EP3938478B1 - Utilisation d'huiles comprenant des additifs anti-usure non neurotoxiques - Google Patents

Utilisation d'huiles comprenant des additifs anti-usure non neurotoxiques Download PDF

Info

Publication number
EP3938478B1
EP3938478B1 EP21725231.1A EP21725231A EP3938478B1 EP 3938478 B1 EP3938478 B1 EP 3938478B1 EP 21725231 A EP21725231 A EP 21725231A EP 3938478 B1 EP3938478 B1 EP 3938478B1
Authority
EP
European Patent Office
Prior art keywords
bis
diphenylphosphate
group
oil
compound
Prior art date
Legal status (The legal status 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 status listed.)
Active
Application number
EP21725231.1A
Other languages
German (de)
English (en)
French (fr)
Other versions
EP3938478A1 (fr
Inventor
Djibril Faye
Marion GAY
Florence Severac
Jean-Louis Mansoux
Grégoire Herve
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Nyco
Original Assignee
Nyco
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
Priority claimed from FR2005253A external-priority patent/FR3110593B1/fr
Priority claimed from US16/878,857 external-priority patent/US11230683B2/en
Application filed by Nyco filed Critical Nyco
Publication of EP3938478A1 publication Critical patent/EP3938478A1/fr
Application granted granted Critical
Publication of EP3938478B1 publication Critical patent/EP3938478B1/fr
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Images

Classifications

    • C—CHEMISTRY; METALLURGY
    • C10—PETROLEUM, GAS OR COKE INDUSTRIES; TECHNICAL GASES CONTAINING CARBON MONOXIDE; FUELS; LUBRICANTS; PEAT
    • C10M—LUBRICATING COMPOSITIONS; USE OF CHEMICAL SUBSTANCES EITHER ALONE OR AS LUBRICATING INGREDIENTS IN A LUBRICATING COMPOSITION
    • C10M137/00—Lubricating compositions characterised by the additive being an organic non-macromolecular compound containing phosphorus
    • C10M137/02—Lubricating compositions characterised by the additive being an organic non-macromolecular compound containing phosphorus having no phosphorus-to-carbon bond
    • C10M137/04—Phosphate esters
    • C—CHEMISTRY; METALLURGY
    • C10—PETROLEUM, GAS OR COKE INDUSTRIES; TECHNICAL GASES CONTAINING CARBON MONOXIDE; FUELS; LUBRICANTS; PEAT
    • C10M—LUBRICATING COMPOSITIONS; USE OF CHEMICAL SUBSTANCES EITHER ALONE OR AS LUBRICATING INGREDIENTS IN A LUBRICATING COMPOSITION
    • C10M105/00—Lubricating compositions characterised by the base-material being a non-macromolecular organic compound
    • C10M105/08—Lubricating compositions characterised by the base-material being a non-macromolecular organic compound containing oxygen
    • C10M105/32—Esters
    • C—CHEMISTRY; METALLURGY
    • C10—PETROLEUM, GAS OR COKE INDUSTRIES; TECHNICAL GASES CONTAINING CARBON MONOXIDE; FUELS; LUBRICANTS; PEAT
    • C10M—LUBRICATING COMPOSITIONS; USE OF CHEMICAL SUBSTANCES EITHER ALONE OR AS LUBRICATING INGREDIENTS IN A LUBRICATING COMPOSITION
    • C10M137/00—Lubricating compositions characterised by the additive being an organic non-macromolecular compound containing phosphorus
    • C10M137/12—Lubricating compositions characterised by the additive being an organic non-macromolecular compound containing phosphorus having a phosphorus-to-carbon bond
    • C—CHEMISTRY; METALLURGY
    • C10—PETROLEUM, GAS OR COKE INDUSTRIES; TECHNICAL GASES CONTAINING CARBON MONOXIDE; FUELS; LUBRICANTS; PEAT
    • C10M—LUBRICATING COMPOSITIONS; USE OF CHEMICAL SUBSTANCES EITHER ALONE OR AS LUBRICATING INGREDIENTS IN A LUBRICATING COMPOSITION
    • C10M137/00—Lubricating compositions characterised by the additive being an organic non-macromolecular compound containing phosphorus
    • C10M137/16—Lubricating compositions characterised by the additive being an organic non-macromolecular compound containing phosphorus having a phosphorus-to-nitrogen bond
    • C—CHEMISTRY; METALLURGY
    • C10—PETROLEUM, GAS OR COKE INDUSTRIES; TECHNICAL GASES CONTAINING CARBON MONOXIDE; FUELS; LUBRICANTS; PEAT
    • C10M—LUBRICATING COMPOSITIONS; USE OF CHEMICAL SUBSTANCES EITHER ALONE OR AS LUBRICATING INGREDIENTS IN A LUBRICATING COMPOSITION
    • C10M2207/00—Organic non-macromolecular hydrocarbon compounds containing hydrogen, carbon and oxygen as ingredients in lubricant compositions
    • C10M2207/28—Esters
    • C10M2207/2805—Esters used as base material
    • C—CHEMISTRY; METALLURGY
    • C10—PETROLEUM, GAS OR COKE INDUSTRIES; TECHNICAL GASES CONTAINING CARBON MONOXIDE; FUELS; LUBRICANTS; PEAT
    • C10M—LUBRICATING COMPOSITIONS; USE OF CHEMICAL SUBSTANCES EITHER ALONE OR AS LUBRICATING INGREDIENTS IN A LUBRICATING COMPOSITION
    • C10M2223/00—Organic non-macromolecular compounds containing phosphorus as ingredients in lubricant compositions
    • C10M2223/02—Organic non-macromolecular compounds containing phosphorus as ingredients in lubricant compositions having no phosphorus-to-carbon bonds
    • C10M2223/04—Phosphate esters
    • C—CHEMISTRY; METALLURGY
    • C10—PETROLEUM, GAS OR COKE INDUSTRIES; TECHNICAL GASES CONTAINING CARBON MONOXIDE; FUELS; LUBRICANTS; PEAT
    • C10M—LUBRICATING COMPOSITIONS; USE OF CHEMICAL SUBSTANCES EITHER ALONE OR AS LUBRICATING INGREDIENTS IN A LUBRICATING COMPOSITION
    • C10M2223/00—Organic non-macromolecular compounds containing phosphorus as ingredients in lubricant compositions
    • C10M2223/02—Organic non-macromolecular compounds containing phosphorus as ingredients in lubricant compositions having no phosphorus-to-carbon bonds
    • C10M2223/04—Phosphate esters
    • C10M2223/041—Triaryl phosphates
    • C—CHEMISTRY; METALLURGY
    • C10—PETROLEUM, GAS OR COKE INDUSTRIES; TECHNICAL GASES CONTAINING CARBON MONOXIDE; FUELS; LUBRICANTS; PEAT
    • C10M—LUBRICATING COMPOSITIONS; USE OF CHEMICAL SUBSTANCES EITHER ALONE OR AS LUBRICATING INGREDIENTS IN A LUBRICATING COMPOSITION
    • C10M2223/00—Organic non-macromolecular compounds containing phosphorus as ingredients in lubricant compositions
    • C10M2223/08—Organic non-macromolecular compounds containing phosphorus as ingredients in lubricant compositions having phosphorus-to-nitrogen bonds
    • C—CHEMISTRY; METALLURGY
    • C10—PETROLEUM, GAS OR COKE INDUSTRIES; TECHNICAL GASES CONTAINING CARBON MONOXIDE; FUELS; LUBRICANTS; PEAT
    • C10N—INDEXING SCHEME ASSOCIATED WITH SUBCLASS C10M RELATING TO LUBRICATING COMPOSITIONS
    • C10N2030/00—Specified physical or chemical properties which is improved by the additive characterising the lubricating composition, e.g. multifunctional additives
    • C10N2030/06—Oiliness; Film-strength; Anti-wear; Resistance to extreme pressure
    • C—CHEMISTRY; METALLURGY
    • C10—PETROLEUM, GAS OR COKE INDUSTRIES; TECHNICAL GASES CONTAINING CARBON MONOXIDE; FUELS; LUBRICANTS; PEAT
    • C10N—INDEXING SCHEME ASSOCIATED WITH SUBCLASS C10M RELATING TO LUBRICATING COMPOSITIONS
    • C10N2030/00—Specified physical or chemical properties which is improved by the additive characterising the lubricating composition, e.g. multifunctional additives
    • C10N2030/10—Inhibition of oxidation, e.g. anti-oxidants
    • C—CHEMISTRY; METALLURGY
    • C10—PETROLEUM, GAS OR COKE INDUSTRIES; TECHNICAL GASES CONTAINING CARBON MONOXIDE; FUELS; LUBRICANTS; PEAT
    • C10N—INDEXING SCHEME ASSOCIATED WITH SUBCLASS C10M RELATING TO LUBRICATING COMPOSITIONS
    • C10N2040/00—Specified use or application for which the lubricating composition is intended
    • C10N2040/04—Oil-bath; Gear-boxes; Automatic transmissions; Traction drives
    • C—CHEMISTRY; METALLURGY
    • C10—PETROLEUM, GAS OR COKE INDUSTRIES; TECHNICAL GASES CONTAINING CARBON MONOXIDE; FUELS; LUBRICANTS; PEAT
    • C10N—INDEXING SCHEME ASSOCIATED WITH SUBCLASS C10M RELATING TO LUBRICATING COMPOSITIONS
    • C10N2040/00—Specified use or application for which the lubricating composition is intended
    • C10N2040/06—Instruments or other precision apparatus, e.g. damping fluids
    • C—CHEMISTRY; METALLURGY
    • C10—PETROLEUM, GAS OR COKE INDUSTRIES; TECHNICAL GASES CONTAINING CARBON MONOXIDE; FUELS; LUBRICANTS; PEAT
    • C10N—INDEXING SCHEME ASSOCIATED WITH SUBCLASS C10M RELATING TO LUBRICATING COMPOSITIONS
    • C10N2040/00—Specified use or application for which the lubricating composition is intended
    • C10N2040/12—Gas-turbines
    • C—CHEMISTRY; METALLURGY
    • C10—PETROLEUM, GAS OR COKE INDUSTRIES; TECHNICAL GASES CONTAINING CARBON MONOXIDE; FUELS; LUBRICANTS; PEAT
    • C10N—INDEXING SCHEME ASSOCIATED WITH SUBCLASS C10M RELATING TO LUBRICATING COMPOSITIONS
    • C10N2040/00—Specified use or application for which the lubricating composition is intended
    • C10N2040/12—Gas-turbines
    • C10N2040/13—Aircraft turbines

