WO2000069265A1

WO2000069265A1 - Microbicidal composition of a 2-alkylbenzisothiazol-3-one and a halopropynyl compound

Info

Publication number: WO2000069265A1
Application number: PCT/GB2000/001777
Authority: WO
Inventors: John Edwards Yates; Philip Charles Hindley
Original assignee: Avecia Limited
Priority date: 1999-05-18
Filing date: 2000-05-09
Publication date: 2000-11-23
Also published as: AU4594400A; GB9911606D0

Abstract

A composition comprising: a) a 1,2-benzisothiazolin-3-one derivative of Formula (1) wherein: R is C1-5-alkyl, C3-5-cycloalkyl or aralkyl; R1 is hydroxy, halogen, C¿1-4?-alkyl or C1-4-alkoxy; r is from 0 to 4; and b) a halopropynyl compound. The compositions are useful for inhibiting the growth of micro-organisms on or in a medium such as a plastic. Also claimed are formulations containing the compositions and a method for inhibiting the growth of micro-organisms using the compositions.

Description

MICOBICIDAL COMPOSITION OF A 2-ALKYLBENZIS0THIAZ0L-3-0NE AND A HALOPROPYNYL COM POUND

The present invention relates to a biocidal composition comprising a N-alkyl- or N-aralkyl-1 ,2-benzisothiazolin-3-one and a halopropynyl compound and its use for inhibiting the growth of micro-organisms such as fungi and algae in industrial media.

WO 96/22023 disclosed the use of N-(C₃_₅-alkyl)-1 ,2-benzisothiazolin-3-one as a 5 biocide and especially a fungicide for plastics materials.

3-lodo-2-propynyl-N-n-butyl carbamate is a commercially important fungicide, especially for use in paint-films.

It has now been found that the microbiological activity of N-alkyl and N-aralkyl 1 ,2-benzisothiazolin-3-ones (hereinafter BIT derivative) may be improved by incorporating o a halopropynyl compound (hereinafter HPC).

According to a first aspect of the present invention there is provided a composition comprising: a) a BIT derivative of the Formula (1 ):

Formula (1 ) wherein:

R is C_1-5-alkyl, C₃-₅-cycloalkyl or aralkyl;

R¹ is hydroxy, halogen, C^-alkyl or C^-alkoxy; 0 r is from 0 to 4; and b) a halopropynyl compound (HPC).

When R¹ is halogen, it is preferably iodine, bromine and especially chlorine.

When R is alkyl it may be linear or branched and is preferably linear.

When R is cycloalkyl, it is preferably cyclopropyl or cyclopentyl. 5 When R is aralkyl, it preferably contains two or more carbon atoms in the alkylene group attaching the aryl group to the isothiazoiinone ring. Preferred aralkyl groups include benzyl, 2-naphthylethyl and especially 2-phenylethyl.

The substituent R¹, when present, is preferably located in the 5 and/or 6 position of the phenyl ring of the benzthiazolinone. However, it is particularly preferred that r is o zero.

It is particularly preferred that R is C₃.₅-alkyl, especially n-butyl. Examples of suitable benzisothiazolinones include N-methyl-, N-ethyl-, N-n-propyl- , N-isopropyl-, N-n-pentyl, N-cyclopropyl-, N-cyclopentyl, N-n-butyl, N-isobutyl-, N-tert- butyl-, N-benzyl- and N-(2-phenylethyl)-1 ,2-benzisothiazolin-3-one. It is especially preferred that the BIT derivative is N-n-butyl-1 ,2-benzisothiazolin-3-one. Preferably, the HPC is a compound of Formula (2):

Formula (2) wherein:

Y is halogen;

R² and R³ are each, independently, C_1-β-alkyl, C₂-₆-alkenyl or C₃.₇-cycloalkyl; m is from 1 to 6; and X is an organic moiety linked to the -CR²R³- group via an oxygen, nitrogen, sulphur or carbon atom.

Preferably, Y is chlorine, bromine and especially iodine. The compound of Formula (2) wherein Y is iodine is an iodopropargyl compound (hereinafter IPC).

The organic moiety linked to the -CR²R³- group via an oxygen, nitrogen, sulphur or carbon atom preferably contains not greater than 20 and especially not greater than 10 carbon atoms.

The compound of Formula (2) wherein the organic moiety is linked to the group -CR²R³- via an oxygen atom is preferably an ether, ester or especially a carbamate.

