MXPA96003022A

MXPA96003022A - Antimicrobial compositions synergistic quecontain methylene-bis- (thiocianate) and an acidoorgan

Info

Publication number: MXPA96003022A
Application number: MXPA/A/1996/003022A
Authority: MX
Inventors: Oppong David; M King Vanja
Original assignee: Buckman Laboratories International Inc
Priority date: 1994-01-27
Filing date: 1995-02-11
Publication date: 1997-06-01

Abstract

The present invention relates to a composition for controlling the growth of at least one microorganism comprising synergistically effective amounts of (A) a methylene-bis- (thiocyanate) and (B) at least one organic acid, its oester salt

Description

ANTIMICROBIAL COMPOSITIONS SYNERGISTIC CONTAINING METHYLENE-BIS- (TIOCYANATE) AND AN ORGANIC ACID The present invention relates to certain compositions and processes useful for controlling the growth of one or more microorganisms and for preventing the decomposition caused by fungi and bacteria in various products. , materials or media, particularly products, materials or media, these products, materials or industrial media that include * "* 'paints, leather, wood, wood pulp, sawdust, starch, protein materials, wood for felling, animal skins, liquors for dyeing vegetables, cosmetics, formulations for toiletries, emulsions of latex acrylic paint, adhesives, coatings, metalworking fluids, water for cooling towers, textiles, petrochemicals, pharmaceutical formulations, geological drilling lubricants, liquors for paper mills, and agrochemical compositions. The novel compositions and processes that incorporate The composition of the present invention show unexpected synergistic activity against microbes, including fungi and bacteria. Specifically, the invention is directed to the use of compositions and processes containing methylene-bis- (thiocyanate) and at least one organic acid, or its salt or ester.

Many of the products, materials or media, referred to above, when wetted or subjected to treatments in water, are susceptible to bacterial and / or fungal deterioration or degradation unless measures are taken to inhibit such degradation or deterioration. To control the degradation or deterioration caused by microorganisms, several industrial microbicides are used, but some of these biocides are of questionable utility because they have undesirable odors, are expensive, show low degree of effectiveness and / or create dangers with respect to storage, use and / or management. For example, the use of popular industrial microbicides such as organomercurium compounds, tin organ and chlorinated phenols has been increased under increasing regulatory pressure in recent times due to its high toxicity and importance of its effects on the environment. Consequently, the industry continues to look for improved biocides that have low toxicity and that are capable of exhibiting prolonged biocidal effects at normal levels of use. Organic acids can be used alone to control microorganisms, and while some of these compounds are generally considered safe, many of them have low efficiency against bacteria and fungi unless extremely high concentrations are used. In excessive concentrations these organic acids can be expensive and even corrosive for certain industrial materials.

