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WO2010081805A1 - Biocide composition and use thereof - Google Patents

Biocide composition and use thereof Download PDF

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Publication number
WO2010081805A1
WO2010081805A1 PCT/EP2010/050296 EP2010050296W WO2010081805A1 WO 2010081805 A1 WO2010081805 A1 WO 2010081805A1 EP 2010050296 W EP2010050296 W EP 2010050296W WO 2010081805 A1 WO2010081805 A1 WO 2010081805A1
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WO
WIPO (PCT)
Prior art keywords
animal pest
species
animal
antibodies
biocide
Prior art date
Application number
PCT/EP2010/050296
Other languages
French (fr)
Inventor
Vincenza Dolo
Original Assignee
Vincenza Dolo
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Vincenza Dolo filed Critical Vincenza Dolo
Publication of WO2010081805A1 publication Critical patent/WO2010081805A1/en

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Classifications

    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N37/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having three bonds to hetero atoms with at the most two bonds to halogen, e.g. carboxylic acids
    • A01N37/44—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having three bonds to hetero atoms with at the most two bonds to halogen, e.g. carboxylic acids containing at least one carboxylic group or a thio analogue, or a derivative thereof, and a nitrogen atom attached to the same carbon skeleton by a single or double bond, this nitrogen atom not being a member of a derivative or of a thio analogue of a carboxylic group, e.g. amino-carboxylic acids
    • A01N37/46—N-acyl derivatives