The compound of Formula (2) wherein the organic moiety is linked to the group -CR²R³- via a nitrogen atom is preferably an amine or amide.

The compound of Formula (2) wherein the organic moiety is linked to the group -CR²R³- via a sulphur atom is preferably a thiane, sulphone or sulphoxide.

The organic moiety can be alkyl, alkenyl, aryl, heteroaryl, aralkyl, cycloalkyl or cycioalkenyl, all of which may be optionally substituted. When the organic moiety is alkyl, it may be linear or branched but is preferably linear.

Preferred optional substituents in the organic moiety are halogen such as chlorine, bromine and iodine, C^-alkyl and C_1-6-alkoxy.

Preferably, R² and R³ are both hydrogen. It is also preferred that m is one.

According to the first aspect of the invention the IPC is a compound of Formula (3):

O l-C≡C-(CH₂) — O— C— NH-|- R^'

Formula (3) wherein:

R⁴ is hydrogen, optionally substituted C_1-20-alkyl, optionally substituted aryl, optionally substituted aralkyl, C₃-₂₀-cycloalkyl or C₃-₂₀-cycloalkenyl; and n and p are each, independently, from 1 to 3. When R⁴ is C₁.₂₀-alkyl, it may be linear or branched. Examples are methyl, ethyl, propyl, n-butyl, s-butyl, t-butyl, pentyl, hexyl, heptyl, octyl, nonyl, decyl, dodecyl and octadecyl.

When R⁴ is optionally substituted aryl, it is preferably optionally substituted phenyl.

When R⁴ is optionally substituted aralkyl, it is preferably optionally substituted 2- phenylethyl or benzyl.

When R⁴ is cycloalkyl, it is preferably C₃.₆-cycloalkyl, more preferably cyclopropyl or cyclohexyl.

When R⁴ is cycioalkenyl, it is preferably cyclohexenyl.

Preferred optional substituents which may be present on R⁴ include halogen (preferably chlorine, bromine or iodine), C^-alkyl or C.,-₆-alkoxy. It is preferred however that R⁴ is unsubstituted.

It is also preferred that n is one and it is also preferred that p is one.

IPC's of Formula (3) are disclosed in US 3,923,870; US 4,259,350; US 4,592,773; US 4,616,004; US 4,719,227 and US 4,945,109. Especially preferred IPC's of Formula (3) are 3-iodo-2-propynyl-N-n-propyl carbamate, 3-iodo-2-propynyl-N-n-butyl carbamate, 3-iodo-2-propynyl-N-n-hexyl carbamate, 3-iodo-2-propynyl-N-cyclohexyl carbamate and 3-iodo-2-propynyl-N-phenyl carbamate.

According to a second aspect of the invention, the IPC is a compound of Formula (4):

R⁵ R⁷ R⁹ ^{1 1 1} l-C ≡C-C-O-C— C— OCONHR ⁶ R⁸ R¹°

Formula (4) wherein: R⁴ is defined hereinbefore;

R⁵ and R⁶ are each, independently, C_1-6-alkyl, C₂-₆-alkenyl, C₃.₇-cycloalkyl or -CR⁵R⁶- represents (-CH₂)_t- where t is from 4 to 6; and

R⁷ to R¹⁰ are each, independently, hydrogen, C^-alkyl, aryl, -CCI₃ or R⁷ with R⁹ or R⁸ with R ⁰ represents -(CH₂)_q- where q is from 3 to 5. The preparation of IPC's of Formula (4) are described in US 4,474,807. Especially, preferred IPC's of Formula (3) are 2-(3-iodo-2-propynyloxy)-ethyl-N- methyl carbamate, 2-(3-iodo-2-propynyloxy)-ethyl-N-n-butyl carbamate,

2-(3-iodo-2-propynyloxy)-ethyl-N-phenyl carbamate and 2-(3-iodo-2-propynyloxy)-ethyl-N- (4-chlorophenyl) carbamate. It is especially preferred that the composition contains an IPC of Formula (3) and that the IPC of Formula (3) is 3-iodo-2-propynyl-N-n-butyl carbamate (hereinafter IPBC).

In an especially preferred embodiment the composition comprises N-n-butyl-1 ,2- benzisothiazolin-3-one and IPBC.

The relative proportions of component (a) and component (b) in the composition can vary between wide limits but is preferably from 100:1 to 1 :100, more preferably from 10:1 to 1 :10, even more preferably from 5:1 to 1 :5 and especially between 3:1 and 1 :3. Useful effects have been obtained where components (a) and (b) are present in equal amounts.

