on TiO 2, didecyldimethyleneammonium chloride, N, N-bis-33-aminopropyl-C 12 -amine, sodium hydroxymethylglycinate, dehydroacetic acid, ethylene glycol formal, 2,4-

Dichlorobenzyl alcohol, 2-phenoxypropanol, 3- (4-chlorophenoxy) -1,2-propanediol, 4-chloro-3,5-dimethylphenol, hexadecylpyridinium chloride and / or 3-iodopropynyl-butyl-carbamate.

Preferably, the germ-inhibiting substances are present in amounts of up to 10, preferably between 0.01 and 5 wt .-%. As already stated above, however, in a preferred embodiment, the addition of antimicrobial agents can be completely dispensed with. Another object of the present invention is a product comprising a detergent according to the invention and a spray dispenser. The spray dispenser is preferably a manually activated spray dispenser, in particular selected from the group consisting of aerosol spray dispensers (pressurized gas containers, also known as spray can), pressure-building spray dispensers, pump spray dispensers and trigger spray dispensers, in particular pump spray dispensers and trigger spray dispensers with a transparent polyethylene or polyethylene terephthalate container. Spray dispensers are described in more detail in WO 96/04940 (Procter & Gamble) and the US patents cited therein about spray dispensers, to which reference is made in this regard and the contents of which are hereby incorporated by reference. Triggersprühspender and pump sprayer have over compressed gas tanks the advantage that no propellant must be used.

In a further preferred embodiment, however, the agent according to the invention is not atomized as an aerosol, in particular if enzymes are present, since in this case possibly small amounts of the enzymes may get into the respiratory tract and under certain circumstances trigger allergic reactions there. By means of suitable particles-passing attachments, nozzles, etc. (so-called "nozzle valves") on the spray dispenser, the enzyme can be added to the agent in a form immobilized on particles and dosed as a cleaning foam. When producing these compact foams, no respirable particles are formed so that the risk of inhaling allergens is substantially eliminated.

Yet another subject of the invention is a method for the hydrolysis of biofilms on hard surfaces, wherein the vitality of the microbial cells is not damaged. For this purpose, the enzyme preparation according to the invention or the cleaning agent according to the invention, optionally using a product according to the invention, applied to the biofilm-coated surface and optionally rinsed with clear water after an exposure time of 1 to 30 minutes, with heavy infestation even a few hours or overnight. The preparation or the agent may also be blurred or rubbed on the surface affected by biofilm before rinsing with a cloth, a sponge, a brush or other suitable for cleaning utensil, which improves the cleaning performance, for example in the presence of abrasives in the detergent. Finally, the surface is with dried off a dry cloth. If the biofilm surface is very heavily attacked, the cleaning process can then be repeated.

Cooling lubricant and anti-corrosion agent

In a particularly preferred embodiment according to the invention, the use of the compounds according to the invention is carried out in a cooling lubricant or anticorrosive agent, in particular in a reactor circulation or open recooling system whose metal surfaces must be protected from corrosion and hardening. The use is preferably carried out in a zinc-free composition. The use of the composition is preferably carried out in a pH range of 8.2 to 9.0. The metal surfaces to be protected are preferably steel, copper or non-ferrous metal surfaces. The composition preferably contains at least one dispersant component, at least one, preferably different, phosphonic acids and / or polycarboxylic acids, and preferably at least one non-ferrous metal inhibitor.

The following examples illustrate the invention without, however, limiting it to:

Examples:

General procedure for the preparation of Dibromoxoalkanoylsäuren

A solution of bromine (0.06 mol) in dry dichloromethane (8 ml) is added slowly to an ice-cooled solution of 4-oxo-2-alkenoic acid (0.03 mol) in dry dichloromethane (30 ml). The mixture is first stirred for 30 minutes in an ice bath and then again for 30 minutes at room temperature. The resulting solution is washed with aqueous sodium metabisulfite (0.5 M, 30 ml) and brine (30 ml). The solution is dried over sodium sulfate and concentrated to dryness. The yield of crude pale brownish oily 2,3-dibromo-4-oxoalkanoylic acid is between 60 and 65%. The crude product can be used for the following reaction steps without purification.

