 RODONTICIDE APPAT AND METHOD FOR CONTROLLING HARMFUL TARGET RODENTS USING SUCH APPAT
专利摘要:
The invention relates to a rodenticide bait comprising: - an edible carrier for harmful target rodents, and; at least one rodenticidal ingestion compound chosen from rodenticidal compounds of chemical structure admitting a plurality of configuration stereoisomers, one of the configuration stereoisomers, said stereoisomer less persistent, of the plurality of stereoisomers of configuration: exhibiting hepatic persistence in target rodents less than the hepatic persistence of at least one other stereoisomer of the plurality of configuration stereoisomers, and; ○ being majority in the plurality of configuration stereoisomers; and wherein the rodenticide compound is present in a mass proportion selected to be non-lethal to harmful target rodents consuming said bait for a 24 hour period and to be lethal to harmful target rodents consuming said bait for several consecutive 24-hour periods . 公开号:FR3022110A1 申请号:FR1455441 申请日:2014-06-13 公开日:2015-12-18 发明作者:Herve Caruel；Bernadette Espana；Stephane Besse；Virginie Lattard；Etienne Benoit 申请人:Liphatech SA；Novozymes BioAg Inc； IPC主号:
专利说明:
[0001] The invention relates to a rodenticide bait and a method for controlling harmful target rodents using such a bait. BACKGROUND OF THE INVENTION [0002] Bait capable of combating target rodent pests causing lethal haemorrhage for them is already known. Such baits include in particular a substance capable of inhibiting a step of the vitamin K cycle and inactivating the blood coagulation cascade, particularly but not exclusively in rodent pests. [0003] In particular, the use of 4-hydroxycoumarin derivatives is known for this purpose. EP 2,090,164 discloses that first-generation anticoagulants - e.g. warfarin, coumachlor, coumatetralyl and coumafuryl are lethal in multiple shots of these first-generation anticoagulants, and that second-generation anticoagulants - e.g. bromadiolone, difenacoum (or diphenacoum), brodifacoum, difethialone, and flocoumafene are lethal by a single dose of one of these second-generation anticoagulants. Furthermore, EP 0 147 052 proposes a rodenticide bait comprising brodifacoum in a proportion of 50 ppm, said bait comprising only trans-brodifacoum and being substantially free of cis-brodifacoum. [0004] EP 0 147 052 also discloses that the use of such a bait limits the mortality of mammals other than rodents consuming such bait and birds consuming a rodent corpse poisoned by such bait. One of the problems raised by the use of baits comprising such 4-hydroxycoumarin derivatives-in particular brodifacoum-is that such baits scattered around areas to be protected from harmful target rodents are certainly effective on target rodent pests but also have blood anticoagulant properties in non-target species, especially in domestic animals, in wild target rodent predators and / or target rodent scavengers - referred to as secondary intoxication, in particular birds, especially belonging to groups of protected birds. Such baits also have anticoagulant properties in non-target species accidentally consuming such baits - it is called primary poisoning -, especially in humans. Although emergency treatments exist to treat hemorrhages caused by such intoxications, alternative solutions must be found to limit the disadvantages associated with the use of such anticoagulants, in particular vis-à-vis the non-target species. The invention therefore aims to solve this problem by proposing a method for controlling harmful target rodents which has a sufficient efficacy to eliminate certain target rodent harmful populations, but which is less dangerous for domestic animals and children accidentally consuming a quantity. of such a bait, but also less toxic - even devoid of toxicity - for predators or scavengers of intoxicated rodents. The invention relates to a rodenticide bait comprising - an edible carrier for harmful target rodents, and; at least one rodenticidal ingestion compound chosen from rodenticidal compounds of chemical structure admitting a plurality of configuration stereoisomers, one of the stereoisomers of configuration, called the less persistent stereoisomer, of the plurality of stereoisomers of configuration: o exhibiting hepatic persistence in target rodents less than the hepatic persistence of at least one other stereoisomer of the plurality of configuration stereoisomers, and; o being a majority in the rodenticide compound; and wherein the rodenticide compound is present in a mass proportion selected to be non-lethal to harmful target rodents consuming said bait for a 24 hour period and to be lethal to harmful target rodents consuming said bait for several consecutive 24-hour periods . Throughout the text: - "stereoisomers" means a rodenticidal compound, the isomers of this rodenticide compound of the same semi-developed formula, but the relative position of the atoms differs in space. In particular, the term "stereoisomers of configuration" means a rodenticidal compound, its isomers of the same semi-developed formula, but the conversion of configuration stereoisomers into one another requires a break / reformation of an interatomic covalent bond. Thus, the expression "configuration stereoisomers" does not include conformational isomers (or "rotamers") whose conversion from one to the other of the conformational isomers is accompanied by only one rotation. a portion of the molecule along the axis of a bond formed by axial overlap of orbitals; the expression "the less persistent stereoisomer is predominant in the rodenticide compound" means that the rodenticide bait rodenticide compound mainly comprises a less persistent stereoisomer, that is to say that the stereo The less persistent isomer is predominant in the plurality of configuration stereo-isomers of the rodenticide compound. In particular, in a rodenticide bait according to the invention: the amount of the less persistent stereoisomer of the rodenticidal compound is greater than the amount of each of the other configuration stereo-isomers of the rodenticide compound; The amount of the less persistent stereoisomer of the rodenticide compound relative to the sum of the amounts of each of the steroisomers of the rodenticide compound is greater than 0.5 (50%): the concentration (for example expressed in g / L in mol / L, mol / g or g / g) of the less persistent stereoisomer of the rodonticidal compound is greater than the concentration of each of the configuration stereoisomers of the rodenticide compound: - the concentration of the stereoisomer The less persistent residue of the rodenticide compound, relative to the sum of the concentrations of each of the steroisomers of the rodenticide compound, is greater than 0.5 (50%): the proportion of the less persistent stereoisomer of the rodenticide compound is greater than the proportion of each stereoisomers of configuration of the rodenticide compound. In a bait according to the invention, the proportion of the stereoisomeric stereoisomer of the rodenticide compound is more than 50% relative to the total rodenticide compound. In a bait according to the invention comprising a rodenticide compound admitting two configuration stereoisomers, including a less persistent stereoisomer, the amount and / or the concentration of said less persistent stereoisomer represents more than half (50%) of the amount and / or concentration of the total rodenticide compound (the sum of the less persistent rodenticide compound and the more remanent rodenticide compound). In such a bait according to the invention comprising a rodenticide compound admitting two stereoisomers of configuration, including a less persistent stereoisomer, the proportion of said less persistent stereoisomer is greater than 50% -particularly greater than 80%, preferably between 70% and 100%, more preferably between 85% and 100%, even more preferably between 75% and 98% - in the rodenticide compound. Advantageously and according to the invention, the proportion of stereoisomer of lower hepatic persistence in target rodents may be of the order of 100% in the rodenticide compound. The inventors have observed that the configuration stereoisomers of a rodonticidal compound whose chemical structure admits a plurality of at least two configuration stereoisomers do not exhibit the same liver remanence in harmful target rodents and that the One of the stereoisomers of configuration of the rodenticide compound is less persistent in the liver of harmful target rodents. The inventors have observed that a rodenticide bait mainly comprising a less persistent stereoisomer of a rodenticide compound makes it possible to limit its hepatic remanence-and, more generally, the persistence of said stereoisomer in the body of the target rodent-but allows also to maintain a high rodenticide efficacy. Such a bait thus makes it possible to limit the risks of secondary intoxication (by reducing the amount of rodenticide compound in the body of poisoned rodents and the corpses of poisoned rodents) but also the risks of primary intoxication by decreasing the mass proportion of rodenticide compound. in the bait. The inventors have observed that it is possible, totally surprisingly and not described in the state of the art, to reduce the mass proportion of a rodenticide compound in a bait by making rodent targets available for a quantity of bait. enough that they can ingest, in several days, a lethal quantity of rodenticide compound and cause their death. The rodenticide bait according to the invention is therefore adapted to be made available to rodents harmful target to allow them sustained or repeated consumption for several days and to cause in these rodent harmful target lethal haemorrhage. Such bait, which is also likely to be accidentally consumed - and thus unreiteredly - by non-target mammals, for example by domestic animals and, where appropriate, by humans, is therefore not likely to be consumed by the latter in quantities insufficient to cause a fatal haemorrhage. [0005] Advantageously and according to the invention, the mass proportion of rodenticide compounds in the bait is less than 200 ppm. Advantageously, the mass proportion of rodenticide compounds in the bait is less than 100 ppm, especially less than 50 ppm. In a preferred