Definitions

  • the present invention relates to a biocide that is formulated so as to be effective on at least one animal pest and to its use as an active component of a food bait directed against at least one animal pest.
  • mice, rats and pigeons in fact often carry diseases and parasites that can be transmitted to human beings by direct contact with them or with their organic products (feces, blood, saliva, for example).
  • rodents such as mice and rats.
  • rodents such as mice and rats.
  • the most common rodenticides are based on substances capable of interfering with the blood coagulation mechanism, preventing the synthesis of coagulation factors, and damaging capillaries, increasing their permeability and causing internal hemorrhages. They are administered to mice and rats through food, by means of food baits, and become effective after a highly variable time, which ranges from the single ingestion of rodenticide to continuous ingestion for several days until the lethal dose accumulates, depending on the type of poison used.
  • rodenticides based on this mechanism of action are not species-selective but perform the same mechanism on any animal species. This is a danger for domestic animals or pets (dogs, cats, et cetera) that might ingest accidentally the bait intended for rodents, and, potentially, also for humans. Moreover, it is believed that the bleeding induced by rodenticides causes suffering to the animals. Finally, there can be the risk of "secondary poisoning" if other animals eat the carcass of poisoned mice or rats. Disclosure of the Invention
  • the aim of the present invention is to provide a new biocide composition that is capable of obviating the drawbacks of currently known substances used as poisons to eliminate animal pests.
  • an object of the invention is to provide a biocide composition that is capable of performing an effective action of selective disinfestation with respect to at least one animal pest.
  • Another object of the invention is to provide a biocide composition that is lethal for one or more animal pests and at the same time is harmless for the other animals that might be exposed to it.
  • biocide composition that is selective for at least one animal pest, comprising liposomes that contain at least one species-specific antibody of the at least one animal pest, said at least one species-specific antibody being directed against a biological molecule of the animal pest that is essential for performing a vital function of the at least one animal pest, said biocide being administered orally.
  • biocide composition described herein as an active component in a food bait for disinfestation from at least one animal pest.
  • a first aspect of the invention consists of a biocide composition that is selective for at least one animal pest, which comprises liposomes that contain at least one species-specific antibody of the at least one animal pest directed against a molecule involved in a vital biological function of the animal.
  • Immunoglobulins are proteins of the immune system, produced by B lymphocytes, whose biological role is to identify foreign organisms, such as viruses, bacteria and other pathogens, by binding to protein or glycoprotein structures that belong to them (antigens).
  • Immunoglobulins are normally present on the surface of B lymphocytes; when a surface immunoglobulin comes into contact with an antigen, the B lymphocyte, thus stimulated, begins to produce rapidly a large number of immunoglobulins, which are secreted and accumulate in the blood and in tissue fluids, where they perform their function of defense against pathogens.
  • the secreted immunoglobulins are known as antibodies.
  • the capacity of immunoglobulins to recognize many molecules that are foreign to the organism depends on some protein domains, known as hypervariable domains, which are coded by portions of the genome that can recombine very differently, giving rise to structures that have a high affinity for a series of different antigens.
  • Target molecules of the antibodies In vivo administration of antibodies specifically aimed at a target molecule of the organism causes antibody precipitation, i.e., the formation of immunocomplexes at the level of the blood and of tissue liquids.
  • the target molecules are thus sequestered by the antibodies and are not available for performing their biological function. If the target molecules of the antibodies are molecules that are essential for an activity of the organism, this activity can be so compromised by the binding with the antibodies to lead the animal to its death.
  • the specificity of the biocide composition is determined by the specificity of the antibodies contained in it.
  • immunoglobulins have a region with a high degree of preservation, in terms of amino acid sequence, within each species: this region is known as Fc region (Fragment, crystallizable).
  • Receptors that recognize and identify the Fc region of immunoglobulins are present on the membrane of the cells that constitute the intestinal wall of animals: once these receptors bind with the immunoglobulins, they facilitate their internalization within the cells and the consequent introduction into blood circulation. This mechanism is fundamentally important for newborns, whose immature immune system does not produce antibodies and thereby assimilate through milk the antibodies produced by the mother.
