CN105473669A - 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
CN105473669A
CN105473669A CN201480041073.3A CN201480041073A CN105473669A CN 105473669 A CN105473669 A CN 105473669A CN 201480041073 A CN201480041073 A CN 201480041073A CN 105473669 A CN105473669 A CN 105473669A
Authority
CN
China
Prior art keywords
dexmedetomidine
handed
coating compositions
group
control agent
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.)
Pending
Application number
CN201480041073.3A
Other languages
Chinese (zh)
Inventor
丹·伊萨克森
莉娜·玛藤松-林德布拉德
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.)
TECH I AB
iTech AB
Original Assignee
TECH I 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 TECH I AB filed Critical TECH I AB
Publication of CN105473669A publication Critical patent/CN105473669A/en
Pending legal-status Critical Current

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

Landscapes

  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Wood Science & Technology (AREA)
  • Organic Chemistry (AREA)
  • Materials Engineering (AREA)
  • Health & Medical Sciences (AREA)
  • Nanotechnology (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)

Abstract

The present invention relates to the use of medetomidine having a relatively higher amount of levomedetomidine, or a salt or solvate thereof, as compared to dexmedetomidine, as a marine antifouling agent. It further relates to surface coating compositions comprising such medetomidine, surfaces coated with such medetomidine, and methods for preventing marine biofouling using such medetomidine.

Description

The left-handed dexmedetomidine of enantiomer as inhibitor is in the application of marine biofouling surface attachment
Technical field
The present invention relates generally to a kind of suppression of marine biofouling surface attachment in ocean environment, and specifically, some reagent are preventing the application of marine biofouling solid surface-attached.More particularly, the present invention relates to the application of dexmedetomidine as the special shape of inhibitor.
Background technology
The biofouling attachment reducing hull and freshwater plant can produce very large economic benefit, the attachment of organic dirt of such as hull can reduce the fuel efficiency of boats and ships, and need the cost plenty of time to clear up these dirts, reduce cooling power of marine engine equipment etc.Except boats and ships, other underwater units, also there is the problem of biofouling attachment in such as aquaculture equipment and offshore oil production gas recovery facility.
At present, in order to prevent and reduce the attaching surface of biodeterioration thing, devise many diverse ways and widely use these methods and solve this kind of problem.Employ some compounds with antifouling activity comprising toxin and biocide as the additive being exposed to subsea equipment topcoating and oil paint.The mechanical type cleaning having introduced marine surface can select oxygenant and sterilant.Especially, the method for water jet and mechanical type brush is used to clean.But most methods belongs to intensive work, and thus cost is high.Have been reported, be selected from the pharmacological compounds that thrombotonin and reduction of Dopamine are worked, can hinder or promote the attachment of barnacle.The serotonin antagonist of such as Cyproheptadine and ketanserin and the dopamine agonists of such as R (-)-NPA and (+)-bromocriptine have inhibit feature too.Another kind of prove that the pharmacological agent that can effectively suppress barnacle to adhere to is the α 2-adrenoceptor agonists rice holder miaow pyridine of highly selective or (±)-4 (5)-[l-(2,3-3,5-dimethylphenyl) ethyl]-lH-imidazoles.Under low concentration 1nM to 10nM, this medicament just can stop the attachment of kentrogon, and dexmedetomidine belongs to a kind of Novel alpha 2-receptor stimulant, comprises 4 substituted imidazole rings, has highly selective to α 2-adrenoceptor.By the acceptor that catecholamine neurotransmitter affects, such as norepinephrine and suprarenin, be called as adrenergic receptor (or adrenoceptor), can be divided into α-and β-subspecies.α 2-adrenoceptor participates in the automatic suppression mechanism of neurotransmitter release, and plays an important role in adjusting hypertension (hypertension), bradyrhythmia (reduced heartbeat rate is slow), even adjustment alertness and analgesia (reducing pain sensitivity) etc.
Patent WO00/42851 discloses the application of dexmedetomidine as the inhibitor of marine biofouling surface attachment.
WO2006/096129 disclose antifouling paint suppress barnacle under water device attachment methods and applications.The method uses the acid sulfate of dexmedetomidine and sulfonation, phosphoric acid, carboxylic acid or acid phosphoric acid ester to be combined the polymer-modified skeleton formed as polystyrene or acrylic ester polymer.