Definitions

  • the present invention relates to the technical field of anti-wear additives used in oils such as oils for lubricating aircraft or aero-derivative turbines or hydraulic oils.
  • Aircraft or aero-derivative turbine engines use synthetic lubricants generally comprising an ester base and a variety of anti-wear additives from the organophosphate family such as triarylphosphates.
  • the most commercially used anti-wear additive is tricresyl phosphate (TCP), which has singular anti-wear properties that can be considered unique to date. Its tri-arylphosphate analogues are also valuable anti-wear additives.
  • Leaks of lubricants, in particular those containing tricresylphosphate or one of its tri-arylphosphate analogues, into the air of aircraft cabins can originate from worn or defective seals, or even under normal conditions of use by passage lubricants in the air for cabin pressurization. These repeated leaks are explained ( Michaelis S et al. Public Health Panorama 2017, 3, 2, p. 198-211 ) as being due to pressure variations between the bearing chamber and the air circuit exerted by normal operating conditions (increase in engine power, take-off). In certain circumstances, the leak can become very important, generally following the breakage of a bearing in the turbine, which leads to an event of smoke, or white fog visible in the cabin.
  • Aerotoxic syndrome is a medical condition combining physical and neurological symptoms, caused by the short and long term effects of exposure to aircraft cabin air contaminated with hydraulic oils or engine oils or any other organic pollutant present in the form of gas and/or aerosols.
  • the reported symptoms are generally non-specific, and cabin air quality studies indicate contaminant levels that are below exposure limits and not dangerous to human health, the difficulty being to measure continuously and in service of oil fumes, by definition non-gaseous, conveyed in the air, settling and concentrating, episodically, at different locations in the aircraft ( Kasper Solbu et al. J. About. Monit. 2011, 13, 1393 ).
  • Aero-derivative turbines operate identically to that of aircraft turbines and use lubricants of similar composition, particularly in terms of anti-wear agents.
  • organophosphate antiwear additives such as tricresylphosphate (TCP), especially its isomer tri-ortho-cresylphosphate (ToCP), are known to exhibit a potent neurotoxic effect ( Craig P et al. Journal of Toxicology and Environmental Health Part B: Critical Reviews 1999, 2, 4, p.281-300 ).
  • TCP tricresylphosphate
  • ToCP isomer tri-ortho-cresylphosphate
  • OPIDN organophosphate-induced delayed neuropathy
  • TCP is also known to be reprotoxic
  • the development of alternative anti-wear additives to tricresylphosphate and its tri-arylphosphate analogues for which an absence of neurotoxicity and reprotoxicity would be established would be advantageous and would make it possible to increase the level aviation security and other aero-derivative applications.
  • the patent application US2016/0002565 discloses a tricresylphosphate-free turbine oil that includes at least one base oil, at least one alkylpolyglycoside, and a phenolic derivative such as 3,5-di-tert-butyl-hydroxytoluene.
  • the replacement of tricresylphosphate by the phenolic derivative contributes to the prevention of the aerotoxic syndrome when this oil is used in aircraft turbines.
  • a compound may, for example, not be reprotoxic, show no sign of acute toxicity, or even show no CMR character (carcinogenicity, mutagenicity, or toxicity for reproduction) on human health and yet be highly neurotoxic ( Or vice versa).
  • V6 tetrakis(2-chloroethyl)dichloroisopentyldiphosphate
  • WO2015/026566 describes a lubricant comprising: (i) a large amount (50% or more by weight relative to the total weight) of a natural or synthetic base oil and (ii) a small amount of an aryl diphosphate ester of the formula ( I) as an anti-wear additive and which may correspond, for example, to resorcinol bis(diphenylphosphate).
  • the document EP 0 612 837 describes a polyphenylene ether lubricant comprising an anti-wear additive comprising a hydrocarbyl bis(dihydrocarbylphosphate) compound, such as resorcinol bis(diphenylphosphate).
  • an anti-wear additive comprising a hydrocarbyl bis(dihydrocarbylphosphate) compound, such as resorcinol bis(diphenylphosphate).
  • a lubricating composition comprising (col.2, lines 11-35) a base oil which may be polyol esters or phosphate esters such as tricresylphosphate, and an aryl diphosphate ester having anti-wear properties.
  • the document US 2001/306530 describes a composition comprising a base oil which may be a polyol ester and a phosphorus compound.
  • the exemplified phosphorus compound includes a diphosphorus compound (" tetraphenyl (m-phenylene) bisphosphate ”) and tricresyl phosphate.
  • polyphosphorus compounds in particular aryl polyphosphorus compounds, which have both anti-wear and satisfactory, or even improved, thermal stability properties, exhibit a greatly reduced neurotoxicity compared to that of anti-wear derivatives. - wear of monophosphates such as TCP, or even zero.
  • These polyphosphorus compounds can therefore be advantageously used in oils, in particular for lubricating aircraft or aeroderivative turbines, for reducing and/or preventing the neurotoxicity of oils and in particular of turbine oils.
  • said oil and/or said at least one anti-wear additive does not comprise tricresylphosphate or one of its triarylphosphate analogues.
  • the polyphosphorus compounds of formula (I) can thus be used to obtain an oil that is non-neurotoxic or has reduced neurotoxicity.
  • the compounds of formula (I) have interesting anti-wear properties, which can be comparable to those of tricresylphosphate or its triarylphosphate analogues. They also present a very low, if not zero, level of risk in terms of neurotoxicity and thus reduce and/or prevent the neurotocixity of the oil in which they are integrated.
  • said oil and/or said at least one anti-wear additive does not comprise tricresylphosphate or one of its triarylphosphate analogues.
  • said oil and/or said at least one anti-wear additive does not comprise tricresylphosphate or one of its triarylphosphate analogues.
  • the term “comprise” and its derivatives should be understood as non-limiting and not excluding the presence of other components or steps.
  • the term “comprising” may be understood as “consisting essentially of” or “consisting of”.
  • “By reducing" the neurotoxicity of an oil it is meant that the compound(s) of formula (I) according to the invention are suitable and/or configured to reduce the neurotoxicity of an oil in which they are included, namely by their presence (generally in the majority), in particular compared to other conventional anti-wear compounds which are generally neurotoxic, the compound(s) of formula (I) make it possible to lower/reduce the neurotoxicity of an oil and obtain a non-neurotoxic oil or at least one with reduced toxicity.
  • preventing the neurotoxicity of an oil
  • the compound(s) of formula (I) make it possible to prevent the oil from being considered neurotoxic and/or to prevent the appearance of neurotoxic symptoms in a mammal, such as a human or an animal that would come into contact with said oil
  • these neurotoxic symptoms can, for example, affect the central nervous system (CNS) and present the following effects: headaches, loss of appetite, drowsiness, mood and personality disorders, cognitive impairment (disorders learning and concentration), or reach the peripheral nervous system (PNS) and present the following effects: motor impairments such as weakness, tremors, incoordination, convulsions. or sensory impairment, such as decreased hearing, color vision, tinnitus, loss of balance; these effects may or may not be reversible depending on the degree of acute or chronic exposure of the mammal.
  • CNS central nervous system
  • PNS peripheral nervous system
  • motor impairments such as weakness, tremors, incoordination, convulsions.
  • sensory impairment such as decreased hearing, color
  • Neurotoxicity means the ability of a substance or compound to induce harmful effects in the nervous system of a mammal, such as a human being.