embodiment of the invention, the mass proportion of rodenticide compounds in the bait is less than 50 ppm -particularly less than 25 ppm, preferably less than 20 ppm, more preferably less than 15 ppm, in particular less than 12 ppm, for example between 4 ppm and 12 ppm-. [0006] Advantageously and according to the invention, the rodenticide compound is selected from the group of vitamin K cycle inhibitory substances in target rodents. Advantageously and according to the invention, at least one rodenticide compound is selected from the group consisting of bromadiolone, difenacoum, difethialone, brodifacoum and flocoumafene. Advantageously and according to the invention, in a variant of a process according to the invention, the rodenticide bait can comprise, as an active rodenticide, one or more rodenticidal compounds admitting a stereoisomer less persistent, the (s) the least conservative stereoisomer (s) being predominant in each rodenticide compound. Advantageously and according to the invention, alternatively or in combination, the rodenticide bait may comprise any other harmful substance such as an insecticidal substance and / or acaricide. The configuration stereoisomer of bromadiolone of lower hepatic remanence is the stereoisomer of the formula 3- [3- (4'-bromo- [1,1'-biphenyl] -4-yl) -3-hydroxy 1-phenylpropyl-4-hydroxy-2H-1-benzopyran-2-one, in which the carbons 1 and 3 of the 3-hydroxy-1-phenylpropyl group of said stereoisomer are of the same absolute configuration determined according to the nomenclature of 20 Cahn, Ingold and Prelog. The configuration stereoisomer of difenacoum with lower hepatic remanence is the stereoisomer of formula 3- (biphenyl-4-yl) -1- (4-hydroxycoumarin-3-yl) -1,2,3,4- tetrahydronaphthalane in which the two carbons 1 and 3 of the 1,2,3,4-tetrahydronaphthalan group of said stereoisomer are of the same absolute configuration determined according to the nomenclature of Cahn, Ingold and Prelog. The configuration stereoisomer of difethialone with lower hepatic remanence is the stereoisomer of formula 3- (4'bromobiphenyl-4-yl) -1- (4-hydroxythiocoumarin-3-yl) -1,2,3 , 4-tetrahydronaphthalene, carbons 1 and 3 of the 1,2,3,4-tetrahydronaphthalene group of said stereoisomer are of the same absolute configuration determined according to the nomenclature of Cahn, Ingold and Prelog. The configuration stereoisomer of brodifacoum of lower hepatic remanence is the stereoisomer of formula 3- (4 'bromobiphenyl-4-yl) -1- (4-hydroxycoumarin-3-yl) -1,2,3, 4-Tetrahydronaphthalan, carbons 1 and 3 of the 1,2,3,4-tetrahydronaphthalan group of said stereoisomer are of the same absolute configuration as determined according to the nomenclature of Cahn, Ingold and Prelog. The configuration stereoisomer of flocoumafene of lower hepatic persistence is the stereoisomer of the formula 3- [4- (4-trifluoromethylbenzyloxy) phenyl) -yl-1- (4-hydroxyc ormarin-3-yl) -1,2,3,4-tetrahydronaphthalan, carbons 1 and 3 of the 1,2,3,4-tetrahydronaphthalan group of said stereoisomer are of the same absolute configuration as determined according to the nomenclature of Cahn, Ingold and Prelog. Alternatively, the invention also relates to a rodenticide bait comprising at least one rodenticidal ingestion compound selected from rodenticide compounds excluding brodifacoum. Advantageously and according to the invention, the rodenticide bait comprises an edible excipient for harmful target rodents and at least one rodenticide compound by ingestion. Advantageously and according to the invention, the edible excipient comprises at least one food selected from the group consisting of cereal seeds-notably dehulled cereal seeds-cereal seed mills, cereal seed flours, flakes cereal seeds, cereal bran, non-cereal seeds, non-cereal grain millet, non-cereal seed meal and non-cereal seed flakes. Advantageously, the edible carrier may comprise at least one food selected from the group consisting of non-cereal seeds, for example alfalfa seeds. [0007] Advantageously, the edible excipient is chosen to allow consumption of the bait by harmful target rodents. In particular, the edible carrier is a non-lethal edible carrier for harmful target rodents. In particular, the edible carrier is not a rodenticide in itself and is free from rodenticide compounds. Advantageously, the edible carrier comprises at least one food selected from the group consisting of foods of plant origin and foods of animal origin. Advantageously, the excipient comprises at least one food chosen to stimulate the appetite of harmful target rodents. In particular, this food is selected from the group consisting of seeds of one or more cereals, seeds of one or more grains, seeds of one or more grains, seed flakes of one or more cereals, the sound of one or more cereals, and the grain meal of one or more cereals. For example, cereals are selected from the group consisting of oats, wheat, barley, corn, soybeans and rice. Advantageously, the food is selected from the group consisting of sweet foods. For example, these may be foods comprising at least one sugar selected from the group consisting of sucrose, lactose, fructose and glucose. It may be a sugar syrup-for example, a sugar syrup obtained by hydrolysis of the starch-or a sugar syrup obtained by hydrolysis of sucrose (invert sugar syrup), or beet sugar syrup, or maple syrup, or cane sugar syrup, or stevia. Advantageously, the food is chosen from the group consisting of flakes and coconut albumen flour (copra). Advantageously, the food is selected from the group consisting of nuts, hazelnuts and almonds-shredded and / or powdered. Advantageously, the food is selected from the group consisting of vegetable fats, vegetable oils (for example rapeseed oil, soy fat, sunflower oil, cocoa butter, peanut oil, peanut butter, corn oil palm oil), animal fats and animal oils (butter, lard, fish oil). Advantageously, the food is selected from the group consisting of animal proteins. By way of example, mention may be made, for example, of powdered milk, particularly skimmed milk powder, eggs, in particular powdered eggs, and hydrolysates of animal proteins. Advantageously and according to the invention, the edible excipient comprises an amount of at least one bitterness agent for non-target mammals. Advantageously, the edible carrier comprises denatonium benzoate as a bittering agent. Advantageously and according to the invention, the edible excipient comprises at least one dye. Such a dye makes it possible in particular to give said bait a color easily detectable and identifiable by a user, a manufacturer or a distributor of said rodenticide bait. Advantageously and according to the invention, the edible excipient comprises at least one preservative capable of ensuring its preservation during storage. Advantageously and according to the invention, the rodenticide bait may be in the solid state or in the pasty state. Advantageously, the rodenticide bait is in the form of a solid in the divided state, particularly in the form of granules, or in the form of a powder. However, advantageously and according to the invention, the rodenticide bait can be in the liquid state. Advantageously and according to the invention, one of the configuration stereo-isomers of the rodenticide compound being of higher hepatic persistence in target rodents, its proportion in the plurality of stereoisomers of configuration of the rodenticide composition is between 0. % (terminal included) and 50% (terminal excluded). [0008] Advantageously and according to the invention, said less persistent stereoisomer of at least one rodenticidal compound, which therefore has hepatic persistence in target rodents less than the hepatic persistence of at least one other stereoisomer of the plurality of stereoisomers of configuration of this rodenticidal compound has hepatic persistence in target rodents less than the hepatic persistence of each of the other stereoisomers of the plurality of configuration stereoisomers. The less remanent stereoisomer may therefore be the least persistent stereoisomer of the plurality of configuration stereo-isomers of the rodenticide compound. [0009] Advantageously and according to the invention, one of the stereo-isomers, said stereoisomer more remanent configuration of rodenticide compound having higher hepatic persistence in target rodents, its proportion in the plurality of configuration stereo-isomers of the bait is less than 50%, that is to say between 0% and 50% (excluding bound), preferably between 0% and 25%. [0010] The term "stereoisomer more remanent" of the rodenticide compound, the configurational stereoisomer having hepatic persistence in target rodents greater than the hepatic persistence of each of the other stereoisomers of the rodenticide compound. The invention also extends to a method of controlling harmful target rodents by dispersing a quantity of bait comprising an edible carrier for harmful target rodents and a mass proportion of at least one rodenticide compound by ingestion with harmful target rodents, said mass proportion and said amount of bait being selected; to be non-lethal to harmful target rodents consuming said bait for a period of 24 hours, and; to be lethal to harmful target rodents consuming said bait for several consecutive periods of 24 hours; wherein at least one rodenticidal compound is selected from rodenticidal compounds having a chemical structure admitting a plurality of configuration stereoisomers, one of the stereoisomers of configuration, said stereoisomer less persistent, of the rodenticide compound having a hepatic persistence in target rodents less than the hepatic persistence of at least one other stereoisomer of the plurality of configuration stereoisomers, said less persistent stereoisomer being predominant in the rodenticide compound. Advantageously and according to the invention, the periods of 24 hours are consecutive periods. The amount of disseminated bait is therefore adapted to allow bait consumption by harmful target rodents for several consecutive days. In particular, the amount of disseminated bait is adapted to the nature, number and appetite of the target rodent. Advantageously and according to the invention, the mass proportion of rodenticide compound in the bait is less than 200 ppm. Advantageously and according