A method that can avoid the excessive use of organic acids and hence reduce the cost, is therefore desirable. Alternatively, methylene bis (thiocyanate) can be used only in low concentrations as low toxicity biocides. However, at low concentrations, methylene-bis- (thiocyanate) tends to have a narrow antimicrobial spectrum and fails to completely prevent the growth of microorganisms. Accordingly, the present invention is directed to microbicidal compositions and processes that incorporate these compositions that substantially make obvious one or more of the problems, limitations, and disadvantages of the prior art. In particular, the compositions of the present invention are capable of controlling the growth of at least one microorganism, especially fungi or bacteria, for extended periods of time, and are safe and economical to use. The present invention is also directed to methods or processes for controlling the growths of at least one microorganism. The present invention provides a composition for controlling the growth of at least one microorganism comprising synergistically effective amounts of methylene-bis- (thiocyanate) and at least one organic acid, its salt or ester. The composition provides superior microbicidal activity at low concentrations against a wide range of microorganisms. The present invention also provides a method for controlling the growth of at least one microorganism within or on a material or medium susceptible to being attacked by the microorganism, which comprises the step of adding to the material or medium a composition of the present invention, wherein the components of the composition are present in synergistically effective amounts. In addition, the present invention provides a method for preventing the decomposition of a product, material or medium caused by bacteria and / or fungi comprising the step of adding to the product, material or medium, a composition of the present invention, wherein the components of the composition are present in synergistically effective amounts. The synergistically effective amounts vary according to the material or medium to be treated and can, for a particular application, be determined routinely without undue experimentation by one skilled in the art. The present invention also embodies the separate addition of methylene bis (thiocyanate) and at least one organic acid, its salt or ester to the products, materials or media described above. According to this modality, the components are added individually to the system so that the final amount of methylene-bis (thiocyanate) and at least one organic acid, its salt or ester present in the system at the same time as the use of that significantly effective amount required to control the growth of at least one microorganism. The compositions of the present invention are also useful in the preservation of various types of products, media or industrial materials that are susceptible to attack by microorganisms. Such products, media or materials include but are not limited to dyes, pulps, wood, skin, textiles, pulp, sawdust, dye liquors, paper mill liquors, polymer emulsions, paints, paper and other coating agents and sizing, fluids for metal working, lubricants for geological drilling, pe rochemicals, cooling tower systems, pharmaceutical formulations, cosmetics and formulations for toiletries. The compositions may also be useful in agrochemical formulations for the purpose of protecting the seeds or crops against microbial decomposition. Additional advantages of the invention will be disclosed in part in the description which follows, and in part will be obvious from the description, or may be learned by practice of the invention. The advantages of the invention can be realized and obtained by means of elements and combinations indicated in the claims. It is understood that the foregoing general description and the following detailed description are only exemplary and explanatory and not limitative of the present invention as claimed. When chemical microbicides are combined into a product or added separately there are three possible outcomes: 1) The chemicals in the product could produce an additive (neutral) effect. 2) The chemicals in the product could produce an antagonistic effect (negative), or 3) The chemicals in the product could produce a synergistic (positive) effect. A negative effect has no economic advantage over the individual components. The antagonistic effect could have a negative impact. Only a synergistic effect, which is less likely than the additive or antagonistic effect, could produce a positive effect and therefore has an economic advantage. It is well known in the microbicidal literature that there is no theoretical method to provide the probability of knowledge, before actually testing, whether antagonistic or synergistic effects of the additive will be obtained when the two biocides are mixed to give a formulation. The microbicidal compositions that combine methylene-bis (thiocyanate) and at least one organic acid, its salt or ester demonstrate an unexpected synergistic effect in comparison with the respective components alone. In this way, these compositions achieve superior, ie, greater additive microbicidal activity at low concentrations against a wide variety of microorganisms. Examples of microorganisms include fungi and bacteria such as, but not limited to, Trichoderma harzianum and Pseudomanas aeruginosa. These two organisms are some of the most common organisms associated with the decomposition of products, materials or media. Because these two are some of the most difficult organisms to control, the composition of the present invention is effective against most fungi and bacteria. Preferably, the compositions of the present invention have low toxicity. The methylene bis (thiocyanate) preparation (MTC) is described in U.S. Patent No. 3,524,871, the disclosure of which is fully incorporated herein by reference. MTC is commercially available and is also easily synthesized from commercially available raw material. A preferred MTC according to the present invention is 2-methylene bis (thiocycle). The organic acids of the present invention are any organic acid that produces a synergistic effect when combined with MTC. Examples of organic acids include aromatic organic acids, cyclic organic acids, organic aliphatic acids, their salts or esters. Specific examples or organic acids effective according to the invention include dehydroacetic acid, octanoic acid, nonanoic acid, formic acid, sorbic acid, acetic acid, oxalic acid, glycolic acid, citric acid, glyconic acid, malic acid, propionic acid, acid lauric, undecylene acid, benzoic acid or benzoic acid derivatives such as 2-hydroxybenzoic acid, 3-hydroxybenzoic acid or 4-hydroxybenzoic acid, methyl paraben or propyl paraben. The salts of the organic acids can be used, preferably those containing calcium, zinc, potassium, or sodium, such as sodium benzoate and potassium sorbate. When such mixtures are used in combination with MTC, at least one of the organic acids in the mixtures has a synergistic relationship with MTC. The organic acids, salts or esters useful in the invention are commercially available and can be synthesized from commercially available raw material. The organic acid can be chosen, for example, based on the compatibility of the acid with the products, materials or medium. Compatibility is easily determined by adding the organic acid to the products, materials or media to be used. The compatibility can be determined by criteria, such as solubility in a fluid system and / or lack of reactivity with the fluid in question. When used in a fluid system, for example, it is preferable that the organic acid be freely soluble or dispersible in the particular fluid system, resulting in a uniform solution or dispersion. Examples of fluid systems are liquor for dyeing, liquor for paper mills, water for cooling towers, and paints. According to the present invention, the composition can be in the form of a solid, dispersion, emulsion or solution, depending on the particular application. In addition, the components of the composition can be applied separately or they can be combined first and then applied to the product, material or medium. The composition of the present invention can be prepared in liquid form by dissolving the components (A) and (B) in an organic solvent. In the following discussion of preferred embodiments, component (A) is 2-methylene bis (thiocyanate) and component (B) is at least one organic acid, its salt or ester. As described above, the components (A) and (B) of the composition are used in synergistically effective amounts. The weight ratios of (A) to (B) vary depending on the type of microorganisms, as well as the products, materials or media to which the composition is applied.