  • the nervous system is divided into central nervous system (CNS) and peripheral nervous system (PNS).
  • the CNS is located in the cranium and spine. It includes the brain, brainstem and spinal cord. Its role is to receive, record and interpret the signals that reach it from the periphery. It then organizes the response to be sent.
  • the PNS is made up of nerve ganglia, sensory nerves responsible for transmitting sensations to the brain, such as pain, and motor nerves responsible for movement by stimulating muscles. They circulate information between the CNS and the organs.
  • a neurotoxic substance or compound usually acts by disturbing or paralyzing nerve impulses, by acting in particular on the synaptic transmitters or receptors or on the enzymes which act on these synaptic transmitters or receptors, such as cholinesterases.
  • a cholinesterase is an enzyme which catalyzes the hydrolysis reaction of a choline ester (acetylcholine, butyrylcholine) into choline and acetic or butyric acid. In physiology, this reaction is necessary to allow cholinergic receptors to return to their resting state after activation.
  • the Applicant has demonstrated the non-neurotoxicity of the specific compounds of formula (I) both by in vitro experimental tests relating to cholinesterases and by modeling tests (3D molecular modeling by spherical harmonics and modeling by QSAR for neurotoxicity and for reprotoxicity).
  • the 50% inhibitory concentration of said at least compound of formula (I) on the biological activity of an acetylcholinesterase (AChE) enzyme, called IC 50 hAChE is greater than or equal to 15 mg/L, preferably greater than or equal to 16 mg/L and the activity on a butyrylcholinesterase enzyme, called IC 50 eqBuChE is greater than or equal to 15 mg/L, in particular greater than or equal to 50 mg/L, preferably equal to or greater than 55 mg/L , in particular equal to or greater than 60 mg/L and typically equal to or greater than 70 mg/L.
  • AChE acetylcholinesterase
  • a value greater than or equal to 15 mg/L for IC 50 hAChE includes the following values and all the intervals between these values: 15; 16; 17; 18; 19; 20; 21; 22; 23; 24; 25; 26; 27; 28; 29; 30 ; 31; 32; 33; 34; 35; 36; 37; 38; 39; 40.
  • a value greater than or equal to 15 mg/L for IC 50 eqBuChE includes the following values and all the intervals between these values: 15; 16; 17; 18; 19; 20; 21; 22; 23; 24; 25; 26; 27; 28; 29; 30 ; 31; 32; 33; 34; 35; 36; 37; 38; 39; 40; 45; 50; 55; 60; 65; 70; 75; 80; 85; 90; 95; 100; 105; 110; 115; 120; 125; 130; 135; 140; 145; 150; 155; 160.
  • the compound(s) of formula (I) belong to Cluster 3 determined according to molecular modeling by spherical harmonics as described in the publication "Benchmarking of HPCC: A novel 3D molecular representation combining shape and pharmacophoric descriptors for efficient molecular similarity assessments", Karaboga et al. 2013 Journal of Molecular Graphics and Modeling 41; 20-30 .
  • the compound(s) of formula (I) exhibit a value in percentage (%) by QSAR modeling (quantitative structure-activity relationship) that is lower or equal to 0.70%, preferably less than or equal to 0.50% and typically less than or equal to 0.15% for the measurement of neurotoxicity (neurotoxic QSAR) and less than or equal to 1.5%, preferably less or equal to 1.15% and typically less than or equal to 0.55% for the reprotoxicity measurement (reprotoxic QSAR).
  • a value less than or equal to 0.70% for neurotoxic QSAR modeling includes the following values and all the intervals between these values: 0.70; 0.69; 0.68; 0.67; 0.66; 0.65; 0.64; 0.63; 0.62; 0.61; 0.60; 0.59; 0.58; 0.57; 0.56; 0.55; 0.54; 0.53; 0.52; 0.51; 0.50; 0.49; 0.48; 0.47; 0.46; 0.45; 0.44; 0.42; 0.40; 0.38; 0.36; 0.34; 0.32; 0.30; 0.28; 0.26; 0.24; 0.22; 0.20; 0.18; 0.16; 0.14; 0.12; 0.10; 0.09; 0.08; 0.07; 0.06; 0.005; 0.04; 0.03; 0.02;0.01; 0.00.
  • a value less than or equal to 1.50% for reprotoxic QSAR modeling includes the following values and all the intervals between these values: 1.50; 1.48; 1.46; 1.44; 1.42; 1.40; 1.38; 1.36; 1.34; 1.32; 1.30; 1.28; 1.26; 1.24; 1.22; 1.20; 1.18; 1.16; 1.14; 1.12; 1.10; 1.08; 1.06; 1.04; 1.02; 1.00; 0.80; 0.60; 0.50; 0.40; 0.30; 0.20; 0.10; 0.00.
  • the compounds of formula (I) according to the invention present a level of risk in terms of neurotoxicity which is very low and which generally corresponds to a score of 0 or to a score of 1 (very low or non-existent risk of neurotoxicity) , preferably a score of 0.
  • the level of risk as defined above and also illustrated in the experimental part below is very exhaustive and encompasses all the data obtained via the various tests on neurotocixity described above and therefore includes both in -house tests vitro than 3D modeling trials.
  • oil in the present invention any organic substance, in particular any hydraulic or turbine oil, capable of creating pollution in the form of gas and/or aerosol in the cabin.
  • the oil is selected from the group consisting of aircraft or aero-derivative turbine oils, helicopter transmission oils, and weapons fluids.
  • the oil is an oil for aircraft or aeroderivative turbines.
  • the oil is preferably used to lubricate aircraft or aeroderivative turbines.
  • R1, R2, R3 and R4 groups of the polyphosphorus compounds of formula (I) according to the invention are independently chosen from: an alkyl group, an O-alkyl group, an aryl group, an O -aryl.
  • alkyl group is meant a linear or branched saturated hydrocarbon group comprising (unless otherwise stated) from 1 to 36 carbon atoms (C 1 to C 36 ), more preferably from 1 to 18 carbon atoms. carbon (C 1 to C 18 ), in particular from 1 to 10 carbon atoms (C 1 to C 10 ), and typically from 1 to 4 carbon atoms (C 1 to C 4 ).
  • alkyl groups according to the invention mention may be made in particular of the methyl, ethyl, propyl, isopropyl, n-butyl and tert-butyl groups.
  • the alkyl group can optionally be a substituted alkyl group.
  • substituted alkyl group denotes a linear or branched saturated hydrocarbon chain as defined above and substituted, at one or more of its atoms, by one or more radicals chosen from: a hydroxyl radical OH, an amine radical NH 2 or primary amine NHR with R alkyl or aryl group, preferably an hydroxyl radical OH.
  • the alkyl group cannot be substituted with a halogen, such as chlorine.
  • O-alkyl group is meant an alkyl group as defined above, linked to the rest of the molecule (here, generally the phosphorus atom) via an oxygen atom.
  • aryl group denotes a monovalent organic group derived from an aromatic hydrocarbon comprising from 5 to 14 carbon atoms and corresponds for example to an aromatic hydrocarbon ring (such as a phenyl) or two fused aromatic hydrocarbon rings (such than a naphthyl).
  • an aryl group can be substituted or unsubstituted.
  • a “substituted aryl group” denotes a ring or two fused aromatic hydrocarbon(s) rings substituted at the level of one or more of its atoms, by at least one substituent consisting of C 1 to C 18 alkyl groups, hydroxyl group OH, an NH 2 amine or NHR primary amine group with R a C 1 to C 18 alkyl or aryl group, preferably by C 1 to C 18 alkyl groups, such as a methyl group, or the hydroxyl group OH.
  • O-aryl group an aryl group, as defined above, linked to the rest of the molecule via an oxygen atom.
  • each alkyl group is an alkyl group comprising from 1 to 22 carbon atoms (C 1 to C 22 ), preferably from 1 to 18 carbon atoms (C 1 to C 18 ), in particular from 1 to 10 carbon atoms (C 1 to C 10 ) and typically from 1 to 4 carbon atoms (C 1 to C 4 ).
  • At least one of R1, R2, R3 and R4 is an aryl or O-aryl group.
  • at least two of R1, R2, R3 and R4 are aryl or O-aryl groups.
  • R1, R2, R3 and R4 are four aryl groups or O-aryl, such as O-phenyl or is a substituted O-aryl group, such as O-dimethylphenyl.
  • R1, R2, R3 and R4 are phenyl.
  • R1, R2, R3 and R4 are phenyl groups.
  • R1, R2, R3 and R4 are unsubstituted phenyl groups or phenyl groups substituted by at least one methyl group, preferably two methyl groups (such as 2,6-dimethylphenyl).
  • R1, R2, R3 and R4 is an O-phenyl group.
  • R1, R2, R3 and R4 are O-phenyl groups.