to the invention, the amount of disseminated bait is adapted to allow bait consumption by target rodents for 2 days to 7 days - especially 3 to 4 days. Of course, the lower the proportion of rodenticide compound in the bait, the longer the period of bait consumption by the target rodent will be long. It is therefore advisable to provide the bait with the target rodent pests for a period of time chosen to poison harmful target rodents and eliminate them. In addition, it is also necessary to adapt the duration of the consumption period by the target rodent harmful to the nature of the rodenticide compound. Advantageously and according to the invention, a sufficient quantity of bait is disseminated to be lethal to harmful target rodents consuming bait daily for at least 2 consecutive periods, in particular from 3 to 7 consecutive periods, said periods being each 24 consecutive hours. Advantageously and according to the invention, the amount of disseminated bait and the mass proportion of rodenticide compound in the bait are chosen to allow a daily ingestion of rodenticide compound by a rodent harmful rodent between 0.2 mg and 10 mg-especially between 0.2 mg and 2 mg-per kilogram of harmful target rodent. Advantageously and according to the invention, the mass proportion of rodenticide compound in the bait and the amount of bait dispersed so as to kill harmful target rodents in 4 days to 12 successive days of consumption of said bait. Advantageously, the bait is disseminated so as to make it available to rodents harmful target and allow consumption. Another independent aspect of the invention extends to a rodenticide bait comprising: - an edible carrier for harmful target rodents, and; flocoumafene of formula 3- [3- [44 [4- (trifluoromethyl) phenyl] methoxy) chromen-4-one of formula (V): o phenyl-1,2,3,4-tetrahydronaphthalan-1 -yll OH CF, (V); wherein asymmetric carbons 1 and 3 of the 1,2,3,4-tetrahydronaphthalane moiety of flocoumafene are indicated; said flocoumafene having a configuration stereoisomer, said homo-stereoisomer, in which the carbons 1 and 3 of the 1,2,3,4-tetrahydronaphthalan group are of the same absolute configuration, characterized in that said homo-stereoisomer of the flocoumafene is predominant in the plurality of configuration stereoisomers of flocoumafene. Advantageously and according to this independent aspect of the invention, the homo-stereoisomer of flocoumafene is of hepatic remanence in target rodents less than the hepatic persistence of at least one other stereoisomer of the plurality of stereoisomers of configuration. [0011] This independent aspect of the invention therefore also extends to a "one-shot" method of combating harmful target rodents by dispersing a quantity of bait according to the invention comprising flocoumafene and in which the proportion of flocoumafene and the amount of disseminated bait is selected so that the bait is lethal to harmful target rodents consuming said bait for a single 24 hour period, the homo-stereoisomer of flocoumafene being predominant in the flocoumafene. The invention also relates to a rodenticide bait and a method for controlling harmful target rodents characterized in combination by all or some of the characteristics mentioned above or below. Other objects, features and advantages of the invention will appear on reading the following description and illustrative examples given without any limitation and with reference to the appended figures in which: FIG. 1 is a proton NMR spectrum; trans-difenacoum "DFC 1"; FIG. 2 is a proton NMR spectrum of cis-difenacoum "DFC 2"; FIG. 3 is a graphic representation of the evolution of the hepatic content of the stereoisomers of brodifacoum; FIG. 4 is a graphical representation of the evolution of the hepatic content of the stereoisomers of difethialone; FIG. 5 is a graphical representation of changes in hepatic concentration of bromadiolone stereoisomers; FIG. 6 is a graphical representation of the effect of repeated dose administration (1 dose per day for 3 days); ) of bromadiolone according to the invention on the coagulation time (Quick time) of rat blood. For the preparation of a bait and the implementation of a process according to the invention, the stereoisomer of the rodenticide compound having the lowest hepatic remanence is identified by analysis of the disappearance of the stereoisomers of the rodent liver. especially rats having ingested one and / or the other stereoisomers of the rodenticide compound. In order to do this, rodents (particularly rats) are administered (at OJ) a dose of rodenticidal compound comprising one and / or the other of the two stereoisomers of said rodenticide compound. Target rodents are kept alive by daily administration of a vitamin K solution. The amount of each of the stereoisomers present in the liver of the rats is measured over time, for example at 1 day after administration. +1), 3 days after administration (D + 3), m days after administration (D + m). At the end, the rodent is sacrificed, the liver of the sacrificed rodent is removed, and the rodenticide compounds are extracted according to the method described in the review article titled "Validation of a New Liquid Chromatography-Tandem Mass Spectrometry Ion-Trap Technique". Thyme Anticoagulant Rodenticides, Drugs, Gold Natural Products. Fourel I. et al., (2010), Journal of Analytical Toxicology, 34, 95-102. Each of the stereoisomers of the rodenticide compound is assayed. The evolution of the hepatic concentration of each of the stereoisomers following the administration of the rodenticide compound is evaluated. The least persistent stereoisomer in the liver is the compound with the lowest liver concentration at a given time. In a process according to the invention, a rodenticide bait is prepared whose active substance comprises a major proportion of the stereo-20 isomer of the rodenticide compound having the lowest hepatic remanence. Such a rodenticide bait is made by mixing 5.0 mg of rodenticide compound, 11.0 mg of blue dye, 1 mg of denatonium benzoate and 1.024 g of glycol solvent. 98.959 g of wheat grains are impregnated with the composition obtained above. The impregnated wheat grains are dried and packaged. In a process according to the invention, the rodenticidal compound is selected from rodenticidal compounds having a chemical structure admitting a plurality of configuration stereoisomers, one of the configuration stereoisomers of the rodenticide compound exhibiting hepatic persistence in rodents. targets less than the hepatic persistence of at least one other stereoisomer and being present in majority proportion in the plurality of configurational stereoisomers of the rodenticide composition. In one variant of a process according to the invention, the rodenticidal compound is difenacoum: 3- (b-phenyl-4-yl) -1- (4-hydroxyc ormarin-3-yl) -1.2,3,4 tetrahydronaphatalane or 3- [3- (1,11-biphenyl) -4-yl-1,2,3,4-tetrahydro-1-naphthenyl] -4-hydroxy-2H-1-benzopyran-2 -one or 2-hydroxy-3- [3- (4-phenylphenyl) -1-tetralinyl] 4-chromenone in the IUPAC nomenclature ("International Union of Pure and Applied Chemistry") of formula (I) below: I); wherein carbons 1 and 3 of the 1,2,3,4-tetrahydronaphatalane group of difenacoum are identified. A separation of the two configuration stereoisomers of difenacoum (DFC) can be carried out by reverse phase column HPLC INERTSIL®ODS2 with a length of 150 mm and 4.6 mm internal diameter. [0012] The reverse stationary phase has a porosity of 80 Å and a surface area of 500 m 2 / g. The mobile phase consists of a mixture of acetonitrile (62%), isopropanol (3%) and ammonium acetate (35%) adjusted to pH 4 with acetic acid. The flow rate of the mobile phase is 1.5 ml / min and the detection is carried out by spectrophotometry at 260 nm. A "DFC 1" configuration stereoisomer is detected and collected, the retention time of which is of the order of 5.74 min and another "DFC 2" configuration stereoisomer distinct from "DFC 1" whose retention time is of the order of 4.87 min. The separation of the "DFC 1" and "DFC 2" isomers can be carried out by high performance liquid chromatography (UPLC) on an Acquity Waters chain comprising a BEH C18 Acquity UPLC column with a particle size of 1.7 μm and dimensions. 2.1 x 50 mm at 35 ° C. The mobile phase is formed by a gradient of an aqueous solution of trifluoroacetic acid (TFA, 0.1%) and a solution of 0.1% TFA in acetonitrile. The flow rate of the mobile phase is 0.6 mL / min. The retention time of the most selected isomer ("DFC 1") is 8.2 min and that of the least retained isomer ("DFC 2") is of the order of 7.3 min. The separation of the "DFC 1" and "DFC 2" isomers can also be carried out by high pressure liquid chromatography (HPLC) on an XBridge C18 column (dimensions 4.6 × 150 mm and 5 μm particle size) and with a phase 45% of an aqueous solution of 0.1% TFA and 55% of a 0.1% TFA solution in acetonitrile. The flow rate of the mobile phase is 1.2 mL / min. The retention time of the most selected isomer ("DFC 1") is 23.7 min and that of the least retained isomer ("DFC 2") is of the order of 21.0 min. The proton NMR spectrum of the "DFC 1" (or trans) configuration stereoisomer of difenacoum is shown in FIG. 1 and the proton NMR spectrum of the "DFC 2" (or cis) configuration stereoisomer of difenacoum is represented FIG. 2. The proton NMR spectrum of "DFC 1" has a triplet (4.5399 ppm, 4.5644 ppm and 4.5876 ppm) characteristic of the proton carried by the carbon 1 of the 1,2,3,4 group. -tétrahydronaphatalane. In comparison, the proton NMR spectrum of "DFC 2" has a quadruplet (4,8180 ppm, 4,8374 ppm, 4,8550 ppm and 4,8721 ppm) characteristic of the proton carried by carbon 1 of the group 1,2 3.4-tétrahydronaphatalane. Difenacoum - Inhibition of complex 1 vitamin K epoxide reductase (VKORC1) in vitro by the "DFC 1" and "DFC 2" isomers of difenacoum The inhibitory potency of vitamin K epoxide reductase activity (VKOR, "Vitamin K epoxide reductase ") of AVK's susceptible liver liver microsomes by the two purified" DFC 1 "and" DFC 2 "isomers was evaluated. Analysis of the inhibition curves of the VKOR activity as a function of the concentration of "DFC 1" or "DFC 2" shows inhibition constant (Ki) values of 30 nM for the "DFC 1" isomer and 60 nM for the "DFC 2" isomer. The inhibitory