WO2015011177A1 - Use of the enantiomer levomedetomidine as inhibitor for marine biofouling of surfaces - Google Patents

Use of the enantiomer levomedetomidine as inhibitor for marine biofouling of surfaces Download PDF

Info

Publication number
WO2015011177A1
WO2015011177A1 PCT/EP2014/065793 EP2014065793W WO2015011177A1 WO 2015011177 A1 WO2015011177 A1 WO 2015011177A1 EP 2014065793 W EP2014065793 W EP 2014065793W WO 2015011177 A1 WO2015011177 A1 WO 2015011177A1
Authority
WO
WIPO (PCT)
Prior art keywords
levomedetomidine
medetomidine
coating composition
surface coating
composition according
Prior art date
Application number
PCT/EP2014/065793
Other languages
English (en)
French (fr)
Inventor
Dan Isaksson
Lena MÅRTENSSON LINDBLAD
Original Assignee
I-Tech Ab
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by I-Tech Ab filed Critical I-Tech Ab
Priority to JP2016528515A priority Critical patent/JP6621407B2/ja
Priority to SG11201510548VA priority patent/SG11201510548VA/en
Priority to CN201480041073.3A priority patent/CN105473669A/zh
Priority to KR1020167002087A priority patent/KR101831536B1/ko
Publication of WO2015011177A1 publication Critical patent/WO2015011177A1/en

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
    • C09D—COATING COMPOSITIONS, e.g. PAINTS, VARNISHES OR LACQUERS; FILLING PASTES; CHEMICAL PAINT OR INK REMOVERS; INKS; CORRECTING FLUIDS; WOODSTAINS; PASTES OR SOLIDS FOR COLOURING OR PRINTING; USE OF MATERIALS THEREFOR
    • C09D5/00—Coating compositions, e.g. paints, varnishes or lacquers, characterised by their physical nature or the effects produced; Filling pastes
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/48—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with two nitrogen atoms as the only ring hetero atoms
    • A01N43/50—1,3-Diazoles; Hydrogenated 1,3-diazoles
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08K—Use of inorganic or non-macromolecular organic substances as compounding ingredients
    • C08K5/00—Use of organic ingredients
    • C—CHEMISTRY; METALLURGY
    • C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
    • C09D—COATING COMPOSITIONS, e.g. PAINTS, VARNISHES OR LACQUERS; FILLING PASTES; CHEMICAL PAINT OR INK REMOVERS; INKS; CORRECTING FLUIDS; WOODSTAINS; PASTES OR SOLIDS FOR COLOURING OR PRINTING; USE OF MATERIALS THEREFOR
    • C09D5/00—Coating compositions, e.g. paints, varnishes or lacquers, characterised by their physical nature or the effects produced; Filling pastes
    • C09D5/16—Antifouling paints; Underwater paints
    • C09D5/1606—Antifouling paints; Underwater paints characterised by the anti-fouling agent
    • C09D5/1612—Non-macromolecular compounds
    • C09D5/1625—Non-macromolecular compounds organic
    • C—CHEMISTRY; METALLURGY
    • C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
    • C09D—COATING COMPOSITIONS, e.g. PAINTS, VARNISHES OR LACQUERS; FILLING PASTES; CHEMICAL PAINT OR INK REMOVERS; INKS; CORRECTING FLUIDS; WOODSTAINS; PASTES OR SOLIDS FOR COLOURING OR PRINTING; USE OF MATERIALS THEREFOR
    • C09D7/00—Features of coating compositions, not provided for in group C09D5/00; Processes for incorporating ingredients in coating compositions
    • C09D7/40—Additives
    • C09D7/66—Additives characterised by particle size
    • C09D7/67—Particle size smaller than 100 nm
    • C—CHEMISTRY; METALLURGY
    • C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
    • C09D—COATING COMPOSITIONS, e.g. PAINTS, VARNISHES OR LACQUERS; FILLING PASTES; CHEMICAL PAINT OR INK REMOVERS; INKS; CORRECTING FLUIDS; WOODSTAINS; PASTES OR SOLIDS FOR COLOURING OR PRINTING; USE OF MATERIALS THEREFOR
    • C09D7/00—Features of coating compositions, not provided for in group C09D5/00; Processes for incorporating ingredients in coating compositions
    • C09D7/40—Additives
    • C09D7/66—Additives characterised by particle size
    • C09D7/68—Particle size between 100-1000 nm
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08K—Use of inorganic or non-macromolecular organic substances as compounding ingredients
    • C08K3/00—Use of inorganic substances as compounding ingredients
    • C08K3/18—Oxygen-containing compounds, e.g. metal carbonyls
    • C08K3/20—Oxides; Hydroxides
    • C08K3/22—Oxides; Hydroxides of metals
    • C08K2003/2217—Oxides; Hydroxides of metals of magnesium
    • C08K2003/222—Magnesia, i.e. magnesium oxide
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08K—Use of inorganic or non-macromolecular organic substances as compounding ingredients
    • C08K3/00—Use of inorganic substances as compounding ingredients
    • C08K3/18—Oxygen-containing compounds, e.g. metal carbonyls
    • C08K3/20—Oxides; Hydroxides
    • C08K3/22—Oxides; Hydroxides of metals
    • C08K2003/2227—Oxides; Hydroxides of metals of aluminium
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08K—Use of inorganic or non-macromolecular organic substances as compounding ingredients
    • C08K3/00—Use of inorganic substances as compounding ingredients
    • C08K3/18—Oxygen-containing compounds, e.g. metal carbonyls
    • C08K3/20—Oxides; Hydroxides
    • C08K3/22—Oxides; Hydroxides of metals
    • C08K2003/2237—Oxides; Hydroxides of metals of titanium
    • C08K2003/2241—Titanium dioxide
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08K—Use of inorganic or non-macromolecular organic substances as compounding ingredients
    • C08K3/00—Use of inorganic substances as compounding ingredients
    • C08K3/18—Oxygen-containing compounds, e.g. metal carbonyls
    • C08K3/20—Oxides; Hydroxides
    • C08K3/22—Oxides; Hydroxides of metals
    • C08K2003/2248—Oxides; Hydroxides of metals of copper
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08K—Use of inorganic or non-macromolecular organic substances as compounding ingredients
    • C08K3/00—Use of inorganic substances as compounding ingredients
    • C08K3/18—Oxygen-containing compounds, e.g. metal carbonyls
    • C08K3/20—Oxides; Hydroxides
    • C08K3/22—Oxides; Hydroxides of metals
    • C08K2003/2296—Oxides; Hydroxides of metals of zinc
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08K—Use of inorganic or non-macromolecular organic substances as compounding ingredients
    • C08K3/00—Use of inorganic substances as compounding ingredients
    • C08K3/34—Silicon-containing compounds
    • C08K3/36—Silica
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08K—Use of inorganic or non-macromolecular organic substances as compounding ingredients
    • C08K5/00—Use of organic ingredients
    • C08K5/16—Nitrogen-containing compounds
    • C08K5/34—Heterocyclic compounds having nitrogen in the ring
    • C08K5/3442—Heterocyclic compounds having nitrogen in the ring having two nitrogen atoms in the ring
    • C08K5/3445—Five-membered rings
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08K—Use of inorganic or non-macromolecular organic substances as compounding ingredients
    • C08K9/00—Use of pretreated ingredients
    • C08K9/12—Adsorbed ingredients, e.g. ingredients on carriers