  • the intestinal receptors of a given animal species are capable of recognizing and internalizing only the immunoglobulins produced by that same animal species, which therefore have the Fc region that is typical of the species involved.
  • These antibodies are therefore termed species-specific, because they perform their action exclusively on one animal species, i.e., the one whose intestinal receptors they are capable of binding with, and instead have no effect on other species.
  • the at least one species-specific antibody of the at least one animal pest is characterized by having its Fc region recognized selectively by the receptors that are present on the membrane of the cells of the intestinal wall of the at least one animal pest. Selectivity in terms of molecular recognition between the Fc region of the antibodies and the membrane receptors at the intestinal level allows the present biocide composition to be effective only on the one or more animal species for which it has been developed.
  • the species-specific antibodies according to the present composition are taken by the animals orally and can reach the intestinal space intact, where they are absorbed, by way of their insertion within particular lipid structures, the liposomes.
  • Liposomes are hollow microvesicles that have a spherical shape and consist of one or more lipid layers (generally a double layer, similar to that of a cell membrane). Liposomes are capable of acting as a vehicle for the transport of various molecules (such as antibodies or drugs) within the organism.
  • the transported molecules can be within the cavity of the liposome, in an aqueous environment (if they are water-soluble molecules), or inserted between the nonpolar tails of lipids (if they are instead non- water-soluble molecules).
  • the use of liposomes as carriers for the administration of drugs or other molecules allows such drugs or molecules to pass through the gastric tract without undergoing degradation by the acids and enzymes produced by the stomach, thus allowing to take these molecules orally. Liposomes are degraded, once they reach the intestine, by enzymes that are capable of dissolving fats, releasing the molecules contained therein, which are thus assimilated at the intestinal level and rapidly enter blood circulation.
  • the species-specific antibodies directed against the essential biological molecules of the animal or animals that one wishes to neutralize are inserted within liposomes and administered to the animal or animals orally: the liposomes ensure transport of the antibodies to the intestinal level, where absorption occurs.
  • the biocide composition can comprise a series of various species-specific antibodies directed against one or more animal pests: i.e., there can be antibodies directed against more than one type of target molecule.
  • the biocide provided according to this embodiment thus acts by damaging simultaneously more than one physiological function of the animal pest or pests.
  • the species-specific antibodies for at least one animal pest that are used in the biocide composition according to the invention can be aimed at a biological molecule having an indispensable function and which is selected from the group consisting of molecules of the glomerular basal membrane and red cell molecules.
  • Acute kidney failure is a clinical syndrome characterized by a significant reduction of glomerular filtration for hours or days and causes a condition of oliguria or anuria. Kidney failure and its complications (such as for example hypervolemia, metabolic acidosis, hyperkalemia, uremia, hemorrhagic diathesis) bring the mortality rate to 100%.
  • the development of acute kidney failure syndrome is painless.
  • the antibodies that recognize proteins that belong to red cells instead cause a hemolytic effect, causing destruction of these cells by the immune system.
  • the biocide composition contains antibodies directed against molecules that have a fundamental physiological function and belong to rodents.
  • the invention relates to a biocide composition that contains antibodies directed against molecules of fundamental physiological importance produced by mice or rats.
  • a biocide composition that contains antibodies directed against molecules of fundamental physiological importance produced by mice or rats.
  • the animal pest can be a rodent, preferably selected from the group consisting of mice and rats.
  • the species-specific antibodies of the animal pest or pests can be prepared according to the procedures commonly used in the immunological field and known to the person skilled in the art.
  • a further application of the invention relates to the use of the biocide composition according to the present invention as an active component in a food bait for disinfestation from one or more animal pests.
  • biocide composition according to the invention ensures several advantages with respect to known poisons currently in use.
  • the main advantage is represented by its absolute selectivity for one or more species of animal pest, thus being entirely harmless for domestic animals that might come into contact with it. Moreover, it does not cause suffering to the animals that ingest it and is entirely free from a potential "secondary poisoning" effect.

