CA2068894A1 - Controlling slime-forming microorganisms - Google Patents
Controlling slime-forming microorganismsInfo
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- CA2068894A1 CA2068894A1 CA002068894A CA2068894A CA2068894A1 CA 2068894 A1 CA2068894 A1 CA 2068894A1 CA 002068894 A CA002068894 A CA 002068894A CA 2068894 A CA2068894 A CA 2068894A CA 2068894 A1 CA2068894 A1 CA 2068894A1
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Abstract
COMBATTING SLIME-FORMING MICROORGANISMS
This invention relates to the use of cysteine and/or cysteine derivatives for controlling slime-forming micro-organisms, to a process for controlling slime-forming mi-croorganisms and to an antimicrobial slime-control prepara-tion containing cysteine and/or a cysteine derivative, either alone or in combination with microbicides, for use in the process.
In the context of the invention, bioslimes are under-stood to be the viscid secretions of microorganisms, par-ticularly bacteria, and the secretion-producing microor-ganisms themselves where they are part of the viscid mass.
This invention relates to the use of cysteine and/or cysteine derivatives for controlling slime-forming micro-organisms, to a process for controlling slime-forming mi-croorganisms and to an antimicrobial slime-control prepara-tion containing cysteine and/or a cysteine derivative, either alone or in combination with microbicides, for use in the process.
In the context of the invention, bioslimes are under-stood to be the viscid secretions of microorganisms, par-ticularly bacteria, and the secretion-producing microor-ganisms themselves where they are part of the viscid mass.
Description
8 9 ~
The adhesion of microorganisms to hard surfaces and the devalopment of bioslimes is a process which play~ a considerable part both in nature and in man-made installa-tions, ~or example in pipelines, water treatment plants, and pipes for cooling liquids. The microorgarlisms which, depending on their environmental conditions, produce the cell enveloping slime layers that are responsible for their adhesion to surfaces of various kinds include both patho-genic and apathogenic species. Microorganism~ such as these form microcolonies and produce biofilms, often in the form of firmly adhering structures. A key factor in the relatively favorable growth conditions for microorganisms in industrial environments is the high percentage of reused liquids or liquids circulating in closed systems.
Since both aerobic and anaerobic microorganisms are capable of slime formationl the problem of bioslimes can also arise in places which are not permanently situated below the liquid level. In addition to the change in the flow properties of the system caused by changes in the vis-cosity of the flowing medium - attributable to dissolved or suspended slimes - and the reduction in pipe diameter or the blockage of membranes by firmly adhering slimes, damage can be caused to the colonized surfaces themselves by the effect o~ extracellular enzymes or aggressive metabolism products of the microorganisms. Accordingly, attempts have long been made to find ways of effectively controlling slime-forming microorganisms.
In principle, substances which have an antimicrobial effect against fre~ly moving bacteria and which do not af-fect the flow properties of the flowing medium in liquid-;` carrying systems may also be used ~or controlling slime-~orming bacteria. Thus, it has been proposed to add chlor-ine, quaternary ammonium compounds, tin compounds, sul-fones, thiocarbamates, guanidine derivatives and thio-- 3s cyanates to the liquids in industrial coolin~ systems (L.E.
Palmer, Chem.-Anl. Verf. 1980, 78). Howeverl bacteria growing in biofilms, i.e. in slime-covered cultures adher-~ 2 ,~
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ing more or less firmly to surfaces, are generally, by vir-tue o~ the protective slime layer surrounding them, far ~ore resistant to biocides than ~reely moving bacteria, ~o that relatively high disinfectant concentrations have to be s used ko control slime-forming bacteria, although this can have unwanted side effects, for example damage to the ma-terial colonized by the microorganisms. ~he complete de-struction of microorganisms in liquid-carrying systems of industrial installations is generally not necessary at all because, normally, individual freely moving bacteria which do not form slimes do not hav~ a significant adverse effeot on the flow properties.
Accordingly, the problem addressed by the present invention was to prevent bacteria in liquid-carrying sys-- 15 tems of industrial installations, particularly in water-carrying pipes and circulation systems or even in central : disinfection dispensing systems, for example in hospitals, from forming bioslimes and from colonizing surfaces and also to remove bioslimes adhering to surfaces.
According to the invention, this problem has been solved by the use of cysteine, particularly L-cysteine, and/or cysteine derivatives 2S an additive to the liquid and, in particular, substantially aqueous medium of the liquid-carrying system. The cysteine derivatives suitable for use in accordance with the invention are, in particu-: lar, N- and/or S-acyl derivatives, among which N-acetyl-L cysteine, S-acetyl-L-cysteine and N,S-diacetyl-L-cysteine and mixtures thereof are particularly preferred.
. The use of cysteine and/or cysteine derivatives in accordance with the inv ntion limits the slime-forming capacity of bacterial populations typically occurrin~ in practice to such an extent that, in general, slime forma-tion is significantly reduced by concentrations o~ only 500 ppm of such compounds, but without stopping the growth of the bacteria - which can often be tolerated without their slime production - ~o the same extent.
Accordingly, in cases where not only the formation of ,, ., ; . ,,:
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The adhesion of microorganisms to hard surfaces and the devalopment of bioslimes is a process which play~ a considerable part both in nature and in man-made installa-tions, ~or example in pipelines, water treatment plants, and pipes for cooling liquids. The microorgarlisms which, depending on their environmental conditions, produce the cell enveloping slime layers that are responsible for their adhesion to surfaces of various kinds include both patho-genic and apathogenic species. Microorganism~ such as these form microcolonies and produce biofilms, often in the form of firmly adhering structures. A key factor in the relatively favorable growth conditions for microorganisms in industrial environments is the high percentage of reused liquids or liquids circulating in closed systems.
Since both aerobic and anaerobic microorganisms are capable of slime formationl the problem of bioslimes can also arise in places which are not permanently situated below the liquid level. In addition to the change in the flow properties of the system caused by changes in the vis-cosity of the flowing medium - attributable to dissolved or suspended slimes - and the reduction in pipe diameter or the blockage of membranes by firmly adhering slimes, damage can be caused to the colonized surfaces themselves by the effect o~ extracellular enzymes or aggressive metabolism products of the microorganisms. Accordingly, attempts have long been made to find ways of effectively controlling slime-forming microorganisms.
In principle, substances which have an antimicrobial effect against fre~ly moving bacteria and which do not af-fect the flow properties of the flowing medium in liquid-;` carrying systems may also be used ~or controlling slime-~orming bacteria. Thus, it has been proposed to add chlor-ine, quaternary ammonium compounds, tin compounds, sul-fones, thiocarbamates, guanidine derivatives and thio-- 3s cyanates to the liquids in industrial coolin~ systems (L.E.
Palmer, Chem.-Anl. Verf. 1980, 78). Howeverl bacteria growing in biofilms, i.e. in slime-covered cultures adher-~ 2 ,~
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ing more or less firmly to surfaces, are generally, by vir-tue o~ the protective slime layer surrounding them, far ~ore resistant to biocides than ~reely moving bacteria, ~o that relatively high disinfectant concentrations have to be s used ko control slime-forming bacteria, although this can have unwanted side effects, for example damage to the ma-terial colonized by the microorganisms. ~he complete de-struction of microorganisms in liquid-carrying systems of industrial installations is generally not necessary at all because, normally, individual freely moving bacteria which do not form slimes do not hav~ a significant adverse effeot on the flow properties.
Accordingly, the problem addressed by the present invention was to prevent bacteria in liquid-carrying sys-- 15 tems of industrial installations, particularly in water-carrying pipes and circulation systems or even in central : disinfection dispensing systems, for example in hospitals, from forming bioslimes and from colonizing surfaces and also to remove bioslimes adhering to surfaces.