Someone skilled in the art can easily determine the appropriate weight ratios for a specific application. In the present invention, the weight ratio of the component (A) to the component (B) is preferably in the range of about 0.01: 99 to 99: 0.1, more preferably of about 1:30 to about 30: 1, and the more preferred from about 1: 5 to about 5: 1. The following approximate range of weight ratios of MTC to the following organic acids is also preferred according to the present invention: * MTC: benzoic acid 1: 5 to 0.1: 100 MTC: sodium benzoate 1: 100 to 0.1: 400 MTC : methyl paraben 1: 5 at 0.1: 100 MTC: propyl paraben 1: 5 at 0.1: 100 MTC: p-hydrobenzoic acid 1: 5 at 0.1: 250 MTC: dehydroacetic acid 1: 5 at 1: 400 MTC: octanoic acid 1 : 5 to 1: 400 MTC: non-organic acid 1:10 to 1: 400 MTC: formic acid 1:50 to 1: 800 MTC: sorbic acid 1: 5 to 0.1: 100 MTC: potassium sorbate 1: 5 to 1: 800 MTC: acetic acid 1: 100 to 1: 200 MTC: oxalic acid 1:50 to 1: 200 MTC: glycolic acid 1: 100 to 1: 400 MTC: citric acid 1: 100 to 1: 400 MTC: malic acid 1 : 100 to 1: 400 MTC: propionic acid 1:10 to 1: 400 MTC: lauric acid 1: 5 to 0.1: 400 5 MTC: undecylenic acid 1: 5 to 0.1: 500 However, in general, an answer can be obtained bactericide and fungicide when the synergistic combination is used in concentrations that are in the range of about 0.01 to about 3000 ppm of -? methylene bis (thiocyanate), preferably from about 0.1 to about 1000 ppm, and more preferably from about 0.1 to 500 ppm, and from about 0.1 ppm to about 1% by weight of the organic acid, preferably from about 0.1 to 500 ppm, and more preferably of approximately 0.1 to 2000 ppm. The present invention also provides a method for controlling the growth of at least one microorganism within or on a material or medium susceptible to attack by the microorganisms comprising the step of applying to the material or means a composition of the present invention, wherein the components of the composition are present in synergistically effective amounts. In addition, the present invention provides a method to prevent the decomposition of a product, material or medium caused by bacteria and / or fungi comprising the step of applying to said product, material or medium, a composition of the present invention wherein the components of the composition are present in synergistically effective amounts. For example, the composition can be used to prevent the decomposition of seeds or crops, for example, cotton, barley, rice, corn, tobacco, etc. The mode and reason for application of the composition depends on the intended use of the composition. For example, the composition can be applied by spraying or spreading it on a material or product. The material or product could also be treated by immersing it within an appropriate formulation of the composition. For a liquid or semi-liquid medium, the composition can be added to the medium by emptying, or by measuring it with an appropriate device, so that a solution or dispersion containing the composition is produced. If used as a liquid preservative, for example, the composition can be prepared as an aqueous emulsion. If necessary, a surfactant can be added to the composition. According to the invention, additional components such as insecticides and the like can be added to the above formulations without affecting the synergistic effects of the composition. Insecticides that may be used include but are not limited to pyrethroids, nicotine, chlorodane, parathion, and methoxychlor. The synergistic activity of the combinations described above has been confirmed using standard laboratory techniques as illustrated below. The following examples are intended to illustrate, not limit, the scope of the present invention. Microbiological evaluation A. Evaluation of fungi A mineral salts-glucose medium was prepared first by adding to 1 liter of deionized water: 0.7 g of K2P04, 0.7 g of MgSO4.7H20, l.Og of NH4N03, 0.005 g of NaCl, 0.002 , or FeS04.7H20, 0.002 g of ZnS04.7H20, 0.001 g of MnS04.7H20, and 10 g of Glucose. The pH of medium was adjusted to 6 with NaOH at IN. The medium was distributed in quantities of 5 ml in test tubes and autoclaved at 121 ° C (for 20 minutes) The fungus, Trichoderma harzianum, was developed on a biased culture of potato dextrose agar from 7 to 10 days and a spore suspension was prepared by washing the spores of the biased culture in a sterile saline solution.After the addition of biocides in the desired concentrations to the sterile mineral salts-glucose medium, the suspension of 0 fungal spores was added. The final spore concentration was approximately 10 cfu / ml The inoculated medium was incubated at 28 ° C for 14 days B. Bacterial evaluation Nutrient broth (2.5 g / liter of deionized water) was prepared and the pH was adjusted to 6 with IN HCl This was distributed in quantities of 5 ml in test tubes and autoclaved for 20 minutes at 121 ° C. After the addition of biocides at the desired concentrations to the nutrient broth, 100 microliters of a A suspension of Pseudo onas aeruginosa cells of approximately 9.3 x 108 CFC / ml were added and incubated at 37 ° C for 48 hours. In Examples 1 to 19, a synergistic effect was demonstrated by testing the combination of methylene-bis (thiocyanate), designated as component A, and the corresponding organic acid, its salt or ester, designated as component B, in a series of tests in various ratios and ranges of concentrations against Trichoderma harzianum and also against the bacterium Pseudomonas aeruginosa using the method described above. For each component A and B in a mixture containing A and B and for each component A and B that acts alone, determined the lowest concentration that completely prevents the growth of the fungus for two weeks and the bacteria for 48 hours. These concentrations were used as endpoints for synergism calculations. The end points for the components alone or in the mixtures described above were then compared with the end points for the pure active ingredients alone in prepared flasks or test tubes. The synergism was demonstrated by the methods described by Kull, E.C., Eisman, P.C., Syl estr icz, H.D., and Mayer, R.