power on the toxicological target of each of the two isomers is therefore similar. Difenacoum - Hepatic retention of the isomers "DFC 1" and "DFC 2" in the male rat At 0, oral gavage of laboratory rats (Sprague Dawley rats, Charles River, Saint germain on the Arbresle, France) is performed. , aged 8 weeks and body weight of the order of 200 g with a mixture comprising 56% of the isomer "DFC 1" and 44% of the isomer "DFC 2" at a rate of 5.2 mg of difenacoum per kilogram of rat. The rats are kept alive by daily subcutaneous injection of a vitamin K solution at a rate of 1 U per rat. At D + 1, D + 3, D + 5, D + 10, D + 14 and D + 21, 4 rats are anesthetized with isoflurane and then sacrificed, the livers are removed and frozen until analysis. The average hepatic contents of the isomers "DFC 1" and "DFC 2" are analyzed by HPLC, given in Table 1 below. Hepatic content, lag J + 1 D + 3 D + 5 D + 10 D + 21 Trans 4,22 1,05 0,25 0.1 0,17 Cis 16,82 8,28 4,86 1,85 1, Table 1 As of D + 1, the average content of the "DFC 1" isomer in the liver of rats is lower than the average content of the "DFC 2" isomer in the liver of gaved rats with substantially the same amount isomer of difenacoum. The "DFC 1" isomer has a significantly lower hepatic persistence than the "DFC 2" isomer. Difenacoum - Comparative analysis of the rodenticide efficacy of baits comprising 50 ppm of "DFC 1" or "DFC 2" by multiple ingestion ("multi-feeding"). Rodenticide baits are dispersed in an amount of 25. difenacoum in a dough made from flour and vegetable fat and so that the bait contains 50 mg of difenacoum per kilogram of bait (50 ppm of difenacoum). A rodenticide bait according to the invention comprising mainly trans-difenacoum (91% of trans-difenacoum "DFC 1" and 9% of cis-difenacoum "DFC 2") is produced, and - as a comparison of the baits comprising: o 4% of "DFC 1" and 96% of "DFC 2", and; o 38% of "DFC 1" and 62% of "DFC 2". Rodents (10 Sprague Dawley rats (SD), including 5 male and 5 female) are placed in individual cages. During 4 days (D1, D2, D3 and D4), each rat is supplied with a quantity of bait sufficient to satisfy his appetite. At the end of these 4 days, a bait free diet is given. The daily consumption of each bait is measured by weighing. Upon death of the animal, the liver of the dead animal is removed, frozen and stored until analysis of hepatic content in stereoisomers of difenacoum configuration. The average daily bait consumption by the rats and the period of occurrence of the death of the animals (mortality) are given in Table 2 below as well as the rat mortality rate (%). Trans- Average bait mass Occurrence of Mortality,% difenacoum daily consumed, death / g / day Cis-difenacoum 91/9 12.9 D4 to D8 100% 38/62 12.5 D4 to D9 100% 4/96 11.8 D5 to D9 100% Table 2 The bait according to the invention (91/9) is consumed by rats with the same average daily amount as baits (2/98 or 18/82) not enriched in trans -difénacoum. The period of occurrence of the death of the animals having consumed the bait according to the invention is shorter (J4-J8) than the period of occurrence of the death of the animals having consumed the baits 38/62 (J4 to J9) and 4 / 96 (J5 to J9). Difenacoum: Comparative analysis of the rodenticide efficacy of baits comprising 15 ppm of "DFC 1" or "DFC 2" by multiple ingestion ("multi-feeding") Bait containing 15 mg of the isomer is prepared "DFC 1" of difenacoum per kilogram of bait (15 ppm of difenacoum). Rodents (10 domestic rats, including 5 male and 5 female) are placed in individual cages. For 4 days (D1, D2, D3 and D4), 50 g of bait raised were made available to each rat. At the end of these 4 days, a diet free of rodenticide is given. The average daily consumption of each bait per kilogram of rodent is measured by weighing. A rodenticide bait is made by dispersing a quantity of difenacoum in a dough made from flour and vegetable fat and so that the bait contains 15 mg of difenacoum per kilogram of bait (15 ppm of difenacoum), said bait comprising predominantly trans-difenacoum (substantially 100% "DFC 1"). Rodents (10 Sprague Dawley rats (SD), including 5 males and 5 females) are placed in individual cages and treated as described above. The average daily bait consumption by the rats and the period of occurrence of the death of the animals (mortality) as well as the rat mortality rate (%) are given in Table 3 below. DFC 1: DFC 2 Average mass of bait Occurrence of Mortality daily consumed, death g / day 100: 0 14.8 D5 to D8 70% Table 3 The bait poorly dosed in difenacoum (15 ppm) mainly comprising DFC 1 "(trans-difenacoum) makes it possible to obtain a 70% mortality rate by minimizing the risk of primary intoxication by accidental ingestion of this secondary bait. [0013] In another variant of a process according to the invention, the rodenticidal compound is bromadiolone: 343- (4'-bromo [1,1'-biphenyl] -4-yl) -3-hydroxy-1-phenylpropyl 4-hydroxy-2H-1-benzopyran-2-one or 3- [3- [444-bromophenyl) phenyl] -3-hydroxy-1-phenylpropyl-2-hydroxychromen-4-one of formula (II) after: (II). wherein carbons 1 and 3 of the 3-hydroxy-1-phenylpropyl group of bromadiolone are identified. The separation of bromadiolone configuration stereoisomers can be carried out on thin-layer silica gel or Nova-15 pak® Silica "flash" silica cartridge with a mobile phase formed of 70% petroleum ether and 30% chloroform (flow rate of 1 mL / min). This same mixture can be analyzed by high pressure liquid chromatography (HPLC) on an XBridge C18 column (dimensions 4.6 x 150 mm and particle size 5 μm) and with a mobile phase formed of a solution comprising 40% by weight. water (0.1% TFA) and 60% acetonitrile (0.1% TFA). The flow rate of the mobile phase is 1.2 mL / min. The retention time of the most adopted configuration stereoisomer is 8.35 min and that of the least retained is of the order of 7.79 min. A separation of the two bromadiolone configuration stereoisomers can be achieved by reverse phase column HPLC "LiChrospher®100 RP-18 Endcapped, Merck" 250 mm long and OH OH 4 mm internal diameter. . The reverse stationary phase has a particle size of λm and a specific surface area of 220 m 2 / g. The mobile phase consists of a mixture of methanol (72%) and water (28%) acidified with H3PO4 0.0025 M. The flow rate of the mobile phase is 1.0 mL / min and the detection is carried out spectrophotometrically at 260 nm. A first bromadiolone configuration stereoisomer "BR 1" is detected and collected, the retention time of which is of the order of 19.44 min, and a second bromadiolone configuration stereoisomer "BR 2" of which the retention time is of the order of 21.71 min. The analysis of this same mixture and the preparation of the "BR 1" and "BR 2" isomers is also carried out by high pressure liquid chromatography (HPLC) on an XBridge C18 column (dimensions 4.6 × 150 mm) and with a mobile phase formed of a gradient of compositions A and B whose characteristics are given in Table 4 below. The flow rate of the mobile phase is 1 mL / min, the temperature of the column is maintained at 40 ° C and the detection is carried out at 265 nm. [0014] The injection volume is 10 lat. Elution time, min Composition A Composition B H20 + 0.2% (v / v) H3PO4 Methanol 0 40% 60% 20% 80% 20.1 40% 60% 40% 60% Table 4 The retention time of the the stereoisomer configuration most retained (BR 2) is 17.9 min and the least retained (BR 1) is of the order of 17.1 min. It should be noted that the replacement of methanol with acetonitrile during the separation of the "BR 1" and "BR 2" isomers is likely to reverse the order of elution of the two isomers. The proton NMR (1H-NMR) study of the "BR 1" and "BR 2" isomers of bromadiolone in CDC133 makes it possible to determine that: the carbons 1 and 3 of the 3-hydroxy-1-phenylpropyl group of the stereo Bromadiolone "BR 1" configuration isomers are of the same absolute configuration as determined according to the nomenclature of Cahn, Ingold and Prelog and that; the carbons 1 and 3 of the 3-hydroxy-1-phenylpropyl group of the bromadiolone "BR 2" stereo-5 isomer are of distinct absolute configurations as determined according to the nomenclature of Cahn, Ingold and Prelog. Bromadiolone - Inhibition of complex 1 vitamin K epoxide reductase (VKORC1) in vitro by the bromadiolone "BR 1" and "BR 2" isomers The inhibitory power of two preparations enriched in "BR 1" and "BR 2" isomers Was evaluated using the measurement of vitamin K epoxide reductase (VKOR, "Vitamin K epoxide reductase") activity catalyzed by rat liver microsomes sensitive to AVK's. The isomers of bromadiolone are partially purified by gradient HPLC chromatography (A / B) as described above. The preparation enriched in "BR 1" consists of 96% of the "BR 1" isomer and 4% of the "BR 2" isomer. The preparation enriched in "BR 2" consists of 96% of the "BR 2" isomer and 4% of the "BR 1" isomer. Analysis of inhibition curves of VKOR activity as a function of inhibitor concentration revealed inhibition constant (Ki) values of 30 nM for the "BR1" isomer and 50 nM for the isomer. "BR2". The inhibitory power on the toxicological target of each of the two isomers is therefore similar. Bromadiolone - Hepatic remission of the "BR 1" and "BR 2" isomers in the rat At the end of the day, laboratory rats (Sprague Dawley, Charles River, Saint Germain, Arbresle, France rats) were fattened with body mass. of the order of 200 g with a mixture (96/4) enriched in isomer "BR 1" or with a mixture (2/98) enriched in isomer "BR2" at a rate of 3.0 mg bromadiolone per kilogram of rat . The rats are kept alive by daily subcutaneous injection of a vitamin K solution at a rate of 0.1 U per rat. At D + 1, D + 3, D + 7, D + 14 and D + 21, 4 rats are anesthetized with isoflurane and then sacrificed, the livers are removed and frozen until analysis. The mean hepatic levels of total bromadiolone in the mixture (96/4) enriched in "BR 1" isomer (a) and in the mixture and (2/98) enriched in "BR 2" isomer (0) are analyzed by HPLC and data in Table 5 below and shown in Figure 5 (the symbol (a) represents the isomer "BR1" and the symbol (0) represents the isomer "BR 2"). Mixture Liver content in total Bromadiolone, lag / g D + 1 D + 3 D + 7 D + 14 D + 21 BR 1 / BR 2 (96/4) 8.27 ± 2.72 2.34 ± 0.43 1 , 57 ± 0.21 0.99 ± 0.06 0.92 ± 0.08 BR 1 / BR 2 (2/98) 