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Title:
ALKYL ETHANOLAMINES FOR THE CONTROL OF MYCOBACTERIA IN FUNCTIONAL FLUID
Document Type and Number:
WIPO Patent Application WO/2005/055720
Kind Code:
A1
Abstract:
An antimicrobial composition for inhibiting the growth of Mycobacteria in industrial fluids is provided. The antimicrobial composition is an alky ethanolamine of the formula Rx-NHz-(CH2CH2OH)y wherein R is a C3 to C16 alkyl group either linear or branched, x and y are 1 or 2, z is 0 or 1, x+y is not greater than 3, when x or y is 2 than z is 0 and when x is 2 the R groups are the same or different C3 to C16 alkyl groups.

Inventors:
Gernon, Michael David (117 Scarlet Oak Drive, Phoenixville, PA, 19640, US)
Dowling, Conor Michael (1657 Sullivan Drive, Blue Bell, PA, 19422, US)
Trumpfheller, Christine Marie (118 West Cottage Avenue, Haddonfield, NJ, 08033, US)
Application Number:
PCT/US2004/028618
Publication Date:
June 23, 2005
Filing Date:
September 02, 2004
Export Citation:
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Assignee:
ARKEMA INC. (2000 Market Street, Philadelphia, PA, 19103-3222, US)
Gernon, Michael David (117 Scarlet Oak Drive, Phoenixville, PA, 19640, US)
Dowling, Conor Michael (1657 Sullivan Drive, Blue Bell, PA, 19422, US)
Trumpfheller, Christine Marie (118 West Cottage Avenue, Haddonfield, NJ, 08033, US)
International Classes:
A01N25/00; A01N33/08; A61K31/13; C10M133/02; C10M173/02; (IPC1-7): A01N33/08; A01N25/00; A61K31/13
Foreign References:
US5132046A1992-07-21
US5431834A1995-07-11
US2541678A1951-02-13
US4781848A1988-11-01
US4781849A1988-11-01
US4828737A1989-05-09
Attorney, Agent or Firm:
Rudman, Gilbert W. (Atofina Chemicals, inc. Patent Department, 26th Floor, 2000 Market Stree, Philadelphia PA, 19103-3222, US)
Download PDF:
Claims:
What is claimed is:
1. A method of inhibiting the growth of Mycobacteria in an aqueous fluid medium susceptible to such growth comprising adding to said medium an antimicrobially effective amount of an alkyl ethanolamine of the formula RXNHz (CH2CH20H) y wherein R is a C3 to C16 alkyl group either linear or branched, x and y are 1 or 2, z is 0 or 1, x+y is not greater than 3, when x or y is 2 than z is 0 and when x is 2 the R groups are the same or different C3 to C16 alkyl groups.
2. The method of claim 1 wherein the concentration of alkyl ethanolamine in said aqueous fluid ranges from about 400 to 2000 parts per million parts by weight of the aqueous medium.
3. The method of claim 1 wherein said alkyl ethanolamine is an octyl ethanolamine.
4. The method of claim 1 wherein said aqueous fluid medium comprises an oil in water or a water in oil emulsion.
5. The method of claim 1 wherein the aqueous fluid medium is a metalworking coolant fluid.
Description:
ALKYL ETHANOLAMINES FOR THE CONTROL OF MYCOBACTERIA IN FUNCTIONAL FLUID [0001] This application claims the benefit of U. S. Provisional Application Serial No. 60/523,469, filed November 19,2003.