L. 1961. Applied microbiology. 9: 538-541 where: QA / Qa + QB / Qb is less than 1 Qa = Concentration of compound A in parts per million, acting alone, which produces a final point. 5 Qb = Concentration of compound B in parts per million, acting alone, which produces a final point. QA = Concentration of compound A in parts per million, in the mixture, which produces a final point. Qb = Concentration of compound B in parts per million, in the _ / «mixture, which produces a final point. When the sum of QA / Qa and QB / Qb is greater than 1, it indicates antagonism and when the sum is equal to one, it indicates additivity, when the sum of this value is one, there is synergism. This method for demonstrating the synergism of the compositions of this invention is widely used and accepted. More detailed information is provided in the article by Kull et al. Additional information concerning this procedure is contained in U.S. Patent No. 3,231,509, the disclosure of which is hereby incorporated herein by reference. The examples demonstrate that in almost all samples, the combination of MTC with a corresponding organic acid produced a synergistic result (indicated by a ratio value of less than one). There were a few samples, such as Table 2, < 1.25 or < 1.5 where the synergistic results were inconclusive because the end points for the acids used alone were not determined. It will be apparent to those skilled in the art that various modifications and variations can be made to the compositions and methods of the present invention without departing from the spirit or scope of the invention. Thus, it is intended that the present invention cover the modifications and variations of this invention with the proviso that they fall within the scope of the appended claims and their equivalents.