18.62 ± 2.22 14.70 ± 1.06 5.20 ± 0, 75 2.67 ± 1.07 0.99 ± 0.07 Table 5 As of D + 1, the average bromadiolone content in the liver of rats fed with the mixture enriched in the "BR 1" isomer (96/4) is more the average bromadiolone content in the liver of rats fed with the "BR 2" isomer enriched mixture (2/98). The "BR 1" isomer has a significantly lower hepatic persistence than the "BR 2" isomer, especially in the male rat. Bromadiolone - Hepatic retention of the "BR 1" and "BR 2" isomers in the female rat One of the previously described chromatography methods describes the compositions enriched in the following "BR 1" or "BR 2" isomers: 1 / BR 2; 80/20; - BR 1 / BR 2; 20/80. The female rats are carried out in the same way as with the male rats as described above. The mean hepatic levels of the BR 1 and BR 2 isomers of the female rats are analyzed by HPLC and given in Table 6 below. [0015] Mixtures Bromadiolone Liver content, lag / g D + 1 D + 3 D + 5 D + 9 Mixture BR 1 19.47 9.05 1.19 80/20 BR 2 5.92 3.54 1.29 Total 25.39 12.6 2.47 BR mixture 1 8.43 2.15 0.87 0.18 20/80 BR 2 24.02 22.05 15.55 7 Total 32.45 24.2 16.42 7.18 Table 6 Administration of a dose of 3.8 mg of the isomeric mixture (BR 1 / BR 2, 80/20) of bromadiolone per kilogram of female rat (average body mass of about g) and the analysis of the hepatic content of the "BR 1" and "BR 2" isomers at D + 1, D + 3 and D + 9 makes it possible to observe that the hepatic concentration of the "BR 1" isomer decreases faster than the hepatic concentration of the "BR 2" isomer. The "BR 1" isomer is therefore less persistent in the liver of female rats than the "BR 2" isomer. Bromadiolone - Multiple feeding ("multi10 feeding") Gavage and for three days (JO, D + 1 and D + 2) were daily administered to groups of 3 laboratory rats (Sprague Dawley rats 200 g) male or females, a bromadiolone composition comprising 96% of the "BR 1" isomer and 4% of the "BR 2" isomer at a rate of: 0.05 mg bromadiolone per kilogram of rat, or; - 0.1 mg bromadiolone per kilogram of rat, or; - 0.25 mg bromadiolone per kilogram of rat, or; - 0.5 mg bromadiolone per kilogram of rat, or; - 0.75 mg bromadiolone per kilogram of rat. On these rats, blood is taken and a measurement of the blood coagulation time is carried out at D + 3 (time of Quick, expressed in seconds). The results obtained are given in FIG. 6, in which the hatched histograms represent the clotting times of the female rats and the solid histograms represent the coagulation times of the male rats. The repeated administration once daily for three days of 0.25 mg of the mixture enriched (96/4) in the "BR 1" isomer of bromadiolone is sufficient to obtain an anticoagulant effect, a haemorrhage in the rat (male or female). female) and his death. Bromadiolone - Bait comprising 50 ppm bromadiolone for multi-feeding by rodents Rodenticide baits made from flour and vegetable fat and containing 50 mg bromadiolone per kilogram of bait ( 50 ppm bromadiolone). Such baits are made with bromadiolone compositions comprising: 93% of "BR 1" isomer and 7% of "BR 2" isomer (93/7), or; 15 - 2% isomer "BR 1" and 98% isomer "BR 2" (2/98), or; 18% isomer "BR 1" and 82% isomer "BR 2" (18/82). Rodents (15 Sprague Dawley rats (SD), including 9 males and 6 females and 15 wild rats, including 9 males and 6 females) are placed in individual cages. For 4 days (D1, D2, D3 and D4), each rat is supplied with a sufficient amount of bait to satisfy his appetite. At the end of these 4 days, a bait free diet is given. The daily consumption of each bait is measured by weighing. When the animal dies, the liver of the dead animal is removed, frozen and stored until hepatic content is assayed for bromadiolone. The average daily bait consumption by the rats and the average time to death of the animals (mortality) are given in Table 7 below. [0016] Bait Average Bait Weight Onset of Mortality,% BR 1 / BR 2 daily consumed, death g / day 93/7 11.45 D4 to D9 100 2/98 11.6 D4 to D8 100 18/82 12.25 J4 to J9 100 Table 7 The results of the liver assays (in ltg / g) of each of the stereoisomers of configuration BR 1 and BR 2 are presented in Table 8 below in which BR 1 / BR 2 represents the ratio of the amount (molar or mass) of stereoisomer "BR 1" and the amount of stereoisomer "BR 2" in the bait provided to the rats and the term "residue" represents the percentage of bromadiolone (BR 1 and BR 2) detected in the liver of the tested rats relative to the total amount of bromadiolone ingested by each rat. BR 1 / BR 2 Liver content, lag / g Residue,% BR 1 BR 2 93/7 7.26 ± 7.55 3.14 ± 1.03 3.7 ± 2.41 18/82 0.80 ± 0 , 37 20.16 ± 6.22 8.70 ± 4.83 2/98 0 26.74 ± 6.04 10.4 ± 3.84 Table 8 - Multiple Intake (Multi-feeding) Content Bromadiolone mean in the liver of dead rats is 87lag per rat treated with 93/7 bait and 231 μg per rat treated with 2/98 bait. The percentage of bromadiolone residue is minimized by the use of 93/7 bait comprising a major proportion of bromadiolone BR1 stereoisomer compared to the use of bromadiolone baits 2/98 and 18 / 82 comprising a majority proportion of "BR 2" stereoisomer. It should be noted that: - in SD rats treated with 93/7 bait, the proportion of "BR 2" in the liver is 27% relative to the total bromadiolone of the liver and constitutes nearly a third of bromadiolone residues; - in wild rats treated with 93/7 bait, the proportion of "BR 2" 5 in the liver is 37% relative to the total bromadiolone of the liver and constitutes more than one third of the residues of bromadiolone. A bait enriched in stereo-isomer configuration "BR 1", that is to say a bait comprising isomers "BR1" and "BR 2" in a proportion of 95/5 or 98/2 is therefore of nature to limit residues of bromadiolone in rodent liver and their secondary toxicity to rodent predators or rodent carcass scavengers. Bromadiolone - Bait comprising 15 ppm bromadiolone for multi-feeding by rodents. Rodenticide baits made from flour and vegetable fat and containing 15 mg bromadiolone per kilogram of bait ( 15 ppm bromadiolone). Such baits are made with bromadiolone compositions comprising: 96% of "BR 1" isomer and 4% of "BR 2" isomer (96/4), or; 2% of "BR 1" isomer and 98% of "BR 2" isomer (2/98). Rodents (10 Sprague Dawley (SD) rats, including 5 male and female) aged 8 weeks and about 200 g are placed in individual cages. During 4 days (D1, D2, D3 and D4), each rat is supplied with a quantity of bait sufficient to satisfy his appetite. At the end of these 4 days, a bait free diet is given. The daily consumption of each bait is measured by weighing. When the animal dies, the liver of the dead animal is removed, frozen and stored until hepatic content is assayed for bromadiolone. 1. BR 1 / BR 2 bait; The average amount of bait consumed daily by each of the 10 SD rats is 13.2 g (± 3.3 g). All rats die between D4 and D7. The average amount of bromadiolone ingested by the SD rats is 0.79 mg (± 0.19 mg), ie 0.76 mg (± 0.19 mg) of stereoisomer BR 1 and 0.03 mg (± 0.008 The mean residual liver content of total bromadiolone expressed as 1 Lg of bromadiolone per gram of rat liver at rat death is 10.61 μg / g. The mean residual hepatic contents of each of the BR 1 and BR 2 stereoisomers at rat death are 9.61 lg / g and 0.99 lg / g, respectively. 2. BR 1 / BR 2 bait; 2/98 at 15 ppm bromadiolone By comparison, the average amount of bait consumed daily by each of the 10 SD rats is 13.8 g (± 2.4 g). Rats usually die between D4 and D8, a dying rat on D10. The mean amount of bromadiolone ingested by SD rats is 0.832 mg (± 0.145 mg), ie 0.016 mg (± 0.003 mg) of BR 1 isomer and 0.816 mg (± 0.143 mg) of BR 2 isomer. Liver content The mean residual total bromadiolone expressed as 1 μg bromadiolone per gram of rat liver at rat death is 18.53 μg / g. The mean residual hepatic contents of the BR 1 and BR 2 isomers at rat death are 0.24 lag / g and 18.29 ag / g, respectively. A bait comprising a majority proportion of stereoisomeric BR1 isomer bromadiolone thus makes it possible to limit the amount of residual bromadiolone in the corpses of rodents who have consumed this bait, while maintaining a sustained rodenticidal efficacy compared to a bait comprising a proportion majority of stereoisomers BR 2 of bromadiolone. The invention therefore relates to a method for controlling harmful target rodents in which a quantity of rodenticide bait comprising a majority proportion of "BR 1" stereoisomer is dispersed in bromadiolone. In another variant of a process according to the invention, the rodenticide compound is brodifacoum: 3- (4'bromobiphenyl-4-yl) -1- (4-hydroxycoumarin-3-yl) -1,2,3, 4-tetrahydronaphthalene of formula (III) below: (III); wherein carbons 1 and 3 of the 1,2,3,4-tetrahydronaphthalene group of brodifacoum are identified. The stereoisomers of configuration of brodifacoum can be separated on a thin-layer silica gel with a mobile phase formed of petroleum ether (70%), ethyl acetate (6%) and dichloromethane ( 24%) -whose conditions are directly transferable on a flash column (50lam) -and makes it possible to separate a first isomer of the brodifacoum whose reference front (front of the compound / solvent front) is 0.17 and a second isomer of brodifacoumoum whose reference face is 0.28. It is also possible to separate the two configuration stereoisomers from brodifacoum by flash silica chromatography (25 g). The mobile phase consists of petroleum ether (70%), dichloromethane (24%) and ethyl alcohol (25%). The flow rate of the mobile phase is 15 mL / min and the detection is carried out spectrophotometrically at 300 nm. A first configuration stereo-isomer is obtained whose retention time is between 6 and 8 min and a second configuration stereo-isomer whose retention time is between 12 and 16 min. The purity of the configuration stereoisomers of brodifacoum 20 is confirmed by high performance liquid chromatography (UPLC, waters) on a column Acquity UPLC BEH C18 particle size of 1.7 μm and dimensions 2.1 × 50 mm. The mobile phase is formed of a solution of acetonitrile and trifluoroacetic acid (TFA). The flow rate of the mobile phase is 0.6 mL / min and the injection volume is 1! Al. The detection is carried out at 254 nm. The retention time of the most retained configuration ("BDF 1") stereoisomer and of less hepatic persistence is 2.3 min and the retention