According to the invention, this problem has been solved by the use of cysteine, particularly L-cysteine, and/or cysteine derivatives 2S an additive to the liquid and, in particular, substantially aqueous medium of the liquid-carrying system. The cysteine derivatives suitable for use in accordance with the invention are, in particu-: lar, N- and/or S-acyl derivatives, among which N-acetyl-L cysteine, S-acetyl-L-cysteine and N,S-diacetyl-L-cysteine and mixtures thereof are particularly preferred.
. The use of cysteine and/or cysteine derivatives in accordance with the inv ntion limits the slime-forming capacity of bacterial populations typically occurrin~ in practice to such an extent that, in general, slime forma-tion is significantly reduced by concentrations o~ only 500 ppm of such compounds, but without stopping the growth of the bacteria - which can often be tolerated without their slime production - ~o the same extent.
Accordingly, in cases where not only the formation of ,, ., ; . ,,:
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bioslimes, but also the growth of the microorganisms is to be reduced to a very considerable extent, a microbicidal agent selected from the group consisting of aldehydic mi-crobicides, quaternary ammonium compounds, phenolic micro-bicides, isothiazolinones and mixtures thereof is prefer-ably add~d to the liquid in addition to cysteine or the cysteine derivative, more particularly L-cysteine, N-acetyl-L-cysteine, S-acetyl-L-cysteine and N,S-diacetyl-L-cysteine and mixtures thereof, N-acetyl-~-cysteine being particularly preferred. It has been found in this regard that thess microbicidal agents are effective in much lower concentrations than in the absence of the cysteine deriva-tive. In addition, the slime-control property of the cys-teine derivative is unexpectedly enhanced by the addition of these microbicides.
Accordingly, the process according to the invention essentially comprises adding cysteine and/or a cysteine de-rivative in combination with one or more of the microbi-cides mentioned above to the liquid of the liquid-carrying ~- 20 system in effective quantities for controlling slime forma-tion. It is preferably carried out in such a way that con-centrations of cysteine and/or cysteine derivative of 50 ppm to 5,000 ppm and concentrations of microbicide of 5 ppm to 5,000 ppm are present in the liquid. Where aldehydic microbicides axe used, the concentrations are preferably from 50 ppm to 3,000 ppm and, more preferably, from 300 ppm to 1,000 ppm aldehydic microbicide and preferably from 50 ppm to 2,000 ppm and, more preferably, from 200 ppm to 1,000 ppm cysteine and/or cysteine derivative. Where quat ernary ammonium compounds are used, the concentrations are preferably from 10 ppm to 500 ppm and, more preferably, ; from 50 ppm to 250 ppm quaternary ammonium compound and preferably from 50 ppm to 1,000 ppm and, more preferably, from 100 ppm to 500 ppm cysteine and/or cysteine deriva-~ive. Whare phe~olic microbicides are used, the concentra-tions are preferably from 5 ppm ts 3,000 ppm and, more preferably, from 10 ppm to 2,000 ppm phenolic microbicide .
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and prefera~ly from 50 ppm to 1,000 ppm and, more preferab-ly, from 100 ppm to 500 ppm cysteine and/or cysteine de-rivative. Where isothiazolinones are used, the concentra-tions are preferably from 5 ppm to 500 ppm and, more pref erably, from 10 ppm to 100 ppm isothiazolinone and prefer-ably from 25 ppm to 1,000 ppm and, more preferably, from 50 ppm to 250 ppm cysteine and/or cysteine derivative.
These concentrations may be established by addition of the individual components both in bulk and, more particu-larly, in aqueous solution, but are advantageously estab-lished by the use of a preparation according to the inven-tion containing a combination of cysteine or cysteine de-rivatives, more particularly L-cysteine, N-acetyl-L-cystP-ine, S-acetyl-L-c.ysteine, N,S-diacetyl-L-cysteine and mix-ture6 thereof, with a microbicide selected from the group consisting of aldehydic compounds, quaternary ammonium com-pounds, phenolic compounds and isothiazolinones, and mix-tures thereof.
L-cysteine is a naturally occurring amino acid and is ~o generally obtained from prot~in hydrolyzates. N-acetyl-L-cystaine may be prepared from L-cysteine or its salts by the process described in U. S. Patent 3,091,569. S-acetyl-L-cysteine may be prepared, for example, by the process described by Y. Trudelle and A. Caille in Int. J. Peptide ~ 25 Prot. Rss. 10 (1977), 291. Th~e preparation of N,S-diacetyl ; cysteine is described, for example, by X.A. Smith and G.
-~ Gorin in J. Org. Chem. 26 (1961), 828.
;~ Cysteine and the cysteine derivatives may be used as such or in the form of their salts, particularly their al-kali metal salts. Their acid adducts, ~or example their hydrochlorides, may also be used. The quantities of cyste-ine or cysteine derivatives mentioned in the context of the - invention always apply to the free compounds.
The aldehydic microbicide suitable for use in the pro-3s cess according to the invention is preferably a compound selected from the group consisting of saturated aliphatic ; aldehydes containing 1 to 6 carbon atoms, saturated alipha-~:, ''~
,, 2~8~
tic dialdehydes containing 2 to 6 carbon atoms, aromatic dialdehydes and mixture~ thereof. Formaldehyde, acetal-dehyde, propionaldehyde, glyoxal, malonic dialdehyde, suc-cinic dialdehyde, glutaric dialdehyde and phthalic dialde-s hyde individually or in admixture are particularly suit-able. The aldehydic microbicide may be present as such or in the f~rm of an adduct which releases it under the in-use conditions, for example an adduct with amines or am-ides. Aldehydic microbicides such as these are preferab-~o ly present in the preparations according to the invention in quantities of 1 % by weight to 25 % by weight and, more preferably, in quantities of 5 % by weight to 15 % by weight.
The quaternary ammonium compounds suitable for the preparation according to the invention are preferably pyr idines N-alkylated with C10_22 alkyl groups and optionally substituted by halogen and/or C~ alkyl groups, imidazo-lines N,N'-dialkylated with Cl_l8 alkyl or benzyl groups and optionally substituted by Cl_l8 alkyl groups, and com-:`i 20 pounds corresponding to formula I
~i, Rl ` R4-N~-R2 ~ (I), i 2s in which Rl and R2 independently of one another represent alkyl radicals containing 1 to 3 carbon atoms or benzyl, . : halogenated or alkylated benzyl radicals; R3 and R4 indepen-dently of one another represent alkyl, benzyl or halogen-ated or alkylated benæyl radicals containing 7 to 22 carbon : atoms; and X~ is an anion from the group consisting of sul-~ate, hydrogen sul~ate, the halides and carboxylates and i mixtures thereof. Quaternary ammonium compounds such as these are preferably present in the preparations according ~'~ 35 to the invention in quantities of from 0.5 % by weight to : 50 ~ by weight and, more preferably, in quantities of 2 %
. by weight to 20 % by weightj based on the preparation as a .: .
. whole.