  • R1, R2, R3 and R4 are unsubstituted O-phenyl groups or O-phenyl groups substituted by at least one methyl group, preferably substituted by two methyl groups (such as 2,6-dimethylphenyl).
  • a of formula (I) according to the invention can be chosen from an alkylene group, an arylene group or even an aralkylene group.
  • alkylene group denotes a divalent linear saturated hydrocarbon group comprising (unless otherwise stated) from 7 to 36 carbon atoms (C 7 to C 36 ), preferably 7 to 22 carbon atoms (C 7 to C 22 ) , preferably from 7 to 18 carbon atoms (C 7 to C 18 ), or a branched saturated divalent hydrocarbon group comprising (unless otherwise stated) preferably from 6 to 36 carbon atoms (C 6 to C 36 ), preferably 6 to 22 carbon atoms (C 6 to C 22 ), preferably from 6 to 18 carbon atoms (C 6 to C 18 ), in particular from 6 to 12 carbon atoms (C 6 to C 12 ).
  • An alkylene group can be substituted or unsubstituted.
  • the alkylene group substituted by an O-phosphate radical can correspond to a 1,3-(2-ethyl 2-[methyl O-diphenylphosphate]) propyl group.
  • arylene group denotes a monocyclic or polycyclic aromatic carbon group derived from an aromatic hydrocarbon and including at least two anchor points (divalent) which are linked to X1 and X2 arranged on the aromatic ring(s) (the two anchor points can be on the same cycle of the polycyclic group).
  • Each aromatic or polyaromatic ring may comprise from 5 to 14 atoms.
  • An arylene group can correspond, for example, to an aromatic hydrocarbon ring (such as a phenylene), to two fused aromatic hydrocarbon rings (such as a naphthalene) or to two aromatic hydrocarbon rings connected by a covalent bond between two distinct atoms each belonging to one of the cycles.
  • the aromatic rings can optionally be interrupted by one or more heteroatoms which can in particular be chosen from the group consisting of a nitrogen atom, an oxygen atom, and a sulfur atom, preferably consisting by an oxygen atom or a sulfur atom.
  • the arylene group does not include a nitrogen atom internal to the monocyclic or polycyclic aromatic carbon group.
  • the arylene group cannot correspond to, for example, a pyridine or a pyrimidine.
  • Each ring can be unsubstituted or can be substituted to form a "substituted arylene group".
  • the substituted arylene group may correspond to an O-diphenylphosphate radical may correspond to a 1,3-(5 O-[(diphenyl)phosphate)]phenyl group.
  • A is or comprises a monocyclic arylene group such as phenylene, or a derivative of thiophene
  • X 1 and X 2 are preferably diametrically opposed, in particular in position 1,4 when the monocyclic arylene group comprises 6 carbon atoms (as phenylene).
  • A is preferably 1,4-phenyl, optionally substituted.
  • X1 and X2 are not in the ortho or meta position unless at least one and preferably all of the groups among R1, R2, R3 and R3 are O-phenyl groups substituted by two groups methyls, in particular in position 2,6. In this case indeed, X1 and X2 can be in meta position.
  • X 1 and X 2 are in position 1, 3 so as to obtain the group 1,3-( 5 O-[(diphenyl)phosphate)]phenyl.
  • A is or comprises a polycyclic group, or a polyaromatic group comprising for example two fused rings, such as the naphthalene group
  • X 1 and X 2 are preferably diametrically opposed in order to maximize the distance between X 1 and X 2 .
  • X1 and X2 are not in the ortho or para position (in particular in the 1,3 position), but can be in the 1,4 or 2,7 position.
  • group A does not include electron-withdrawing groups or atoms, such as chlorine, carbonyl functions (aldehyde, carboxylic acid, C(O)-O), one or more nitrogens internal to the monocyclic or polycyclic carbon group (pyridine or pyrimidine).
  • Group A therefore cannot be a pyridine or a pyrimidine.
  • polycyclic arylene groups include, in particular, 4,4'-biphenyl, 4,4'-diphenylthioether, 4,4'-diphenylether, 4,4'-diphenylphenylethylidene, 4,4'- dimethyldiphenylmethylidene, 4,4'-diphenylsulfone, 4,4'benzophenone, 2,2'benzophenone, 1,4-naphthalene, 1,3-naphthalene, 2,7-naphthalene, 2,6- anthracene, 9,10-anthracene and phenanthrene.
  • aralkylene group denotes an alkyl group covalently bonded to an aryl group and comprising two (divalent) anchor points located on the alkyl group and/or on the aryl group.
  • an "aralkylene” group may or may not be substituted.
  • aralkylene groups particular mention may be made of the 4,4'-[diphenyl(dimethyl)methylidene] group and the 4,4'-diphenylhexafluoropropane group.
  • A is selected from the group consisting of 1,4-phenyl group, 4,4'-biphenyl group, 4,4'-diphenylthioether group, 4,4'-diphenyl ether group, a 1,3-(5 O-[(diphenyl)phosphate)]phenyl group, a 1,3-(2-ethyl 2-butyl)propyl group, a 1,3-(2-ethyl 2-[methyl O -diphenylphosphate])propyl, a 4,4'-[diphenyl(dimethyl)methylidene] group, a 2,2'-benzophenone group, a 2,7-naphthalene group and a 1,2-ethyl group.
  • A is selected from the group consisting of 1,4-phenyl group, 4,4'-biphenyl group, 4,4'-diphenylthioether group, 4,4'-diphenyl ether group , a 1,3-(5 O-[(diphenyl)phosphate)]phenyl group, a 1,3-(2-ethyl 2-butyl)propyl group, a 1,3-(2-ethyl 2-[methyl O-diphenylphosphate])propyl.
  • A is selected from the group consisting of a 4,4'-diphenylthioether group, a 4,4'-diphenylether group, a 1,3-(5 O-[(diphenyl)phosphate)]phenyl group, a 1,3-(2-ethyl 2-butyl)propyl, a 1,3-(2-ethyl 2-[methyl O-diphenylphosphate])propyl group.
  • A is an optionally substituted alkylene group, a substituted monocyclic arylene group or a polycyclic arylene group in which at least two rings are connected by at least one covalent bond between two distinct atoms each belonging to one of the rings, the covalent bond between the two rings being interrupted by at least one heteroatom or heteroatomic group.
  • halogen atom denotes (unless otherwise indicated) an atom chosen from the group consisting of chlorine, bromine, fluorine and iodine.
  • Each of X 1 and X 2 is independently selected from the group consisting of a single bond, an oxygen atom and a nitrogen atom, preferably a single bond or an oxygen atom.
  • X 1 and X 2 are two oxygen atoms; in other embodiments, X 1 and X 2 are two nitrogen atoms; finally, in last embodiments, one of X 1 and X 2 is an oxygen atom and the other of X 1 and X 2 is a nitrogen atom.
  • X 1 or X 2 is a nitrogen atom, it may be in the form of an NH group or an NR group, R being an alkyl or aryl group.
  • n is an integer between 1 and 5. n can in particular be equal to 1, 2, 3, 4 or 5. In certain embodiments, “n” is equal to 1.
  • the polyphosphorus compounds used according to the invention are aryl diphosphates, that is to say they are such that X 1 and X 2 are two oxygen atoms, and each of R1 , R2, R3 and R4 is an O-aryl group (as defined above), optionally substituted for example by two methyl groups
  • the Applicant has demonstrated the non-toxicity, in particular the non-neurotoxicity, or even the non-reprotoxicity, of the polyphosphorus compounds of formula (I).
  • polyphosphorus compounds in particular aryl diphosphates
  • the polyphosphorus compounds exhibit an anti-wear effectiveness at least as advantageous as that obtained with conventional anti-wear additives such as TCP.
  • said oil and/or said at least one anti-wear additive does not comprise tricresylphosphate or one of its triarylphosphate analogues.
  • an oil or anti-wear agent not comprising tricresylphosphate is meant an oil or an anti-wear agent in which the quantity of tricresyl phosphate, whatever its type of substitution (ortho, meta, para) is below the detection limit of the usual analysis techniques such as gas chromatography coupled with mass spectrometry for example.
  • a suitable technique for the detection of tricresylphosphate in an oil is described for example in De Nola G et al. J. Chromatogr. In 2008; 1200 (2), p.211-216 .
  • the oil used according to the invention or the antiwear agent used according to the invention substantially does not comprise, preferably does not comprise, any aryl monophosphate antiwear additive, whatever be it. In certain embodiments, the oil used according to the invention or the anti-wear agent used according to the invention substantially does not comprise, preferably does not comprise, any organophosphate anti-wear additive other than the additive(s) polyphosphorus compounds.