Summary of the invention
The present invention mainly solves the problem reducing and be present in the dexmedetomidine that prevents marine biofouling from adhering to and affect people.
Main purpose of the present invention be used alone dexmedetomidine special enantiomer (as left-handed dexmedetomidine) as the anti-fouling attachment reagent of marine organisms, this reagent on people impact very little.Another object of the present invention uses the special enantiomer composition of the less dexmedetomidine of the impact of the mankind as the anti-fouling attachment inhibitor of marine organisms.Different from the ratio of (1:1) in racemic mixture, in the present composition, left-handed dexmedetomidine accounts for main component.Another object of the present invention uses the blend compositions of dexmedetomidine two kinds of enantiomers to suppress the surface attachment of sea biological pollution, and wherein, left-handed dexmedetomidine is at least 90%, 80% of this blend compositions, 70%, 60%, 50%.Other object of the present invention and advantage will more detailedly in disclosure and accessory claim below be discussed.
brief Description Of Drawings
Fig. 1: the structure (embodiment is shown as its hydrochloride) of left-handed dexmedetomidine
Fig. 2 a: the barnacle adhiesion test with racemize dexmedetomidine
Fig. 2 b: the barnacle adhiesion test of laevororotatory enantiomer dexmedetomidine
Detailed description of the invention and preferred embodiment
Now will by illustrate and method is described in greater detail aforementioned and other side of the present invention herein.The present invention should be understood and can have multi-form embodiment, and should not be limited to proposed embodiment scheme herein.On the contrary, for those of ordinary skill in the art, these embodiments provided herein full disclosure, and given full expression to range of application of the present invention.
The term used in this specification sheets is only used to describe concrete embodiment, instead of in order to limit range of application of the present invention.Unless illustrated in addition in literary composition, the singulative " " used in specification sheets of the present invention, " one " and " being somebody's turn to do " also comprise plural form.It is also to be understood that, word "and/or" used here refers to and comprises any and all possible combination of one or more listed continuous item.In addition, term " about " described herein, when relating to measurable magnitude (amount, dosage, time, temperature etc. of a such as compound), is intended to the change comprising 20%, 10%, 5%, 1%, 0.5% or even 0.1% specified amount.When restriction scope (as from x to y), it represents that the scope surveyed of this observed value is from x to y, or any range wherein, as from x 1to y 1deng.Will be further understood that, when term " comprise ", " comprising " etc. in this specification sheets time, it specifies described feature, integer, step, operation, key element and/or composition to exist, but and the existence of one or more further features of non-excluded, integer, step, operation, key element, composition and/or its group or add.Unless described in detail separately, the meaning of of the present invention all terms (comprising technical term and scientific terminology) that this specification sheets uses is consistent with the usual understanding of technician belonging to the art.
The all patent mentioned herein, patent application and publication are all incorporated in reference.Running into when some contradict term and should be as the criterion with this specification sheets.Further, some aspects in embodiments of the invention are not limited to the aspect described it.As long as these embodiments do not hinder the enforcement of these aspect re-set targets of the present invention, these embodiments also can be applied to other different aspect of the present invention.
The present invention relates generally to marine biofouling surface attachment in a kind of suppression ocean environment, specifically, uses some materials as preventing marine biofouling at the reagent of solid surface-attached and the composition as the topcoating be exposed in ocean environment.In particular, the present invention relates to the special enantiomeric forms (left-handed dexmedetomidine (Fig. 1)) of use dexmedetomidine as this inhibitor.
An aspect of of the present present invention relates to a kind of surface-coating compositions comprising dexmedetomidine, and wherein, described composition comprises the left-handed dexmedetomidine relative to dexmedetomidine with higher amount.Surface-coating compositions as known in the art, this surface-coating compositions also comprises tackiness agent, pigment and suitable solvent.This surface-coating compositions can be used as such as from the ship coating of polishing ship coating.