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9 ~1 Particularly suitable quaternary ammonium salts are pyridinium compounds N alkylated with C10_l~ alkyl groups, N,N'-dialkylated 2-imidazolinium compounds substituted in the 2-position by Cl_18 al~yl groups, and/or compounds cor-s responding to formula I in which R1 and R~ are methyl rad-icals, R3 is a C8_18 alkyl radical or a benzyl or chlorin-ated benzyl radical, and Rg is a C8_18 alkyl radical. Ex-amples of such quaternary ammonium salts are N-decyl pyri-dinium chloride, N-dodecyl pyridinium chloride, N-tetra-o decyl pyridinium chloride, N-hexadecyl pyridinium chloride, 1,3-dimethyl-2-heptyl imidazolinium chloride, 1,3-dimethyl-2-nonyl imidazolinium chloride, 1-methyl-2-heptadecyl-3~
benzyl imidazolinium chloride, 1-decyl-2,3-dimethyl imid-azolinium chloride, l-dodecyl-~-methyl-3-benzyl imidazolin-S ium chloride, 1-benzyl-2-methyl-3-octadecyl imidazolinium chloride, 1-benzyl-2-methyl-3-dodecyl imidazolinium chlo-ride, dimethyl dioctyl ammonium chloride, didecyl dimethyl ammonium chloride, didodecyl dimethyl ammonium chloride, dimethyl ditetradecyl ammonium chloride, dihexadecyl di-20 methyl ammonium chloride, dimethyl dioctadecyl ammoniumchloride, decyl dimethyl octyl ammonium chloride, dimethyl dodecyl octyl ammonium chloride, benzyl decyl dimethyl ~ ammonium chloride, benzyl dimethyl dodecyl ammonium chlo-:~ ride, benzyl dimethyl tetradecyl ammonium chloride, chloro-Z5 benzyl decyl dimethyl ammonillm chloride, decyl-(dichloro-; benzyl)-dimethyl ammonium chloride, and the corresponding compounds containing bromide, iodide, sulfate, acetate or propionate instead of chloride as anions.
Phenolic microbicides suitable for the process accord-30 ing to the invention are, in particular, compounds from the : group consisting of phenol, o-phenylphenol, cresyl, thymol, and mono- or poly-halogenated derivatives thereof, includ-' ing for example p-chloro-m-cresol, 4-chlorothymol, 5-: chloro-2-(Z,4-dichlorophenoxy)-phenol, and 2,2'-thio-bis-3s (4-chlorophenol), and mixtures thereo~. These phenolic microbicides are preferably present in the preparations according to the invention in quantities of 0.5 % by weight ....
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to 50 % by weight and, more preferably, in quantities of 3 % by weight to 20 % by weight, based on the preparation as a whole.
Isothiazolinones suitable for use in the preparatlons according to the invention are, in particular, 1~2-benzlso thiazolin~3-one, 2-methyl-4-isothiazolin-3-one, 5-chloro-2-methyl-4-isothiazolin-3-one and 2-octyl-4-isothiazolin-3-one. The isothiazolinones are preferably present in the preparations according to the invention in quantities of 0.2 % by weight to 20 % by weight and, more preferably, in quantities of 0.5 % by weight to 10 % by weight, based on the preparation as a whole.
The slime-control preparation according to the inven-: tion preferably contains 0.5 % by weight to 75 % by weight and, more preferably, 5 % by weight to 50 % by weight of cysteine and/or cysteine derivative. This quantity may vary in dependence upon the microbicides present and, in the presence of aldehydic microbicides, is preferably from 1 0.5 ~ by weight to 25 % by weight and, more preferably, `. 20 from 2 % by weight to 10 % by weight; in the presence of isothiazolinones, it is preferably from 1 % by weight to 20 % by weight and, more preferably, from 2 % by weight to 10 ~ by weight and, in the presence of phenolic microbi-cides, is preferably from 2 % by weight to 50 ~ by weight ~, 25 and, more preferably, ~rom 5 % by wei~ht to 20 ~ by weight, j ~ based in each case on the preparation as a whoIe.
The pH value of the slime-control preparations accord-. : ing to the invention may optionally be adjusted to the val-: ue required for the particular application envisaged ky the '~ 30 addition of small quantities and, more particularly, not more than 1 ~ by weiyht, based on the preparation as a whole, of known acids or bases. However, the preparations according to the invention are preferably free from such acids or bases.
; 35 In addition, the slime~control preparation according to the invention may contain components typically encoun-tered in microbicidal preparations, such as dyes, corrosion ~.: .. . .
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2~ g~4 inhibitors, antioxidants, surfactants, and/or complexing agents, and optionally other antimicrobial compounds.
These components are preferably present in quantities of not more than 15 % by weight and, more preferably, in quantities of not more than 5 % by weight, based on the preparation as a whole.
~he production of the prepar~tions according to the invention has no special features and is advantageously carried out simply by mixing the components. The individu-al components may be used in bulk or, preferably in the production of liquid preparations, in the form of aqueous solutions of which some are commercially available.
The preparations according to the invention may be present in the form of concentrated aqueous solutions which are diluted to the desired in-use concentration by addition of water or the liquid flowing through the liquid-carrying system. Where solid microbicides are incorporated, how-ever, the preparations according to the invention are pref-erably present in solid form, for example in powder form.
The unexpectedly advantageous antimicrobial effect of the process according to the invention is reflected in the fact that, through the use of cysteine and/or a cysteine derivative in combination with a microbicidal agent, the formation o~ bioslimes is prevented much more effectively, , 25 i.e. in lower active-substance concentrations, than would ha~e been expected from a knowledge of the effect of the individual components. In addition, the process according to the invention also enables existing slime-covered, ~irmly-adhering bacterial colonies and films to be effec-tively removed from the colonized surfaces.
Ex~mples Exalllpl0 1 The substances to be used in accordance with the invention, L-cysteine (Il), N-acetyl-L-cysteine (I2), S-acetyl-L-cysteine (~3) and N,S-diacetyl-L-cysteine ~I~3, and also the amino acids or amino acid derivatives, L-methionine (Cl~, N-acetyl L-methionine (C~) and L-serine ' - ' ".'' . ~
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(C3), were tested aga~nst representative slime-forming isolates ~rom (A~ a lavatory cist2rn, (B) a paint coagula-tion bath of an automobile manufacturer and (C3 a polyure-thane block of a pipe system carrying tap water.
Quantities of 40 ml of a presterilized nutrient medium consisting of 10 g of malt extract, 4 g of yeast extract, 4 g of glucose, 0.1 g of CaCO3, 15 g of agar and 750 ml distilled water were inoculated with the isolates in an Erlenmeyer flask. Each substance was added in a defined concentration. Aftar thorough mixing, quantities of 3 x 10 ml were removed from each flask and applied to agar plates.
The samples were incubated for 24 hours at 30C and then for another 6 days at room temperature. The agar plates were then visually evaluated for percentage growth. The growth values set out in Table 1 are average values from three tests; the evaluation was differentiated according to growth (~) and a combination of growt~ and slime formation ~G + ~)~
Exa~pl~ 2 ,~ 20 The preparations P~ to P12 characterized by their oom~
position in Table 2 (quantities in % by weight) were pre-pared by mixing N-acetyl-L-cysteine (I2~ with aqueous solu-'~ tions of the microbicidal compounds.
- EY~P1~ 3 Tests for assessing the microbicidal effect 2s Solutions containing the respective active substances in the concentrations shown in Table 3 were produced from preparations Pl to P4 by corresponding dilution with water.
Th~ antimicrobial activity was tested a~ainst the slime-forming bacterial species Enterobacter cloacae in a quan-titative suspension test carried out in accordance with the "Richtlinien fur die Pr~fung und Bewertung chemischer Des-inf~ktionsverfahren (Guidelines for the Testing and Evalua-tion of Chemical Disinfection Processes)" of the Deutsche Gesellschaft ~ilr ~ygiene und Mikrobiologie ~DGHNJ, 1981.