time of the configuration stereoisomer least retained and with greater persistence ("BDF 2") is of the order of 2.1 min. It is also possible to separate the two configuration stereoisomers from the brodifacoum by chromatography on a Zorbax Eclipse column (150 × 4.6) with a particle size distribution maintained at 40 ° C. The mobile phase consists of acetonitrile (72%) and an aqueous solution of phosphoric acid at 0.0025 N (28%). The detection is carried out by spectrophotometry at 260 nm. A configuration stereo-isomer is obtained whose retention time is of the order of 6.02 min and another configuration stereo-isomer whose retention time is of the order of 6.73 min. Carbons 1 and 3 of the 1,2,3,4-tetrahydronaphthalene group of the most preferred embroidery thiophosphoric configuration isomer ("BDF 1" or transbrodifacoum) and of lesser hepatic remanence are of the same absolute configuration as determined according to US Pat. nomenclature of Cahn, Ingold and Prelog. [0017] Brodifacoum - Hepatic and Plasma Persistence of Configuration Stereoisomers in the Rat Oral rats (Sprague Dawley, Charles River, Saint Germain en l'Arbresle, France) rats, 8 weeks old, were weighed orally of the order of 200 g, a solution enriched in one of the configuration stereoisomers of brodifacoum (BDF 1 or BDF 2) in a gavage mixture. The solution comprising "BDF 1" is administered (at 0) to 20 rats and the solution comprising "BDF 2" is administered to 20 rats so that the amount of brodifacoum ingested by each rat is of the order of 3 mg of brodifacoum. per kilogram of rat. The 40 gavaged rats are treated daily by subcutaneous administration of a dose of vitamin K1 at a rate of 0.1U per 200 g of live rat weight. At 1 day (D + 1), 3 days (D + 3), 7 days (D + 7), 14 days (D + 14) and 21 days (D + 21) after force-feeding, 4 previously anesthetized rats are sacrificed isoflurane, the liver is taken from the sacrificed rats and then extracted from the liver and the amount of brodifacoum present in the liver of the gaved rats is measured. The results are given in Table 9 below in which the hepatic contents of brodifacoum are the average of the contents measured on 4 rats and expressed in! Lig of brodifacoum per gram of liver and represented in FIG. 3 in which the hepatic content in brodifacoum of rats treated with the mixture enriched in "BDF 1" is represented by solid squares (a) and the hepatic content in brodifacoum rats treated with the mixture enriched in "BDF 2" is represented by open circles (0). Mix Hepatic content in total brodifacoum, lug / g D + 1 D + 3 D + 7 D + 14 D + 21 Rich in BDF 1 12.65 ± 0.99 8.29 ± 0.83 3.10 ± 0.92 1.56 ± 0.22 1.12 ± 0.07 Rich in BDF 2 29.84 ± 3.31 24.24 ± 3.76 9.55 ± 3.29 8.08 ± 0.25 3.09 ± 0.58 Table 9 The average content of brodifacoum in the liver of rats ingested the BDF-1 enriched solution was lower than the average content of brodifacoum in the liver of rats ingested the BDF-enriched solution after gavage of said rats. with the same amount of brodifacoum. The most retained "BDF 1" (trans-brodifacoum) isomer in the UPLC chromatographic conditions described above shows significantly decreased hepatic persistence relative to the hepatic persistence of the "BDF 2" isomer (cis-brodifacoum). . The invention therefore relates to a method for controlling harmful target rodents in which a quantity of rodenticide bait comprising a major proportion of isomer "BDF 1" is dispersed relative to "BDF 2". In another variant of a rodenticide bait according to the invention, the rodenticide compound is difethialone: 3- (4'bromobiphenyl-4-yl) -1- (4-hydroxythiocoumarin-3-yl) -1.2 , 3,4-tetrahydronaphthalane or 3- [3- [4- (4-bromophenyl) phenyl] -1-tetralinyl-2-hydroxy-4-thiochromenone of formula (IV) below: (TV); wherein carbons 1 and 3 of the 1,2,3,4-tetrahydronaphthalane group of the difethialone are identified. The separation of the configuration stereoisomers of the difethialone can be carried out on silica gel with a mobile phase formed of petroleum ether (80%), ethyl acetate (4%) and dichloromethane (16%) whose conditions are transposable on a flash column (50lam) and makes it possible to separate a first isomer from the difethialone whose reference front (front of the compound / solvent front) is 0.27 and a second isomer of the difethialone whose the reference edge is 0.31. It is possible to separate the two configuration stereoisomers from the difethialone by reverse phase column HPLC INERTSIL®ODS2 with a length of 150 mm and 4.6 mm internal diameter. The reverse stationary phase has a porosity of 80 Å and a surface area of 500 m 2 / g. The mobile phase consists of a mixture of acetonitrile (62%), isopropanol (3%) and ammonium acetate (35%) adjusted to pH 4 with acetic acid. The flow rate of the mobile phase is 1.5 ml / min and the detection is carried out by spectrophotometry at 260 nm. A configuration stereo-isomer is detected and collected whose retention time is of the order of 11.8 min and a configuration stereo-isomer whose retention time is of the order of 10.4 min. The purity of the first and second stereoisomers of configuration is confirmed by high performance liquid chromatography (UPLC, waters) on a column Acquity UPLC BEH C18 particle size of 1.7! Am and dimensions 2.1 x 50 mm at 35 ° vs. The mobile phase is formed of a gradient obtained by adding a solution of acetonitrile comprising 0.1% trifluoroacetic acid (TFA) in water supplemented with 0.1% TFA. The flow rate of the mobile phase is 0.6 mL / min. The retention time of the most-adopted configuration stereoisomer ("DFT 1") is 4.1 min and that of the least retained ("DFT 2") is of the order of 3.9 min. [0018] The proton NMR (11-I-NMR) study of the "DFT 1" isomer of the difethialone in CDC133 shows that this isomer is the "trans" configuration stereoisomer in which the carbons 1 and 3 of the group 1,2,3,4-tetrahydronaphthalan are of the same absolute configuration. Difethialone - Hepatic remodeling of stereoisomers of configuration in rats Oral ("peros") rats were administered to laboratory rats (Sprague Dawley rats, Charles River, Saint germain on Arbresle, France) aged 8 weeks and weighing in the order of 200 g, a solution of a mixture of two configuration stereoisomers of difethialone ("DFT 1" 54% and "DFT 2" 46%) in a mixture of gavage. To avoid hemorrhage, fed rats are treated daily by subcutaneous administration of a dose of vitamin K1 at 0.1U per 200 g of live rat weight. At 1 day (D + 1), 3 days (D + 3), 7 days (D + 7), 14 days (D + 14) and 21 days (D + 21) after force-feeding, 4 previously anesthetized rats are sacrificed isoflurane, the liver is removed from the sacrificed rats and then extracted from the liver and the amount of each of the configuration stereoisomers of difethialone present in the liver of the gaved rats is assayed. The results are given in Table 10 below in which the hepatic levels of difethialone are the average of the contents measured on 4 rats and expressed in ltg of difethialone per g of liver (lag / g) and represented in FIG. "DFT 1" content in the liver is represented by open circles (0) and the content of "DFT 2" in the liver is represented by solid squares (a). [0019] Hepatic content D + 1 D + 3 D + 7 D + 14 D + 21 DFT 1, lag / g 8.55 5.23 2.40 0.38 0.19 DFT 2, lag / g 8.98 5.49 3.58 1.69 1.44 Table 10 The average content of the "DFT 1" isomer in the liver of rats is lower than the average content of the "DFT 2" isomer in the liver of rats after gavage of said rats with the same amount of difethialone isomer. The most favored "DFT 1" isomer in the chromatographic conditions described above has a significantly reduced hepatic remanence compared with the hepatic persistence of the "DFT 2" isomer. Difethialone - Difethialone-based rat bait Two types of baits are prepared, each comprising a mass proportion of difethialone of 15 ppm (ie 15 mg of difethialone per kilogram of bait): - the type of bait comprising as the active substance 94% isomer "DFT 1" and 6% isomer "DFT 2", and - 2nd type of bait comprising as active substance 1% isomer "DFT 1" and 99% isomer "DFT 2". In individual cages, 10 rats (5 male and 5 female rats) from the laboratory (Sprague Dawley rats, Charles River, Saint germain on the Arbresle, France), aged 8 weeks and 200 g of body weight, were made available. body, continuously for 4 days a quantity of the first type of bait (mainly comprising "DFT 1") sufficient to satisfy the nutrition of each of these 10 rats. A further quantity of the second type of bait (mainly comprising "DFT 2") sufficient to satisfy the nutrition of each of these other rats is also available to 10 other rats. At the end of these 4 days, rats a diet free of rodenticide. [0020] The amount of bait consumed by each of the 10 live rats is measured daily. At the death of each animal, the liver of each animal is collected and the difethialone content of each liver is measured. The mean hepatic amount of difethialone is expressed as lug of difethialone measured per gram of rat liver. Mean hepatic proportions (hepatic proportion,% ("DFT 1"), hepatic proportion,% ("DFT 2"), and hepatic proportion,% ("difethialone") represent the proportion of residual difethialone in the liver of rats by in relation to the total quantity of difethialone ingested. The results are given in Table 11 below. DFT 1 / DFT 2 DFT 1 / DFT 2 94/6 1/99 Average amount of bait consumed, g 53.76 53.54 Difethialone 1 consumed (average), lug 758.02 8.03 Difethialone 2 consumed (average) , ltg 48.38 795.07 Difthialone consumed (average), lg 806.4 803.1 Hepatic Difthialone 1 (mean), lug / g 8.06 0.17 Hepatic Difthialone 2 (mean), lug / g 0.74 16.33 Hepatic Difetialone (mean), lug / g 8.80 16.50 Hepatic proportion,% ("DFT 1") 6.1 0.1 Hepatic proportion,% ("DFT 2") 0.6 13.7 Hepatic proportion,% ("difethialone") 6.7 13.8 Table 11 In the group of rats treated with the type of bait ("DFT 1"), two rats died on D + 3 (1 male, 1 female), one rat died on D + 4 (1 male), two rats died on D + 5 (2 males), two rats died on D + 7 (2 females), two rats died on D + 8 (2 females) and one rat died on D + 9 (1 male). In the group of rats treated with the 2nd type of bait ("DFT 2"), four rats died on D + 4 (2 males, 2 females), two rats died on D + 5 (1 male, 1 female ) and four rats died on day 6 (2 males, two