BACKGROUND OF THE INVENTION [0002] Antimicrobial compositions are often added to various kinds of aqueous fluid media to reduce or inhibit the growth of microorganisms. In particular, a wide variety of industrial aqueous fluid media such as metalworking fluids used with metalworking equipment, lubricants, coolants, cleaners, protecting fluids, treating fluids and/or process fluids require antimicrobial compositions to control the growth of microorganisms. Generally, these fluids are pure organic liquids (referred to as straight oils), emulsions or aqueous solutions. The emulsions and aqueous solutions are prone to degradation via the proliferation of microscopic biological organisms. The proliferation of biological organisms results in contamination of the fluid with the byproducts of microbiological metabolism. Such biological growth may also result in a decrease in pH, selective consumption of fluid components, the formation of macroscopic microbiological communities (e. g., pads of fungus, slimy biofilms, filamentous growths) and also possibly the buildup of toxic chemicals (e. g., membrane endotoxins).

[0003] One of the more pernicious of the microbiological problems faced by industry involves the genus Mycobacterium. Mycobacteria are a class of microorganisms which includes the species that cause tuberculosis, leprosy and a host of other human and animal diseases. Recently, Mycobacteria have been linked to a lung condition known as Hypersensitivity Pneumonitis (HP). HP is an infrequent but troubling condition that develops in operators and other industrial personnel who work intimately with certain types of emulsion based and aqueous based industrial fluids. Owing to the emerging understanding of the link between Mycobacteria and HP, a number of industrial concerns have started considering investigating the possibility of setting permissible limits for Mycobacteria in industrial fluids.

[0004] It would be desirable to have an additive that has anti-Mycobacteria activity and is compatible with the other components of industrial fluids.

[0005] A number of suggestions have been made for inhibiting the growth of bacteria in aqueous fluids. U. S. Pat. No. 4,749, 503 discloses methods for inhibiting microbial growth in aqueous fluid media comprising adding an antimicrobially effective amount of n-hexyl ethanolamine to the aqueous fluid medium. U. S. Pat. No. 4,925, 582 discloses methods and compositions for enhancing the activity of antimicrobial agents in industrial water based fluids comprising adding alkanolamines and alkyl alkanolamines to the fluids. U. S. Pat. No. 5,132, 046 discloses water-based metal working fluids containing at least one alkanolamine antimicrobial agent.

[0006] Considerable advantages would result if an industrial fluid could be formulated with an ingredient which has several different functions in regard to metalworking while, at the same time, exhibiting antimicrobial properties towards Mycobacteria to provide partial or complete microbial control. In this way, it would be possible to partially control increasing Costs of these lubricants, as well as provide increased life under industrial conditions.

[0007] Antimicrobial agents and corrosion inhibitors constitute two important ingredients of metalworking fluids which commonly are depleted faster than the other components of the products. Quite often, both of these materials must be added to a coolant at periodic intervals in order to compensate for their loss from the coolants.

[0008] Preservatives are removed from the fluid as the chemicals combine 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 sub-inhibitory levels in only a few weeks.

[0009] Mycobacteria are a unique genus within the kingdom Monera (single celled organisms with genetic material dispersed throughout the cell, also known as prokaryotes). Generally, the unique character of the genus Mycobacterium causes it to be treated as distinct from more abundant bacterial genre like Pseudomonas, enteric genre, Klebsiella, Proteus and others. In particular, Mycobacteria prefer to live in a more hydrophobic environment (i. e. , prefer oil to water) than do most other bacteria, and Mycobacteria are slow growing organisms that typically can't compete with more prolific hydrophilic bacteria (e. g., genus Pseudomonas). However, if Mycobacteria do manage to establish themselves, then they can be very problematic. For instance, certain Mycobacterial species can cause an accumulation of lung irritating endotoxins within their fluid environment SUMMARY OF THE INVENTION [0010] The present invention provides an antimicrobial composition useful for inhibiting the growth of Mycobacteria microorganisms in an aqueous medium susceptible to microbial growth. The method involves adding to the aqueous medium an antimicrobially effective amount of an alkyl ethanolamine. The alkyl ethanolamine, when added to an aqueous fluid medium, provides an unexpected degree of preservation and antimicrobial activity over what one would expect from results obtained by using the chemically close antimicrobial alkyl alkanolamine agent, 2-amino-2-methyl-1-propanol.