Knownly can cause its calm and motion inhibit feature (Sinclair, 2003 when α 2-3 adrenergic receptor agonists dexmedetomidine is used Mammals and fish; Ruuskanenetal., 2005).In cyprid larvae, find phenomenon in contrast to this, the dexmedetomidine of 10nM concentration can strengthen the bounce-back frequency (per minute is greater than 100 times) (MolPharmacol78:237 – 248,2010) of cyprid larvae consumingly.Therefore, dexmedetomidine can produce different physiological effects in vertebrates and invertebrates, is different from the calmness/motion shown in vertebrates and suppresses.Dexmedetomidine induction cyprid larvae produces motion-activated response, and this most likely suppresses its reason of adhering to.More particularly, before cyprid larvae, the increase of attached foot movable (leg) is considered to the foundation that dexmedetomidine has anti-attached function.
Be originally presented in dexmedetomidine (±)-4-[1-(2 of European patent document EP72615,3-3,5-dimethylphenyl) ethyl]-1H-imidazoles is the racemic mixture of two kinds of optical enantiomorphs equal proportions mixing, this kind of left-handed and dextrorotation optical isomer (MacDonaldetal., 1991; SavolaandVirtanen, 1991) popular name is respectively left-handed dexmedetomidine and dexmedetomidine.Patent WO2011/070069 discloses dexmedetomidine ((±)-4-[1-(2,3-3,5-dimethylphenyl) ethyl] racemic mixture of-1H-imidazoles and the preparation method of intermediate thereof.Many synthesis steps before all adopt expensive 4 substituted ramification of imidazole as synthesis starting raw material.But synthesis step disclosed in patent WO2011/070069 adopts a kind of economically viable raw material as synthesis starting raw material, and wherein imidazole ring obtains in building-up process.
Dexmedetomidine is applied to human clinical trial, and adopts its S-enantiomer, and the dexmedetomidine as its active ingredient is applied to Animal Anesthesia agent.On the other hand, left-handed dexmedetomidine does not possess significantly calm and analgesic effect (Kuuselaetal.JVetPharamacolTher23 (1), 15-20,2000), but effect (Kuuselaetal.AmJVetRes62 (4) that is calm and that anaesthetize can be weakened when the left-handed dexmedetomidine of high dosage and dexmedetomidine administration simultaneously, 616-621,2001).These results illustrate that the calmness of injection dexmedetomidine separately and the calmness of anaesthetic effect ratio injection dexmedetomidine racemic mixture (this racemic mixture contains the dexmedetomidine of equivalent and left-handed dexmedetomidine) and anaesthetic effect are better.Based on above research, the purification of dexmedetomidine is proved to be significant, and its product is introduced to the market with various item, as (OrionPharmaAB).Europe medical association/789509/2011, the medication council of people from European Union (CHMP) point out Dexdor can be used as Intensive Care Therapy adult patient gentle narcotic use, and (OrionPharmaAB) can be applicable to animal doctor's application.Dexmedetomidine mainly from the racemic mixture of dexmedetomidine separation and purification prepare, wherein left-handed dexmedetomidine is considered to the major impurity composition of pure dexmedetomidine.
As mentioned above, the racemic mixture of dexmedetomidine or (±)-4 (5)-[1-(2,3-3,5-dimethylphenyl) ethyl]-1H-imidazoles be previously proved to be can by effectively suppressing the attachment of barnacle.Surprisingly, as demonstrated by the present invention, the racemic mixture of dexmedetomidine and two enantiomers (dexmedetomidine and left-handed dexmedetomidine) have identical inhibition.This and other can only use the usage had good grounds of one of specific molecular enantiomeric forms antithesis, such as in pharmaceutical industry Chinese traditional medicine, comprise dexmedetomidine, wherein only have a kind of enantiomeric forms to be active and the enantiomer of another form is inertia.Especially unexpected and it should be noted that left-handed dexmedetomidine has similar inhibition equally.It adheres to restraining effect as shown in embodiment 1, Fig. 2 A and Fig. 2 B below to the larva of barnacle cyprid.
Therefore, the preferred embodiments of the present invention use left-handed dexmedetomidine as the activeconstituents/component of ship-bottom paint, for preventing from being soaked in the attachment of the marine biofouling on various surface in ocean environment.
