Abstract:
Alkane alkanolamines of the formula 
     
       RNHR.sup.1 OH 
     
     wherein 
     R is hydrogen or normal C 1-6  alkyl; and R 1  is a normal or branched chain C 2-4  alkyl or hydroxymethyl C 2-4  alkyl 
     are effective to potentiate the activity of and prolong the useful life of antimicrobial agents in controlling the growth of microorganisms in industrial water based fluids. A specific example of the alkanolamines of this invention is n-hexyl ethanolamine.

Description:
BACKGROUND OF THE INVENTION 
     Antimicrobial compositions are generally added to various kinds of industrial water based fluids to reduce or inhibit the growth of microorganisms. In particular, a wide variety of industrial water based fluids such as metal-working fluids, latex paints, water based hydraulic fluids, require antimicrobial compositions to control the growth microorganisms which eventually render the fluids rancid. 
     One of the problems often associated with water based fluids is the susceptibility of the fluid to the infestation and growth of various microorganisms such as bacteria and fungi (which particularly feed on the organic components thereof). The presence and buildup of such microorganisms can often lead to interference of mechanical operations as a result of the clogging of filters, buildup of slime and sludge, development of odors, rust, emulsion instability, reduced tool life and poor finish. Furthermore, where the workers&#39; hands necessarily come in contact with these deteriorated fluids, usually containing finely divided sharp metal cuttings, serious problems of dermatitis may arise. These and other such similar problems have resulted in the continuing need for better antimicrobial additives for industrial water based fluids. Much effort has been devoted in recent years to controlling this problem; however, it continues to be a major annoyance which costs industry many millions of dollars each year. 
     Antimicrobial agents constitute an important ingredient of industrial fluids which are commonly depleted faster than the other components of the fluids. Quite often, additional antimicrobial agents must be added to the industrial water based fluid at periodic intervals in order to compensate for their loss from the fluid after continuous use. 
     Preservatives are removed from the fluid after interacting with the microbes to bring about their inhibition or death. The greater the microbial population, the more quickly they are lost from the system. Thus, the concentration of any preservative declines with time and may be reduced to subinhibitory levels in only a few days. 
     A number of suggestions have been made for inhibiting the growth of bacteria in aqueous fluids such as those described in U.S. Pat. Nos. 4,172,140, 3,951,830, 3,799,876, 3,515,671, and 2,976,244. The use of various formaldehyde preservatives for metalworking fluids including monomethylol dimethyl hydantoin and dimethylol dimethyl hydantoin has also been proposed (see Bennett, E. O., Int. Biodetn. Bull. 9: 95-100 (1973) and Maeda et al, Agr. Biol. Chem., 40: 1111-2222 (1976)). 
     Gray and Wilkinson in J. Gen. Microbiol., 39: 385-399 (1965) and J. App. Bact., 28: 153-164 (1965) describe the action of the ethylenediaminetetraacetic acid (EDTA) on some bacteria. The effectiveness of such chelating agents as EDTA along for bacterial control in aqueous systems is disputed as evidenced by U.S. Pat. Nos. 3,240,701, 3,408,843, and 3,591,679. 
     The antimicrobial compositions used in industrial water based fluids seem to suffer from one or more disadvantages including high cost, unacceptable toxicity or low degree of effectiveness at the present state of the art. 
     The present invention provides agents which when combined with antimicrobial agents are effective to potentiate the activity of the antimicrobial agent in controlling the growth of microorganisms in industrial water based fluids. Hence, less antimicrobial agent is required to produce the same antimicrobial effect as compared to using the antimicrobial agent alone. 
     SUMMARY OF THE INVENTION 
     The present invention provides antimicrobial potentiating agents. The antimicrobial potentiating agents of the invention are alkanolamines and alkyl alkanolamines of the formula: 
     
         RNHR.sup.1 OH 
    
     wherein 
     R is hydrogen or normal C 1-6  alkyl; and R 1  is a normal or branched chain C 2-4  alkyl or hydoxymethyl C 2-4  alkyl. 
     Representative examples of alkanolamines which potentiate the activity of antimicrobial agents include n-hexyl ethanolamine, 2-methyl ethanolamine, 2-hydroxymethyl ethanolamine, n-amyl ethanolamine, 2-amine-1-butanol, 3-amino-1-propanol, and isopropanolamine. 
     The alkanolamines of this invention when combined with antimicrobial agents are effective to potentiate the activity of and extend the useful life the antimicrobial agents in preventing and controlling the fouling of industrial water based fluids. In particular, the use of the antimicrobial potentiating agents of the invention reduces the amount of antimicrobial agent needed to effect a desired control of microbial (including bacterial and fungal) growth in industrial water based fluids. Alternatively, the use of the antimicrobial potentiating agents of this invention can extend the useful life of the antimicrobial agent used to control microbial growth in industrial water based fluids. For example, 500-1500 ppm of the antimicrobial potentiating agents can reduce the needed amount of anitmicrobial agent by about 20-50%. Alternatively, 500-1500 ppm of the antimicrobial potentiating agent admixed with an antimicrobial agent will extend the normal useful life of the antimicrobial agent by about 20-100% or more. 
     In the context of this invention, the amount of potentiating agent added to the industrial water fluid does not by itself exhibit sufficient activity to control microbial growth in the fluid. 
    