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  • Life Sciences & Earth Sciences (AREA)
  • Agronomy & Crop Science (AREA)
  • Pest Control & Pesticides (AREA)
  • Plant Pathology (AREA)
  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Dentistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Wood Science & Technology (AREA)
  • Zoology (AREA)
  • Environmental Sciences (AREA)
  • Agricultural Chemicals And Associated Chemicals (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)

Abstract

A biocide composition that is selective for at least one animal pest, comprising liposomes that contain at least one species-specific antibody of the at least one animal pest, wherein the at least one species-specific antibody is aimed at a biological molecule of the animal pest that is essential for performing a vital function in the animal, the biocide being administered orally. Use of the biocide composition described herein as active component in a food bait for disinfestation from at least one animal pest.

Description

BIOCIDE COMPOSITION AND USE THEREOF Technical field
The present invention relates to a biocide that is formulated so as to be effective on at least one animal pest and to its use as an active component of a food bait directed against at least one animal pest. Background Art
Many unwanted animal species can occasionally or customarily populate regions that are inhabited or frequented by humans, with severe risks for human health. These animal pests, such as for example mice, rats and pigeons, in fact often carry diseases and parasites that can be transmitted to human beings by direct contact with them or with their organic products (feces, blood, saliva, for example).
Disinfestation campaigns, aimed at eliminating or at least reducing their presence, are periodically necessary against these animals. The species that humans most wish to keep away include rodents, such as mice and rats. Currently, the most common rodenticides are based on substances capable of interfering with the blood coagulation mechanism, preventing the synthesis of coagulation factors, and damaging capillaries, increasing their permeability and causing internal hemorrhages. They are administered to mice and rats through food, by means of food baits, and become effective after a highly variable time, which ranges from the single ingestion of rodenticide to continuous ingestion for several days until the lethal dose accumulates, depending on the type of poison used.
Although effective, rodenticides based on this mechanism of action are not species-selective but perform the same mechanism on any animal species. This is a danger for domestic animals or pets (dogs, cats, et cetera) that might ingest accidentally the bait intended for rodents, and, potentially, also for humans. Moreover, it is believed that the bleeding induced by rodenticides causes suffering to the animals. Finally, there can be the risk of "secondary poisoning" if other animals eat the carcass of poisoned mice or rats. Disclosure of the Invention
The aim of the present invention is to provide a new biocide composition that is capable of obviating the drawbacks of currently known substances used as poisons to eliminate animal pests.
Within this aim, an object of the invention is to provide a biocide composition that is capable of performing an effective action of selective disinfestation with respect to at least one animal pest.
Another object of the invention is to provide a biocide composition that is lethal for one or more animal pests and at the same time is harmless for the other animals that might be exposed to it.
This aim, as well as these and other objects that will become better apparent hereinafter, are achieved by a biocide composition that is selective for at least one animal pest, comprising liposomes that contain at least one species-specific antibody of the at least one animal pest, said at least one species-specific antibody being directed against a biological molecule of the animal pest that is essential for performing a vital function of the at least one animal pest, said biocide being administered orally.
The aim and objects of the invention are also achieved by the use of the biocide composition described herein as an active component in a food bait for disinfestation from at least one animal pest. Ways of carrying out the Invention
Further objects, characteristics and advantages of the invention will become better apparent from the detailed description that follows. A first aspect of the invention consists of a biocide composition that is selective for at least one animal pest, which comprises liposomes that contain at least one species-specific antibody of the at least one animal pest directed against a molecule involved in a vital biological function of the animal. Immunoglobulins are proteins of the immune system, produced by B lymphocytes, whose biological role is to identify foreign organisms, such as viruses, bacteria and other pathogens, by binding to protein or glycoprotein structures that belong to them (antigens). Immunoglobulins are normally present on the surface of B lymphocytes; when a surface immunoglobulin comes into contact with an antigen, the B lymphocyte, thus stimulated, begins to produce rapidly a large number of immunoglobulins, which are secreted and accumulate in the blood and in tissue fluids, where they perform their function of defense against pathogens. The secreted immunoglobulins are known as antibodies. The capacity of immunoglobulins to recognize many molecules that are foreign to the organism depends on some protein domains, known as hypervariable domains, which are coded by portions of the genome that can recombine very differently, giving rise to structures that have a high affinity for a series of different antigens. In vivo administration of antibodies specifically aimed at a target molecule of the organism causes antibody precipitation, i.e., the formation of immunocomplexes at the level of the blood and of tissue liquids. The target molecules are thus sequestered by the antibodies and are not available for performing their biological function. If the target molecules of the antibodies are molecules that are essential for an activity of the organism, this activity can be so compromised by the binding with the antibodies to lead the animal to its death.
The specificity of the biocide composition is determined by the specificity of the antibodies contained in it. In addition to the hypervariable region that recognizes the antigens, immunoglobulins have a region with a high degree of preservation, in terms of amino acid sequence, within each species: this region is known as Fc region (Fragment, crystallizable).
Receptors that recognize and identify the Fc region of immunoglobulins are present on the membrane of the cells that constitute the intestinal wall of animals: once these receptors bind with the immunoglobulins, they facilitate their internalization within the cells and the consequent introduction into blood circulation. This mechanism is fundamentally important for newborns, whose immature immune system does not produce antibodies and thereby assimilate through milk the antibodies produced by the mother.