Compare with dexmedetomidine enantiomer with the racemic mixture of dexmedetomidine, left-handed dexmedetomidine is considered to very limited on the impact of human and animal, and therefore the use of left-handed dexmedetomidine enantiomer will provide the solution of the mankind without the end product of impact.Use left-handed dexmedetomidine by replacing, can reduce final user manufacturing, transport, use (such as, during librarian use coating) containing danger when dexmedetomidine or any product of dexmedetomidine in storage and application process.Further, compared with using the racemic mixture of dexmedetomidine or dexmedetomidine, use left-handed dexmedetomidine advantageously, verified left-handed dexmedetomidine has metabolic rate faster in Mammals.In addition, owing to preparing purifying in the dexmedetomidine process of clinical trial, left-handed dexmedetomidine is often being taken as impurity and is being dropped, and therefore left-handed dexmedetomidine also possesses certain price advantage.This also means, the present invention also contributes to the problem solving refuse process in dexmedetomidine production process.Patent WO2013069025 discloses the purification technique of dexmedetomidine, and use the method product yield very high, enantiomeric purity is greater than 99%.Chinese patent CN200910093379 discloses the method being separated left-handed dexmedetomidine and dexmedetomidine.The similar approach of same process is used to may be used for preparing left-handed dexmedetomidine.Chinese patent CN200910093379 discloses the method being separated left-handed dexmedetomidine and dexmedetomidine.European patent EP 0858338 discloses and uses left-handed dexmedetomidine to come the overexpression of prevention and therapy and adrenergic receptor or the relevant illness of allergy as medicament.
A preferred embodiment of the present invention is the form using a kind of specific dexmedetomidine enantiomer individually, left-handed dexmedetomidine, respectively as can on the mankind less affect prerequisite under, prevent the reagent of the attachment of pollutent in ocean environment.
In another preferred embodiment of the present invention, use the enantiomer composition of the less dexmedetomidine of anthropogenic influence as marine biofouling attachment inhibitor, said composition is different from its racemic mixture (1:1), and left-handed like this dexmedetomidine is main enantiomeric forms.Another preferred embodiment uses the blend compositions comprising two kinds of enantiomers as marine biological polution thing attachment inhibitor, wherein left-handed dexmedetomidine is at least 90% of this blend compositions, 80%, 70%, 60%, 50%, and the impact of its racemic mixture of use on the mankind of comparing is less.
A preferred embodiment of the present invention, disclosed in WO2006/096129, adopts a kind of complex compound of sterilant-polymkeric substance can realize the controllable release of self-polishing coating as paint additive.Specifically, the preferred embodiment relates to use one effectively can suppress attachment, such as, barnacle, the method of the antifouling paint under water on device, left-handed dexmedetomidine molecule combines with the acid sulfate of a sulfonation, phosphoric acid, carboxylic acid, acid phosphoric acid ester and forms the polymer backbone of the modification of such as polystyrene or acrylate by the method respectively.Another preferred object of the present invention creates a kind of anti-fouling method reducing sterilant dosage, and the method is realized by the speed reasonably controlling fouling resistance component and discharge from coating.Left-handed dexmedetomidine molecule is combined with polystyrene-poly (Ethylene/Butylene)-polystyrene, can make that active compound is slow to controllably from coating to be discharged in water.This left-handed dexmedetomidine-polymer ions is to dissolving at the surface film of reality, and upon contact with water, left-handed dexmedetomidine molecule is released.Because surface active cpd can the compound concentration of accretion surface, the compound slowly released from coating of therefore comparing, has the attachment that surface active cpd can suppress barnacle more efficiently in antifouling paint.
In relevant preferred embodiment, the nano particle be made up of cupric oxide, zinc oxide, titanium oxide, aluminum oxide, silicon oxide, magnesium oxide etc. also can be used for the controllable release of stain control agent, and preferably, zinc oxide and cupric oxide are prepared into nano particle as release composition.Owing to having very large specific surface area (surface to volume ratio of particle), nanoparticle is conducive to adsorbing following stain control agent, such as left-handed dexmedetomidine, m-tetrachlorophthalodinitrile, Pecudin, SeaNine, Irgarol, Diuron Tech and tolylfluanid.Cupric oxide and Zinc oxide nanoparticle can generate 29 and 21m respectively 2.g -1specific surface area.So just can design a coating system containing a small amount of left-handed dexmedetomidine and nano particle to spread out from coating to limit stain control agent.When using micron particles to carry out alternative nano particle, the adsorption of particle exists hardly.It is most important that these results show that bigger serface is adsorbed in particle surface for stain control agent.Stain control agent, such as left-handed dexmedetomidine is combined the compound generated with nanosize metal oxide, and this compound can spread in a controlled manner from coating in water.Compare and be used alone stain control agent particle, the particulate matter that stain control agent and nano-metal-oxide effect are formed owing to having large-size so possess extraordinary dispersion stabilization.Due to size reason, stain control agent-metal oxide particle is fixed in coating, and can not spread in water.Therefore, in time limit of service, stain control agent particle concentration in the coating still keeps constant.Consequently in whole coating, the concentration of stain control agent is identical.And the surface-area of total nano particle enough adsorbs all stain control agents, and the waste of biocide can not be caused.