The composition of the present invention has antimicrobial properties and has been found to be effective as a fungicide. The compositions are especially effective for inhibiting the growth of fungi which are commonly found in paint-films, on wood and in metal-working fluids. Examples of such organisms include for example, Alternaria alternata and Aureobasidium pullulans.

Furthermore, the composition according to the present invention exhibits a sum of the Fractional Inhibitory Concentration (hereinafter FIC) for each component which is below 1. Preferably, the sum of the FIC values is not greater than 0.8, more preferably not greater than 0.7 and especially not greater than 0.5. The FIC is the ratio of the amount of each component in the composition relative to its Minimum Inhibitory Concentration (MIC) when used alone. Thus, when the sum of the FIC values is one, the two components exhibit a mere additive effect. When the sum of the FIC values is below one, the mixture is synergistic. When the sum of the FIC values is between one and two the two components are considered to be independent. When the sum of the FIC values is greater than two, the mixture is antagonistic. The FIC values are preferably determined by constructing an isobologram wherein each component in a matrix array is varied stepwise from a concentration in excess of the MIC down to zero ppm. The isobologram, therefore, allows the smallest value of the sum of the FIC's for each component in the composition to be determined and hence the optimal concentration for each component in the composition.

The composition according to the invention is useful to inhibit the growth of micro- organisms in a medium which is susceptible to microbiological degradation. Component (a) and component (b) of the composition may be added to the medium either sequentially or preferably simultaneously. Where appropriate, the composition may be added directly to the medium, especially where the medium is a solid such as a plastics material. In other uses, it is more convenient to treat the medium with a formulation comprising component (a), component (b) and a carrier.

When the composition according to the invention is used as a biocide for inhibiting the growth of deteriogens for plastics materials, the plastic is preferably an organic polymeric material containing a plasticiser or stabiliser. Examples of plastics materials are polyurethanes, polyvinylhalides such as polyvinylchloride (PVC), polyalkylenes such as polypropylene, polyalkylene vinyl acetate such as polyethylene vinyl acetate, polyester such as polyethyleneterephthalate, polyamide and polyacrylonitrile. Suitable plastics materials are caulks, sealants, such as silicone sealants and especially plasticised PVC. The amount of the composition according to the invention which is present in the plastics material may vary over wide limits from a minimum amount which just inhibits microbiological growth up to many times this amount. Thus, where the plastics material containing the composition is to be used as a master-batch for mixing with untreated plastics material the amount of the composition may be two or three magnitudes greater than that required to inhibit microbiological growth. Preferably, the amount of the composition in the plastics material which is required to inhibit microbial degradation is not less than 10, more preferably not less than 100, even more preferably not less than 500 and especially not less than 1000 ppm relative to the amount of the plastics material. It is also preferred that the amount of the composition which is required to inhibit microbial degradation is not greater than 5000 ppm, more preferably not greater than 4000 ppm and especially not greater than 3000 ppm relative to the amount of the plastics material.

The composition according to the invention may be applied to the plastics material after fabrication to form the finished article but is preferably applied to the plastics material prior to fabrication. In one preferred method, component (a) and component (b) are applied sequentially or preferably simultaneously to the dry plastics material which may be any solid form such as powder, flake, chip or pellet to form a master-batch. Thus, according to a further aspect of the invention there is provided a master-batch which is a composition comprising a plastics material together with component (a) and component (b).

Where the plastics material is fabricated with a plasticiser or stabiliser, the composition comprising component (a) and component (b) may be conveniently added with a carrier which is a stabiliser and/or plasticiser for a plastics material.

The plasticiser or stabiliser may be any of those commonly used in the plastics material fabrication industry and is preferably a liquid. Examples of suitable plasticiser/stabiliser are esters of aromatic and aliphatic mono- and di-carboxylic acids and linear or branched alcohols especially C₈.₁₀-alcohols; epoxidised fatty acid esters and epoxidised vegetable oils. Specific examples of plasticisers are di-hexyl-, di-octyl-, di-nonyl, di-isodecyl-, and di-(2-ethylhexyl)- adipates, sebacates, trimellitates and phthalates; epoxidised octyl stearate, epoxidised soya bean oil and phosphate esters of formula O=P (OR¹¹)₃ wherein R¹¹ is hydrocarbyl, particularly phenyl and especially C -alkyl and low molecular weight oligo- and poly-esters such as those obtainable by reacting 1 ,3-butanediol with adipic acid.