  • the oil used according to the invention or the anti-wear agent used according to the invention substantially does not comprise, preferably does not comprise, any anti-wear additive other than the compound additive(s) polyphosphates.
  • the anti-wear agent according to the invention of general formula (I) represents, by mass, relative to the total mass of the anti-wear agents present in the oil, from 50% to 100%, preferably from 80% to 100%, and in particular from 90% to 100% and typically 100%.
  • “50% to 100%” means the following values or any interval between these values: 50; 55; 60; 65; 70; 75; 80; 85; 90; 95; 100.
  • the polyphosphorus compounds are present in the oil used in the present invention in an amount such as those conventionally used in the art.
  • they can be used in an amount of 0.1 to 10% by weight, preferably 0.5 to 5% by weight, based on the total weight of the oil.
  • the oil used according to the invention can comprise all the conventional constituents and additives known in the art for this type of oil.
  • the oil used according to the invention preferably comprises an ester base, at least one amine antioxidant, and at least one polyphosphorus anti-wear additive of formula (I).
  • the oil used according to the invention also comprises at least one other additive.
  • the at least one other additive may in particular be chosen from the group consisting of lubricating agents, other anti-wear additives, antioxidants, inhibitors corrosion inhibitors, passivators, viscosity index improvers, detergents or dispersing agents, antifoaming agents, surfactants, blowing agents, tackifying agents, stabilizers, bulking agents, hydrolysis stabilizers, extreme pressure additives, pigments and odor masking agents.
  • Such additives and agents are well known to those skilled in the art and are commonly available commercially.
  • the ester base is a conventional ester base, well known in the art. It is typically a synthetic oil which can be chosen from esters of mono-alcohol or polyol, preferably polyol, with a mono or dicarboxylic acid reactant.
  • Particularly suitable polyols are neo-polyols such as neopentylglycol, 2-ethyl 2-methylpropane 1,3-diol, trimethylolethane, trimethylolpropane, trimethylolbutane and mono-, di- or tri-pentaerythritol.
  • neo-polyols such as neopentylglycol, 2-ethyl 2-methylpropane 1,3-diol, trimethylolethane, trimethylolpropane, trimethylolbutane and mono-, di- or tri-pentaerythritol.
  • any polyol of formula R(OH)p in which R is an optionally substituted linear, branched or cyclic aliphatic hydrocarbon group and p is an integer greater than or equal to 2.
  • the polyol can be chosen from the group consisting of 2-ethyl-1,3-hexanediol, 2- propyl-3,3-heptanediol, 2-butyl-1,3-butanediol, 2,4-dimethyl-1,3-butanediol, ethylene glycol, propylene glycol and polyalkylene glycols.
  • Particularly suitable mono-alcohols are neo-alcohols such as 2,2,4-trimethylpentanol and 2,2-dimethylpropanol.
  • the mono-alcohol can be selected from the group consisting of methyl, butyl, isooctyl and octadecyl alcohols.
  • the carboxylic acid reactant used to form the ester with the polyol or the mono-alcohol can be chosen from optionally substituted aliphatic carboxylic acids comprising one or two carboxylic acid functions or any of their mixtures.
  • a person skilled in the art will know how to select the carboxylic acids to be used depending on the properties desired for the ester and the mono-alcohol or polyol used.
  • ester bases which may be contained in an oil used according to the invention, mention may be made of the monoesters of octyl acetate, of decyl acetate, of octadecyl acetate, of methyl myristate, of stearate butyl, methyl oleate, as well as polyesters of dibutyl phthalate, di-octyl adipate, di-2-ethylhexyl azelate and ethylhexyl sebacate.
  • the polyol ester base oil can be an oil prepared from technical pentaerythritol or trimethylol propane and a mixture of carboxylic acids having 4 to 12 carbon atoms.
  • Technical pentaerythritol is a mixture which comprises approximately 85% to 92% by weight of monopentaerythritol and 8% to 15% by weight of dipentaerythritol.
  • a typical commercial technical pentaerythritol contains about 88% by weight monopentaerythritol and about 12% by weight dipentaerythritol, based on the total weight of said ester base oil.
  • Technical pentaerythritol may also contain a certain amount of tri- and tetra-pentaerythritols which are usually formed as by-products during the production of technical pentaerythritol.
  • Aromatic amine antioxidants are well known in the art and can be monomeric or polymeric aromatic amine antioxidants, belonging to the family of aromatic amines and/or phenolic compounds.
  • the monomeric aromatic amine antioxidants may comprise in particular at least one diphenylamine which is unsubstituted or substituted by at least one hydrocarbon group, at least one naphthylphenylamine which is unsubstituted or substituted by at least one hydrocarbon group, at least one phenothiazine which is unsubstituted or substituted by at least one hydrocarbon group, or any mixture thereof.
  • the hydrocarbon groups substituting the amines are C 1 to C 30 alkyl groups, or styrene.
  • Polymeric aromatic amine antioxidants are the products of polymerization of aromatic amine antioxidants as defined above, either with each other or in the presence of a different comonomer.
  • Examples of oligomeric or polymeric aromatic amino antioxidants which can be used in turbine oils according to the invention are in particular described in the patent applications FR 2 924 122 and WO 2009/071857 .
  • the pathology referred to as "aerotoxic syndrome” is a pathology comprising at least in part the same neurological and reproductive symptoms as those observed in airplanes for aerotoxic syndrome, but which is contracted by exposure to organophosphates, such as tricresylphosphate in installations comprising industrial turbines on the ground such as offshore platforms.
  • prophylaxis of the aerotoxic syndrome is meant the reduction in the occurrence and/or intensity, or even the virtual disappearance or total disappearance, of at least one symptom identified as being linked to an acute or chronic exposure.
  • individuals to aircraft cabin air contaminated with oils such as turbine oils or hydraulic oils under form of gases and/or aerosols.
  • the prophylaxis of the aerotoxic syndrome refers to the reduction in the occurrence, or even the virtual disappearance or total disappearance, of several symptoms, preferably of all the symptoms, identified as being related to an acute or chronic exposure.
  • the symptom may be a neurological, neurobehavioral, neuromotor and/or reproductive related symptom.
  • the symptoms whose occurrence and/or intensity can be reduced by the use according to the invention, mention may be made, for example, of psychological or psychosomatic disorders, chronic fatigue syndrome, severe migraines, multiple chemical sensitivity , mysterious viral infections, sleep disturbances, depression, stress and anxiety.
  • smoke event is meant the acute or chronic, preferably acute, exposure of at least one individual to aircraft cabin air contaminated by oils such as turbine oils or hydraulic oils. in gas and/or aerosol form.
  • oils such as turbine oils or hydraulic oils. in gas and/or aerosol form.
  • a smoke event if significant, can in particular be detected by the perception of an unpleasant characteristic odor, typical of “dirty socks” or “wet dog”. In the most severe cases, for example following the breakage of a bearing in the turbine, smoke or a thick white mist may be visible.
  • Example 1 Study of toxicity and in particular of neurotoxicity
  • the polyphosphorus compounds according to the invention have been studied and compared with other phosphorus compounds, in particular with TCP, in terms of inhibition of cholinesterases, 3D molecular modeling by spherical harmonics, and in terms of QSAR modeling for neurotoxicity and for reprotoxicity.