General procedure for the preparation of 3- (bromomethylene) -2-alkanones and 2-bromo-4-oxo-2-alkenoylic acids

A solution of triethylamine (8.7 mmol) in dichloromethane (5 mL) is added dropwise with stirring to an ice-cooled solution of dibromo-4-oxoalkanoic acid (3.5 mmol) in dry dichloromethane (10 mL). The resulting mixture is stirred first on ice for 2 hours and then at room temperature overnight. The mixture is then poured into dilute hydrochloric acid (50 mL, 2M) and then extracted with dichloromethane (3 x 20 mL). The combined dichloromethane extracts are washed with brine (100 ml), dried over anhydrous sodium sulfate and then concentrated to dryness. The resulting 3- (bromomethylene) -2-alkanone shows a slightly brownish color. The crude product is chromatographed on silica gel using dichloromethane as eluent. The yield of colorless 3- (bromomethylene) -2-alkanone oil is between 52 and 70%. Continuing the elution with dichloromethane / ethyl acetate in the ratio 3: 1 gives 2-bromo-4-oxo-2-alkenoylic acid in a yield of 20 to 30% as an oil, which solidifies on standing at room temperature. Example:

A) The following furanone compounds and halomethylene-alkanone derivative (123) were tested:

(149)

B) Use of QSB active ingredients in technical fluids for the reduction of P. aeruginosa biofilms on glass surfaces

Execution:

The seed Pseudomonas aeruginosa DSM 939 is grown overnight on Caso agar at 37 ° C. A CFU (colony forming unit) from the solid medium is incubated rpm 150 (1st passage) in 50 ml Caso broth for 7h at 37 ⁰ C and. From the grown liquid culture 100 .mu.l germs are transferred to 50 ml of fresh Caso-nutrient medium and incubated for about 16h at 37 ° C and 150 upm. (2nd passage). From this second passage, a bacterial count of 10 ⁶ cfu / ml is used in the biofilm test. For the biofilm experiment, the germs in the above-mentioned concentration are pipetted together with a diluted complete medium (20 times DGYM-diluted TBY) into a microtiter plate (6-well chamber), which is used as a miniaturized biofilm test system. To the mixture (3 ml), the drugs to be tested are added in the desired concentration, in addition run controls without drug or without cells with. Negative controls are approaches with active ingredient, but without germ, as the active ingredients could already have an intrinsic color. As a positive control diluted full medium with germ, but without active ingredient (furanone Dehvat) is used. In addition, 1 sterile glass slide (coverslip for microscopy) of size 18x18 is placed in the 6-well chambers, on the surface of which the biofilm growth is examined. In addition, a commercially available water treatment agent is added, in whose presence (50 ppm use concentration) the effect of the furanone or the open-chain halomethylene-alkanone derivative is to be investigated. The commercially available water treatment agent is a liquid, zinc-free combination product based on various phosphonic acids, polycarboxylic acids and a non-ferrous metal inhibitor. It has a corrosion inhibiting effect on steel, copper and non-ferrous metal surfaces in the pH range from 8.2 to 9.0 and prevents deposits on pipe walls due to a dispersant component, thus guaranteeing the formation of an optimum corrosion protection film.

From each approach, triple determinations are made, ie, three coverslips are tested per batch. The 6-well plates are shaken for 6 hours or 24 hours at 30 ^° C. and 60 rpm. After the given incubation times are per approach ever 1 ml taken for germ count, diluted in Tryptone-NaCl solution and plated on Caso agar. The resulting plates are incubated at 37 ° C for 24 h and then counted. The coverslips are removed from the 6-wells at room temperature to dry and then stained for 15 minutes in new 6-wells containing 3 ml of 0.01% safranine-O solution (prepared with distilled water). Thereafter, the staining solution is filtered off with suction, removed with HaObidest non-bound dye from the glasses and the colored coverslips dried. The stained and dried surfaces of the coverslips are scanned and evaluated with Corel Draw Paint 9. In order to be able to subtract the background value (caused by the glass) from the measured value, untreated coverslips are additionally scanned.

Results and explanation of the illustrations:

Five different substances (50 ppm) were tested for their ability to suppress the biofilm of P. aeruginosa (Figure 1). After 6 hours of incubation, differences in biofilm formation in the control (in FIG. 1) can be recognized in comparison to the approaches with the QSB active substances. The three best acting substances (105, 123, 139) were tested in two concentrations (5 ppm and 50 ppm) alone and in addition to the commercial water treatment agent to find the most effective compound. In each case 5 ppm (first column) and 50 ppm (second column) QSB concentrations were added to the batches in the absence (in FIG. 2A) or present (in FIG. 2B) of the water treatment agent. The batch with 50 ppm substance 123 showed a biofilm reduction of almost 70% without the addition of the water treatment agent, while in the presence of the water treatment agent the biofilm reduction was still 50%. When using 5 ppm substance 123, only small biofilm reductions (about 10%) were observed in batches without and with water treatment agent compared to the control. Without water treatment, Furanone 105 and 139 showed the best effect (compound biofilm reduction above 30%). In combination with the water treatment agent, the effect of substances 105 and 139 diminishes, but they still have significant activity. However, by far the best activity shows substance 123. This new finding was confirmed by a concentration series of substance 123 in the presence of the water treatment agent (FIG. 3). There is a clear dependency between biofilm reduction and the active ingredient concentration used, since with the use of 25 ppm of substance 123, a significant reduction in biofilm (approx. 30%) could be achieved, in contrast to the approach of 5 ppm. The effect of a QSB agent depends on its concentration and the chemical composition of the fluid in which it is to be used. Cell growth was not disturbed in all approaches, ie the biofilm reduction is based on a non-biocidal effect.

