Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Heterocyclic carbon compounds containing a hetero ring...
Reexamination Certificate
2001-02-15
2002-11-19
Pryor, Alton (Department: 1616)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Heterocyclic carbon compounds containing a hetero ring...
C514S185000, C514S186000, C514S226500
Reexamination Certificate
active
06482814
ABSTRACT:
The present invention relates to a biocidal composition comprising a N-alkyl-1,2-benzisothiazolin-3-one and a metal complex of a cyclic thiohydroxamic acid and its use to inhibit the growth of micro-organisms in a medium which is susceptible to microbiological degradation and especially the use to inhibit the growth of deteriogens of plastics materials in soil burial conditions.
WO 96/22023 discloses the use of N-(C
3-5
-alkyl)-1,2-benzisothiazolin-3-one as a biocide and especially a fungicide for plastics materials. It has now been found that the antimicrobial activity of these isothiazolinones is significantly improved by incorporating a metal complex of a cyclic thiohydroxamic acid.
According to the invention there is provided a composition comprising (a) a benzisothiazolinone of formula 1 and (b) a metal complex of a cyclic thiohydroxamic acid.
wherein
R
1
is hydroxy, halogen, C
1-4
-alkyl or C
1-4
-alkoxy;
R is C
1-5
-alkyl, C
3-5
-cycloalkyl or aralkyl; and
n is from 0 to 4.
Preferably, halogen is 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.
When R is aralkyl, it preferably contains two or more carbon atoms in the alkylene group attaching the aryl group to the isothiazolinone ring. Preferably the aralkyl group is 2-phenylethyl. Other examples of aralkyl are benzyl and 2-naphthylethyl.
The substituent R
1
, 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 n is zero.
It is particularly preferred that R is C
3-5
-alkyl, for example n-butyl.
Other examples of suitable benzisothiazolinones are N-methyl-, N-ethyl-, N-n-propyl-, N-isopropyl-, N-n-pentyl-, N-cyclopropyl-, N-isobutyl-, and N-tert-butyl-1 ,2-benzisothiazolin-3-one.
The cyclic thiohydroxamic acid preferably contains a 5- or 6-membered ring which is optionally substituted. It is preferably a metal complex of a compound of formula 2
wherein
A is a group —C(R
2
)
2
—, —C(R
2
)═ or —CR
2
═CR
2
—;
B is a group —C(R
2
)
2
—, —C(R
2
)═ or —C(NR
2
)—;
D is a group —C(R
2
)
2
—, —C(R
2
)═, —NR
2
— or sulphur;
R
2
is hydrogen, optionally substituted C
1-6
-hydrocarbyl or two groups R
2
together with the carbon atom to which they are attached form a C
3-6
-hydrocarbon ring or two groups R
2
together with the two carbon atoms to which they are attached form a fused ring.
When R
2
is hydrocarbyl it is preferably alkyl or phenyl and the alkyl group may be branched or preferably linear. It is particularly preferred that R
2
is hydrogen or C
1-4
-alkyl, for example methyl.
When R
2
is substituted, the substituent may be any group or atom which does not significantly adversely affect the microbiological properties of the cyclic thiohydroxamic ring system. Preferred substituents are hydroxy, halogen and nitrile. It is particularly preferred that R
2
is unsubstituted.
When two moieties R
2
together with the carbon atom to which they are attached form a ring, the ring is preferably cyclohexyl.
When two moieties R
2
together with the carbon atoms to which they are attached form a fused ring, the ring is preferably a fused phenyl ring.
When D is sulphur, the compound of formula 2 is preferably a thiazol-2(3H)-thione wherein both A and B are either the group —C(R
2
)
2
— or especially the group —C(R
2
)═.
When D is the group —NR
2
—, the compound of formula 2 is preferably an imidazolidine-2-thione. When D is the group —NR
2
—, it is also preferred that A is the group —C(R
2
)
2
— or —C(R
2
)═ and B is the group —C(NR
2
)—.
When D is a group —C(R
2
)
2
— or a group —C(R
2
)═, it is preferred that both A and B are also the groups —C(R
2
)
2
— or —C(R
2
)═. In this case, the compound of formula 2 is preferably a pyrrolinethione, pyrrolidinethione or an isoindolinethione.
When A is the group —CR
2
═CR
2
—, it is preferably the group —CH═CH— and both B and D are the group —C(R
2
)═ when the compound of formula 2 is a pyridine-2-thione.
Examples of the compound of formula 2 are:
3-hydroxy-4-methylthiazol-2(3H)-thione,
3-hydroxy-4-phenylthiazol-2(3H)-thione,
3-hydroxy-4,5,6,7-tetrahydrobenzothiazol-2(3H)-thione,
5,5-dimethyl-1 -hydroxy-4-imino-3-phenylimidazolidine-2-thione,
1 -hydroxy-4-imino-3-phenyl-2-thiono-1 ,3-diazaspiro[4,5]-decane,
1 -hydroxy-5-methyl-4-phenylimidazoline-2-thione,
4, 5-dimethyl-3-hydroxythiazol-2(3H)-thione,
4-ethyl-3-hydroxy-5-methylthiazol-2(3H)-thione,
4-(4-chlorophenyl)-3-hydroxythiazol-2(3H)-thione,
3-hydroxy-5-methyl-4-phenylthiazol-2(3H)-thione,
1-hydroxypyrrolidin-2-thione,
5,5-dimethyl-1-hydroxypyrrolidin-2-thione,
2-hydroxy-2,3-dihyro-1H-isoindol-1-thione, and
1-hydroxypyridine-2-thione.
The metal which forms the complex of the compound of formula 2 is preferably a metal from Groups IIIA to VA or IB to VIIB or a transition metal of the Periodic Table according to Mendeleef as set out on the inside rear cover of “Handbook of Chemistry and Physics” 49
th
edition (1968-9) published by The Chemical Rubber Co., Cleveland, Ohio, USA. Preferably, the metal is a metal of Group IIB and is especially zinc.
Particularly useful effects have been obtained when the benzisothiazolinone is N-n-butyl-1,2-benzisothiazolin-3-one and the metal complex of the compound of formula 2 is the 2:1 zinc complex of 3-hydroxy-4-methylthiazol-2(3H)-thione or the 2:1 zinc complex of 1-hydroxypridine-2-thione. The preparation of the benzisothiazolinones is described in GB 484,130 and the preparation of the cyclic thiohydroxamic acids is described in EP 249,328 and U.S. Pat. No. 5,120,856. The preparation of metal complexes of 1-hydroxypyridine-2-thione is specifically disclosed in U.S. Pat. Nos. 2,686,786, 2,758,116 and 2,809,971.
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 and especially from 2:1 to 1:2, for example about 1:1.
The composition of the present invention has antimicrobial properties and has been found particularly effective against deteriogens for plastics materials, especially in soil burial applications. 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 and especially below 0.9. 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 FIC is one, the two components exhibit a mere additive effect. When the sum of the FIC values is below one, the mixture is synergistic and when the sum of the FIC values is greater than one, 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 composition comprising component (a), component (b) and a carrier.
As noted hereinbefore, the composition according to the invention has been found particularly useful as a biocide for inhibiting the growth of deteriogens for plastics materials, especially organic polymeric material containing a plasticiser or stabiliser. Examples of p
Bath Colin
McGeechan Paula Louise
Payne John David
Avecia Limited
Pillsbury & Winthrop LLP
Pryor Alton
LandOfFree
Biocidal composition and its use does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Biocidal composition and its use, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Biocidal composition and its use will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-2943107