  • the correlation of the results obtained made it possible to determine a “level of safety” for the use of these compounds as anti-wear agent in oils for aircraft or aero-derived turbines.
  • Acetylthiocholine and butyrylthiocholine iodide, and 5,5-dithiobis(2-nitrobenzoic) acid (DTNB) were purchased from Sigma Aldrich (Steinheim, Germany).
  • Freeze-dried BuChE from equine serum (eqBuChE, Sigma Aldrich) was dissolved in 0.1M phosphate buffer (pH 7.4) to obtain enzyme stock solutions with an enzyme activity of 2.5 units/mL .
  • AChE from human erythrocytes ( hAChE, aqueous buffer solution, ⁇ 500 units/mg protein (BCA), Sigma Aldrich) was diluted in 20 mM HEPES buffer pH 8 with 0.1% Triton X- 100 to obtain an enzyme solution with an enzyme activity of 0.25 units/mL.
  • the percentage inhibition due to the presence of the compounds to be tested was calculated by the following expression v 0 ⁇ vi / v 0 ⁇ 100 in which v i is the level calculated in the presence of the inhibitor, and v 0 is the enzymatic activity.
  • Clusters 1 and 2 Two clusters (clusters 1 and 2) were defined by similarity based in particular on monophosphate compounds known to be neurotoxic and reprotoxic such as tri( ortho -cresyl)phosphate ToCP, tri( meta -cresyl)phosphate, tri( para -cresyl )phosphate, trixylylphosphate and cresylphosphate of saligenin.
  • cluster 5 A third cluster of probably toxic compounds has been identified (cluster 5), including in particular a CMR reprotoxic mutagenic carcinogenic compound such as tri(n-butylphosphate).
  • the training set was defined with chemical structures compiled from several publicly available sources: HSBD (Hazardous Substances Data Bank), EPA (U.S. Environmental Protection Agency), ECHA (European Chemicals Agency), and NTP (National Toxicology program). 247 compounds were classified as neurotoxic compounds, 2214 compounds were classified as reprotoxic compounds, and 1697 compounds were classified as neither neurotoxic nor reprotoxic and forming the nontoxic training set.
  • HSBD Hazardous Substances Data Bank
  • EPA U.S. Environmental Protection Agency
  • ECHA European Chemicals Agency
  • NTP National Toxicology program
  • the validation set was built using compounds from different datasets than those used for the training set. Molecules already present in the training set have been removed.
  • the validation set was composed of 70 compounds classified as neurotoxic compounds, 506 compounds classified as reprotoxic and 256 compounds classified as neither neurotoxic nor reprotoxic and forming the non-toxic validation set.
  • a generalized linear model (GLM) method was chosen to perform a quantitative structure-activity relationship (QSAR) approach.
  • the GLM models were trained separately to discriminate the chemical structures (i) between neurotoxic and non-neurotoxic compounds and (ii) between reprotoxic and non-reprotoxic compounds. This approach resulted in a GLM model with 210 significant descriptors within the training sets.
  • the performance of QSAR models was measured by Receiver Operator Characteristic (ROC) curves and resulted in area under the curve (AUC) values of 0.90 and greater for the prediction of neurotoxicity and reprotoxicity, respectively.
  • ROC Receiver Operator Characteristic
  • the neurotoxicity categories of the compounds in the validation set i.e. the neurotoxic/non-neurotoxic categorization
  • the categories of reprotoxicity of the compounds in the validation set i.e. reprotoxic/non-reprotoxic categorization
  • AUC area under the curve
  • the GLM-based QSAR models were then used to study the polyphosphorus compounds according to the invention.
  • reagent A dialcohol, diamine, or aminoalcohol
  • triethylamine 1 molar equivalent of reagent A (dialcohol, diamine, or aminoalcohol) and 3.35 molar equivalents of triethylamine.
  • the reaction medium is diluted with toluene, approximately 10 volumes relative to reagent A.
  • the reaction medium is heated to between 25-110° C. then using the dropping funnel, 2.2 molar equivalents of phosphate chloride are introduced drop by drop.
  • the triethylamine salt formed is eliminated by filtration then washed with 5 volumes of ethyl acetate.
  • the filtrate is then washed twice with a 0.1N HCl solution, twice with a 0.1N KOH solution and then with water until neutral pH.
  • the organic phase is then dried with MgSO 4 , filtered and then concentrated under reduced pressure.
  • the reaction crude thus obtained is purified either by chromatography on silica gel, or by liquid-liquid extraction, or by precipitation.
  • the products thus obtained are characterized by GC (gas chromatography) or GPC (gel permeation chromatography) chromatography, by 1 H and/or 31 P NMR analyses. The yields obtained vary between 15 and 75%.
  • the results of the tests carried out are presented on the Fig.2. at 9 .
  • the penultimate column corresponds to a risk level score with respect to the safety of these molecules that can be used in oils such as turbine oils and their alleged toxicity in the cabin.
  • a score of 5 corresponds to a very high risk in terms of neurotoxicity and/or reprotoxicity, while scores of 0 or 1 correspond to a very low or non-existent level of risk.
  • the level of risk is determined by the sum of the factors corresponding to each of the risks assessed independently based on the experimental in vitro results of inhibition (IC 50 hAChE and IC 50 eqBuChE), semi-empirical prediction (QSAR neurotoxicity and QSAR reprotoxicity models ), and molecular modeling via spherical harmonics (classification in clusters) and it can range from 0 to 5.
  • a value of 0 indicates an absence of risk, and a value of 5 indicates a very significant multiple risk.
  • a factor of 0 or 1 is assigned depending on whether the value is above or below a threshold. The following thresholds are applied: 15 mg/L for the IC 50 for hAChE, 15 mg/L for the IC 50 for eqBuChE, 0.2% for neurotoxicity, 3% for reprotoxicity.
  • TCP family Compounds of the triarylphosphate type (TCP family) entirely belong to cluster 1 presenting a level of risk varying from 2 to 5 with an average of 3.6 out of the 8 molecules presenting complete characteristics.
  • compounds 1 to 10 which correspond to formula (I) according to the invention present high IC 50 values for hAChE and eqBuChE, belong to a cluster of non-toxic molecules (Cluster 3), present a low level neurotoxicity and reprotoxicity, and therefore a level of risk equal to 0.
  • the compounds of cluster 1 are presented, according to the 3D modeling approach of spherical harmonics, in the form of a "three-bladed helix" on the basis of two perpendicular planes at the level of the center or the core of the molecule, whereas the compounds of cluster 3 have a rather deployed and flattened shape resembling a butterfly shape.
  • the molecules resulting from the work of modeling by the spherical harmonics are represented on the figure 1 . These compounds are therefore non-neurotoxic and non-reprotoxic alternatives to tricresylphosphate and its tri-arylphosphate analogues.
  • the compound I2 described in the patent application WO2010/149690 , exhibits reduced inhibition on butyrylcholinesterase, but is active against acetylcholinesterase.
  • the modeling classifies the latter as part of cluster 1, which confirms the experimental result on acetylcholinesterase.
  • this subassembly is able to/configure for the prophylaxis of the aerotoxic syndrome in particular in the event of a smoke event.
  • This subassembly by virtue of its characteristics, makes it possible to form a turbine oil, for example for aviation, which is suitable for and/or configured to make it possible to increase the level of safety in aviation and in other aero-derivative applications.
  • the other polyphosphorus compounds and in particular the other polyphosphorus compounds used as anti-wear agent in an oil and known from the prior art do not exhibit this new technical effect (i.e.: reducing and/or prevent the neurotoxicity of an oil or for the prophylaxis of the aerotoxic syndrome).
  • the other anti-wear compounds and other organophosphorus compounds known and used in the field of aeronautical lubricants and oils are neurotoxic (such as compounds E, P, I1-3, L, R, and M, the latter being used in aviation hydraulic fluids).