3s To this end, quantities of 10 ml of the diluted slime-~-on-trol agent to be tested were mixed with 0.1 ml of a germ suspension (about 109 germs per ml) at 20C. After a con-:~ 10 .:
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Table l S Compound Concentratlon A B C
tRPml G G + S G G + S ~ G ~ S
~ [~1 [%~ 196] [~] 1%]
_ _ _ _ _ 100 100 100 100 100 100 _ _ I Il 250 lO0 lO0 lO0 lO0 lO0 lO0 Il 500 lO0 0 lO0 90 lO0 lO0 Il 750 0 0 lO0 R0 lO0 lO0 Il lO00 0 0 0 0 0 0 .' _ . I2 250 lO0 lO0 lO0 50 100 100 I2 500 lO0 0 100 50 lO0 80 I2 750 0 0 lO0 30 lO0 50 ~,~ I3 250 100 lO0 lO0 70 lOo lO0 I3 500 lO0 0 lO0 50 lO0 lO0 I3 750 0 0 lO0 20 lO0 lO0 I3 lO00 0 0 lO0 0 lO0 20 ,, _ _ _ : I4 250 10 nd. 10 nd. nd. nd.
I4 500 5 nd. 5 nd. nd. nd.
I4 750 0 nd. 0 nd. nd. nd.
~ 30 I4 lO00 0 nd. 0 nd. nd.nd.
., _ Cl 250 lO0 lO0 lO0 lO0 lO0lO0 : ~l 500 lO0 lO0 lO0 lO0 100lO0 ~' : Cl 750 lO0 lO0 lO0 lO0 100lO0 Cl lO00 :lO0 lO0 I00 lO0 100lO0 C2 250 lO0 lO0 lO0 lO0 100lO0 : C2 500 lO0 lO0 lO0 lO0 lO0lO0 C2 750 l~0 lO0 lO0 lO0 lO0100 ' ~ ~40 C2 : lO00 lO0lO0 lO0 lO0 lO0lO0 : : _ : C3 250 l~0lO0 lO0 lO0 lO0lO0 : ~ ~3 500 lO0lO0 lO0 100 lO0lO0 ! C3 750 lO0lQ0 lO0 lO0 lO0100 C3 lO00 ;lO0lO0 lO0 lO0 lO0lO0 . nd.: not determin~d ;: ;
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20~94 Tabl~ 2: Composltlon [~ by weight]
Pl P2 P3 P4 PS P6 P7 P~ P9 P10 ~11 Pla _ Formald~hyd~ 14 ~lyoxal - 14 - 8.8 Glutaric dlaldehyd~ - - 6 4.5 - - - - - - - -Dodigen~1611 ) - - - - 5 Bardac~22b) - - - - - 5 Kathon3CGC) - - - - - - 1.5 5 Phenol - - - - - - - - 20 40 o-Phenylphenol - - - - - - - - - - 1 5 Water .............. ad 100 ): ~ixture of b~nzyl dimethyl dodecyl ammonium chloride and benzyl d1methyl t~tradecyl ammonium chloride, suppli~r: Hoech~t ): Dldecyl dimethyl ammonium chloride, supplier: Lonza c) M~xture of 5 chloro-2-methyl-4-i~othiazolln-3-one and 2-methyl-4-i~othia~olin-3-one, supplier: Rohm & Haas contact time of 6 hours, ~uantities of 1 ml of the mixtures were introduced into 10 ml of an aqueous disinhibiting so-`~ lution containing 3.0 ~ by weight Tween~80, 0.3 ~ by weight lecithin and 0.1 % by weight histidine. Quantities of 0.1 ml of~1:hese samples and further 1:10 dilution series were ~ ~ applied to caseinjsoya/agar plates. A~ter these subcul-- ~ tures had been incubated (24 hours at 30C), the number of germs capable of proliferating was determined. For compar-i90n, aqueous solutions of the individual components and lo water free from active substances were tested under the same conditions.
B~ample ~
;: As in Example 3, solutions having the concentrations shown in ~able 4 were prepared from preparations P5 and P6 and were used against s1ime-forming microorganisms ,~ , i - ;
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Table 3: Gen~ counts per ml A~tlve substanca Concontration aft~r 6 h tPPm~
Formaldehyde 700 8.8 x lO
Formaldehyd~ + ~2 700 + 500 U~der lO
Glyoxal 700 3.1 x lO
Glyoxal + I2 700 + 500 Under lO
Glutaric dialdehyde 300 1. a x lo Glutaric dialdehyde + I2 300 + 500 Under lO
Glyoxal + glutaric dialdehyde 440 + 225 1.1 x lO
Glyoxal + glutaric dialdehyd~ + I2 440 + 225 + SOO Under lO
Wat~r 3.3 x lO
_. _ . . , ~
___. _ Table 4: Germ count~ per ml Active ~ub~tance Concentration Germ count after tPPm] 6 h 24 h Dodi~en~1611 ) 50 l.O x lO 4.0 x lO
DodLgen01611 ) + I2 50 ~ 500 7.0 x lO Under lO
Bardac~22 ) 50 8.0 x lO Under lO
Bardac~22 ) + I2 50 + 500 Under lO Under lO
I~ 500 3.5 x lO 4.2 x lO
Water 3.8 x 1O7 4.0 x lO
)~ ~ixtur~ of ben~yl dimethyl dodecyl ammonium chloride and benzyl dimethyl tetradecyl ammonium chloridP, ~upplier: ~oech~t ): Didecyl dimethyl ammonium chl~ride, supplier: Lonza (Enterobacter cloacae); contact time 6 hours and 24 hours.
~x~mple 5 As in Example 3, aqueous solutions having the concen-trations shown in ~able 5 were produced ~rom preparations P7 to P12 and used against slime-forming microorganisms (germ 1 - Agrobacterium radiobacter; germ 2 = Enterobacter cloacae); contact time 6 hours and 24 hours.
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,, . .,, . ~ , , : ',. .; , . , 2~894 Table 5: Germ count~ per ml Active Concen- Germ count after 6 h Germ count after 24 h sub~tance tration Ippm] Germ 1 Germ 2 Germ 1 Germ 2 . _ _ Kathon~CG ) 50 1.0 x 10 1.8 x 10 Under 10 Under 10 _ _ .
. Kathon~CG ~ 15 1.9 x 10 2.5 x 10 2.0 x 10 1.3 x 10 _ _ .
Kathon0CG ) 50 Under 10 Under 10 Under 10 Under 10 Kathon~CG ) lS Undor 10 Under 10 Under 10 Under 10 Phenol 500 6.0 x 10 4.0 x 106 3.8 x 10 4.7 x 10 _ _ Phenol 2000 1.9 x 10 4.3 10 9.6 x 10 1.3 x 10 . Phenol 500 1.4 x 10 2.3 x 10 Under 10 Under 10 :~ I2 500 _ Phenol2000 Under 10 Under 10 Under 10 Under 10 .`
phenol250 Over 10 Over 10 4 x 10 1 x 105 phenol500 Over 10 Under 10 Under 10 Under 10 : :
~: o-Phenyl 4 S 2 2 ~phenol 10 3 x 10 1 x 10 Under 10 Under 10 :~ . _ o Phenyl 2 2 2 2 phenol 50 Under 10 under 10 Under 10 Under 10 _ .
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' , : :, 2~68894 Tables 2, 3, 4 and 5 clearly show that the prepara-tions containing the combination according to the inven-tion of cysteine d~rivative and microbicide show signifi-cantly stronger antimicrobial activity than the prepara-tions containiny only the microbicide. This enables the preparations according to the invention for controlling slime in liquid-carrying systems of industrial installa-tions to be used in much lower concentration than would be necsssary using the microbicides alone.
~x~ple b: Detachment test A so-called Robbins device (of. W.F. McCoy, J.D.