According to a still further aspect of the invention there is provided a composition comprising a composition according to the first aspect of the present invention and a plasticiser and/or stabiliser for a plastics materials.

According to another aspect of the present invention there is provided a formulation comprising a composition according to the first aspect of the present invention and a carrier.

The carrier may be a solid, or more preferably a liquid. When the carrier is a liquid it is preferably a non-polar organic liquid, a polar organic liquid, water or mixtures thereof. It is especially preferred that the carrier is water or a mixture of water and one or more water-soluble organic liquids.

The BIT derivatives (component (a) of the composition) are mainly liquids at ambient temperature (20°C) and are generally soluble in organic liquids. This is especially true where the BIT derivative is a C^-alkyl or C₃.₅-cycloalkyl-1 ,2- benzisothiazolin-3-one. Consequently, for many end-uses, the BIT derivative may be dissolved in an organic liquid without recourse to the use of dispersants or emulsifiers.

However, if such liquid BIT derivatives or solutions of BIT derivatives in an organic liquid are added to water as a carrier it is preferable to uniformly distribute the BIT derivative (or solution thereof) in the aqueous phase in the presence of an emulsifier, thereby forming an emulsion or micro-emulsion. Preferred emulsifiers are non-ionic, anionic or a mixture thereof. Preferred anionic emulsifiers include alkylarylsulfonates (for example calcium dodecylbenzenesulfonate), alkylsulfates (for example sodium dodecylsulfate), sulfosuccinates (for example sodium dioctylsulfosuccinate), alkylethersulfates, alkylarylethersulfates, alkylether carboxylates, alkylarylethercarboxylates, lignin sulfonates or phosphate esters. Preferred non-ionic emulsifiers include fatty acid ethoxylates, ester ethoxylates, glyceride ethoxylates (for example castor oil ethoxylate), alkylaryl polyglycol ethers (for example nonylphenol ethoxylates), alcohol ethoxylates, propylene oxide-ethylene oxide condensation products, amine ethoxylates, amide ethoxylates, amine oxides, alkyl polyglucosides, sorbitan fatty acid esters, polyoxyethylene sorbitan fatty acid esters, polyoxyethylenesorbitol esters or alcohol ethoxy carboxylates, especially those obtainable from C₁₂.₁₄-alcohols.

When the BIT derivative is a solid, such as 2-phenylethyl- 1 ,2-benzisothiazolin-3-one and the carrier is water, it is preferable to use a dispersant to distribute the BIT derivative in the carrier. The HPC (component (b) of the composition) is generally insoluble or only sparingly soluble in a carrier such as a non-polar organic liquid, polar organic liquid or water and consequently it is preferable to uniformly distribute the HPC in the carrier by means of a dispersant. When a dispersant is used in the formulation the choice of dispersant is dependent on the nature of the carrier.

When the carrier is water, the dispersant is preferably anionic, non-ionic or a mixture thereof. Examples of suitable anionic dispersants are lignin sulphonates and formaldehyde-naphthalene sulphonate condensates. Examples of suitable non-ionic dispersants are polyethers and especially the ethyleneoxide/propyleneoxide block copolymers, nonylphenolethoxylate, β-naphtholethoxylate, alcohol ethoxylates such as those obtainable from C₁₂.₁₄-alcohols, amine ethoxylates and amide ethoxylates.

When the carrier is a polar organic liquid, the dispersant is preferably a polyester, especially one obtainable by (co)polymerising a C^-hydroxyalkylcarboxylic acid or lactone(s) thereof, and where the polyester is subsequently reacted with an amine or polyimine. Other preferred dispersants where the carrier is a polar organic liquid are polyester phosphates and polyisocyanates reacted with polyesters.

When the carrier is a non-polar organic liquid, the dispersant is preferably a polyester derivable from a C₆.₁₈-hydroxyalkylcarboxylic acid which is subsequently reacted with an amine or polyimine and optionally quatemised. Examples of suitable dispersants for non-polar organic liquids are the reaction product of 12-hydroxystearic acid and dimethylaminopropylamine which is quatemised with dimethylsulphate.

The amount of dispersant used in the formulation depends on the type of solid and nature of the liquid carrier but is generally between 1 and 100% and preferably between 5 and 15% based on the amount of solid.