Definitions

  • the present invention generally relates to the inhibition of marine bio fouling of surfaces in marine environments, specifically to the use of substances as an agent for prevention of marine biofouling of solid surfaces. More specifically, the invention concerns the use of a specific form of medetomidine, acting as such agent.
  • Serotonine antagonists such as Cyproheptadine and Ketanserin
  • dopamine agonists such as R (-)-NPA and (+)- Bromocriptine
  • Another pharmacological agent that has proven to be an efficient inhibitor with regards to barnacle settlement is the highly selective alpha2-adrenoreceptor agonist Medetomidine or ( ⁇ )-4(5)-[l-(2,3-dimethylphenyl)ethyl]-lH- imidazole.
  • the larval settlement is impeded already at low concentrations, 1 nM to 10 nM.
  • Medetomidine belongs to a new class of alpha2 -receptor agonists containing a 4-substituted imidazole ring with, high selectivity towards 2-adrenoreceptors.
  • Receptors affected by catecholamine neurotransimitters, such as norepinephrine and epinephrine, are termed adrenergic receptors (or adrenoceptors) and can be divided into alpha- and beta- subclasses.
  • alpha2-adrenoreceptors are involved in the autoinhibitory mechanism of neurotransmitter release and play a significant part in the regulation of hypertension (high blood pressure), bradycardia (reduced heartbeat rate) and even regulation of alertness and analgesia (reduced sensitivity to pain).
  • WO00/42851 discloses use of medetomidine as an agent for the inhibition of marine bio fouling on a surface.
  • WO2006/096129 discloses a method and use in an antifouling paint that impede settlement of barnacles on aquatic structures, using medetomidine bound to a sulfonated, acid sulphate ester, phosphonic acid, carboxylic acid or acid phosphate ester modified polymer backbone such as polystyrene or acrylate polymers.
  • the present invention solves the issue of reducing effects in humans of the medetomidine present in various products used for prevention of marine biofouling.
  • a primary object of the present invention is to use a specific enantiomeric form of
  • Another object of the invention is to use a composition of the enantiomeric forms of medetomidine with less effects in humans, as a substance acting as an agent for antifouling in marine environments, which differ from the racemic mixture (1 : 1) in such a way that the levomedetomidine is the dominant enantiomeric form.
  • Another object of the invention is to use a composition of the mixture of the two enantiomeric forms, where the levomedetomidine constitute at least 90, 80, 70, 60, 50% of the mixture, as a substance acting as an agent for antifouling in marine environments, which has less effects in humans than the racemic mixture of medetomidine.
  • a range e.g., a range from x to y
  • the measurable value is a range from about x to about y, or any range therein, such as about xi to about y l s etc. It will be further understood that the terms
  • the present invention generally relates to the inhibition of marine bio fouling of surfaces in marine environments, specifically to the use of substances as an agent for prevention of marine biofouling of solid surfaces and compositions for coating of surfaces exposed to marine environments. More specifically, the invention concerns the use of a specific enantiomeric form of medetomidine, namely levomedetomidine (figure 1), acting as such agent.
  • the invention thus relates to a surface coating composition comprising medetomidine, wherein the composition comprises a relatively higher amount of
  • the surface coating composition may further comprise a binder phase, pigments, and a suitable solvent, as known in the art of surface coating compositions.
  • the surface coating composition may be a paint for marine use, such as a self-polishing paint composition for marine use.
  • medetomidine The a2-adrenoceptor agonist medetomidine is known to result in sedation and locomotor inhibition when given to mammals and fish (Sinclair, 2003; Ruuskanen et al., 2005). The opposite was found in cyprid larvae since medetomidine (10 nM) strongly enhanced kicking of the cyprid larvae, with more than 100 kicks per minute (Mol Pharmacol 78:237-248, 2010). Thus, medetomidine has different physiological effects in vertebrates and invertebrates and instead demonstrate hyperactivity than sedation/locomotor inhibition as in vertebrates.