Claims

claims

1. Use of one or more compounds selected from compounds of the formula (I)

I and compounds of the formula (II)

for the control of processes based on microbial interaction, in particular for the control of the formation and / or maturation of biofilms, particularly preferably of biofilms in which Gram-negative bacteria are involved, in the industrial and / or institutional field, the radicals R ^< | R2 and R3, which may be different or identical, and the radicals Ra, Rb ₁ Rc and Rd, which may also be different or identical, are independently selected from halogen, in particular chlorine, bromine, fluorine or iodine, trifluoromethyl, hydrogen , Alkyl, cycloalkyl, alkenyl, alkynyl, heteroalkyl, alkoxy, alkylsulfanyl, alkylsulfonyl, alkylsulfoxidyl, alkanoyl, acyl, alkoxycarbonyl, alkylaminocarbonyl, alkylsulfanylcarbonyl, hydroxy, monoalkylamino, dialkylamino, aryl, heteroaryl, heterocycloalkyl, arylalkyl, arylsulfonyl, arylsulfoxidyl, arylcarbonyl, aryloxycarbonyl , Arylaminocarbonyl, formyl and cyano, and wherein X is halogen, in particular fluorine, chlorine, bromine or iodine.

2. Use according to claim 1, characterized in that the radicals Ri, R ₂ and R ₃ and the radicals Ra, Rb, Rc and Rd independently selected from halogen, Ci.i ₂ alkyl, Ci- ₁₂ alkoxy, C ₂ -i ₂ alkenyl, C _2- i2-alkynyl, C ₆ H aryl, and C ₆ aryl-Ci -i _{4 4} alkyl.

3. Use according to claim 1 or 2, characterized in that Ri and R ₂ are independently selected from ₄ alkyl, R ₃ is Ci- from hydrogen and X is bromine.

4. Use according to claim 3, characterized in that Ri is ethyl, R _{2 is} methyl, R _{3 is} hydrogen and X is bromine.

5. Use according to claim 1 or 2, characterized in that Ra is halogen, Rb is di ₂ alkyl, Rc is hydrogen or Ci- ₄ alkyl and Rd is halogen.

6. Use according to claim 1 or 2, characterized in that Ra is C ₁₂ -alkyl, Rb is halogen, Rc is hydrogen or C- _M- alkyl and Rd is halogen.

7. Use according to one of claims 1 to 6, characterized in that the use in institutional and / or industrial sterilization, disinfection, impregnation, preservation, corrosion protection, washing, dishwashing or cleaning agents, cooling or cooling lubricants (technical application solutions) or in the field of water purification / water treatment.

8. Use according to one of claims 1 to 6, characterized in that the use in means for finishing or treatment of surfaces, food, filter media, adhesives, building materials, building aids, ceramics, plastics, metals, textiles, furs, paper, skins, Polymer, leather or packaging in the industrial and / or institutional area takes place.

9. Use according to one of claims 1 to 8, characterized in that the application in the pharmaceutical, food, brewery, dairy, medical technology, paint, wood, textile, cosmetics, leather, tobacco , Fur, rope, paper, pulp, plastics, fuel, oil, rubber, automotive, polymer, steel or engineering industries.

10. Use according to one of claims 1 to 6, characterized in that the application is carried out in medical devices, instruments and apparatus, in particular in catheters or endoscopes.

11. Use according to one of claims 1 to 6, characterized in that the application is carried out in industrial and / or institutional machinery, apparatus or equipment.

12. Use according to one of claims 1 to 8, characterized in that the application in hospitals, hotels, schools, swimming pools, baths, cisterns, public transport, public buildings, public sanitary facilities, saunas, sports facilities or doctor or massage practices takes place ,

13. Use according to one of claims 1 to 12, characterized in that the compound or the compounds of the formula (I) and / or according to formula (II) in a concentration in the range of 1 ppm to 1000 ppm, in particular 2 to 500 ppm and more preferably 5 to 50 ppm are used.

