Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Reexamination Certificate
2000-07-31
2002-07-09
Pryor, Alton (Department: 1614)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
Reexamination Certificate
active
06417211
ABSTRACT:
BACKGROUND
This invention relates to highly concentrated solutions of isothiazolones, in particular, 2-methyl-3-isothiazolone, in water, and their preparation.
Microbicides are used commercially to prevent the growth of microbes in a variety of environments, such as cooling towers, metal working fluid systems, latices (such as paints) and cosmetics. One of the more important classes of microbicides is 3-isothiazolones. Many 3-isothiazolones have achieved commercial success because they are very effective in preventing microbial growth under a wide variety of conditions. Among the most important 3-isothiazolones are the water-soluble isothiazolones, such as 2-methyl-3-isothiazolone.
While 3-isothiazolones are very effective microbicides, they suffer from being unstable under certain conditions. Without the presence of a stabilizer, many 3-isothiazolones chemically degrade and lose microbicidal efficacy. Much research has been devoted to stabilizing 3-isothiazolones, especially with regard to aqueous formulations of 3-isothiazolones, that is, where the concentration of active ingredient in the solution is from about 5 to about 35% by weight (typically 12 to 15%); see U.S. Pat. No. 5,910,503. These solutions typically require the use of stabilizers, such as, for example, nitrate salts and copper salts. Organic compound stabilizers are also used for protecting 3-isothiazolones in antagonistic environments; see U.S. Pat. No. 5,142,058. Up until now, the concentration of active ingredient (3-isothiazolone) in aqueous concentrate compositions provided to formulators has been in the aforementioned range of 5 to 35% (typically 12 to 15%), or up to about 50% in the case of certain organic solvent (such as propylene glycol) concentrates. (see U.S. Pat. No. 5,756,005).
The problem addressed by the present invention is to overcome the difficulties of using conventional microbicide solutions (for example, 5 to 50% concentration of active ingredient) or solid technical grade materials where (a) the relatively low concentration of active ingredient in conventional aqueous concentrates severely limits the range of dilutions that the formulator can consider and (b) the solid technical grade materials require additional processing, for example, melting of the solid, with possible consequent product degradation and darkening.
STATEMENT OF INVENTION
The present invention provides a stable liquid microbicide composition comprising (a) 60 to 95 percent, based on the weight of the composition, of at least one water-soluble, non-halogenated 3-isothiazolone; and (b) 5 to 40 percent, based on the weight of the composition, of at least one solvent selected from water, (C
1
-C
4
)alkanol, water-miscible (C
2
-C
8
)alkoxy/hydroxy compound and water-miscible (C
2
-C
4
)aprotic compound.
In another embodiment, the present invention provides a method for preparing a stable liquid microbicide composition comprising combining (a) from 60 to 95 percent, based on weight of the composition, of at least one water-soluble, non-halogenated 3-isothiazolone; and (b) from 5 to 40 percent, based on the weight of the composition, of at least one solvent selected from water, (C
1
-C
4
)alkanol, water-miscible (C
2
-C
8
)alkoxy/hydroxy compound and water-miscible (C
2
-C
4
)aprotic compound; wherein the liquid microbicide composition remains homogeneous and fluid at temperatures of 20 to 25° C. for at least 24 hours.
In a further embodiment, the present invention provides a method for preparing formulated microbicide solutions, comprising combining from 0.005 to 1 part, by weight, of the aforementioned liquid microbicide composition with 1 part, by weight, of a compatible diluent.
DETAILED DESCRIPTION
We have discovered that non-halogenated 3-isothiazolone concentrate compositions can be prepared at active ingredient (3-isothiazolone) concentrations in excess of 50 percent, based on total weight of the composition, while maintaining both physical and chemical stability of the liquid concentrate. We have discovered that mixtures of specific 3-isothiazolones and specific solvents used in specific relative proportions unexpectedly provide the stable, highly concentrated, non-halogenated 3-isothiazolone solutions of the present invention.