Example 1 Component A: MTC Component B: Bezoic acid Test organism Quantities that produce endpoints (ppm) Example 2 Component A: MTC Component B: Sodium Benzoate Test Organizer Quantities that produce endpoints (ppm) Example 3 Component A: MTC Component B: sorbic acid Test Organizer Quantities that produce endpoints (ppm) Example 4 Component A: MTC Component B: potassium sorbate Test Organizer Quantities that produce endpoints (ppm) Example 5 Component A: MTC Component B: p-hydroxybenzoic acid Test organism Quantities that produce endpoints (ppm) Example 6, Component A: MTC Component B: Dehydroacetic acid Test organism Quantities that produce endpoints (ppm) Example 7 Component A: MTC Component B: Propiodic acid Test organism Quantities that produce endpoints (ppm) Example 8 Component A: MTC Component B: Methyl paraben Test Organizer Quantities that produce endpoints (ppm) Example 9 Component A: MTC Component B: Propil paraben Test Organism Quantities that produce endpoints (ppm) Example 10 Component A: MTC Component B: nonannoic acid Test Organizer Quantities that produce endpoints (ppm) Example 11 Component A: MTC Component B: octanoic acid Test Organizer Quantities that produce endpoints (ppm) Example 12 Component A: MTC Component B: undecylenic acid Test Organizer Quantities that produce endpoints (ppm) Example 13 Component A: MTC Component B: Lauric acid Test Organizer Quantities that produce endpoints (ppm) Example 14 Component A: MTC Component B: formic acid Test Organizer Quantities that produce endpoints (ppm) Example 15 Component A: MTC Component B: Acetic acid Test Organizer Quantities that produce endpoints (ppm) Example 16 Component A: MTC Component B: oxalic acid Test Organizer Quantities that produce endpoints (ppm) Example 17 Component A: MTC Component B: citric acid Test Organizer Quantities that produce endpoints (ppm) Example 18 Component A: MTC Component B: malic acid Test Organizer Quantities that produce endpoints (ppm) Example 19 Component A: MTC Component B: glycolic acid Test Organizer Quantities that produce endpoints (ppm)

Claims

R E I V I N D I C A C I O N S 1. A composition for controlling the growth of at least one microorganism comprising synergistically effective amounts of (A) a methylene-bis- (thiocyanate) and (B) at least one organic acid, its salt or ester.
2. The composition of claim 1, wherein the microorganism is a fungus or bacteria.
3. The composition of claim 2, wherein the fungus or bacterium is Trichoderma harzianu or Pseudomonas aeruginosa.
4. The composition of claim 1, wherein the methylene-bis (thiocyanate) is 2-methylene-bis (thiocyanate).
5. The composition of claim 1, wherein the organic acid is selected from the group consisting of organic acids, cyclic organic acids, aliphatic organic acids, their respective salts and esters, and mixtures thereof.
6. The composition of claim 5, wherein the organic acid is selected from the group consisting of benzoic acid, sodium benzoate, p-hydroxybenzoic acid, methyl paraben, propyl paraben, dehydroacetic acid, octanoic acid, nonanoic acid, acid formic acid, sorbic acid, potassium sorbate, acetic acid, oxalic acid, glycolic acid, citric acid, malic acid, propionic acid, lauric acid, undecylenic acid, their respective salts and. esters, and their mixtures.
7. - The composition of claims 1-6, wherein the weight ratio of (A) to (B) is from about 1:30 to 30: 1.
8. The composition of claim 7, wherein the weight ratio of (A) to (B) is from about 1: 5 to 5: 1.
9. The composition of claims 1-6, wherein the weight ratio of the concentrations are from about 0.1 to about 500 ppm of methylene-bis (thiocyanate), and from about 0.1 to about 2000 ppm of the organic acid.
10. A method for controlling the growth of at least one microorganism in or on a product, material or medium susceptible to attack by said microorganism comprising the step of applying to the product, material or medium a composition according to any of claims 1 -9.
11. The method according to claim 10, wherein said material or medium product is pulp, sawdust, felling wood, paints, skin, adhesive coatings, * animal skins, tanning liquors, liquors for paper mills, fluids for working metals, petrochemicals, pharmaceutical formulations, water cooling towers, cosmetics, bath formulations, textiles, geological drilling lubricants, lubricants or agrochemical compositions for protection of crops or seeds.
12. - The method according to claim 10, wherein said components (A) and (B) are applied separately to the product, material or medium.
13. - A method for preventing the decomposition of a product, material or medium caused by bacteria, fungi or both, the step of applying to said product, material or medium, comprising a composition according to any of claims 1-9 in effective amounts to avoid such decomposition. ? flijypiiiip Compositions are disclosed for controlling the growth of microorganisms within or on a product, material or medium, comprising synergistically effective amounts of methylene-bis (thiocyanate) and at least one organic acid, its salt or ester. Also disclosed are methods for controlling the growth of microorganisms and preventing the decomposition caused by microorganisms with the use of the compositions of the present invention.