M.Composition containing, equipped and / or coated with at least one substance selected from compounds of the formula (I)

and compounds of the formula (II)

wherein the radicals Ri, R ₂ and R ₃ , which may be different or identical, and the radicals Ra ₁ Rb, Rc and Rd, which may also be different or identical, are independently selected from halogen, in particular chlorine, bromine, fluorine or iodine, trifluoromethyl, hydrogen, alkyl, cycloalkyl, alkenyl, alkynyl, heteroalkyl, alkoxy, alkylsulfanyl, alkylsulfonyl, alkylsulfoxidyl, alkanoyl, acyl, alkoxycarbonyl, alkylaminocarbonyl, alkylsulfanylcarbonyl, hydroxy, monoalkylamino, dialkylamino, aryl, heteroaryl, heterocycloalkyl, arylalkyl, arylsulfonyl , Arylsulfoxidyl, arylcarbonyl, aryloxycarbonyl, arylaminocarbonyl, formyl and cyano, and wherein X is halogen, in particular fluorine, chlorine, bromine or iodine, characterized in that it is an institutional and / or industrial sterilization, disinfection, impregnation , Preservatives, detergents, dishwashing or cleaning agents, cooling or cooling lubricants or a Wasserbehandmittmitt el acts.

15. The composition according to claim 14, characterized in that it is an anti-corrosive agent containing at least one dispersant, at least one, preferably different, phosphonic acids and / or polycarboxylic acids, and at least one non-ferrous metal inhibitor.

16. Composition comprising, equipped and / or coated with at least one substance selected from compounds of the formula (I) and compounds of the formula (II) where the radicals Ri, R ₂ and R ₃ , which may be different or identical, and the radicals Ra, Rb, Rc and Rd ₁ which may also be different or identical, are independently selected from halogen, in particular chlorine, bromine, fluorine or iodine, trifluoromethyl, hydrogen, alkyl, cycloalkyl, alkenyl, alkynyl, heteroalkyl, alkoxy, alkylsulfanyl, alkylsulfonyl, alkylsulfoxidyl, alkanoyl, acyl, Alkoxycarbonyl, alkylaminocarbonyl, alkylsulfanylcarbonyl, hydroxy, monoalkylamino, dialkylamino, aryl, heteroaryl, heterocycloalkyl, arylalkyl, arylsulfonyl, arylsulfoxidyl, arylcarbonyl, aryloxycarbonyl, arylaminocarbonyl, formyl and cyano, and wherein X is halogen, in particular fluorine, chlorine, bromine or iodine , characterized in that it is filter media, adhesives, building materials, building aids, textiles, furs, paper, hides, leather, ceramics, plastics, polymers, packaging or metals.

17. A composition comprising, equipped and / or coated with at least one substance selected from compounds of the formula (I) and compounds of the formula (II) wherein the radicals R ₁ , R ₂ and R ₃ , which may be different or identical, and the Radicals Ra, Rb, Rc and Rd, which may also be different or identical, are independently selected from halogen, in particular chlorine, bromine, fluorine or iodine, trifluoromethyl, hydrogen, alkyl, cycloalkyl, alkenyl, alkynyl, heteroalkyl, alkoxy, alkylsulfanyl , Alkylsulfonyl, alkylsulfoxidyl, alkanoyl, acyl, alkoxycarbonyl, alkylaminocarbonyl, alkylsulfanylcarbonyl, hydroxy, monoalkylamino, dialkylamino, aryl, heteroaryl, heterocycloalkyl, arylalkyl, arylsulfonyl, arylsulfoxidyl, arylcarbonyl, aryloxycarbonyl, arylaminocarbonyl, formyl and cyano, and wherein X is halogen, in particular Fluorine, chlorine, bromine or iodine, characterized in that it is a means of equipment or treatment of Surfaces, foods, filter media, adhesives, building materials, building aids, ceramics, plastics, metals, textiles, furs, paper, hides, polymers, leather or packaging in the industrial and / or institutional area.

18. The composition according to any one of claims 14 to 17, characterized in that Ri and R _{2 are} independently selected from

R _{3 is} hydrogen and X is bromine.

19. A composition according to claim 18, characterized in that Ri is ethyl, R _{2 is} methyl, R _{3 is} hydrogen and X is bromine.

20. A process for the control of processes based on microbial interaction in the industrial and / or institutional field, characterized in that a) optionally determines the interacting microorganisms, b) optionally among the compounds of formula (I) and formula (II) the appropriate And c) adding the compound or compounds of formula (I) and / or formula (II) in sufficient amount for the desired control to the medium in which the microbial interaction takes place.

21. The method according to claim 20, characterized in that the microorganisms are selected from bacteria, algae or fungi, in particular bacteria, preferably Gram-negative bacteria.

22. The method according to claim 20 or 21, characterized in that the microbial interaction is selected from the formation and / or maturation of biofilms, multicellular Schwärmverhalten, the concerted formation of antibiotic resistance, the concerted synthesis of antibiotics, the concerted synthesis of pigments , the concerted production of extracellular enzymes, especially hydrolytic enzymes, as well as the concerted production of virulence factors, preferably the formation and / or maturation of biofilms.