females). [0021] The amount of residual difethialone in the liver of rat cadavers is twice as low when rats ingest DFT 1 bait (8.8 ltg / g) rather than DFT 2 bait (16.5 μg / g). The amount of residual difethialone in the cadaver of the rats is twice as low when the rats ingest the DFT 1 bait (6.7! Lig) rather than the DFT 2 bait (13.8 Lig). The bait according to the invention is as effective as the bait mainly comprising DFT 2 and is less dangerous for non-target animals likely to consume poisoned rodents or dead poisoned rodents. [0022] Difethialone - Bait for "Rattus norvegicus" rats made from difethialone Warfarin-sensitive rats "Rattus norvegicus" are provided: - A) a solid bait based on wheat according to the invention comprising 100% of DFT 1 in difethialone at a rate of 10 ppm or 5 ppm of difethialone in the bait, or - B) a wheat-based solid bait according to the invention comprising 100% of DFT 1 in difethialone at a rate of 25 ppm or 10 ppm difethialone in the bait, or 20 - C) a solid wheat bait for comparison and comprising 100% DFT 2 in difethialone at 25 ppm or 10 ppm difethialone in the bait. The mortality rates of the rats obtained with each of these baits (A to C) according to the modalities described are given in Table 12 below according to the proportion (in ppm or mg / kg) of difethialone in the bait and the number of successive days of baiting by the rats. [0023] Bait Proportion Number of days Mortality A) 100% DFT 1 10 ppm 3 days 80% A) 100% DFT 1 5 ppm 3 days 50% B) 100% DFT 1 25 ppm 1 day 90% B) 100% DFT 1 10 ppm 1 day 30% C) 100% DFT 2 25 ppm 1 day 90% C) 100% DFT 2 10 ppm 1 day 100% Table 12 A rodenticide bait according to the invention comprising predominantly DFT 1 (baits A) and B)) has a high efficacy rodenticide when it is provided rodents to allow consumption in a single dose or repeated over several days. Because of the low hepatic persistence of DFT 1, such a bait according to the invention limits the risk of poisoning of non-target mammals accidentally consuming such bait and the risk of poisoning of predatory birds or scavengers of dead or dead rodents. alive having consumed such a bait. [0024] In another variant of a rodenticide bait according to the invention, the rodenticide compound is flocoumafene: 3- [3- [4 - ([4- (trifluoromethyl) phenyl] methoxy) phenyl -1,2,3,4 tetrahydronaphthol-1-yl-chromen-4-one of formula (V) below: OH CF, (V); wherein carbons 1 and 3 of the 1,2,3,4-tetrahydronaphthalan moiety of flocoumafene are identified. The separation of configuration stereoisomers of flocoumafene can be carried out on silica gel with a mobile phase formed of petroleum ether (70%), ethyl acetate (6%) and dichloromethane (24%). whose conditions are transposable on a flash column (50lam) - makes it possible to separate a first configuration stereoisomer from flocoumafene whose reference front (front of the compound / solvent front) is 0.15 and a second stereoisomer of configuration of flocoumafen with a reference edge of 0.26. It is also possible to separate the two configurational stereoisomers of flocoumafene by reverse phase column HPLC "LiChrospher®100 RP-18 Endcapped, Merck" with a length of 125 mm and 4 mm internal diameter. The reverse stationary phase has a particle size of 5 μm and a surface area of 350 m 2 / g. The mobile phase consists of a mixture of methanol (75%) and water (25%) acidified with 0.01N H3PO4. The flow rate of the mobile phase is 1.0 ml / min and the detection is carried out by spectrophotometry at 220 nm. A stereo-isomer of configuration (FL 1) is detected and collected whose retention time is of the order of 21.05 min and a configuration stereo-isomer (FL 2) whose retention time is order of 19.17 min. The stereoisomer of configuration "FL1" is the stereoisomer in which the carbons 1 and 3 of the 1,2,3,4-tetrahydronaphthalan group are of the same absolute configuration. Flocoumafen - Hepatic remanence of stereoisomers of flocoumafen configuration in male and female rats Oral rats ("peros") were administered to laboratory rats (Sprague Dawley rats, Charles River, Saint germain on Arbresle , France) male or female, aged 8 weeks and weighing between 180 and 200 g, a solution comprising the two isomers of flocoumafene ("FL 1" and "FL 2") in proportions 59/41 in an oil mixture plant and 5% DMSO so that the amount of flocoumafen ingested by each rat is of the order of 2.3 mg per kilogram of rat. The gaved rats are treated daily by subcutaneous administration of a dose of vitamin K1 at a rate of 1U per rat. At 1 day (D + 1), 3 days (D + 3), 7 days (D + 7), 14 days (D + 14) and 21 days (D + 21) after force-feeding, 4 previously anesthetized rats are sacrificed to isoflurane, the liver is removed from the sacrificed rats and then extracted from the liver and the amounts of each of the configuration stereoisomers (FL 1 and FL 2) of the flocoumafene in the liver of the gaved rats are assayed. The results obtained on male rats and female rats are given respectively in Tables 13 and 14 below, in which the liver contents of each of the configuration stereoisomers (FL 1 and FL 2) of flocoumafene are the average of the measured contents. on 4 rats and expressed in microgram (tg) per gram of liver. Hepatic content, g / g D + 1 D + 3 D + 7 D + 14 D + 21 FL 1 5.37 ± 0.19 3.09 ± 0.26 1.30 ± 0.04 0.57 ± 0 , 09 0.41 ± 0.06 FL 2 6.01 ± 0.59 7.14 ± 2.2 2.71 ± 0.42 1.26 ± 0.25 0.9 ± 0.1 Table 13 (rats males) Liver content, g / g D + 1 D + 3 D + 7 D + 14 D + 21 FL 1 8.02 ± 2.25 4.3 ± 0.85 1.84 ± 0.21 1.02 ± 0.18 0.56 ± 0.13 FL 2 10.85 ± 3.05 8.15 ± 1.55 6 ± 0.86 3.60 ± 1.39 2.50 ± 0.35 Table 14 (rats females) The mean level of the "FL 1" isomer in the liver of male and female rats is lower than the mean level of the "FL 2" isomer. [0025] The most preferred "FL 1" isomer under the chromatographic conditions described above has a significantly decreased hepatic remanence compared with the hepatic persistence of the "FL 2" isomer. The invention can be subject to many variations without departing from the scope of protection claimed. In particular, it relates to a method for controlling harmful target rodents and to a rodenticide bait for carrying out such a method in which any rodenticidal compound having a stereoisomer with a liver remanence configuration lower than the liver remanence is chosen. at least one other configuration stereoisomer and a bait is prepared in which this stereoisomer of least hepatic persistence is predominant among the configuration stereoisomers of the rodenticide compound.
权利要求:
Claims (5) [0001] CLAIMS 1 / - Rodenticide bait comprising: - an edible carrier for harmful target rodents, and; at least one rodenticidal ingestion compound chosen from rodenticidal compounds of chemical structure admitting a plurality of configuration stereoisomers, one of the stereoisomers of configuration, said stereoisomer less persistent, of the plurality of stereo-isomers; configuration isomers: o having hepatic persistence in target rodents less than the hepatic persistence of at least one other stereoisomer of the plurality of configuration stereo-isomers, and; o being majority in the plurality of configuration stereoisomers; and wherein the rodenticide compound is present in a mass proportion selected to be non-lethal to harmful target rodents consuming said bait for a period of 24 hours and to be lethal to harmful target rodents consuming said bait for several consecutive periods of time. hours. [0002] 2 / - Bait according to claim 1, characterized in that the mass proportion of rodenticide compounds in the bait is less than 200 ppm. [0003] 3 / - Bait according to one of claims 1 or 2, characterized in that the rodenticide compound is selected from the group of vitamin K cycle inhibitory substances in rodents target. [0004] 4 / - Bait according to one of claims 1 to 3, characterized in that the rodenticide compound is selected from the group consisting of bromadiolone, difenacoum, difethialone, brodifacoum and flocoumafène. [0005] 5 / - Bait according to one of claims 1 to 4, characterized in that the edible carrier comprises at least one food selected from the group consisting of cereal seeds, cereal grain mills, rice seed meal, cereals, cereal grain flakes, cereal bran, non-cereal grains, non-cereal seeds, non-cereal flours and non-cereal flakes. 6 / - Bait according to one of the claims 1 to 5, characterized in that one of the stereo-isomers, said stereoisomer more remanent configuration rodenticide compound being of higher hepatic persistence in target rodents, its proportion in the plurality of stereoisomers configuration bait is less than 50%. 7 / - A method of controlling harmful target rodents by dispersing a quantity of bait comprising an edible carrier for harmful target rodents and a mass proportion of at least one rodenticidal compound by ingestion by harmful target rodents, said proportion mass and said amount of bait being selected; to be non-lethal to harmful target rodents consuming said bait for a period of 24 hours, and to be lethal to harmful target rodents consuming said bait for several consecutive periods of 24 hours; wherein at least one rodenticidal compound is selected from rodenticidal compounds having a chemical structure admitting a plurality of configuration stereoisomers, one of the stereoisomers of configuration, said stereoisomers less remanent, of the plurality of stereoisomers configuration having hepatic persistence in target rodents less than the hepatic persistence of at least one other stereoisomer of the plurality of configuration stereoisomers, said stereoisomeric less persistent being predominant in the rodenticide compound. 8 / - Method according to claim 7, characterized in that the mass proportion of rodenticide compound is less than 200 ppm. 9 / - Method according to one of claims 7 or 8, characterized in that the amount of disseminated bait and the mass proportion of rodenticide compound in the bait are chosen to allow a daily ingestion of rodenticide compound by a rodent harmful target between 0.2 mg and 10 mg per kilogram of harmful target rodent. 10 / - Method according to one of Claims 7 to 9, characterized in that a quantity of bait sufficient to be lethal for the target rodents is disseminated. pests consuming daily bait for at least 2 consecutive periods.