Due to the amino acid preservation of this region, the intestinal receptors of a given animal species are capable of recognizing and internalizing only the immunoglobulins produced by that same animal species, which therefore have the Fc region that is typical of the species involved. These antibodies are therefore termed species-specific, because they perform their action exclusively on one animal species, i.e., the one whose intestinal receptors they are capable of binding with, and instead have no effect on other species. In a preferred embodiment of the composition according to the invention, the at least one species-specific antibody of the at least one animal pest is characterized by having its Fc region recognized selectively by the receptors that are present on the membrane of the cells of the intestinal wall of the at least one animal pest. Selectivity in terms of molecular recognition between the Fc region of the antibodies and the membrane receptors at the intestinal level allows the present biocide composition to be effective only on the one or more animal species for which it has been developed.
In this manner, even if harmless or domestic animals should ingest the biocide composition, it would have no harmful function on the organism of these animals, since the species-specific antibodies contained therein would not be assimilated by the intestine of these animals, since these animals lack the specific receptors for the recognition of antibodies that belong to a foreign species. This mechanism also avoids the risk of "secondary poisoning" on the part of animals that feed on the carcasses of animals that have died as a consequence of treatment with the biocide composition according to the invention.
The species-specific antibodies according to the present composition are taken by the animals orally and can reach the intestinal space intact, where they are absorbed, by way of their insertion within particular lipid structures, the liposomes.
Liposomes are hollow microvesicles that have a spherical shape and consist of one or more lipid layers (generally a double layer, similar to that of a cell membrane). Liposomes are capable of acting as a vehicle for the transport of various molecules (such as antibodies or drugs) within the organism. The transported molecules can be within the cavity of the liposome, in an aqueous environment (if they are water-soluble molecules), or inserted between the nonpolar tails of lipids (if they are instead non- water-soluble molecules). The use of liposomes as carriers for the administration of drugs or other molecules allows such drugs or molecules to pass through the gastric tract without undergoing degradation by the acids and enzymes produced by the stomach, thus allowing to take these molecules orally. Liposomes are degraded, once they reach the intestine, by enzymes that are capable of dissolving fats, releasing the molecules contained therein, which are thus assimilated at the intestinal level and rapidly enter blood circulation.
Advantageously, in the composition according to the invention the species-specific antibodies directed against the essential biological molecules of the animal or animals that one wishes to neutralize are inserted within liposomes and administered to the animal or animals orally: the liposomes ensure transport of the antibodies to the intestinal level, where absorption occurs.
The animal pest or pests that eat food containing liposomes containing the species-specific antibodies directed against molecules that have a vital function die within a few days (generally 2 or 3). In a preferred embodiment of the invention, the biocide composition can comprise a series of various species-specific antibodies directed against one or more animal pests: i.e., there can be antibodies directed against more than one type of target molecule. The biocide provided according to this embodiment thus acts by damaging simultaneously more than one physiological function of the animal pest or pests.
In another preferred application of the invention, the species-specific antibodies for at least one animal pest that are used in the biocide composition according to the invention can be aimed at a biological molecule having an indispensable function and which is selected from the group consisting of molecules of the glomerular basal membrane and red cell molecules.
In particular, the antibodies that recognize the molecules of the glomerular basal membrane cause acute kidney failure. Acute kidney failure is a clinical syndrome characterized by a significant reduction of glomerular filtration for hours or days and causes a condition of oliguria or anuria. Kidney failure and its complications (such as for example hypervolemia, metabolic acidosis, hyperkalemia, uremia, hemorrhagic diathesis) bring the mortality rate to 100%. However, it must be noted that the development of acute kidney failure syndrome is painless.
The antibodies that recognize proteins that belong to red cells instead cause a hemolytic effect, causing destruction of these cells by the immune system.
In a preferred embodiment of the invention, the biocide composition contains antibodies directed against molecules that have a fundamental physiological function and belong to rodents. Preferably, the invention relates to a biocide composition that contains antibodies directed against molecules of fundamental physiological importance produced by mice or rats. For example, it is possible to use antibodies aimed at the glomerular basal membrane of the rat (anti-GBM rat IgG for glomerulonephritis) or aimed at red cell molecules of the rat (anti-Rat rat IgG, hemolytic antibodies).
Therefore, in a preferred embodiment of the present invention, the animal pest can be a rodent, preferably selected from the group consisting of mice and rats.
In the context of the present invention, the species-specific antibodies of the animal pest or pests can be prepared according to the procedures commonly used in the immunological field and known to the person skilled in the art.
A further application of the invention relates to the use of the biocide composition according to the present invention as an active component in a food bait for disinfestation from one or more animal pests.
It is therefore evident from the description that the biocide composition according to the invention ensures several advantages with respect to known poisons currently in use. The main advantage is represented by its absolute selectivity for one or more species of animal pest, thus being entirely harmless for domestic animals that might come into contact with it. Moreover, it does not cause suffering to the animals that ingest it and is entirely free from a potential "secondary poisoning" effect.
The disclosures in Italian Patent Application No. BO2009A000012 from which this application claims priority are incorporated herein by reference.