Be previously published the compound that some have interference nerve signal or anti-marine biofouling (barnacle) attached function, such as, U.S. Patent No. 6,762, compound dexmedetomidine disclosed in 227, the compound spiral shell tetrahydroglyoxaline (Catemine3) disclosed in Swedish patent application 0300863-8 with identical function all belongs to this compounds.But these products almost do not have effect for algae.Such as, dexmedetomidine has special role for cyprid larvae, but owing to lacking corresponding target protein in algae, does not have effect for suppressing the attachment of algae.There is multiple method can suppress the growth of algae, comprising the copper or other metal that use rather high concentration.Algicide selects weedicide and inhibitor of photosynthesis usually, DiuronTM [the 3-(3 such as produced by Du Pont's agricultural-food Wilmington DuPontAgriculturalProductsWilmington company of the U.S., Germany, 4-dichlorophenyl)-1,1-Dimethylurea] and by vapour Bagong, USA New York Si Talidun CibaInc, the Irgarol1051 that Tarrytown company produces tM(the tertiary fourth amino of 2-methylthio group-4--6-cyclopropylamino-S-triazine).One more common method uses sterilant as the zinc pyrithione (ZPT) produced by ArcChemicalsInc company and Zinc Pyrithione, by Bayer chemistry-pittsburgh,U.S.A, Pennsylvania BayerChemicalsPittsburgh, Pa., N-(the dichloro fluorine first) sulfenyl-N-p-methylphenyl-N' that USA company produces, N'-dimethyl sulphide acid diamide and N'-dimethyl-N-phenyl sulphonamide, the ZINEB produced by FMCcorp. company tMzineb, the ZINRAM produced by Taminco company tMtwo-dimethylthiocarbamate zinc, MANEB ethylidene dithiocarbamate manganese or its quarternary ammonium salt compound, the 3rd method uses to have short-decayed toxic compounds, as RohmandHaasCompany, the SEANINE that Philadelphia, Pa., USA company produces tM(the chloro-2-n-octyl-3 of 4,5-bis-(2H) isothiazolones and related compound thereof.Principle of the present invention be use compound and reagent (in the present invention left-handed dexmedetomidine) can cyprid larvae body internal interference or stop to target cell send nerve signal, can respectively with algae-resistant compound as ZPT and copper pyrithion, sterilant is as tolylfluanid and Pecudin, weedicide is as DiuronTM and IrgarolTM, or other common insecticides is as SeaNine tMor EcoNea tM(the bromo-5-trifluoromethane of 2-(p-chloro-phenyl-)-3-cyanogen-4-) is combined, and mentioned reagent is produced by the JanssenPharmaceutical company of New Jersey Titusville.The preferred embodiment of the invention is made an addition to by above-mentioned substance in the base polymer coating of coating shell.Therefore, a relevant embodiment of the present invention, be coated on substrate by a kind of protective cover, this protective cover comprises following component: a) a kind of attachment material that can disturb barnacle biodeterioration, and this material is made up of left-handed dexmedetomidine; B) a kind of algicide.Algicide preferably copper, zinc or other metal, Diuron Tech [3-(3,4-dichlorophenyl)-1,1-Dimethylurea], Irgarol1051 tM(the tertiary fourth amino of 2-methylthio group-4--6-cyclopropylamino-S-triazine), ZPT [two (1-hydroxyl-2 (lH)-pyrithione-O, S)-(T-4)-zinc], copper pyrithion [two (1-hydroxyl-2 (lH)-pyridine thiosulfuric acid-O, S)-(T-4)-copper], Pecudin (N'-dimethyl-N-phenyl sulphonamide), zineb tM(zineb), Zinram tM(two-dimethylthiocarbamate zinc), MANEB (ethylidene dithiocarbamate manganese) or quarternary ammonium salt compound, SeaNine tM(4,5-bis-chloro-2-n-octyl-3 (2H) isothiazolones), and EcoNea tM(the bromo-5-trifluoromethane of 2-(p-chloro-phenyl-)-3-cyanogen-4-).