  • Medetomidine induces a locomotor activation response in barnacle cyprids, which is the most likely cause of settling inhibition. More specifically the increase in the movement (kicking) of the anterior appendices (legs) is suggested to be the anti-settling mode of action of medetomidine.
  • Medetomidine ( ⁇ ) 4-[l-(2, 3-Dimethylphenyl) ethyl] -lH-imidazole, first described in EP 72615, is a racemic mixture of equal proportions of two optical enantiomers, the levo- and dextro-rotatory optical isomers (MacDonald et al., 1991; Savola and Virtanen, 1991) with generic names levomedetomidine and dexmedetomidine respectively.
  • WO 2011/070069 disclose a process for the preparation of the racemic mixture of medetomidine (( ⁇ )4-[l-(2, 3- dimethylphenyl) ethyl] -lH-imidazole) and related intermediates. Many of the previous synthesis use expensive 4-substituted imidazole derivatives as starting material, however in WO 2011/070069 the synthesis is made from affordable commercially available starting materials, where the imidazole ring is instead built up during the
  • Medetomidine has been studied in human clinical trials and has also been used as anaesthetics for animals with the (S)-enantiomer, dexmedetomidine, being the active component.
  • Levomedetomidine on the other hand has no apparent sedative or analgesic effect (Kuusela et al. J Vet Pharamacol Ther 23(1), 15-20, 2000), however higher dosage of levomedetomidine indicated reduced sedative and analgesic effects associated with administration of dexmedetomidine (Kuusela et al. Am J Vet Res 62(4), 616-621, 2001).
  • dexmedetomidine alone for sedative and analgesic effect should be beneficial over administration of the racemic mixture of medetomidine, which contain equal amounts of dexmedetomidine and levomedetomidine.
  • pure preparations of dexmedetomidine have been justified and are marketed under various names such as Dexdor® (Orion PharmaAB).
  • Dexdor is indicated for the light to moderate sedation of adult ICU patients, EMA/789509/2011 Committee for Medicinal Products for Human Use (CHMP)) and Dexdomitor® (Orion Pharma AB) for veterinary applications.
  • CHMP EMA/789509/2011 Committee for Medicinal Products for Human Use
  • Dexdomitor® Orion Pharma AB
  • Such pure preparations are performed by separation and purification of the dexmedetomidine from racemic mixtures, where levomedetomidine is considered the main impurity of the pure dexmedetomidine.
  • racemic mixture of medetomidine or ( ⁇ )-4(5)-[l-(2,3- dimethylphenyl)ethyl]-lH-imidazole has previously been shown to be an efficient inhibitor with regards to barnacle settlement.
  • the racemic mixture and both of the enantiomeric forms (dexmedetomidine and
  • levomedetomidine of medetomidine has similar inhibitory effects. This is contrary to other well documented usage of only one of the specific enantiomeric forms of a molecule e.g. in drugs in the pharmaceutical industry, including medetomidine, where only one of the enantiomeric forms is active and the other enantiomeric form is inactive. It is especially unexpected and remarkable effect that levomedetomidine has a similar inhibitory effect. Inhibiton of settlement of the barnacle cyprid larvae is described in example 1 and figure 2a and 2b below.
  • a preferred embodiment of the invention is therefore to use levomedetomidine as an active ingredient/component in marine paint applications to prevent bio fouling on various surfaces that are submerged in marine environments.
  • levomedetomidine Since levomedetomidine has been documented to have a very limited effect on humans and animals compared to the racemic mixture of medetomidine and the other enantiomer dexmedetomidine, the use of the enantiomeric form levomedetomidine will provide a solution for end-products with less effects in humans. Any risk of handling any product(s) containing medetomidine or dexmedetomidme during e.g manufacture, transport, storage and applications for end-users, such as personnel involved in paint applications, is thereby reduced by the use of levomedetomidine instead. Also, the metabolism of the
  • levomedetomidine has been shown to be more rapid in mammals, which is beneficial compared to the use of the racemic mixture of medetomidine or the enantiomer
  • dexmedetomidme may have a beneficial pricing level as it is considered an impurity and thus discarded when processing and purifying the enantiomer dexmedetomidme for clinical applications.
  • the invention herein also helps in solving the problem of handling the waste from the production of dexmedetomidme.