Claims

1. A biocide composition that is selective for at least one animal pest comprising liposomes that contain at least one species-specific antibody of the at least one animal pest, said at least one species-specific antibody being directed against a biological molecule of the animal pest that is essential for performing a vital function of the at least one animal pest, said biocide being administered orally.
2. The composition according to claim 1, wherein the at least one species-specific antibody of the at least one animal pest is characterized in that it has the Fc region recognized selectively by the receptors that are present on the membrane of the cells of the intestinal wall of the at least one animal pest.
3. The composition according to claim 1 or 2, further comprising a plurality of species-specific antibodies of the at least one animal pest, each one of said antibodies being directed against a distinct biological molecule of the animal pest that is essential for performing a vital function of the at least one animal pest.
4. The composition according to one or more of the preceding claims, wherein the biological molecule of the animal pest that is essential for performing a vital function is selected from the group consisting of molecules of the glomerular basal membrane and red cell molecules.
5. The composition according to one or more of the preceding claims, wherein the animal pest is a rodent.
6. The composition according to claim 5, wherein the rodent is selected from the group consisting of mouse and rat.
7. Use of the biocide according to one or more of claims 1-6 as an active component in a food bait for disinfestation from at least one animal pest.
PCT/EP2010/050296 2009-01-15 2010-01-12 Biocide composition and use thereof WO2010081805A1 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
IT000012A ITBO20090012A1 (en) 2009-01-15 2009-01-15 BIOCIDAL COMPOSITION AND ITS USE.
ITBO2009A000012 2009-01-15

Publications (1)

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WO2010081805A1 true WO2010081805A1 (en) 2010-07-22

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
ITBO20120094A1 (en) * 2012-02-28 2013-08-29 Vincenza Dolo BIOCIDAL COMPOSITION

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0280503A2 (en) * 1987-02-23 1988-08-31 Research Development Foundation Multivesicular liposomes having a biologically active substance encapsulated therein in the presence of a hydrochloride
WO2001058955A1 (en) * 2000-02-10 2001-08-16 Research Development Foundation Targeted destruction of pests
WO2006095128A2 (en) * 2005-03-11 2006-09-14 Syngenta Limited Rodent pest control

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0280503A2 (en) * 1987-02-23 1988-08-31 Research Development Foundation Multivesicular liposomes having a biologically active substance encapsulated therein in the presence of a hydrochloride
WO2001058955A1 (en) * 2000-02-10 2001-08-16 Research Development Foundation Targeted destruction of pests
WO2006095128A2 (en) * 2005-03-11 2006-09-14 Syngenta Limited Rodent pest control

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
FOSSATI-JIMACK, L., ET AL: "High Pathogenic Potential of Low-Affinity Autoantibodies in Experimental Autoimmune Hemolytic Anemia", THE JOURNAL OF EXPERIMENTAL MEDICINE, vol. 191, no. 8, 17 April 2000 (2000-04-17), pages 1293 - 1302, XP002571479 *
NAKANO, Y. ET AL.: "New rat model induced by anti-glomerular basement membrane antibody shows severe glomerular adhesion in early stage and quickly progresses to end-stage renal failure", PATHOLOGY INTERNATIONAL, vol. 58, June 2008 (2008-06-01), pages 361 - 370, XP002571541 *

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
ITBO20120094A1 (en) * 2012-02-28 2013-08-29 Vincenza Dolo BIOCIDAL COMPOSITION
WO2013127568A1 (en) * 2012-02-28 2013-09-06 Vincenza Dolo Biocidal composition

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