Landscapes

  • Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Oil, Petroleum & Natural Gas (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Emergency Medicine (AREA)
  • Lubricants (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)
  • Medicines Containing Plant Substances (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
EP21725231.1A 2020-05-20 2021-05-18 Utilisation d'huiles comprenant des additifs anti-usure non neurotoxiques Active EP3938478B1 (fr)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
FR2005253A FR3110593B1 (fr) 2020-05-20 2020-05-20 Utilisation d’huiles comprenant des additifs anti-usure non neurotoxiques
US16/878,857 US11230683B2 (en) 2020-05-20 2020-05-20 Use of oils comprising non-neurotoxic anti-wear additives
PCT/EP2021/063200 WO2021233946A1 (fr) 2020-05-20 2021-05-18 Utilisation d'huiles comprenant des additifs anti-usure non neurotoxiques

Publications (2)

Publication Number Publication Date
EP3938478A1 EP3938478A1 (fr) 2022-01-19
EP3938478B1 true EP3938478B1 (fr) 2023-01-18

Family

ID=75904962

Family Applications (1)

Application Number Title Priority Date Filing Date
EP21725231.1A Active EP3938478B1 (fr) 2020-05-20 2021-05-18 Utilisation d'huiles comprenant des additifs anti-usure non neurotoxiques

Country Status (8)

Country Link
US (1) US20230242830A1 (zh)
EP (1) EP3938478B1 (zh)
JP (1) JP2023525929A (zh)
CN (1) CN115916929B (zh)
AU (1) AU2021277484A1 (zh)
BR (1) BR112022023447A2 (zh)
CA (1) CA3179169A1 (zh)
WO (1) WO2021233946A1 (zh)

Family Cites Families (13)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0612837A1 (en) 1993-01-06 1994-08-31 Akzo Nobel N.V. Polyphenylene ether lubricant containing hydrocarbyl bis(dihydrocarbylphosphate) compound
US5560849A (en) 1994-12-23 1996-10-01 Fmc Corporation Synthetic ester lubricant having improved antiwear properties
JP2001306530A (ja) 2000-04-25 2001-11-02 Canon Inc ネットワークシステム、リモートアクセス実行装置、方法、及びコンピュータ読み取り可能な記憶媒体
US20080182770A1 (en) * 2007-01-26 2008-07-31 The Lubrizol Corporation Antiwear Agent and Lubricating Compositions Thereof
FR2924122B1 (fr) 2007-11-28 2009-12-25 Nyco Sa Agent anti-oxydant et/ou anti-corrosion, composition lubrifiante contenant ledit agent et procede pour preparer celui-ci
JP5395453B2 (ja) * 2009-02-16 2014-01-22 Ｊｘ日鉱日石エネルギー株式会社 無段変速機油組成物
FR2946983B1 (fr) * 2009-06-23 2011-12-23 Nyco Agents anti-usure a neurotoxicite reduite
EP2554643A4 (en) 2010-03-26 2013-12-04 Adeka Corp LUBRICANT ADDITION AND LUBRICANT COMPOSITION WITH LUBRICANT ADDITIVE
US8623795B2 (en) * 2010-07-27 2014-01-07 Exxonmobil Research And Engineering Company Method for maintaining antiwear performance of turbine oils containing polymerized amine antioxidants and for improving the deposit formation resistance performance of turbine oils containing monomeric and/or polymeric antioxidants
SG187186A1 (en) 2010-07-27 2013-02-28 Exxonmobil Res & Eng Co Method for improving the deposit formation resistance performance of turbine oils containing amine antioxidants
DE102013003282B4 (de) 2013-02-27 2016-09-29 Fraunhofer-Gesellschaft zur Förderung der angewandten Forschung e.V. Trikresylphosphat-freies Öl und dessen Verwendung
US9200230B2 (en) * 2013-03-01 2015-12-01 VORA Inc. Lubricating compositions and methods of use thereof
WO2015026566A1 (en) 2013-08-20 2015-02-26 Icl-Ip America Inc. Lubricant having improved antiwear properties