  • Purification of dexmedetomidme is disclosed in WO2013069025, Process for the preparation of dexmedetomidme, where the dexmedetomidme is prepared in high yield and with enantiomeric purity of more than 99%. A similar approach using the same methodology would of course be applicable for the preparation of levomedetomidine instead.
  • levomedetomidine as a medicament for use in preventing or treating conditions associated with overexpression or hypersenzitation of adrenergic a-2 receptors as described in
  • a preferred embodiment of the present invention is therefore to use a specific enantiomeric form of medetomidine, levomedetomidine, individually and separately as a substance acting as an agent for antifouling in marine environments with less effect in humans.
  • Another preferred embodiment of the invention is to use a composition of the enantiomeric forms of medetomidine with less effect in humans, as a substance acting as an agent for antifouling in marine environments, which differ from the racemic mixture (1 : 1) in such a way that the levomedetomidine is the dominant enantiomeric form.
  • Another preferred embodiment of the invention is to use a composition of the mixture of the two enantiomeric forms, where the levomedetomidine constitute at least 90, 80, 70, 60, 50% of the mixture, as a substance acting as an agent for antifouling in marine environments, with less effect in humans than the racemic mixture of medetomidine.
  • a related preferred embodiment of the invention is to employ a combination of a biocide- polymer complex as additives in a self-polishing paint for controlled release purposes as disclosed in WO2006/096129.
  • a preferred embodiment relates to a method and the use of an antifouling paint that specifically and efficiently impede settlement of, for example, barnacles on aquatic structures, using levomedetomidine, bound to a sulfonated, acid sulphate ester, phosphonic acid, carboxylic acid or acid phosphate ester modified polymer backbone such as polystyrene or acrylate polymers.
  • Another preferred object of the invention is to create an antifouling method requiring decreased biocide dose, through a proper control of the release of the antifouling substance from the paint film.
  • levomedetomidine molecule bound to e.g. Polystyrene-block-poly(ethylene-ran-butylene)- block-polystyrene will create a slow leakage of the active compound from the paint into the water in a controlled fashion.
  • the levomedetomidine-polymer ion pair will only be dissolved at the actual film surface, when in contact with water, resulting in the release of
  • a surface-active compound in antifouling paint is thus likely to have a greater impact on settlements of barnacle larvae than a compound leaking out of the paint into the water since surface activity will increase the concentration close to the surface.
  • a controlled release of antifouling agents may also utilize nanoparticles consisting of CuO, ZnO, Ti0 2 , A1 2 0 3 , Si0 2 , MgO, preferably copper(II)- and zinc(II)oxide formulated into nanoparticle sizes. Due to the large specific surface area (ratio between surface area and particle volume), the nanoparticles contribute to adsorb the antifouling agent, e.g. levomedetomidine, or other antifouling agents such as Chlorothalonil, Dichlofluanid, SeaNine, Irgarol, Diuron, and Tolylfluanid.
  • the CuO and ZnO particle generates specific surface areas of 29 and 21 m 2 .g-1, respectively. This allows the possibility to design a paint system containing low amounts of both levomedetomidine and nanoparticles in order to restrict the diffusional motion of antifouling agent through the paint film. When substituting a nanoparticle with a micrometer-sized particle, the adsorption appeared to be negligible. These results show the importance of large surface areas with regard to adsorption of antifouling agents onto particle surfaces.
  • the antifouling agents e.g. levomedetomidine bound to nanosized metal oxide is a compound that leaks out of the paint into water in a controlled fashion.
  • the antifouling agent bound to nanosized metal oxide thus has excellent dispersion stability because of its large size, compared to the antifouling agent particle alone.
  • size property the antifouling agent-metal oxide particles are stationary in a paint film and do not leak out into the water.
  • concentration of antifouling particles in the paint film remains homologous during "lifetime”.
  • concentration of antifouling agent will be equal in the entire paint film.