    
     DETAILED DESCRIPTION OF THE INVENTION 
     The present invention provides compositions of antimicrobial potentiating agents together with antimicrobial agents. The compositions of the present invention when added to industrial water based fluids are useful to control the growth of microorganisms, including for example bacteria, algae and fungi, which tend to foul the industrial waters. 
     In the context of this invention, the term &#34;industrial water based fluid&#34; is meant to encompass water, oil in water, water in oil emulsions and like compositions which are susceptible to the infestation and growth of microorganisms. Thus, for example, soaps and detergent fluids, cosmetics, latex paints, paper pulping fluids, drilling muds, water based hydraulic fluids, water for coolant towers, metalworking fluids or cutting fluids, are included. 
     As used herein, the term &#34;antimicrobial effective amount&#34; means that amount of the antimicrobial agent which when added to the industrial water based fluid will adequately inhibit the growth of microorganisms in that fluid. The term &#34;antimicrobial potentiating effective amount&#34; or words to that effect, mean the amount of the antimicrobial potentiating agent which when combined with the antimicrobial agent is effective to enhance the activity of or prolong the useful life of the antimicrobial agent in controlling the growth of microorganisms in the industrial water based fluids. 
     Generally, from about 500 to 1500 parts of the alkanolamine, antimicrobial potentiating agent are admixed with the recommended effective amount of the antimicrobial agent per million parts of the industrial water based fluid. 
     In general, the antimicrobial agents which are potentiated by the alkanolamines of this invention include triazines, phenols, morpholines, &#34;formaldehyde releasers (compounds which will hydrolyze into formaldehyde and other non-persistent fragments in aqueous solution including, e.g., tris(hydroxymethyl)nitromethane, hexahydro-1,3,5-tris(2-hydroxyethyl)-S-triazine, hexahydro-1,3,5-triethyl-S-triazine, hexahydro-1,3,5-tris(2-hydroxyethyl)-S-triazine iodine complex, and 1-(3-chloroallyl)-3,5,7-triaza-1-azoniaadamantane chloride),&#34; azoniatricylodecanes, omadines and oxazolidines. Commericial products of such agents are currently marketed under the tradenames: Triadine 10, Grotan, Vancide TH, Dowicil, Dowicide A, Bioban P-1487, Tris Nitro, Busan 1024, Cosan 101, Nuosept 95. 
     The following examples are offered to more fully illustrate the invention, but are not intended to limit the scope thereof. 
     Experimental Procedures 
     The test units consisted of quart jars placed in rows. Above each row, a metal framework was constructed to support the aeration system which consisted of aquarium valves connected together with plastic tubing. The amount of aeration of each unit was controlled by adjusting the valves. Capillary pipettes were employed as aerators to produce a fine steam of bubbles in the diluted coolants. 
     Five hundred ml of tap water (120 ppm hardness) was added to each jar. The n-hexyl ethanolamine and selected antimicrobial agent were added to each jar along with 15.0 ml of cutting fluid concentrate to produce the desired coolant concentration. Each unit was then made up to a total volume of 600.0 ml by adding additional tap water. 
     Each test unit was inoculated with a mixture of bacteria and fungi which were obtained and maintained as described in Bennett, &#34;The Deterioration of Metal Cutting Fluids&#34;, Prog. Indust. Microbiol. 13: 121-249 (1974), the entire contents of which are incorporated herein by reference. Each unit was inoculated once each week with 1.0 ml of a 50-50 mixture of both inocula. 
     Each unit was examined once each week for its microbial content for as long as the count remained below 100,000 organisms/ml. Two consecutive counts in excess of this figure at weekly intervals was considered to constitute a failure and the test was discontinued at that time. 
     Two different types of control experiments were included. Each shipment of fresh coolant was tested upon arrival to determine if the product exhibited any inhibitory properties, as defined in the previous paragraph. All of the coolants used in the investigation were especially prepared by coolant manufacturers for this work and they did not contain a preservative. None of the products employed in this investation exhibited any inhibitory properties and failed in the first week of testing. The second set of controls consisted of a particular cutting fluid preserved with a commonly used antimicrobial agent. Normally, these control units failed within 21 days due to mold growth. The controls functioned normally during the test period. A third control consisted of representative cutting fluids with added n-hexyl ethanolamine. Normally, such controls failed within less than 7 days. 
     Since the test units were under constant aeration, there was considerable evaporation from each unit. The units were calibrated at the 600.0 ml mark and, once or twice each week, depending upon environmental conditions, distilled water was added to each unit to bring the liquid level back to this mark. Distilled water was used in order to avoid a buildup of inorganic salts in the test units. 
     Results 
     A series of sample jars were prepared according to the procedure outlined above to ascertain the antimicrobial potentiating effects of n-hexyl ethanolamine (HEA) when admixed with a selected antimicrobial agent. The sample coolants were mixed with water in a ratio of 1:40 (coolant to water). The results are set forth below, wherein the time in days is recorded when the microbial count in such test reached the level of 100,000 or the test discontinued. 
     The n-hexyl ethanolamine used in these examples was prepared according to the alternate synthesis scheme described in U.S. Pat. No. 4,749,503, issued Jun. 7, 1988. 
     As used in the following tables, the underlined numbers indicate that the test failed due to slime at the time noted, and the * means the test continued to show inhibitory action at the time the test was discontinued. 
     