Bryers, J. Robbins and J.W. Costerton in Can. J . Microbi-ol 27 (1981), 910), into which polyethylene stoppers had been inserted, was integrated into a circular hose system provided with a pump. After this arrangement had been steriliz~d in an autoclave, the hos~ system was filled with a nutrient medium consisting of 5.3 g of glucose, 5.3 g of yeast extract, 13.3 g of m~lt extract and 0.13 g of calcium carbonate per liter aqueous solution and inoculated with a slime-forming bacterial strain which had been isolated from the central disin~ectant supp].y line of a hospital. After th~ nutrient solution had been pump-circulated through the device for 72 hours, 60 to 70 % of the surface o~ the poly-ethylene parts in the tube was covered with a slime layer.
The nutrient solution was removed and an aqueous solution which had been obtained by dilution of preparation P4 and which contained 440 ppm glyoxal, 225 ppm glutaraldehyde and 500 ppm N-acetyl-L-cysteine was introduced into the hose system. A~ter circulation for 24 hours, only about 10 % of the surface of the plastic parts in the tube was covered with bioslime. In a control experiment in which water free from slime control preparation was used instead of a solu-tion of the preparation according to the invention, about 50 % by weight of the surface of the plastic parts was still covered with bioslime. When the same test was car-ried out using plastic parts of polyvinyl chloride, 50 ~ of th~ surface of the plastic parts was covered with bioslime ,: ,~ : ', . .. ; . , , : '" .: ~ ., . :
~.... . .
~$8~
before and 5 to 10 % after treatment with preparation P~
according to invention; in the control exp~riment with water, 40 % o~ their surface was covered with bioslime.
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bioslimes, but also the growth of the microorganisms is to be reduced to a very considerable extent, a microbicidal agent selected from the group consisting of aldehydic mi-crobicides, quaternary ammonium compounds, phenolic micro-bicides, isothiazolinones and mixtures thereof is prefer-ably add~d to the liquid in addition to cysteine or the cysteine derivative, more particularly L-cysteine, N-acetyl-L-cysteine, S-acetyl-L-cysteine and N,S-diacetyl-L-cysteine and mixtures thereof, N-acetyl-~-cysteine being particularly preferred. It has been found in this regard that thess microbicidal agents are effective in much lower concentrations than in the absence of the cysteine deriva-tive. In addition, the slime-control property of the cys-teine derivative is unexpectedly enhanced by the addition of these microbicides.
Accordingly, the process according to the invention essentially comprises adding cysteine and/or a cysteine de-rivative in combination with one or more of the microbi-cides mentioned above to the liquid of the liquid-carrying ~- 20 system in effective quantities for controlling slime forma-tion. It is preferably carried out in such a way that con-centrations of cysteine and/or cysteine derivative of 50 ppm to 5,000 ppm and concentrations of microbicide of 5 ppm to 5,000 ppm are present in the liquid. Where aldehydic microbicides axe used, the concentrations are preferably from 50 ppm to 3,000 ppm and, more preferably, from 300 ppm to 1,000 ppm aldehydic microbicide and preferably from 50 ppm to 2,000 ppm and, more preferably, from 200 ppm to 1,000 ppm cysteine and/or cysteine derivative. Where quat ernary ammonium compounds are used, the concentrations are preferably from 10 ppm to 500 ppm and, more preferably, ; from 50 ppm to 250 ppm quaternary ammonium compound and preferably from 50 ppm to 1,000 ppm and, more preferably, from 100 ppm to 500 ppm cysteine and/or cysteine deriva-~ive. Whare phe~olic microbicides are used, the concentra-tions are preferably from 5 ppm ts 3,000 ppm and, more preferably, from 10 ppm to 2,000 ppm phenolic microbicide .
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and prefera~ly from 50 ppm to 1,000 ppm and, more preferab-ly, from 100 ppm to 500 ppm cysteine and/or cysteine de-rivative. Where isothiazolinones are used, the concentra-tions are preferably from 5 ppm to 500 ppm and, more pref erably, from 10 ppm to 100 ppm isothiazolinone and prefer-ably from 25 ppm to 1,000 ppm and, more preferably, from 50 ppm to 250 ppm cysteine and/or cysteine derivative.
These concentrations may be established by addition of the individual components both in bulk and, more particu-larly, in aqueous solution, but are advantageously estab-lished by the use of a preparation according to the inven-tion containing a combination of cysteine or cysteine de-rivatives, more particularly L-cysteine, N-acetyl-L-cystP-ine, S-acetyl-L-c.ysteine, N,S-diacetyl-L-cysteine and mix-ture6 thereof, with a microbicide selected from the group consisting of aldehydic compounds, quaternary ammonium com-pounds, phenolic compounds and isothiazolinones, and mix-tures thereof.
L-cysteine is a naturally occurring amino acid and is ~o generally obtained from prot~in hydrolyzates. N-acetyl-L-cystaine may be prepared from L-cysteine or its salts by the process described in U. S. Patent 3,091,569. S-acetyl-L-cysteine may be prepared, for example, by the process described by Y. Trudelle and A. Caille in Int. J. Peptide ~ 25 Prot. Rss. 10 (1977), 291. Th~e preparation of N,S-diacetyl ; cysteine is described, for example, by X.A. Smith and G.
-~ Gorin in J. Org. Chem. 26 (1961), 828.
;~ Cysteine and the cysteine derivatives may be used as such or in the form of their salts, particularly their al-kali metal salts. Their acid adducts, ~or example their hydrochlorides, may also be used. The quantities of cyste-ine or cysteine derivatives mentioned in the context of the - invention always apply to the free compounds.
The aldehydic microbicide suitable for use in the pro-3s cess according to the invention is preferably a compound selected from the group consisting of saturated aliphatic ; aldehydes containing 1 to 6 carbon atoms, saturated alipha-~:, ''~
,, 2~8~
tic dialdehydes containing 2 to 6 carbon atoms, aromatic dialdehydes and mixture~ thereof. Formaldehyde, acetal-dehyde, propionaldehyde, glyoxal, malonic dialdehyde, suc-cinic dialdehyde, glutaric dialdehyde and phthalic dialde-s hyde individually or in admixture are particularly suit-able. The aldehydic microbicide may be present as such or in the f~rm of an adduct which releases it under the in-use conditions, for example an adduct with amines or am-ides. Aldehydic microbicides such as these are preferab-~o ly present in the preparations according to the invention in quantities of 1 % by weight to 25 % by weight and, more preferably, in quantities of 5 % by weight to 15 % by weight.
The quaternary ammonium compounds suitable for the preparation according to the invention are preferably pyr idines N-alkylated with C10_22 alkyl groups and optionally substituted by halogen and/or C~ alkyl groups, imidazo-lines N,N'-dialkylated with Cl_l8 alkyl or benzyl groups and optionally substituted by Cl_l8 alkyl groups, and com-:`i 20 pounds corresponding to formula I
~i, Rl ` R4-N~-R2 ~ (I), i 2s in which Rl and R2 independently of one another represent alkyl radicals containing 1 to 3 carbon atoms or benzyl, . : halogenated or alkylated benzyl radicals; R3 and R4 indepen-dently of one another represent alkyl, benzyl or halogen-ated or alkylated benæyl radicals containing 7 to 22 carbon : atoms; and X~ is an anion from the group consisting of sul-~ate, hydrogen sul~ate, the halides and carboxylates and i mixtures thereof. Quaternary ammonium compounds such as these are preferably present in the preparations according ~'~ 35 to the invention in quantities of from 0.5 % by weight to : 50 ~ by weight and, more preferably, in quantities of 2 %
. by weight to 20 % by weightj based on the preparation as a .: .
. whole.
., : ', .