类似技术:
公开号 | 公开日 | 专利标题 FR3022110A1|2015-12-18|RODONTICIDE APPAT AND METHOD FOR CONTROLLING HARMFUL TARGET RODENTS USING SUCH APPAT EP3154340B1|2018-08-15|Bromadiolone containing composition, rodenticidal bait and process for controlling target rodent pests WO2015189321A1|2015-12-17|Composition comprising difethialone, rodenticide bait and method for controlling target rodent pests EP3154341B1|2018-11-07|Difenacoum containing composition, rodenticidal bait and process for controlling target rodent pests WO2017097749A1|2017-06-15|Stereoisomer of flocoumafen, composition and rodenticide bait comprising same, and method for controlling target rodent pests EP3386962A1|2018-10-17|Stereoisomer of flocoumafen, composition and rodenticide bait comprising same, and method for controlling target rodent pests EP3386964A1|2018-10-17|Stereoisomer of bromadiolone, composition and rodenticide bait comprising same, and method for controlling target rodent pests FR3044874A1|2017-06-16|RODONTICIDE APPAT COMPRISING BRODIFACOUM AND METHOD FOR CONTROLLING HARMFUL TARGET RODENTS WO2017097750A1|2017-06-15|Stereoisomer of flocoumafen, composition and rodenticide bait comprising same, and method for controlling target rodent pests WO2017097752A1|2017-06-15|Stereoisomer of flocoumafen, composition and rodenticide bait comprising same, and method for controlling target rodent pests WO2017097756A1|2017-06-15|Stereoisomer of bromadiolone, composition and rodenticide bait comprising same, and method for controlling target rodent pests FR3045044A1|2017-06-16|COMPOSITION AND RODONTICIDE APPAT COMPRISING FLOCOUMAFENE, METHOD FOR CONTROLLING HARMFUL TARGET RODENTS FR3044875A1|2017-06-16|RODONTICIDE APPAT COMPRISING BRODIFACOUM AND METHOD FOR CONTROLLING HARMFUL TARGET RODENTS FR3044873A1|2017-06-16|RODONTICIDE APPAT COMPRISING BRODIFACOUM AND METHOD FOR CONTROLLING HARMFUL TARGET RODENTS EP3386969A1|2018-10-17|Configurational stereoisomer of difethialone, composition and rodenticide bait comprising same, and method for controlling target rodent pests FR3044872A1|2017-06-16|RODONTICIDE APPAT COMPRISING BRODIFACOUM AND METHOD FOR CONTROLLING HARMFUL TARGET RODENTS FR3044871A1|2017-06-16|RODONTICIDE APPAT COMPRISING BRODIFACOUM AND METHOD FOR CONTROLLING HARMFUL TARGET RODENTS FR3044870A1|2017-06-16|RODONTICIDE APPAT COMPRISING DIFENACOUM, METHOD FOR CONTROLLING HARMFUL TARGET RODENTS AND METHOD OF OBTAINING THE SAME EP3386970A1|2018-10-17|Configurational stereoisomer of difethialone, composition and rodenticide bait comprising same, and method for controlling target rodent pests FR3045052A1|2017-06-16|COMPOSITION AND RODONTICIDE APPAT COMPRISING DIFETHIALONE, METHOD FOR CONTROLLING HARMFUL TARGET RODENTS FR3045051A1|2017-06-16|DIFETHIALONE CONFIGURATION STEREO-ISOMER, COMPOSITION AND RODONTICIDE APPAT COMPRISING THE SAME AND METHOD OF CONTROLLING HARMFUL TARGET RODENTS
同族专利:
公开号 | 公开日 WO2015189320A1|2015-12-17| FR3022110B1|2016-07-01|
引用文献:
公开号 | 申请日 | 公开日 | 申请人 | 专利标题 EP0147052A2|1983-12-14|1985-07-03|Imperial Chemical Industries Plc|Rodenticides| EP2090164A1|2008-02-15|2009-08-19|Zapi Industrie Chimiche S.p.A.|A rodenticide bait based on a synergetic association of anticoagulant active ingredients| FR3045043B1|2015-12-11|2019-04-12|Liphatech|STEREO-ISOMER FOR CONFIGURING FLOCOUMAFENE, COMPOSITION AND RODONTICIDE APPAT COMPRISING SAME, METHOD FOR CONTROLLING HARMFUL TARGET RODENTS| FR3045049B1|2015-12-11|2019-04-05|Liphatech|DIFETHIALONE CONFIGURATION STEREO-ISOMER, COMPOSITION AND RODONTICIDE APPAT COMPRISING THE SAME, AND METHOD OF CONTROLLING HARMFUL TARGET RODENTS| FR3045044B1|2015-12-11|2019-04-19|Liphatech|COMPOSITION AND RODONTICIDE APPAT COMPRISING FLOCOUMAFENE, METHOD FOR CONTROLLING HARMFUL TARGET RODENTS| FR3045046B1|2015-12-11|2019-06-21|Liphatech|STEREO-ISOMER FOR CONFIGURING BROMADIOLONE, COMPOSITION AND RODONTICIDE APPAT COMPRISING SAME AND METHOD FOR CONTROLLING HARMFUL TARGET RODENTS| FR3045048B1|2015-12-11|2019-04-05|Liphatech|DIFETHIALONE CONFIGURATION STEREO-ISOMER, COMPOSITION AND RODONTICIDE APPAT COMPRISING THE SAME AND METHOD OF CONTROLLING HARMFUL TARGET RODENTS| FR3044871B1|2015-12-11|2020-01-10|Liphatech|RODONTICIDE BAIT COMPRISING BRODIFACOUM AND METHOD FOR CONTROLLING HARMFUL TARGET RODENTS| FR3045042B1|2015-12-11|2019-04-12|Liphatech|STEREO-ISOMER FOR CONFIGURING FLOCOUMAFENE, COMPOSITION AND RODONTICIDE APPAT COMPRISING SAME, METHOD FOR CONTROLLING HARMFUL TARGET RODENTS| FR3045052B1|2015-12-11|2017-12-29|Liphatech Inc|COMPOSITION AND RODONTICIDE APPAT COMPRISING DIFETHIALONE, METHOD FOR CONTROLLING HARMFUL TARGET RODENTS| FR3045041B1|2015-12-11|2019-05-31|Liphatech|STEREO-ISOMER FOR CONFIGURING FLOCOUMAFENE, COMPOSITION AND RODONTICIDE APPAT COMPRISING SAME, METHOD FOR CONTROLLING HARMFUL TARGET RODENTS| FR3045051B1|2015-12-11|2019-04-05|Liphatech|DIFETHIALONE CONFIGURATION STEREO-ISOMER, COMPOSITION AND RODONTICIDE APPAT COMPRISING THE SAME, AND METHOD OF CONTROLLING HARMFUL TARGET RODENTS| FR3045047B1|2015-12-11|2019-08-23|Liphatech|STEREO-ISOMER FOR CONFIGURING BROMADIOLONE, COMPOSITION AND RODONTICIDE APPAT COMPRISING SAME AND METHOD FOR CONTROLLING HARMFUL TARGET RODENTS| FR3044873B1|2015-12-11|2020-01-10|Liphatech|RODONTICIDE BAIT COMPRISING BRODIFACOUM AND METHOD FOR CONTROLLING HARMFUL TARGET RODENTS| FR3044874B1|2015-12-11|2020-01-10|Liphatech|RODONTICIDE BAIT COMPRISING BRODIFACOUM AND METHOD FOR CONTROLLING HARMFUL TARGET RODENTS| FR3045040B1|2015-12-11|2019-04-19|Liphatech|STEREO-ISOMER FOR CONFIGURING FLOCOUMAFENE, COMPOSITION AND RODONTICIDE APPAT COMPRISING SAME, METHOD FOR CONTROLLING HARMFUL TARGET RODENTS| FR3044872B1|2015-12-11|2020-01-10|Liphatech|RODONTICIDE BAIT COMPRISING BRODIFACOUM AND METHOD FOR CONTROLLING HARMFUL TARGET RODENTS| FR3045045B1|2015-12-11|2019-04-05|Liphatech|STEREO-ISOMER FOR CONFIGURING BROMADIOLONE, COMPOSITION AND RODONTICIDE APPAT COMPRISING SAME AND METHOD FOR CONTROLLING HARMFUL TARGET RODENTS| FR3045050B1|2015-12-11|2019-06-21|Liphatech|DIFETHIALONE CONFIGURATION STEREO-ISOMER, COMPOSITION AND RODONTICIDE APPAT COMPRISING THE SAME AND METHOD OF CONTROLLING HARMFUL TARGET RODENTS| EP3452578A4|2016-05-05|2019-12-04|Children's Hospital Medical Center|Methods for the in vitro manufacture of gastric fundus tissue and compositions related to same|
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2015-06-23| PLFP| Fee payment|Year of fee payment: 2 | 2015-12-18| EXTE| Extension to a french territory|Extension state: PF | 2015-12-18| PLSC| Search report ready|Effective date: 20151218 | 2016-06-23| PLFP| Fee payment|Year of fee payment: 3 | 2016-12-23| TQ| Partial transmission of property|Owner name: LIPHATECH, FR Effective date: 20161123 Owner name: VETAGRO SUP, FR Effective date: 20161123 | 2017-06-22| PLFP| Fee payment|Year of fee payment: 4 | 2018-06-22| PLFP| Fee payment|Year of fee payment: 5 | 2020-06-19| PLFP| Fee payment|Year of fee payment: 7 | 2021-06-22| PLFP| Fee payment|Year of fee payment: 8 |
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申请号 | 申请日 | 专利标题 FR1455441A|FR3022110B1|2014-06-13|2014-06-13|RODONTICIDE APPAT AND METHOD FOR CONTROLLING HARMFUL TARGET RODENTS USING SUCH APPAT|FR1455441A| FR3022110B1|2014-06-13|2014-06-13|RODONTICIDE APPAT AND METHOD FOR CONTROLLING HARMFUL TARGET RODENTS USING SUCH APPAT| PCT/EP2015/063027| WO2015189320A1|2014-06-13|2015-06-11|Rodenticide bait and method for controlling target rodent pests using such a bait| 相关专利
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