When the formulation contains a dispersion of solids, the formulation may contain other adjuvants which stabilise solids in a liquid carrier. These include humectants and adjuvants which provide structure to the liquid carrier and inhibit separation and/or sedimentation of the solid. Where the carrier is an organic liquid, compounds which give structure to the organic liquid are naturally occurring clays such as bentonite and particularly organically treated clays. These organically treated clays are preferably used together with an activator such as mixtures of propylene carbonate and water. The preferred ratio of propylene carbonate to water is 95:5. Where the liquid carrier is water, compounds which give structure to the water are polyacrylamides, alginates and naturally occurring resins, especially Xanthan gum.

The amount of adjuvant which provides structure to the liquid carrier is preferably from 0.1 to 0.5% based on the total amount of the formulation. Dispersions containing solid component (b) and/or component (a) (if a solid) can be prepared by any means known to the art and include bead, pebble or ball milling the solid in the liquid carrier until the desired particle size of the solid is attained. Preferably, the particle size is less than 20, more preferably less than 10 and especially less than 5μ. In recent years there has been an increasing demand for industrial biocide formulations which contain low levels of volatile organic compounds (hereinafter low VOC) and particularly a demand for aqueous low VOC formulations. Hitherto, this has been difficult to achieve in the case of HPC's such as IPBC because of their low but significant aqueous solubility. As a result, there is a tendency for small particles to dissolve and to be deposited on larger particles. There is, thus, a tendency for the particle size distribution of the aqueous dispersion to change on storage to fewer particles of larger size. This coarsening of the particle size is referred to as "Ostwald ripening" as discussed, for example, in "Crystallisation" by J.W.Mullin, 3^rd edition, published by Butterworth/Heinemann, paperback edition 1997, pages 288 to 290. This Ostwald ripening manifests itself in instability of the aqueous dispersion, especially under adverse storage conditions and results in layering and sedimentation of the HPC. There is therefore, a need for a low VOC aqueous formulation which is stable under adverse storage conditions.

According to a further aspect of the present invention there is provided a micro- emulsion or more preferably an emulsion comprising a continuous aqueous phase and an oil phase; wherein the oil phase comprises a solution of a HPC in a liquid BIT derivative of the hereinbefore defined Formula (1 ).

The preferred HPC is as hereinbefore defined in relation to the first aspect of the present invention, especially IPBC. Preferably the liquid BIT derivative in the emulsion/micro-emulsion is a BIT derivative of the hereinbefore defined Formula (1 ) which is a liquid at ambient temperature (20°C), more preferably a N-C^-alkyl-l ^-benzisothiazolin-S-one and especially N-n-butyl-1 ,2-benzisothiazolin-3-one. The liquid BIT derivative acts as a solvent for the HPC and thereby enables a stable oil-in-water emulsion/micro-emulsion to be formed without the need for additional organic solvents (for example high VOC solvents) in the oil phase.

In a preferred embodiment the oil phase of the emulsion/micro-emulsion comprises a solution of IPBC in n-butyl-1 ,2-benzisothiazolin-3-one.

Preferably the emulsion/micro-emulsion contains less than 5% by weight VOC, more preferably less than 1 % VOC and especially substantially no VOC.

The emulsions/micro-emulsions according to this aspect of the invention are stable under adverse storage conditions as such as extremes of temperature and/or extended time periods. The emulsion/micro-emulsion may be prepared using conventional methods for the formation of emulsions and micro-emulsions. For example an emulsion may be formed by adding a solution of the HPC in the liquid BIT derivative to water containing suitable emulsifying agents, especially surfactants, whilst mixing thoroughly using a suitable mixing means such as a Silverson mixer equipped with an emulsifier head. Preferred emulsifying agents are as hereinbefore defined. When a surfactant is used as an emulsifying agent it is preferably anionic, non-ionic. It is especially preferred that the emulsifying agent is a mixture comprising a non-ionic and anionic surfactant, because we have found that this provides an emulsion with a particularly good stability. To further improve the stability of the emulsion/micro-emulsion to adverse storage conditions, the emuision/micro-emulsion may contain a humectant. Preferred humectants are those with a low vapour pressure at ambient temperatures and therefore a low volatility (i.e. low VOC). Suitable humectants include diols, preferably diols having from 2 to 12 carbon atoms, for example pentane-1 ,5-diol, ethylene glycol, propylene glycol, butylene glycol, pentylene glycol, hexylene glycol and thiodiglycol and oligo- and poly-alkyleneglycols, preferably diethylene glycol, thethylene glycol, polyethylene glycol (preferably with an average M_n <1000, more preferably <500) and polypropylene glycol (preferably with an average M_n <1000); triols, preferably glycerol and 1 ,2,6-hexanethol; mono-C_M-alkyl ethers of diols, preferably rπono-C^-alkyl ethers of diols having 2 to 12 carbon atoms, especially 2-methoxyethanol, 2-(2-methoxyethoxy)ethanol,