                       TABLE 1______________________________________EFFECTIVENESS OF DIFFERENT COMBINATIONSOF HEA AND GROTAN IN CUTTING FLUIDS______________________________________Compound    Concentration in ppmGrotan      500    1000   1500HEA                            500  1000 1500Coolant     Days of controlIRMCO emulsion       7      21     14   0    7    7Monroe Primecut       7      21     21   0    0    0Stuart emulsion       7      21     14   0    0    0Sanson coolant       7      21     14   0    7    14Buckeye emulsion       7      21     14   0    7    7Compound    Concentration in ppmGrotan       500    500   1000 1000 1500 1500 1500HEA         1000   1500    500 1000  500 1000 1500Coolant     Days of controlIRMCO emulsion       28     49     21   35   42   35   70Monroe Primecut       48     42     28   21   35   21   84Stuart emulsion       14     42     21   21   28   21   91Sanson coolant       21     84     21   28   28   35   98Buckeye emulsion       63     91     84   98   77   91   105*______________________________________ 
    
     
                       TABLE 2______________________________________EFFECTIVENESS OF DIFFERENTCOMBINATIONS OF HEA ANDBIOBAN P-1487 IN CUTTING FLUIDS______________________________________Compound    Concentration in ppmBioban P-1487       250    500    1000 500   250  500 1000HEA                            500  1500 1500 1500Coolants    Days of stabilityIRMCO emulsion       0      14     35   21   28   42   84Monroe Primecut       28     56     84   14   35   56   63Stuart emulsion       7      42     49   21   21   42   56Sanson coolant       7      35     42   21   21   112  140*Buckeye emulsion       35     42     49   35   119  112  140*______________________________________ 
    
     
                                           TABLE 3__________________________________________________________________________EFFECTIVENESS OF DIFFERENT COMBINATIONS OF HEA ANDNA OMADINE IN CUTTING FLUIDS__________________________________________________________________________Compound  Concentration in ppmNa Omadine  100 250 500 100  100                      250                         250                            500  500HEA                1500 2000                      1500                         2000                            1000 1500Coolants  Days of stabilityIRMCO  0   0   0   14   105                       28                         119                            7    112Monroe 0   0   21  28    196*                       28                         119                            7     28Stuart 0   21  35  42   147                       49                         119                            49   112Sanson 0   7   21  21    77                       28                         112                            7     140*Buckeye  0   21  21  42    196*                       140*                          140*                            77    140*__________________________________________________________________________ 
    
     
                       TABLE 4______________________________________EFFECTIVENESS OF DIFFERENTCOMBINATIONS OF HEA ANDTRIADINE 10 IN CUTTING FLUIDS______________________________________Compound Concentration in ppmTriadine 10    250    500    1000  250  250  500  500 1000HEA                         1500 2000 1000 1500 1500Coolant  Days of stabilityIRMCO    21     28     35   28   77   63   56   175emulsionMonroe   49     49     77   42   84   49   42   112PrimecutStuart   35     77     98   42   91   70   98   161emulsionSanson   28     42     56   77   63   42   140* 182*coolantBuckeye  35     49     42   140* 105* 105* 140* 182*coolant______________________________________ *Still inhibitory when taken off test 
    
     
                       TABLE 5______________________________________EFFECTIVENESS OF DIFFERENTCOMBINATIONS OF HEA ANDAMINE CS 1135 IN CUTTING FLUIDS______________________________________Compound    Concentration in ppmAmine CS 1135       500    1000             1000  500 1000HEA                       1000 1500 1000 1500 1500Coolants    Days of stabilityIRMCO emulsion       28     28     7    7    49   35   84Monroe Primecut       28     28     0    0    35   35   77Stuart emulsion       28     21     0    0    49   35   84Sanson coolant       28     14     7    14   35   35   91Buckeye emulsion       28     14     7    7    84   48   126______________________________________ 
    
