Drug – bio-affecting and body treating compositions – Inorganic active ingredient containing – Heavy metal or compound thereof
Reexamination Certificate
1999-02-09
2002-07-30
Dees, Jose′ G. (Department: 1616)
Drug, bio-affecting and body treating compositions
Inorganic active ingredient containing
Heavy metal or compound thereof
C424S617000, C424S630000, C424S639000, C424S641000, C424S644000, C424S646000, C424S649000, C424S650000, C424S652000, C424S654000, C424S655000, C424SDIG006, C514S184000, C514S185000, C514S190000, C514S292000, C514S492000, C514S494000, C514S496000, C514S497000, C514S498000, C514S499000, C514S500000, C514S501000, C514S502000, C514S505000, C514S731000, C514S737000, C514S836000
Reexamination Certificate
active
06426093
ABSTRACT:
BACKGROUND OF THE INVENTION
Public concern is increasing over the contamination of our environment with industrial wastes, including from polyhalogenated compounds. While the effects of acute toxicity are very clear, the effects of chronic exposure to low levels of these chemicals are not well understood. Pentachlorophenol (PCP) is listed as a priority pollutant by the U.S. Environmental Protection Agency because of its toxicity and carcinogenicity. PCP is a general biocide mainly used as a wood preservative. After more than half a century of extensive uses, PCP is considered to be ubiquitously present in the environment and even was found in body fluids of people who were not occupationally exposed to it. Moreover, some of its metabolites have been identified to be carcinogenic and/or mutagenic. Many of these biocides exert their biological damage through the free radical mechanism.
It has been shown that oxidative damage to biological systems is markedly potentiated by the presence of transition metals, especially iron and copper. By virtue of their reactivity with activated oxygen, iron and/or copper can mediate the formation of powerful reactive oxygen species, such as hydroxyl radical, through Fenton reaction. Perhaps for this reason, most cells and organisms handle these metals with great caution; “free” metal is practically absent in biological fluids and the delivery and storage of metals is effected by a series of metal-binding proteins that sequester the metal in such a way as to limit its reactivity.
The evaluation of toxicity of environmental pollutants has been based mainly on the effect of single substances. However, environmental chemicals generally appear as complex mixtures in air, water and soil. It is known that more than one third of sites polluted with organic compounds also contain inorganic pollutants, such as heavy metals. Waste associated with the wood preserving industry is one of the typical cases, since both the organic PCP and inorganic chromated-copper-arsenate wood preservatives have been extensively used. These substances may interact within the mixture to produce combination effects. There is little knowledge on these effects, especially when substances occur at subtoxic concentrations.
In the literature, three classes of combination effects are discussed. They are additive (zero interaction) when the effect of the combination is precisely what is “expected” from the effects of the single compounds; they are synergistic or antagonistic if the response is greater or less than expected. Additive effects are expected in combinations of similar or identical acting chemicals. Every concentration of the single substances will add to the combination's effect. Toxic combination effects may occur from concentrations below the “no observed effect concentration” of single compounds, if the sum of their concentrations exceeds the toxic threshold level. This concept of “concentration addition” is in some countries taken into consideration when threshold limits are defined.
If chemicals have a different mode of toxic action and attack different targets, they are designated as dissimilar chemicals. As long as they act independently, subtoxic concentrations of these substances should not result in toxic combination effects. However, combinations of dissimilar chemicals may interact whereby one chemical alters the biological response of the other in a qualitative or quantitative manner. In this case the combination effects are greater or smaller than predicted from the single compounds. Synergistic or antagonistic effects occur. If single components of a mixture at their no observed effect concentration interact synergistically they should lead to toxic combination effects.
SUMMARY OF THE INVENTION
It has now been discovered that a ternary complex of a negatively-charged biocide (component A), a transition metal ion (component B) and a chelator (preferably a neutral or positively-charged chelator) (component C) has significant biocidal effects on living cells including those of microorganisms, such as bacteria and fungi, cell culture systems, plants and animals. The biocidal effects of the ternary complexes of the three components are synergistic in that the combined biocidal effects are greater than would be expected from the additive effects of each of the components used alone.
Thus, the present invention relates to biocidal compositions comprising such ternary complexes, as well as methods for killing or inhibiting the growth of living cells using an effective amount of such compositions.
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Chevion Mordechai
Schechtman Svetlana
Zhu Benzhan
Browdy and Neimark
Choi Frank
Dees Jose′ G.
Yissum Research Development Company of the Hebrew University of
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