2-(2-ethoxyethoxy)-ethanol, 2-[2-(2-methoxyethoxy)ethoxy]ethanol,

2-[2-(2-ethoxyethoxy)-ethoxy]-ethanol and ethyleneglycol monoallylether; and urea. More preferably the humectant is ethyleneglycol, propyleneglycol, polyethyieneglycol and especially glycerol. The amount of humectant (if present) in the emulsion/micro-emulsion is preferably from 1 to 10% and especially from 2 to 7% by weight of the total emulsion/micro- emulsion.

Preferably the emulsion/micro-emulsion has a pH in the range of from 5.5 to 8.5, more preferably from 6 to 8 and especially from 6.5 to 7.5. The emulsion/micro-emulsion may further comprise additional components, for example pH adjusters, colorants or viscocity modifiers such as polyacrylamides, alginates and naturally occurring resins, especially Xanthan gum.

The composition according to the first aspect of the invention, or the formulations thereof, may further comprise one or more further antimicrobial compound(s) in addition to the HPC and BIT derivative. The presence of further antimicrobial compound(s) can provide a broader spectrum of antimicrobial activity than the HPC and BIT derivative alone. Furthermore, the combination of the HPC, BIT derivative and further additional antimicrobial compound(s) may provide a synergistic effect. The further antimicrobial compound or compounds may possess anti-bacterial, anti-fungal, anti-algal or other antimicrobial activity.

Suitable further antimicrobial compounds which may be used, together with the HPC and BIT derivative include quaternary ammonium compounds, urea derivatives, antimicrobial amino compounds for example dodecylamine or 2-[(hydroxymethyl)- aminojethanol, antimicrobial imidazole derivatives, antimicrobial nitrile compounds for example 2-bromo-2-bromomethyl-glutaronitrile, antimicrobial thiocyanate derivatives for example methylene(bis)thiocyanate, antimicrobial tin compounds or complexes for example tributyltinoxide, chloride, naphthoate, benzoate or 2-hydroxybenzoate; isothiazolin-3-ones, thiazole derivatives, antimicrobial nitro compounds, iodine compounds aldehydes and aldehyde release agents, for example glutaraldehyde (pentanedial), formaldehyde or glyoxal; amides for example chloracetamide, guanidine derivatives; antimicrobial thiones, antimicrobial triazine derivatives, oxazolidine and derivatives thereof, furan and derivatives thereof, antimicrobial carboxylic acids and the salts and esters thereof, phenol and derivatives thereof, antimicrobial sulphone derivatives, imides, thioamides, azole fungicides and strobiluhn fungicides.

The amount of further antimicrobial compound(s) used will depend upon the further antimicrobial compound and the medium which is treated to protect against microbial degradation. Preferably the weight ratio of the further antimicrobial compound(s): total weight of the HPC and BIT derivative is from 10:1 to 1 :10, more preferably from 5:1 to 1 :5 and especially from 2:1 to 1 :2.

The composition and formulations thereof according to the invention have been found to be particularly useful at inhibiting the growth of deteriogens for plastics materials. It will be readily appreciated that the compositions/formulations may also be used to protect other media, especially industrial media, which are susceptible to microbiological and especially fungal degradation. Examples of such industrial media are cooling tower liquors, metal working fluids, geological drilling muds, latices, paints, lacquers, wood, leather and pigments. Generally, the amount of the composition according to the first aspect of the invention required to protect such industrial media is less than that required to protect plastics materials and good protection may be obtained with from 1 to 250 ppm and preferably from 1 to 100 ppm of the composition relative to the medium.

According to a further aspect of the invention there is provided a method for inhibiting the growth of micro-organisms, especially fungi, on or in a medium which comprises treating the medium with a composition or formulation thereof according to the present invention.

According to a still further aspect of the present invention there is provided the use of a composition according to the first aspect of the invention, or a formulation thereof, to inhibit the growth of micro-organisms (especially fungi) on or in a medium, especially an industrial medium.