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9 ~1 Particularly suitable quaternary ammonium salts are pyridinium compounds N alkylated with C10_l~ alkyl groups, N,N'-dialkylated 2-imidazolinium compounds substituted in the 2-position by Cl_18 al~yl groups, and/or compounds cor-s responding to formula I in which R1 and R~ are methyl rad-icals, R3 is a C8_18 alkyl radical or a benzyl or chlorin-ated benzyl radical, and Rg is a C8_18 alkyl radical. Ex-amples of such quaternary ammonium salts are N-decyl pyri-dinium chloride, N-dodecyl pyridinium chloride, N-tetra-o decyl pyridinium chloride, N-hexadecyl pyridinium chloride, 1,3-dimethyl-2-heptyl imidazolinium chloride, 1,3-dimethyl-2-nonyl imidazolinium chloride, 1-methyl-2-heptadecyl-3~
benzyl imidazolinium chloride, 1-decyl-2,3-dimethyl imid-azolinium chloride, l-dodecyl-~-methyl-3-benzyl imidazolin-S ium chloride, 1-benzyl-2-methyl-3-octadecyl imidazolinium chloride, 1-benzyl-2-methyl-3-dodecyl imidazolinium chlo-ride, dimethyl dioctyl ammonium chloride, didecyl dimethyl ammonium chloride, didodecyl dimethyl ammonium chloride, dimethyl ditetradecyl ammonium chloride, dihexadecyl di-20 methyl ammonium chloride, dimethyl dioctadecyl ammoniumchloride, decyl dimethyl octyl ammonium chloride, dimethyl dodecyl octyl ammonium chloride, benzyl decyl dimethyl ~ ammonium chloride, benzyl dimethyl dodecyl ammonium chlo-:~ ride, benzyl dimethyl tetradecyl ammonium chloride, chloro-Z5 benzyl decyl dimethyl ammonillm chloride, decyl-(dichloro-; benzyl)-dimethyl ammonium chloride, and the corresponding compounds containing bromide, iodide, sulfate, acetate or propionate instead of chloride as anions.
Phenolic microbicides suitable for the process accord-30 ing to the invention are, in particular, compounds from the : group consisting of phenol, o-phenylphenol, cresyl, thymol, and mono- or poly-halogenated derivatives thereof, includ-' ing for example p-chloro-m-cresol, 4-chlorothymol, 5-: chloro-2-(Z,4-dichlorophenoxy)-phenol, and 2,2'-thio-bis-3s (4-chlorophenol), and mixtures thereo~. These phenolic microbicides are preferably present in the preparations according to the invention in quantities of 0.5 % by weight ....
. . .
.. . . ..
- 2 ~
to 50 % by weight and, more preferably, in quantities of 3 % by weight to 20 % by weight, based on the preparation as a whole.
Isothiazolinones suitable for use in the preparatlons according to the invention are, in particular, 1~2-benzlso thiazolin~3-one, 2-methyl-4-isothiazolin-3-one, 5-chloro-2-methyl-4-isothiazolin-3-one and 2-octyl-4-isothiazolin-3-one. The isothiazolinones are preferably present in the preparations according to the invention in quantities of 0.2 % by weight to 20 % by weight and, more preferably, in quantities of 0.5 % by weight to 10 % by weight, based on the preparation as a whole.
The slime-control preparation according to the inven-: tion preferably contains 0.5 % by weight to 75 % by weight and, more preferably, 5 % by weight to 50 % by weight of cysteine and/or cysteine derivative. This quantity may vary in dependence upon the microbicides present and, in the presence of aldehydic microbicides, is preferably from 1 0.5 ~ by weight to 25 % by weight and, more preferably, `. 20 from 2 % by weight to 10 % by weight; in the presence of isothiazolinones, it is preferably from 1 % by weight to 20 % by weight and, more preferably, from 2 % by weight to 10 ~ by weight and, in the presence of phenolic microbi-cides, is preferably from 2 % by weight to 50 ~ by weight ~, 25 and, more preferably, ~rom 5 % by wei~ht to 20 ~ by weight, j ~ based in each case on the preparation as a whoIe.
The pH value of the slime-control preparations accord-. : ing to the invention may optionally be adjusted to the val-: ue required for the particular application envisaged ky the '~ 30 addition of small quantities and, more particularly, not more than 1 ~ by weiyht, based on the preparation as a whole, of known acids or bases. However, the preparations according to the invention are preferably free from such acids or bases.
; 35 In addition, the slime~control preparation according to the invention may contain components typically encoun-tered in microbicidal preparations, such as dyes, corrosion ~.: .. . .
.
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2~ g~4 inhibitors, antioxidants, surfactants, and/or complexing agents, and optionally other antimicrobial compounds.
These components are preferably present in quantities of not more than 15 % by weight and, more preferably, in quantities of not more than 5 % by weight, based on the preparation as a whole.
~he production of the prepar~tions according to the invention has no special features and is advantageously carried out simply by mixing the components. The individu-al components may be used in bulk or, preferably in the production of liquid preparations, in the form of aqueous solutions of which some are commercially available.
The preparations according to the invention may be present in the form of concentrated aqueous solutions which are diluted to the desired in-use concentration by addition of water or the liquid flowing through the liquid-carrying system. Where solid microbicides are incorporated, how-ever, the preparations according to the invention are pref-erably present in solid form, for example in powder form.
The unexpectedly advantageous antimicrobial effect of the process according to the invention is reflected in the fact that, through the use of cysteine and/or a cysteine derivative in combination with a microbicidal agent, the formation o~ bioslimes is prevented much more effectively, , 25 i.e. in lower active-substance concentrations, than would ha~e been expected from a knowledge of the effect of the individual components. In addition, the process according to the invention also enables existing slime-covered, ~irmly-adhering bacterial colonies and films to be effec-tively removed from the colonized surfaces.
Ex~mples Exalllpl0 1 The substances to be used in accordance with the invention, L-cysteine (Il), N-acetyl-L-cysteine (I2), S-acetyl-L-cysteine (~3) and N,S-diacetyl-L-cysteine ~I~3, and also the amino acids or amino acid derivatives, L-methionine (Cl~, N-acetyl L-methionine (C~) and L-serine ' - ' ".'' . ~
., '', . . .
2~g8g~
(C3), were tested aga~nst representative slime-forming isolates ~rom (A~ a lavatory cist2rn, (B) a paint coagula-tion bath of an automobile manufacturer and (C3 a polyure-thane block of a pipe system carrying tap water.
Quantities of 40 ml of a presterilized nutrient medium consisting of 10 g of malt extract, 4 g of yeast extract, 4 g of glucose, 0.1 g of CaCO3, 15 g of agar and 750 ml distilled water were inoculated with the isolates in an Erlenmeyer flask. Each substance was added in a defined concentration. Aftar thorough mixing, quantities of 3 x 10 ml were removed from each flask and applied to agar plates.
The samples were incubated for 24 hours at 30C and then for another 6 days at room temperature. The agar plates were then visually evaluated for percentage growth. The growth values set out in Table 1 are average values from three tests; the evaluation was differentiated according to growth (~) and a combination of growt~ and slime formation ~G + ~)~
Exa~pl~ 2 ,~ 20 The preparations P~ to P12 characterized by their oom~
position in Table 2 (quantities in % by weight) were pre-pared by mixing N-acetyl-L-cysteine (I2~ with aqueous solu-'~ tions of the microbicidal compounds.
- EY~P1~ 3 Tests for assessing the microbicidal effect 2s Solutions containing the respective active substances in the concentrations shown in Table 3 were produced from preparations Pl to P4 by corresponding dilution with water.
Th~ antimicrobial activity was tested a~ainst the slime-forming bacterial species Enterobacter cloacae in a quan-titative suspension test carried out in accordance with the "Richtlinien fur die Pr~fung und Bewertung chemischer Des-inf~ktionsverfahren (Guidelines for the Testing and Evalua-tion of Chemical Disinfection Processes)" of the Deutsche Gesellschaft ~ilr ~ygiene und Mikrobiologie ~DGHNJ, 1981.