DETAILED DESCRIPTION OF THE INVENTION [0011] The antimicrobial composition of the present invention comprises an antimicrobially effective amount of alkyl ethanolamines as the active antimicrobial ingredient. The alkyl ethanolamines of the present invention preferable have the structure: Rx-NHz- (CH2CH20H) y wherein R is a C3 to C16 alkyl group either linear or branched, x and y are 1 or 2, z is 0 or 1, x+y is not greater than 3, when x or y is 2 than z is 0 and when x is 2 the R groups are the same or different C3 to C16 alkyl groups. More preferably, R is a Cs allcyl group, z is 1, xis 1 and y is 1.

[0012] The concentration of the alkyl ethanolamine needed to provide antimicrobial control will vary depending on the nature of the fluid, the presence of other antimicrobial agents in the fluid and on the structure of the specific allcyl ethanolamine employed. Generally a concentration between 40.0 parts per million and 2000 parts per million part alkyl ethanolamine by weight of the fluid is sufficient. The concentration of the alkyl ethanolamine may be increased as in a concentrate that is ultimately diluted to yield the functioning fluid. The enhanced control of Mycobacteria is obtained by simply adding an appropriate amount of the alkyl ethanolamine, as defined above, to the fluid formulation. The allcyl ethanolamine is also useful as a neutralizing agent, corrosion inhibitor and multifunctional additive in the functional fluid. The alkyl ethanolamine can be used in combination with other additives for the functional fluid such as other antimicrobial agents, lubricants, corrosion inhibitors, neutralizing agents etc. The alkyl ethanolamines described herein are useful in metalworking fluids, cutting fluids, lubricants, cleaners, coolants and all other industrial fluids wherein, among other things, the control of Mycobacteria is necessary.

[0013] As used herein, the term"aqueous fluid medium"is meant to encompass water, oil in water, water in oil emulsions (including concentrates) and like compositions susceptible to the infestation and growth of Mycobacterial microorganisms. Thus, for instance, metalworking fluids or cutting oil fluids (in diluted as well as undiluted form), together with conventional additives such as corrosion inhibitors, etc. , are included.

[0014] The antimicrobial compositions may be added directly to undiluted metalworking fluids. As used herein, the term"metalworking fluid"is intended to encompass those compositions known in the art as"metal cutting fluids", "cutting fluids", "coolants", "lubricants", "rolling oils", "drawing fluids", "mold release fluids","grinding fluids"and like products used in the processing of metals. Emulsifiable or water miscible oils are widely used in the industry. Mixed with water, they form emulsions for use in rolling, drawing, machining and grinding where the need is for both cooling and lubrication. More recently, water miscible fluids using less oil (or no oils) and based on chemicals with or without surface active agents, have provided industry with products of even greater heat conducting properties for still higher machining rates.

[0015] The following examples are offered in order to more fully illustrate the invention, but are not to be construed as limiting the scope thereof EXAMPLES Example 1 [0016] The impact of various N-alkyl alkanolamines on the control of the bacterial species Mycobacterium smegrnatis (ATCC # 19420) was evaluated by measuring optical absorbance of samples treated with various concentrations of N-alkyl alkanolamines. Bacterial concentration in the experimental media, consisting of a standardized solution of clear nutrient broth (Middlebrook 7H9), amine, buffer (Tris) and water, was monitored indirectly via optical absorbance at 590 nm. The pH was adjusted initially to 8.5 with Tris buffer. An additional absorbance reading at 750 nm was used to insure that light scattering and turbidity were not adversely affecting the data. A tetrazolium dye was employed to increase the sensitivity of the optical measurement.

The values reported in Table 1 are end-point optical densities in milliOD units after 72 hours. In Table 1, AMP is 2-amino-2-methyl-1-propanol, BAE is butylaminoethanol, DBAE is dibutylaminoethanol, OAE is octylaminoethanol. The first column in Table 1 gives the treatment amine concentration in parts per million by weight.