Also Published As

Publication number Publication date
WO2021233946A1 (fr) 2021-11-25
AU2021277484A1 (en) 2023-01-05
JP2023525929A (ja) 2023-06-19
EP3938478A1 (fr) 2022-01-19
US20230242830A1 (en) 2023-08-03
CN115916929B (zh) 2024-01-30
CA3179169A1 (fr) 2021-11-25
CN115916929A (zh) 2023-04-04
BR112022023447A2 (pt) 2022-12-20

Similar Documents

Publication Publication Date Title
Mangas et al. New insights on molecular interactions of organophosphorus pesticides with esterases
Abou-Donia et al. Sarin (GB, O-isopropyl methylphosphonofluoridate) neurotoxicity: critical review
Mangas et al. Neurotoxic effects associated with current uses of organophosphorus compounds
Liyasova et al. Exposure to tri-o-cresyl phosphate detected in jet airplane passengers
Takaeidi et al. The effect of date seed (Phoenix dactylifera) extract on paraoxonase and arylesterase activities in hypercholesterolemic rats
US6525090B1 (en) Methods of treating mental diseases, inflammation and pain
Ferchmin et al. 4R-cembranoid protects against diisopropylfluorophosphate-mediated neurodegeneration
DE69726449T2 (de) Aminophosphonsäure-derivate als arzneimittel
Weiner et al. Organophosphate-Induced Delayed Neurotoxicity
Kim et al. Bisretinoid phospholipid and vitamin A aldehyde: shining a light
Gupta et al. Toxicity of organophosphates and carbamates
EP3938478B1 (fr) Utilisation d'huiles comprenant des additifs anti-usure non neurotoxiques
EP4114910B1 (fr) Composés organophosphorés spécifiques comme agents antiusure non neurotoxiques
FR3110593A1 (fr) Utilisation d’huiles comprenant des additifs anti-usure non neurotoxiques
CN106588917B (zh) 咔啉类化合物及其合成方法与抗乙酰胆碱酯酶活性
Johnson The mechanism of delayed neuropathy caused by some organophosphorus esters: using the understanding to improve safety
Schopfer et al. Reaction kinetics of biotinylated organophosphorus toxicant, FP-biotin, with human acetylcholinesterase and human butyrylcholinesterase
US20100036141A1 (en) Processes for the preparation of phosphatides
EP1165573B1 (fr) Composes inhibitant selectivement les lymphocytes t gamma 9 delta 2
US11230683B2 (en) Use of oils comprising non-neurotoxic anti-wear additives
Rajai et al. Formulation and preparation of oil in water cream sample based on OPH enzyme and evaluate enzyme performance in the cream
Mangas Nadal Brain carboxylesterases interacting with organophosphorus compounds: Kinetic characterization and approaches to purification and molecular identification
Moralev et al. Investigation of cholinesterases of different origin by the method of inhibitor analysis (variation of structure of phosphoryl part of alkoxyalkylthiophosphonates)
PT105914A (pt) Utilização de um extracto de bagaço de azeitona inibidor da enzima acetilcolinesterase no tratamento de perturbações colinérgicas
US20050113445A1 (en) Methods of treating mental diseases, inflammation and pain

Legal Events

Date Code Title Description
STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: UNKNOWN

STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: THE INTERNATIONAL PUBLICATION HAS BEEN MADE

PUAI Public reference made under article 153(3) epc to a published international application that has entered the european phase

Free format text: ORIGINAL CODE: 0009012

STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: REQUEST FOR EXAMINATION WAS MADE

17P Request for examination filed

Effective date: 20210809

AK Designated contracting states

Kind code of ref document: A1

Designated state(s): AL AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HR HU IE IS IT LI LT LU LV MC MK MT NL NO PL PT RO RS SE SI SK SM TR

GRAJ Information related to disapproval of communication of intention to grant by the applicant or resumption of examination proceedings by the epo deleted

Free format text: ORIGINAL CODE: EPIDOSDIGR1

INTG Intention to grant announced

Effective date: 20220624

INTG Intention to grant announced

Effective date: 20220708

INTG Intention to grant announced

Effective date: 20220708

INTC Intention to grant announced (deleted)
GRAP Despatch of communication of intention to grant a patent

Free format text: ORIGINAL CODE: EPIDOSNIGR1

STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: GRANT OF PATENT IS INTENDED

INTG Intention to grant announced

Effective date: 20220824

GRAS Grant fee paid

Free format text: ORIGINAL CODE: EPIDOSNIGR3

GRAA (expected) grant

Free format text: ORIGINAL CODE: 0009210

STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: THE PATENT HAS BEEN GRANTED

AK Designated contracting states

Kind code of ref document: B1

Designated state(s): AL AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HR HU IE IS IT LI LT LU LV MC MK MT NL NO PL PT RO RS SE SI SK SM TR

DAV Request for validation of the european patent (deleted)
DAX Request for extension of the european patent (deleted)
REG Reference to a national code

Ref country code: GB

Ref legal event code: FG4D

Free format text: NOT ENGLISH

REG Reference to a national code

Ref country code: CH

Ref legal event code: EP

REG Reference to a national code

Ref country code: DE

Ref legal event code: R096

Ref document number: 602021001275

Country of ref document: DE

REG Reference to a national code

Ref country code: AT

Ref legal event code: REF

Ref document number: 1544699

Country of ref document: AT

Kind code of ref document: T

Effective date: 20230215

Ref country code: IE

Ref legal event code: FG4D

Free format text: LANGUAGE OF EP DOCUMENT: FRENCH

REG Reference to a national code

Ref country code: LT

Ref legal event code: MG9D

REG Reference to a national code

Ref country code: NL

Ref legal event code: MP

Effective date: 20230118

REG Reference to a national code

Ref country code: AT

Ref legal event code: MK05

Ref document number: 1544699

Country of ref document: AT

Kind code of ref document: T

Effective date: 20230118

P01 Opt-out of the competence of the unified patent court (upc) registered

Effective date: 20230516

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: NL

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20230118

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: RS

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20230118

Ref country code: PT

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20230518

Ref country code: NO

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20230418

Ref country code: LV

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20230118

Ref country code: LT

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20230118

Ref country code: HR

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20230118

Ref country code: ES

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20230118

Ref country code: AT

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20230118

PGFP Annual fee paid to national office [announced via postgrant information from national office to epo]

Ref country code: DE

Payment date: 20230313

Year of fee payment: 3

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: SE

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20230118

Ref country code: PL

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20230118

Ref country code: IS

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20230518

Ref country code: GR

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20230419

Ref country code: FI

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20230118

REG Reference to a national code

Ref country code: DE

Ref legal event code: R097

Ref document number: 602021001275

Country of ref document: DE

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: SM

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20230118

Ref country code: RO

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20230118

Ref country code: EE

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20230118

Ref country code: DK

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20230118

Ref country code: CZ

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20230118

PLBE No opposition filed within time limit

Free format text: ORIGINAL CODE: 0009261

STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: NO OPPOSITION FILED WITHIN TIME LIMIT

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: SK

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20230118

26N No opposition filed

Effective date: 20231019

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: MC

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20230118

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: SI

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20230118

Ref country code: MC

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20230118

Ref country code: LU

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20230518

REG Reference to a national code

Ref country code: IE

Ref legal event code: MM4A

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: IE

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20230518

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: IE

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20230518

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: IT

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20230118

PGFP Annual fee paid to national office [announced via postgrant information from national office to epo]

Ref country code: BE

Payment date: 20240214

Year of fee payment: 4

Ref country code: FR

Payment date: 20240209

Year of fee payment: 4