The invention is further illustrated by the following examples wherein all references to amounts are in parts by weight unless expressed to the contrary.

Example 1 a) Determination of MIC of N-n-butyl-1 ,2-benzisothiazolin-3-one (BBIT) and 3-iodo-2- propynyl-N-n-butyl carbamate (IPBC)

The fungi shown in Table 1 were grown in malt agar for 7-14 days at 25°C to give a mycelial mat and then the spores were harvested from the surface using physiological saline to give a suspension containing about 10⁶ fungal spores/ml. This was then diluted with malt broth to give a spore suspension containing 10⁴ spores/ml. A 100μl aliquot of this spore suspension was added to each well of a microtitre plate except for the first well which contained 180μl. BBIT was dissolved in dimethylformamide at a concentration of 0.25mg/ml. A 20μl aliquot of this solution was added to the first well of the microtitre plate and thoroughly mixed. 100μl was withdrawn from the first well, added to the second well and mixed. This process was repeated along each row of the wells in the microtitre plate so that the concentration of the chemical under evaluation was progressively reduced by a doubling dilution technique. The growth of fungi was assessed by visual inspection after incubation for 5 days at 25°C to determine the MIC value of BBIT against each of the fungi in Table 1. This procedure was repeated to determine the MIC of IPBC. The results are given in Table 1 :

Table 1

Footnote to Table 1

BBIT is N-n-butyl-1 ,2-benzisothiazolin-3-one IPBC is 3-iodo-2-propynyl-N-n-butyl carbamate PRA is Paint Research Association, UK. b) Determination of FIC Fractional Inhibitory Concentration

A matrix was constructed in a 10 x 10 array in microtitre wells wherein the concentration of each chemical was varied stepwise by serial dilution from a concentration of twice the MIC down to zero. As each microtitre plate contains only 96 wells the combination of the two compounds making up the extreme concentrations (highest and lowest) were omitted. Each mixture (100μl) was added to the plate so that the total volume was maintained at 200μl. By transferring 100μl from each well to the adjacent well containing 100μl nutrient the concentration of the chemical was reduced from twice the MIC to zero in a stepwise manner. The presence or absence of growth was determined visually after incubation. The plates containing fungi were incubated for 40-72 hours at 25°C. From the matrix an isobologram was created and the FIC for each chemical of the composition calculated. The FIC is the ratio of the concentration of chemical which inhibits growth when applied as a combination of chemicals relative to the MIC for that chemical when applied alone. FIC values for both compounds in the mixture were calculated and results are shown in Table 2. The sum of these two figures gives an indication of the action of the two biocides. A value less than one indicates a synergistic effect, if the total is unity or greater the action is additive and if the value is greater than two the biocides are antagonistic. If a graph is constructed with axes representing biocide Fractional Inhibitory concentrations on linear scales, when the combination is additive the isobole (i.e. the line joining the points that represent all combinations with the same effect including the equally effective concentrations of the Biocides used alone) is straight, synergistic combinations give concave isoboles and antagonistic combinations give convex isoboles

Table 2

Table 2 shows that the composition of BBIT and IPBC is synergistic against the fungi Alternaria alternata and Aureobasidium pullulans.

Example 2

An aqueous emulsion was prepared containing the following ingredients:- 200 parts N-n-butyl-1 ,2-benzisothiazolin-3-one (BBIT) 200 parts 3-iodo-2-propynyl-N-n-butyl carbamate (IPBC) 80 parts non-ionic surfactant (Atiox 4894 ex ICI) 15 parts anionic surfactant¹ (Empicol CED 5S ex Albright and Wilson) 50 parts glycerol 3 parts Xanthan gum (Keltrol RD) 452 parts water

(Note 1. Refers to the parts of 100% anionic surfactant- Empicol CED 5S is supplied as a 22% aqueous solution)

The BBIT and IPBC were mixed and stirred at 40°C to dissolve the IPBC in the

BBIT. After cooling to 20°C, this mixture was poured into water containing the surfactants and glycerol in a continuous stream whilst mixing thoroughly using a Silverson mixer equipped with an emulsifier head at 5600 rpm. The emulsion was stirred for a further 2 minutes before adding the Xanthan gum.

The resulting emulsion was subjected to 14 freeze/thaw cycles involving 12 hours at -10°C followed by 12 hours at 40°C (representing approximately two years simulated storage). The emulsion was stable to the repeated freeze thaw cycles.