  • Another consequence is that the total surface area of nanoparticles is enough to adsorb all of the antifouling agent and there will be no waste of the biocide.
  • Medetomidine has a specific action on barnacle cyprids but no effect of algal growth due to the target protein being lacking within algae.
  • Algicides are often invented as herbicides and are photosynthesis-inhibitors such as
  • DIURONTM (3-(3,4-dichlorophenyl)-l,l-dimethylurea) by DuPont Agricultural Products Wilmington, Del, USA
  • IRGAROLTM 1051 (2-methylthio-4-tert-butylamino-6- cyclopropylamino-s-triziane) by Ciba Inc, Tarrytown, N.Y., USA.
  • a more common strategy is to use fungicides such as zincpyrithione (Zinc, bis(l-hydroxy-2(lH)-pyridinethionato- 0,S)— , (T-4)-) by Arc Chemicals Inc and copperpyrithione (Copper, bis(l-hydroxy-2(lH)- pyridinethionato-0,S)— , (T-4)-) by Arc Chemicals Inc, tolylfluanide (N-
  • a third strategy is to use toxic compounds but with short half life such as SEANINETM (4,5-dichloro-2-n-octyl-3(2H)-isothiazolone) by Rohm and Haas Company, Philadelphia, Pa., USA and related compounds.
  • SEANINETM 4,5-dichloro-2-n-octyl-3(2H)-isothiazolone
  • the principle of the method of the invention would thus include the use of substances or agents which disturb or block the nerve signaling to the target cells in the cyprid larvae, in the present case
  • levomedetomidine in combination with anti-algae compounds, such as zinc- and copper pyrothion, fungicides like tolyfluanide and diclofluanide, herbicides such as Diuron(TM) and IrgarolTM, or more general biocides such as SeaNineTM or EcoNeaTM (2-(p- chlorophenyl)-3- cyano-4-bromo-5-trifluoromethyl) by Janssen Pharmaceutical, Titusville, NJ, USA.
  • a preferred embodiment of the invention is to add the substances in a base polymer paint, which is applied on ship hulls for example.
  • the invention comprise applying a protective coating to a substrate, said coating containing a) a substance that interferes with barnacle bio fouling comprising levomedetomidine, and b) an algicide.
  • algicides include copper, zinc and other metals, Diuron (3-(3,4- dichlorophenyl)-l,l-dimethylurea), Irgarol 1051TM (2-methylthio- 4-tert-butylamino-6- cyclopropylamino-s-triazine), zincpyrothione (Zinc, bis(l- hydroxy-2(lH)-pyridinethionato- 0,S)-, (T-4)-), copperpyrothione (Copper, bis(l- hydroxy-2(lH)-pyridinethionato-0,S)-, (T-4)- ), diclofluanide (N' -dimethyl-N- phenylsulphamide), zinebTM (zinc
  • ZinramTM ZinramTM (Zinc bis(dimethylthiocarbamates)
  • maneb manganese ethylene bisdithiocarbamate
  • quaternary ammonium compounds SeaNineTM (4,5-dichloro-2- n-octyl-3(2H)-isothiazolone), and EcoNeaTM (2-(p-chlorophenyl)- 3-cyano-4-bromo-5- trifluoromethy 1) .
  • medetomidine “dexmedetomidine”, and “levomedetomidine” as used herein include salts and solvates thereof unless specifically stated otherwise.
  • Acceptable salts of levomedetomidine include acid addition salts and base addition salts.
  • Such salts may be formed by conventional means, for example by reaction of a free acid or a free base form of a compound of the invention with one or more equivalents of an appropriate acid or base, optionally in a solvent, or in a medium in which the salt is insoluble, followed by removal of said solvent, or said medium, using standard techniques (e.g. in vacuo or by freeze-drying).
  • Salts may also be prepared by exchanging a counter-ion of a compound of the invention in the form of a salt with another counter-ion, for example using a suitable ion exchange resin.
  • a suitable ion exchange resin for example, e.g. solvates, prodrugs etc.
  • Preferable solvents are, but not limited to; n-butanol, iso-butanol, methanol, benzyl alcohol and l-methoxy-2-propanol.
  • the enantiomers of medetomidine may be isolated and separated from each other by separation of racemic or other mixtures of the enantiomers using chiral resolution or chiral column chromatography known in the art.
  • the desired enantiomer may be prepared by enantio selective synthesis, also called chiral synthesis or asymmetric synthesis, which is defined as a chemical reaction (or reaction sequence) in which one or more new elements of chirality are formed in a substrate molecule and which produces the
  • the protective coating further comprises a marine paint.
  • the settlement assay was performed using Petri dishes containing 5 ml filtered sea water with the salinity of 32 ⁇ l%o. Approximately 20 barnacle cyprid larvae were added to each