3s To this end, quantities of 10 ml of the diluted slime-~-on-trol agent to be tested were mixed with 0.1 ml of a germ suspension (about 109 germs per ml) at 20C. After a con-:~ 10 .:
' ~889~
Table l S Compound Concentratlon A B C
tRPml G G + S G G + S ~ G ~ S
~ [~1 [%~ 196] [~] 1%]
_ _ _ _ _ 100 100 100 100 100 100 _ _ I Il 250 lO0 lO0 lO0 lO0 lO0 lO0 Il 500 lO0 0 lO0 90 lO0 lO0 Il 750 0 0 lO0 R0 lO0 lO0 Il lO00 0 0 0 0 0 0 .' _ . I2 250 lO0 lO0 lO0 50 100 100 I2 500 lO0 0 100 50 lO0 80 I2 750 0 0 lO0 30 lO0 50 ~,~ I3 250 100 lO0 lO0 70 lOo lO0 I3 500 lO0 0 lO0 50 lO0 lO0 I3 750 0 0 lO0 20 lO0 lO0 I3 lO00 0 0 lO0 0 lO0 20 ,, _ _ _ : I4 250 10 nd. 10 nd. nd. nd.
I4 500 5 nd. 5 nd. nd. nd.
I4 750 0 nd. 0 nd. nd. nd.
~ 30 I4 lO00 0 nd. 0 nd. nd.nd.
., _ Cl 250 lO0 lO0 lO0 lO0 lO0lO0 : ~l 500 lO0 lO0 lO0 lO0 100lO0 ~' : Cl 750 lO0 lO0 lO0 lO0 100lO0 Cl lO00 :lO0 lO0 I00 lO0 100lO0 C2 250 lO0 lO0 lO0 lO0 100lO0 : C2 500 lO0 lO0 lO0 lO0 lO0lO0 C2 750 l~0 lO0 lO0 lO0 lO0100 ' ~ ~40 C2 : lO00 lO0lO0 lO0 lO0 lO0lO0 : : _ : C3 250 l~0lO0 lO0 lO0 lO0lO0 : ~ ~3 500 lO0lO0 lO0 100 lO0lO0 ! C3 750 lO0lQ0 lO0 lO0 lO0100 C3 lO00 ;lO0lO0 lO0 lO0 lO0lO0 . nd.: not determin~d ;: ;
: ~ :
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20~94 Tabl~ 2: Composltlon [~ by weight]
Pl P2 P3 P4 PS P6 P7 P~ P9 P10 ~11 Pla _ Formald~hyd~ 14 ~lyoxal - 14 - 8.8 Glutaric dlaldehyd~ - - 6 4.5 - - - - - - - -Dodigen~1611 ) - - - - 5 Bardac~22b) - - - - - 5 Kathon3CGC) - - - - - - 1.5 5 Phenol - - - - - - - - 20 40 o-Phenylphenol - - - - - - - - - - 1 5 Water .............. ad 100 ): ~ixture of b~nzyl dimethyl dodecyl ammonium chloride and benzyl d1methyl t~tradecyl ammonium chloride, suppli~r: Hoech~t ): Dldecyl dimethyl ammonium chloride, supplier: Lonza c) M~xture of 5 chloro-2-methyl-4-i~othiazolln-3-one and 2-methyl-4-i~othia~olin-3-one, supplier: Rohm & Haas contact time of 6 hours, ~uantities of 1 ml of the mixtures were introduced into 10 ml of an aqueous disinhibiting so-`~ lution containing 3.0 ~ by weight Tween~80, 0.3 ~ by weight lecithin and 0.1 % by weight histidine. Quantities of 0.1 ml of~1:hese samples and further 1:10 dilution series were ~ ~ applied to caseinjsoya/agar plates. A~ter these subcul-- ~ tures had been incubated (24 hours at 30C), the number of germs capable of proliferating was determined. For compar-i90n, aqueous solutions of the individual components and lo water free from active substances were tested under the same conditions.
B~ample ~
;: As in Example 3, solutions having the concentrations shown in ~able 4 were prepared from preparations P5 and P6 and were used against s1ime-forming microorganisms ,~ , i - ;
.
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-2~6~89~
Table 3: Gen~ counts per ml A~tlve substanca Concontration aft~r 6 h tPPm~
Formaldehyde 700 8.8 x lO
Formaldehyd~ + ~2 700 + 500 U~der lO
Glyoxal 700 3.1 x lO
Glyoxal + I2 700 + 500 Under lO
Glutaric dialdehyde 300 1. a x lo Glutaric dialdehyde + I2 300 + 500 Under lO
Glyoxal + glutaric dialdehyde 440 + 225 1.1 x lO
Glyoxal + glutaric dialdehyd~ + I2 440 + 225 + SOO Under lO
Wat~r 3.3 x lO
_. _ . . , ~
___. _ Table 4: Germ count~ per ml Active ~ub~tance Concentration Germ count after tPPm] 6 h 24 h Dodi~en~1611 ) 50 l.O x lO 4.0 x lO
DodLgen01611 ) + I2 50 ~ 500 7.0 x lO Under lO
Bardac~22 ) 50 8.0 x lO Under lO
Bardac~22 ) + I2 50 + 500 Under lO Under lO
I~ 500 3.5 x lO 4.2 x lO
Water 3.8 x 1O7 4.0 x lO
)~ ~ixtur~ of ben~yl dimethyl dodecyl ammonium chloride and benzyl dimethyl tetradecyl ammonium chloridP, ~upplier: ~oech~t ): Didecyl dimethyl ammonium chl~ride, supplier: Lonza (Enterobacter cloacae); contact time 6 hours and 24 hours.
~x~mple 5 As in Example 3, aqueous solutions having the concen-trations shown in ~able 5 were produced ~rom preparations P7 to P12 and used against slime-forming microorganisms (germ 1 - Agrobacterium radiobacter; germ 2 = Enterobacter cloacae); contact time 6 hours and 24 hours.
, ~.
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,, . .,, . ~ , , : ',. .; , . , 2~894 Table 5: Germ count~ per ml Active Concen- Germ count after 6 h Germ count after 24 h sub~tance tration Ippm] Germ 1 Germ 2 Germ 1 Germ 2 . _ _ Kathon~CG ) 50 1.0 x 10 1.8 x 10 Under 10 Under 10 _ _ .
. Kathon~CG ~ 15 1.9 x 10 2.5 x 10 2.0 x 10 1.3 x 10 _ _ .
Kathon0CG ) 50 Under 10 Under 10 Under 10 Under 10 Kathon~CG ) lS Undor 10 Under 10 Under 10 Under 10 Phenol 500 6.0 x 10 4.0 x 106 3.8 x 10 4.7 x 10 _ _ Phenol 2000 1.9 x 10 4.3 10 9.6 x 10 1.3 x 10 . Phenol 500 1.4 x 10 2.3 x 10 Under 10 Under 10 :~ I2 500 _ Phenol2000 Under 10 Under 10 Under 10 Under 10 .`
phenol250 Over 10 Over 10 4 x 10 1 x 105 phenol500 Over 10 Under 10 Under 10 Under 10 : :
~: o-Phenyl 4 S 2 2 ~phenol 10 3 x 10 1 x 10 Under 10 Under 10 :~ . _ o Phenyl 2 2 2 2 phenol 50 Under 10 under 10 Under 10 Under 10 _ .
~`' , :
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' , : :, 2~68894 Tables 2, 3, 4 and 5 clearly show that the prepara-tions containing the combination according to the inven-tion of cysteine d~rivative and microbicide show signifi-cantly stronger antimicrobial activity than the prepara-tions containiny only the microbicide. This enables the preparations according to the invention for controlling slime in liquid-carrying systems of industrial installa-tions to be used in much lower concentration than would be necsssary using the microbicides alone.