Claims

1. A composition comprising: a) a 1 ,2-benzisothiazolin-3-one derivative of Formula (1 )

Formula (1 ) wherein:

R is C_1- -alkyl, C₃.₅-cycloalkyl or aralkyl; R¹ is hydroxy, halogen, C^-alkyl or C^-alkoxy; r is from 0 to 4; and b) a halopropynyl compound.

2. A composition as claimed in claim 1 wherein r is zero.

3. A composition as claimed in either claim 1 or claim 2 wherein R is methyl, ethyl, n- propyl, isopropyl, n-butyl, n-pentyl, isobutyl, tert-butyl, cyclopropyl, cyclopentyl, benzyl or 2-phenylethyl.

4. A composition according to claim 1 or Claim 2 wherein R is C₃.₅-alkyl.

5. A composition as claimed in any one of claims 1 to 4 wherein the halopropynyl compound is a compound of Formula (2):

Formula (2) wherein:

Y is halogen;

R² and R³ are each, independently, C^-alkyl, C₂-₆-alkenyl or C₃.₇-cycloalkyl; m is from 1 to 6; and

X is an organic moiety linked to the -CR²R³- group via an oxygen, nitrogen, sulphur or carbon atom.

6. A composition according to any one of claims 1 to 4 wherein the halopropynyl compound is a compound of Formula (3):

O

-C=C-(CH '2₂')p — O— C— NH-f- R⁴

Formula (3) 5 wherein:

R⁴ is hydrogen, optionally substituted C.,.₂₀-alkyl, optionally substituted aryl, optionally substituted aralkyl, C₃.₂₀-cycloalkyl or C₃.₂₀-cycloalkenyl; and n and p are each, independently, from 1 to 3.

0 7. A composition according to any one of claims 1 to 4 wherein the halopropynyl compound is a compound of Formula (4):

R⁵ R⁷ R⁹

I I

I-C ≡C-C-O- CC—— CC— 0 CONH R⁴ l » I .

R^u R^B R¹⁰ Formula (4) 5 wherein:

R⁴ is hydrogen, optionally substituted C.,.₂₀-alkyl, optionally substituted aryl, optionally substituted aralkyl, C₃.₂₀-cycloalkyl or C₃.₂₀-cycloalkenyl;

R⁵ and R⁶ are each, independently, C_1-6-alkyl, C₂.₆-alkenyl, C_3-7-cycloalkyl or -CR⁵R⁶- represents (-CH₂)_t- where t is from 4 to 6; and 0 R⁷ to R¹⁰ are each, independently, hydrogen, C_1-4-alkyl, aryl, -CCI₃ or R⁷ with R⁹ or

R⁸ with R¹⁰ represents -(CH₂)_q- where q is from 3 to 5.

8. A composition as claimed in claim 1 wherein component (a) is N-n-butyl-1 ,2- benzisothiazolin-3-one and component (b) is 3-iodo-2-propynyl-N-n-butyl carbamate. 5

9. A composition as claimed in any one of claims 1 to 8 wherein the sum of the Fractional Inhibitory Concentration of the components is less than 0.5.

10. A composition as claimed in any one of claims 1 to 9 wherein the ratio of o component (a) to component (b) is from 100: 1 to 1 : 100.

11. A master-batch comprising a composition according to any one of claims 1 to 10 and a plastics material.

12. A formulation comprising a composition according to any one of claims 1 to 10 and a carrier.

13. A composition comprising a composition according to any one of claims 1 to 10 and a plasticiser and/or a stabiliser for a plastics materials.

14. An emulsion or micro-emulsion comprising a continuous aqueous phase and an oil phase; wherein the oil phase comprises a solution of a halopropynyl compound in a liquid BIT derivative of Formula (1 ) as defined in claim 1.

15. An emulsion or micro-emulsion according to claim 14 wherein the halopropynyl compound is 3-iodo-2-propynyl-N-n-butyl carbamate and the liquid BIT derivative is N-n- butyl-1 ,2-benzisothiazolin-3-one.

16. An emulsion or micro-emulsion according to either claim 14 or claim 15 which further comprises a humectant.

17. A method for inhibiting the growth of micro-organisms in a medium which comprises treating the medium with a composition as claimed in any one of claims 1 to 10.

18. The use of a composition according to any one of claims 1 to 10 to inhibit the growth of micro-organisms on or in a medium.

19. An industrial medium containing a composition as claimed in any one of claims 1 to 10.