Landscapes

  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Wood Science & Technology (AREA)
  • Organic Chemistry (AREA)
  • Materials Engineering (AREA)
  • Nanotechnology (AREA)
  • Health & Medical Sciences (AREA)
  • Plant Pathology (AREA)
  • Agronomy & Crop Science (AREA)
  • Polymers & Plastics (AREA)
  • Pest Control & Pesticides (AREA)
  • Medicinal Chemistry (AREA)
  • Dentistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Zoology (AREA)
  • Environmental Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Agricultural Chemicals And Associated Chemicals (AREA)
  • Paints Or Removers (AREA)
PCT/EP2014/065793 2013-07-24 2014-07-23 Use of the enantiomer levomedetomidine as inhibitor for marine biofouling of surfaces WO2015011177A1 (en)

Priority Applications (4)

Application Number Priority Date Filing Date Title
JP2016528515A JP6621407B2 (ja) 2013-07-24 2014-07-23 表面の海洋生物付着に対する阻害剤としてのエナンチオマーレボメデトミジンの使用
SG11201510548VA SG11201510548VA (en) 2013-07-24 2014-07-23 Use of the enantiomer levomedetomidine as inhibitor for marine biofouling of surfaces
CN201480041073.3A CN105473669A (zh) 2013-07-24 2014-07-23 作为抑制剂的对映异构体左旋美托咪啶在海洋生物污损表面附着的应用
KR1020167002087A KR101831536B1 (ko) 2013-07-24 2014-07-23 표면의 해양 바이오파울링 억제제로서 거울상 이성질체 레보메데토미딘의 용도

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US201361857910P 2013-07-24 2013-07-24
US61/857,910 2013-07-24

Publications (1)

Publication Number Publication Date
WO2015011177A1 true WO2015011177A1 (en) 2015-01-29

Family

ID=51292926

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/EP2014/065793 WO2015011177A1 (en) 2013-07-24 2014-07-23 Use of the enantiomer levomedetomidine as inhibitor for marine biofouling of surfaces

Country Status (5)

Country Link
JP (2) JP6621407B2 (enrdf_load_stackoverflow)
KR (1) KR101831536B1 (enrdf_load_stackoverflow)
CN (1) CN105473669A (enrdf_load_stackoverflow)
SG (1) SG11201510548VA (enrdf_load_stackoverflow)
WO (1) WO2015011177A1 (enrdf_load_stackoverflow)