     
                       TABLE 6______________________________________EFFECTIVENESS OF HEA ANDCOSAN 101 IN CUTTING FLUIDS      1000 ppm    1500 ppm CombinationCoolants   Cosan 101   HEA      of both______________________________________IRMCO emulsion      14          7        84Monroe emulsion      21          0        91Stuart emulsion      21          0        70Sanson coolant      21          14       98Buckeye emulsion      21          7        140*______________________________________ 
    
     
                       TABLE 7______________________________________EFFECTIVENESS OF HEA IN COMBINATIONWITH BUSAN 85 IN CUTTING FLUIDS      1000 ppm    1500 ppm CombinationCoolants   Busan 85    HEA      of both______________________________________IRMCO emulsion      7           7        63Monroe Primecut      7           0         7Stuart emulsion      14          0        91Sanson coolant      7           14       49Buckeye emulsion      7           7        140*______________________________________ 
    
     
                       TABLE 8______________________________________EFFECTIVENESS OF HEA IN COMBINATIONWITH BUSAN 1024 IN CUTTING FLUIDS      1000 ppm    1500 ppm CombinationCoolants   Busan 1024  HEA      of both______________________________________IRMCO emulsion      0           7        14Monroe Primecut      0           0        7Stuart emulsion      7           0        7Sanson coolant      0           14       7Buckeye emulsion      0           7        49______________________________________ 
    
     
                       TABLE 9______________________________________EFFECTIVENESS OF HEA IN COMBINATIONWITH TRIS NITRO IN CUTTING FLUIDS      1000 ppm    1500 ppm CombinationCoolants   Tris Nitro  HEA      of both______________________________________IRMCO emulsion      7           7         0Monroe Primecut      49          0        35Stuart emulsion      0           0        28Sanson coolant      14          14       42Buckeye emulsion      7           7        56______________________________________ 
    
     
                       TABLE 10______________________________________EFFECTIVENESS OF HEA IN COMBINATIONWITH AMINE CS-1246 IN CUTTING FLUIDS      1000 ppm    1500 ppm CombinationCoolants   CS-1246     HEA      of both______________________________________IRMCO emulsion      7           7        21Monroe Primecut      7           0        42Stuart emulsion      7           0        21Sanson coolant      7           14       21Buckeye emulsion      7           7        105*______________________________________ 
    
     
                       TABLE 11______________________________________EFFECTIVENESS OF HEA IN COMBINATIONWITH NUOSEPT 95 IN CUTTING FLUIDS      1000 ppm    1500 ppm CombinationCoolants   Nuosept 95  HEA      of both______________________________________IRMCO emulsion      7           7        28Monroe Primecut      7           0        28Stuart emulsion      0           0        21Sanson coolant      7           14       21Buckeye emulsion      7           7        105*______________________________________ 
    
     
                       TABLE 12______________________________________EFFECTIVENESS OF HEA IN COMBINATIONWITH TROYSAN 174 IN CUTTING FLUIDS       1000 ppm   1500 ppm   CombinationCoolants    Troysan 174                  HEA        of both______________________________________IRMCO emulsion       28         0          98Monroe Primecut       42         14         98Stuart emulsion       28         0          84Sanson coolant       28         14         91Buckeye emulsion       28         21         136______________________________________ 
    
     Grotan is 78.5% active solution of hexahydro-1,3,5-tris (2-hydroxyethyl)-S-triazine. 
     Bioban P-1487 is a mixture of 70% 4-(2-nitrobutyl) morpholine and 20% 4,4-(2-ethyl-2-nitromethylene) dimorpholine. 
     Triadine 10 is a mixture of sodium 2-pyridinethiol-1-oxide 6.4% and hexahydro-1,3,5-tris-(2-hydroxyethyl)-S-triazine 63.6%. 
     Amine CS 1246 is 4,4-dimethyloxazolidine p-toluenesulfonic acid. 
     Cosan 101 is 74.9% 4,4 dimethyloxazolidine and 2.8% 3, 4, 6 trimethyloxazolidine. 
     Busan 85 is 90% by weight of barium metaborate. 
     Busan 1024 is a 40% aqueous solution of sodium salt of 1-carboxymethyl-3,5,7-triaza-1-azoniatricyclodecane chloride. 
     Tris Nitro is a 50% active solution of tris(hydroxymethyl)-nitromethane. 
     Nuosept 95 is a mixture of bicylicpolyoxymethylene oxazolidines. 
     Troysan 174 is 2-hydroxymethyl ethanolamine. 
     While the invention has been explained in relation to certain illustrative embodiments of it, it is understood that many modifications and substitutions may be made in any of the specific embodiments within the scope of the appended claims which are intended also to cover equivalents of them.