Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Heterocyclic carbon compounds containing a hetero ring...
Reexamination Certificate
1999-08-09
2002-01-15
Gerstl, Robert (Department: 1613)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Heterocyclic carbon compounds containing a hetero ring...
C548S101000, C548S103000, C548S105000
Reexamination Certificate
active
06339081
ABSTRACT:
This application is the national phase of international application PCT/GB97/03379 filed Dec. 5, 1997 which designated the U.S.
The present invention relates to stabilised compositions containing a metal complex of a cyclic thiohydroxamic acid or a 1-hydroxy-2-pyrrolidinthione and to improved antibacterial activity.
EP 249328 discloses metal complexes of cyclic thiohydroxamic acids and 1-hydroxy-2-pyrrolidinthiones and their use as industrial biocides. These metal complexes may also be used in personal care formulations as disclosed in EP 498636.
It has now been found that when these metal complexes are used in the presence of certain chemical compounds which act as ligands for the metal, the metal is removed at least in part from the metal complex and this results in a reduction in microbiological activity and/or a reduction in chemical stability, especially under acidic conditions. It has now been found that the metal complexes of cyclic thiohydroxamic acids (hereinafter ‘CTHA’) and the metal complexes of 1-hydroxy-2-pyrrolidinthiones (hereinafter ‘HPT’) may be stabilised by adding a salt of the metal and/or a metal complex of the metal derived from a ligand which is weaker than the CTHA or HPT. In many instances the metal complex of the CTHA and HPT exhibit increased antimicrobial activity in the presence of a salt of the metal, especially where the metal is zinc.
According to the invention there is provided a composition comprising
(a) a metal complex of a compound of formula 1
wherein
A is —CR
2
— or —CR═;
B is —CR
2
—, —CR═ or >C═NR; or
A and B or B and D together form a 6-membered fused hydrocarbon ring;
D is sulphur, —NR—, —CR
2
— or —CR=;
R is C
1-6
-hydrocarbyl optionally substituted by halogen or two groups R together with the carbon atom to which they are attached form a 6-membered ring; and
(b) a salt of the metal and/or a metal complex of the metal obtainable from a ligand which is weaker than the compound of formula 1.
When R is hydrocarbyl, it may be phenyl. However, R is preferably alkyl, which may be linear or branched but is preferably linear. Examples of these alkyl groups are ethyl, isopropyl, n-butyl, tert-butyl, amyl, hexyl and especially methyl.
When A and B or B and D form a ring, the ring is preferably cyclohexenyl, cyclohexyl and especially phenyl.
When R is substituted by halogen, the substituent may be iodine, bromine or preferably chlorine.
When two groups R together with the carbon atom to which they are attached form a ring, the ring is preferably cyclohexyl.
The metal forming the complex with the compound of formula 1 may be any of the metals in groups 1b, 2a, 2b, 3a or 8 of the Periodic Table according to Mendeleef as published, for example, on the inside cover of the Handbook of Chemistry and Physics, The Chemical Rubber Company. It is preferred that the metal is from group 2b and that it is especially zinc.
The metal salt which is component (b) may be the salt of an inorganic or organic acid. In this context, a metal oxide is considered to be a salt of an inorganic acid. Preferred inorganic acids are hydrohalic acids, especially hydrochloric acid, nitric acid and sulphuric acid. It is particularly preferred that the salt is that of an organic acid or a metal oxide. Preferred organic acids are monocarboxylic acids, particularly those containing not greater than 10 and especially not greater than 6 carbon atoms excluding the —COOH group. Examples of organic acids are propionic and especially acetic acid.
When component (b) is a metal complex, it is preferably obtainable from an organic compound wherein the ligand(s) is a hydroxy group. The organic compound which forms a complex with the metal has a MW which is preferably not greater than 300, more preferably not greater than 250 and especially not greater than 200.
One preferred class of compounds of formula 1 is a cyclic thiohydroxamic acid wherein D is sulphur. Examples 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 and
3-hydroxy-5-methyl-4-phenylthiazol-2(3H)-thione.
Another preferred class of compounds of formula 1 is a 1-hydroxy-2-pyrrolidinthione wherein D is —CR
2
— or —CR=. Examples are
2-hydroxy-2,3-dihydro-1H-isoindol-1-thione,
1-hydroxy-2-pyrrolidinthione and
5,5-dimethyl-1-hydroxy-2-pyrrolidinthione.
Particularly useful effects have been obtained when component (a) is the 2:1 zinc complex of 3-hydroxy-4-methylthiazol-2(3H)-thione and component (b) is zinc acetate, zinc chloride or zinc oxide.
The composition according to the invention may be a mixture of component (a) and component (b) in solid form or it may further comprise a liquid medium when the composition comprises a dispersion of component (a) in the liquid medium containing component (b).
The liquid medium is preferably water.
The dispersion may also contain other adjuvants which are conventionally used to aid the dispersion of particulate solids in a liquid medium. These adjuvants include dispersants and compounds capable of forming a structured network of the liquid medium which aids the suspension of particulate solids (hereinafter “Structuring Agent”).
The dispersant may be non-ionic, anionic, cationic or amphoteric. Preferred dispersants are non-ionic and are preferably ethoxylated fatty alcohols especially C
12-18
-alkanols containing from 5 to 20 ethylene oxide units.
Preferred Structuring Agents are cellulose derivatives, naturally occurring clays and especially polysaccharide thickeners. Examples are hydroxyethylcellulose, Bentonite and Zanthan gum.
Component (b) may be soluble in or dispersible in the liquid medium but is preferably soluble.
The dispersion may be made by any means known to the art and may be made by grinding or milling component (a) in the presence of an attrition aid such as glass beads in order to reduce the particle size. The particle size of component (a) is preferably reduced below 20 &mgr;, more preferably below 10 &mgr; and especially to below 3 &mgr;. The fine particle of component (a) may then be added to component (b) and the liquid medium. Alternatively, components (a) and (b) may be ground or milled together and then added to the liquid medium. It is preferred, however, to grind or mill component (a) in the liquid medium containing component (b).
The amount of component (b) relative to component (a) may be just sufficient to provide enhanced microbiological activity and/or a stabilising effect but is preferably present in larger amounts. Preferably the weight ratio of component (b) to component (a) is between 5:1 and 1:5, more preferably between 3:1 and 1:2 and especially between 2:1 and 1:1.
The amount of component (a) in the dispersion is from 1 to 30% relative to the total weight of the dispersion. Preferably the amount of component (a) is not less than 3% and especially not less than 5% relative to the total weight of the dispersion. It is also preferred that the amount of component (a) is not greater than 20%, more preferably not greater than 15% and especially not greater than 10% relative to the total weight of the dispersion.
The amount of dispersant depends on the amount of component (a) but is generally between 5% and 200% based on the weight of component (a). Preferably the amount of dispersant is not greater than 100% and especially not greater than 50% based on the weight of component (a).
The amount of Structuring Agent, when present, depends on the total weight of the dispersion and is preferably not less than 0.05%, more preferably not less than 0.1% and especially not less than 0.2% based on the total weight of the dispersion. It is also preferred that the amount of Structuring Agent is not greater than 1% and especial
Avecia Limited
Gerstl Robert
Pillsbury & Winthrop LLP
LandOfFree
Composition and 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 Composition and use, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Composition and use will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-2825277