Cited By (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2016177884A1 (en) * 2015-05-06 2016-11-10 I-Tech Ab Medetomidine for use in controlling parasitic crustaceans on fish
DE202018001813U1 (de) 2018-04-09 2018-05-22 I-Tech Ab Löslicher Behälter für Beschichtungskomponenten
JP2018080275A (ja) * 2016-11-17 2018-05-24 中国塗料株式会社 防汚塗料組成物、防汚塗膜およびこれらの用途
EP3339387A1 (de) 2016-12-22 2018-06-27 Evonik Degussa GmbH Verbindungen auf basis von addukten mit isocyanaten für beschichtungszusammensetzungen
US10519327B2 (en) 2018-04-20 2019-12-31 Redjak, L.L.C. Methods and coatings for protecting surfaces from bio-fouling species
US10689527B2 (en) 2018-04-20 2020-06-23 Redjak, L.L.C Methods and coatings for protecting surfaces from bio-fouling species
US20200200928A1 (en) * 2018-12-19 2020-06-25 Pgs Geophysical As Medetomidine Compositions Having Improved Anti-Fouling Characteristics
US10829649B2 (en) 2018-04-20 2020-11-10 Redjak, L.L.C. Methods and coatings for protecting surfaces from bio-fouling species
WO2024047144A1 (en) * 2022-09-01 2024-03-07 I-Tech Ab Composition protecting wood against marine woodborers
EP4417056A4 (en) * 2021-10-13 2024-12-18 Daikin Industries, Ltd. COMPOSITION FOR FIGHTING HARMFUL ORGANISMS

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR101831536B1 (ko) * 2013-07-24 2018-04-04 아이-테크 에이비 표면의 해양 바이오파울링 억제제로서 거울상 이성질체 레보메데토미딘의 용도

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2006096129A1 (en) * 2005-03-11 2006-09-14 I-Tech Method and use of acidified modified polymers to bind biocides in paints
WO2010069767A1 (en) * 2008-12-19 2010-06-24 Ppg B.V. Resin composition, antifouling coating comprising barnacle antifoulant and processes of production thereof
WO2011070069A1 (en) * 2009-12-09 2011-06-16 I-Tech Ab Process for preparation of medetomidine

Family Cites Families (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH07315282A (ja) * 1994-05-26 1995-12-05 Daikyo Manabu Ｆｒｐ船体の防汚塗装方法および防汚ｆｒｐ船体
GB9521680D0 (en) 1995-10-23 1996-01-03 Orion Yhtymo Oy New use of imidazole derivatives
AR015744A1 (es) 1998-04-01 2001-05-16 Orion Corp Uso de dexmedetomidina para sedacion en terapia intensiva
US20060189686A1 (en) * 2005-01-27 2006-08-24 Lena Martensson Use of a combination of substances to prevent biofouling organisms
US7311766B2 (en) * 2005-03-11 2007-12-25 I-Tech Ab Method and use of nanoparticles to bind biocides in paints
US7670416B2 (en) * 2005-08-04 2010-03-02 I-Tech Ab Use of a combination of substances to prevent biofouling organisms
US20110274763A1 (en) * 2009-05-19 2011-11-10 Nyden Bo Magnus Slow releasing microcapsules and microspheres containing an active substance
CN101671305A (zh) * 2009-09-29 2010-03-17 北京华禧联合科技发展有限公司 一种拆分美托咪定的左旋及右旋对映体的方法
KR101581995B1 (ko) * 2010-03-23 2015-12-31 주고꾸 도료 가부시키가이샤 방오도료 조성물 및 그의 용도
JPWO2012176809A1 (ja) * 2011-06-23 2015-02-23 中国塗料株式会社 二液型加水分解型防汚塗料組成物、防汚塗膜および防汚基材の製造方法
KR101831536B1 (ko) * 2013-07-24 2018-04-04 아이-테크 에이비 표면의 해양 바이오파울링 억제제로서 거울상 이성질체 레보메데토미딘의 용도

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2006096129A1 (en) * 2005-03-11 2006-09-14 I-Tech Method and use of acidified modified polymers to bind biocides in paints
WO2010069767A1 (en) * 2008-12-19 2010-06-24 Ppg B.V. Resin composition, antifouling coating comprising barnacle antifoulant and processes of production thereof
WO2011070069A1 (en) * 2009-12-09 2011-06-16 I-Tech Ab Process for preparation of medetomidine

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
BELLAS J ET AL: "Effects of medetomidine, a novel antifouling agent, on the burrowing bivalve Abra nitida (Muller)", CHEMOSPHERE, PERGAMON PRESS, OXFORD, GB, vol. 65, no. 4, 1 October 2006 (2006-10-01), pages 575 - 582, XP027904273, ISSN: 0045-6535, [retrieved on 20061001] *
CHAMBERS L D ET AL: "Modern approaches to marine antifouling coatings", SURFACE AND COATINGS TECHNOLOGY, ELSEVIER, AMSTERDAM, NL, vol. 201, no. 6, 4 December 2006 (2006-12-04), pages 3642 - 3652, XP024996410, ISSN: 0257-8972, [retrieved on 20061204], DOI: 10.1016/J.SURFCOAT.2006.08.129 *
HANDA P ET AL: "Antifouling agent release from marine coatings-ion pair formation/dissolution for controlled release", PROGRESS IN ORGANIC COATINGS, ELSEVIER BV, NL, vol. 57, no. 4, 1 December 2006 (2006-12-01), pages 376 - 382, XP027906311, ISSN: 0300-9440, [retrieved on 20061201] *