TABLE 1 Amine AMP BAE DBAE OAE (ppm) 470 2100 2200 2000 0 940 2200 2100 2000 0 1880 2100 2000 2000 0 3750 2000 1900 1900 0 7500 1700 1700 1200 0 [0017] It is clear from the data shown that OAE is markedly more effective than AMP against Mycobacteria.

Example 2 [0018] An experiment similar to Example 1 was run with the following amines: DCHA = Dicyclohexylamine OAE = Octylaminoethanol ODEA = Octyldiethanolamine [0019] The impact of these N-alkyl alkanolamines on the control of the bacterial species Mycobacterium smegmatis (ATCC # 19420) is given in the Table 2. Bacterial concentration in the experimental media was monitored indirectly via optical absorbance at 660 nm. The values reported are end-point optical densities in milliOD units after 48 hours. The media consisted of a standardized solution of clear nutrient broth (Middlebrook 7H10 with OADC supplement), amine, buffer (Tris) and water. The pH was adjusted initially to 8.5 with Tris buffer. The first column in the Table gives the amine concentration in parts per million by weight. The final two columns give data for cells that also contained 2 grams per liter of boric acid. In all cases, the values are averages of at least three replicate runs. The final row of Table 2 gives an estimate of the concentration range in which the amine in question starts to inhibit the growth of this bacterial, species (minimum inhibitor concentration MIC).

TABLE 2 Amine OAE ODEA DCHA OAE DCHA (ppm) Boric Acid Boric Acid 0 1.13 1.13 1.13 0.925 0.925 500 0.184 0. 847 1.02 0.100 1.125 1000 0.149 0.117 0. 802 0.121 0.855 1500 0.213 0.260 0. 995 2000 0 226 0.225 0.268 0.015 0. 085 4000 0. 205 MIC (ppm) < 500 500-1000 1500-2000 < 500 1000-2000 Examples 3 [0020] An experiment similar to Example 1 was run with the following amines: DCHA = Dicyclohexylamine OAE= Octylaminoethanol ODEA = Octyldiethanolamine BAE = Butylaminoethanol [0021] The impact of these N-alkyl alkanolamines on the control of the bacterial species Mycobacterium marinum (ATCC # 927) is given in Table 3. Bacterial concentration in the experimental media was monitored indirectly via optical absorbance at 660 nm. The values reported are end-point optical densities in milliOD units after 72 hours. The media consisted of a standardized solution of clear nutrient broth (Middlebrook 7H10 with OADC supplement), amine, buffer (Tris) and water. The pH was adjusted initially to 8. 5 with Tris buffer. The first column in Table 3 gives the amine concentration in parts per million by weight. In all cases, the values are averages of at least three replicates. The final row of Table 3 gives an estimate of the concentration range in which the amine in question starts to inhibit the growth of this bacterial species (minimum inhibitor concentration MIC).

TABLE 3 Amine OAE ODEA DCHA BAE (ppm) 0 0. 8 0.8 0. 8 0. 8 400 0.4 0. 6 0. 6- 800 0.4 0.4 0.6 0.7 1200 0.4 0.4 0.5 0.7 2000 0 0.1 0.4 0.6 4000 0 0 0.4 0.6 MIC (ppm) 1200-2000 1200-2000 > 4000 > 4000 [0022] The results in the examples shows that alkyl ethanolamines exhibit highly effective antimicrobial activity against Mycobacteria as compared to the chemically close, structurally related compound 2-amino-2-methyl-1-propanol.

[0023] While the present invention has been described with respect to particular embodiments thereof, it is apparent that numerous other forms and modifications of this invention will be obvious to those skilled in the art. The appended claims and this invention generally should be construed to cover all such obvious forms and modifications, which are within the true spirit and scope of the present invention.