~x~ple b: Detachment test A so-called Robbins device (of. W.F. McCoy, J.D.
Bryers, J. Robbins and J.W. Costerton in Can. J . Microbi-ol 27 (1981), 910), into which polyethylene stoppers had been inserted, was integrated into a circular hose system provided with a pump. After this arrangement had been steriliz~d in an autoclave, the hos~ system was filled with a nutrient medium consisting of 5.3 g of glucose, 5.3 g of yeast extract, 13.3 g of m~lt extract and 0.13 g of calcium carbonate per liter aqueous solution and inoculated with a slime-forming bacterial strain which had been isolated from the central disin~ectant supp].y line of a hospital. After th~ nutrient solution had been pump-circulated through the device for 72 hours, 60 to 70 % of the surface o~ the poly-ethylene parts in the tube was covered with a slime layer.
The nutrient solution was removed and an aqueous solution which had been obtained by dilution of preparation P4 and which contained 440 ppm glyoxal, 225 ppm glutaraldehyde and 500 ppm N-acetyl-L-cysteine was introduced into the hose system. A~ter circulation for 24 hours, only about 10 % of the surface of the plastic parts in the tube was covered with bioslime. In a control experiment in which water free from slime control preparation was used instead of a solu-tion of the preparation according to the invention, about 50 % by weight of the surface of the plastic parts was still covered with bioslime. When the same test was car-ried out using plastic parts of polyvinyl chloride, 50 ~ of th~ surface of the plastic parts was covered with bioslime ,: ,~ : ', . .. ; . , , : '" .: ~ ., . :
~.... . .
~$8~
before and 5 to 10 % after treatment with preparation P~
according to invention; in the control exp~riment with water, 40 % o~ their surface was covered with bioslime.
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Claims (7)
ORIGINAL OF AN ANNEX TO THE INTERNATIONAL PRELIMINARY
EXAMINATION REPORT FOR PCT APPLICATION NO. PCT/EP 90/01869 FILED ON NOVEMBER 8, 1990.
1. A preparation for controlling bacterially formed bio-slime and bioslime-forming bacteria in liquid-carrying sys-tems of industrial installations, characterized in that it contains a combination of cysteine and/or cysteine deriv-atives with a microbicide selected from the group consist-ing of aldehydic microbicides, quaternary ammonium com-pounds, phenolic microbicides, isothiazolinones, and mixtures thereof.
2. A preparation as claimed in claim 1, characterized in that the cysteine derivative is L-cysteine, N-acetyl-L-cysteine, S-acetyl-L-cysteine, N,S-diacetyl-L-cysteine or a mixture thereof.
3. A preparation as claimed in claim 1 or 2, character-ized in that it contains 0.5 % by weight to 75 % by weight and, more particularly, 2 % by weight to 50 % by weight of cysteine and/or cysteine derivative and 0.5 % by weight to 50 % by weight and, more particularly, 1 % by weight to 20 % by weight of microbicide.
4. A preparation as claimed in any of claims 1 to 3, characterized in that it contains 0.5 % by weight to 25 %
by weight and, more particularly, 2 % by weight to 10 % by weight of cysteine and/or cysteine derivative and 1 % by weight to 25 % by weight and, more particularly, 5 % by weight to 15 % by weight of aldehydic microbicide selected from the group consisting of the class of saturated, ali-phatic C1-6 aldehydes, the class of saturated, aliphatic C2-6 dialdehydes and the class of aromatic dialdehydes and mixtures thereof.
by weight and, more particularly, 2 % by weight to 10 % by weight of cysteine and/or cysteine derivative and 1 % by weight to 25 % by weight and, more particularly, 5 % by weight to 15 % by weight of aldehydic microbicide selected from the group consisting of the class of saturated, ali-phatic C1-6 aldehydes, the class of saturated, aliphatic C2-6 dialdehydes and the class of aromatic dialdehydes and mixtures thereof.
5. A preparation as claimed in any of claims 1 to 4, characterized in that it contains 0.5 % by weight to 50 %
by weight and, more particularly, 2 % by weight to 20 % by weight of quaternary ammonium compounds selected from pyri-dines N-alkylated with C10-18 alkyl groups, N,N'-dialkylated 2-imidazolines substituted in the 2-position by C1-18 alkyl groups and compounds corresponding to formula I, in which R1 and R2 are methyl radicals, R3 is a C8-18 alkyl radical or a benzyl or chlorinated benzyl radical and R4 is a C8-18 alkyl radical, and mixtures thereof.
by weight and, more particularly, 2 % by weight to 20 % by weight of quaternary ammonium compounds selected from pyri-dines N-alkylated with C10-18 alkyl groups, N,N'-dialkylated 2-imidazolines substituted in the 2-position by C1-18 alkyl groups and compounds corresponding to formula I, in which R1 and R2 are methyl radicals, R3 is a C8-18 alkyl radical or a benzyl or chlorinated benzyl radical and R4 is a C8-18 alkyl radical, and mixtures thereof.
6. A preparation as claimed in any of claims 1 to 5, characterized in that it contains 1 % by weight to 20 % by weight and, more particularly, 2 % by weight to 10 % by weight of cysteine and/or cysteine derivative and 0.2 % by weight to 20 % by weight and, more particularly, 0.5 % by weight to 10 % by weight of isothiazolinone.
7. A preparation as claimed in any of claims 1 to 6, characterized in that it contains 2 % by weight to 50 % by weight and, more particularly, 5 % by weight to 20 % by weight cysteine and/or cysteine derivative and 0.5 % by weight to 50 % by weight and, more particularly, 3 % by weight to 30 % by weight phenolic microbicide, more par-ticularly selected from the group consisting of phenol, o-phenyl phenol, cresol, thymol and mono- or polyhalogenated derivatives thereof and also mixtures thereof.
Applications Claiming Priority (7)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DEP3938103.7 | 1989-11-16 | ||
| DE3938103 | 1989-11-16 | ||
| DE19904007227 DE4007227A1 (en) | 1990-03-07 | 1990-03-07 | Control of bio-slimes |
| DEP4007227.4 | 1990-03-07 | ||
| DE19904028245 DE4028245A1 (en) | 1990-09-06 | 1990-09-06 | Control of bio-slimes |
| DEP4028245.7 | 1990-09-06 | ||
| PCT/EP1990/001869 WO1991007090A1 (en) | 1989-11-16 | 1990-11-08 | Combatting slime-forming microorganisms |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2068894A1 true CA2068894A1 (en) | 1991-05-17 |
Family
ID=28678486
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002068894A Abandoned CA2068894A1 (en) | 1989-11-16 | 1990-11-08 | Controlling slime-forming microorganisms |
Country Status (1)
| Country | Link |
|---|---|
| CA (1) | CA2068894A1 (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8563612B2 (en) | 2005-03-21 | 2013-10-22 | Cytacoat Ab | Antimicrobial agent comprising a cysteine component covalently bound to a substrate in particular by binding through an S-S bridge via a spacer molecule |
-
1990
- 1990-11-08 CA CA002068894A patent/CA2068894A1/en not_active Abandoned
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8563612B2 (en) | 2005-03-21 | 2013-10-22 | Cytacoat Ab | Antimicrobial agent comprising a cysteine component covalently bound to a substrate in particular by binding through an S-S bridge via a spacer molecule |
| US9155301B2 (en) | 2005-03-21 | 2015-10-13 | Cytacoat Ab | Antimicrobial agent comprising a cysteine component covalently bound to a substrate in particular by binding through an S-S bridge via a spacer molecule |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FZDE | Discontinued |