Cited By (13)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2016177884A1 (en) * 2015-05-06 2016-11-10 I-Tech Ab Medetomidine for use in controlling parasitic crustaceans on fish
CN107613977A (zh) * 2015-05-06 2018-01-19 I-技术有限公司 用于控制鱼上寄生甲壳纲动物的美托咪定
JP2018080275A (ja) * 2016-11-17 2018-05-24 中国塗料株式会社 防汚塗料組成物、防汚塗膜およびこれらの用途
EP3339387A1 (de) 2016-12-22 2018-06-27 Evonik Degussa GmbH Verbindungen auf basis von addukten mit isocyanaten für beschichtungszusammensetzungen
US10239898B2 (en) 2016-12-22 2019-03-26 Evonik Degussa Gmbh Compounds based on adducts with isocyanates for coating compositions
DE202018001813U1 (de) 2018-04-09 2018-05-22 I-Tech Ab Löslicher Behälter für Beschichtungskomponenten
US10519327B2 (en) 2018-04-20 2019-12-31 Redjak, L.L.C. Methods and coatings for protecting surfaces from bio-fouling species
US10689527B2 (en) 2018-04-20 2020-06-23 Redjak, L.L.C Methods and coatings for protecting surfaces from bio-fouling species
US10829649B2 (en) 2018-04-20 2020-11-10 Redjak, L.L.C. Methods and coatings for protecting surfaces from bio-fouling species
US20200200928A1 (en) * 2018-12-19 2020-06-25 Pgs Geophysical As Medetomidine Compositions Having Improved Anti-Fouling Characteristics
US12050293B2 (en) * 2018-12-19 2024-07-30 Pgs Geophysical As Medetomidine compositions having improved anti-fouling characteristics
EP4417056A4 (en) * 2021-10-13 2024-12-18 Daikin Industries, Ltd. COMPOSITION FOR FIGHTING HARMFUL ORGANISMS
WO2024047144A1 (en) * 2022-09-01 2024-03-07 I-Tech Ab Composition protecting wood against marine woodborers

Also Published As

Publication number Publication date
JP6621407B2 (ja) 2019-12-18
JP2016527243A (ja) 2016-09-08
CN105473669A (zh) 2016-04-06
SG11201510548VA (en) 2016-02-26
KR101831536B1 (ko) 2018-04-04
JP2018158932A (ja) 2018-10-11
KR20160034311A (ko) 2016-03-29

Similar Documents

Publication Publication Date Title
WO2015011177A1 (en) Use of the enantiomer levomedetomidine as inhibitor for marine biofouling of surfaces
WO2015011178A1 (en) Use of the enantiomer dexmedetomidine as inhibitor for marine biofouling of surfaces
US7311766B2 (en) Method and use of nanoparticles to bind biocides in paints
FI112434B (fi) Menetelmä bakteerien ja kasvusto-organismien kontrolloimiseksi sekä pinnoitekoostumus
US7531581B2 (en) Method and use of acidified modified polymers to bind biocides in paints
US20080095737A1 (en) Non-toxic coating composition, methods of use thereof and articles protected from attachment of biofouling organisms
EP1615974B1 (en) Non-toxic coating composition, methods of use thereof and articles protected from attachment of biofouling organisms
JP2011519968A (ja) 防汚塗料用の環境に優しい新規な微生物付着防止剤及び該防止剤を含有する防汚塗料
EP1639894A1 (en) Non-toxic coating composition, methods of use thereof and articles protected from attachment of biofouling organisms
HK1058880A (en) Non-toxic coating composition, methods of use thereof and articles protected from attachment of biofouling organisms
HK1118305B (en) Method and use of nanoparticles to bind biocides in paints

Legal Events

Date Code Title Description
WWE Wipo information: entry into national phase

Ref document number: 201480041073.3

Country of ref document: CN

121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 14747877

Country of ref document: EP

Kind code of ref document: A1

ENP Entry into the national phase

Ref document number: 2016528515

Country of ref document: JP

Kind code of ref document: A

ENP Entry into the national phase

Ref document number: 20167002087

Country of ref document: KR

Kind code of ref document: A

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 14747877

Country of ref document: EP

Kind code of ref document: A1