As used throughout this specification, the following terms shall have the indicated meanings, unless the context clearly indicates otherwise. The term “microbicide” refers to a compound capable of inhibiting the growth of or controlling the growth of microorganisms in a certain environment. The term “water-miscible” refers to compatibility with or solubility in a formulation upon dilution with aqueous media, such as may be used by formulators. As used in this specification, the following abbreviations are applied: HPLC=high performance liquid chromatography; C=centigrade. All amounts are percent (%) by weight, unless otherwise noted and all percent by weight ranges are inclusive; all ratios are by weight and all ratio ranges are inclusive.
Any water soluble, non-halogenated 3-isothiazolone (NHITA) compound is useful in the compositions of the present invention. Water soluble NHITA compounds are those having a water solubility greater than 5%. Suitable NHITA compounds include, for example, substituted and unsubstituted 2-(C
1
-C
4
)alkyl-3-isothiazolones, where the substituted isothiazolones may contain (C
1
-C
4
)alkyl groups at one or both of the 4- and 5-positions of the isothiazolone ring. Specific NHITA compounds include, for example, 2-methyl-3-isothiazolone, 2-ethyl-3-isothiazolone, 2-propyl-3-isothiazolone, 2-isopropyl-3-isothiazolone, 2-butyl-3-isothiazolone (includes 2-n-butyl-, 2-isobutyl- and 2-secbutyl-derivatives). Preferably, the NHITA compound is 2-methyl-3-isothiazolone.
The stable liquid microbicide compositions of the present invention typically contain 60 to 95%, preferably 70 to 95%, more preferably 75 to 94%, and most preferably from 80 to 90% NHITA, based on weight of the composition.
The amount of solvent useful in the stable liquid microbicide compositions of the present invention is typically from 5 to 40%, preferably 5 to 30%, more preferably 10 to 25%, and most preferably from 10 to 20%, based on weight of the composition.
Solvents suitable for use in the compositions of the present invention include, for example, water and water-miscible organic solvents. Suitable water-miscible solvents include, (C
1
-C
4
)alkanols, such as, for example, methanol, ethanol, 1-propanol, 2-propanol and isobutyl alcohol; (C
2
-C
8
)alkoxy/hydroxy compounds, such as, for example, 2-methoxyethanol, 2-butoxyethanol, 2-(2-butoxyethoxyl)ethanol, phenoxyethanol, benzyl alcohol, phenethyl alcohol, ethylene glycol, 1,2-dimethoxyethane, diethylene glycol, propylene glycol, dipropylene glycol and glycerine; and (C
2
-C
4
)aprotic compounds, such as, for example, dimethyl sulfoxide, diethyl carbonate and propylene carbonate. Preferably, the solvent is water. When used, the water-miscible organic solvent is preferably selected from 2-propanol, ethylene glycol and propylene glycol. Mixtures of water and one or more water-miscible solvents, as well as mixtures of one or more water-miscible solvents in the absence of water, may also be used.
An advantage of the compositions of the present invention is that they are both physically and chemically stable as prepared and upon storage. That is, these highly concentrated solutions of NHITA remain physically stable upon storage and do not settle, separate or precipitate into different phases. By “physically stable” we mean that the compositions are homogeneous and fluid at temperatures of 20 to 25° C. for at least 24 hours. Preferably the compositions are physically stable at 20° C. and below for at least 3 days, more preferably for at least 2 weeks, and most preferably for at least 4 weeks. In addition, it is desirable that the compositions retain their physical stability for similar time periods at temperatures of 15° C. and below, and preferably at 5° C. and below.
In addition, the liquid microbicide compositions of the present invention
Garrett Christine Elizabeth
Petigard Ramesh Balubhai
Howell Thomas J.
Pryor Alton
LandOfFree
Isothiazolone concentrates does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Isothiazolone concentrates, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Isothiazolone concentrates will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-2865260