Unless according to another explanation, in the present invention, term used " dexmedetomidine ", " dexmedetomidine ", " left-handed dexmedetomidine " comprise its salt and solvate.Spendable dexmedetomidine salt comprises its acid salt and base addition salt.These salt are prepared by traditional technology, namely in a solvent, or in the medium that described salt is insoluble, by the free acid form of the compounds of this invention or free alkali form and equivalent or excessive a kind of suitable acid or alkali reaction, use subsequently standard technology (as vacuum-drying or lyophilize) by solvent or as described in medium remove and finally prepare.The mode that these salt can also be exchanged by a kind of gegenion of compound that exists in a salt form in the present invention and another gegenion prepares described salt, as used suitable ion exchange resin.In order to avoid misreading, the derivative (as solvent, prerequisite medicine) of other selectable dexmedetomidine is also all in limited field of the present invention.Preferred solvent comprises, but is not limited to: propyl carbinol, isopropylcarbinol, methyl alcohol, phenylcarbinol and 1-methoxy-2-propanol.Can by the currently known methods in use this field such as chiral separation or chiral column chromatography by the single stage enantiomer separation of the dexmedetomidine in racemic mixture or other enantiomeric mixture out.Ultimate aim enantiomer also can synthesize (also referred to as chiral synthesize or asymmetric synthesis) method by enantioselectivity obtains, enantioselectivity synthesis is also under the jurisdiction of the category of chemical reaction (or successive reaction), generate one or more new chiral structure compounds with same molecular structure in process, and generate stereoisomerism (enantiomer or the diastereomer) product (IUPAC) of inequality.
Preferred protective cover also comprises Marine Paints.
Embodiment 1
Materials and methods
The attachment inhibitor of cyprid larvae
Attachment experiment and measuring method: in each culture dish, add the seawater that 5ml salinity is 32 ± 1 ‰ respectively.About 20 cyprid larvae are positioned in each culture dish.Subsequently dexmedetomidine and left-handed dexmedetomidine are added in culture dish respectively that (ultimate density is respectively 10 -9and10 -10m).Experiment contrast group only comprises the seawater of filtration.Often group test repetition 5 times, continues 3 days.Evaluated by the attachment restraining effect of larva quantity to compound using stereoscopic microscope observing inspection to adhere to or do not adhered to.Result as shown in Figure 2.
References
Sinclair2003:Sinclair,M.D.,CanVetJ44,885-897(2003)
Ruuskanen2005:Ruuskanen,J.O.etal.,JournalofNeurochemistry,94,1559–1569(2005)
MacDonald1991:MacDonald,E.etal.,JPharmacolExpTher.259,848-854(1991)
SavolaandVirtanen1991:Savola,J.M.,Virtanen,R.,EurJPharmacol,195,193-199(1991)

Claims (27)

1. comprise a surface-coating compositions for dexmedetomidine, it is characterized in that, described surface-coating compositions comprises and has the dexmedetomidine of the left-handed dexmedetomidine of higher amount or salt or solvate relative to dexmedetomidine.
2. surface-coating compositions as claimed in claim 1, wherein, the quantity of described left-handed dexmedetomidine is more than 50% of the total amount of dexmedetomidine, is such as at least 60% of the total amount of dexmedetomidine, 70%, 80%, 90% or 100%.
3. surface-coating compositions as claimed in claim 1 or 2, wherein, described surface-coating compositions is the coating of a kind of marine organisms.
4. the surface-coating compositions as described in as arbitrary in claim 1-3, wherein, described left-handed dexmedetomidine is incorporated into the polymer backbone of modification of the acid sulfate of a sulfonation, phosphoric acid, carboxylic acid, acid phosphoric acid ester.
5. surface-coating compositions as claimed in claim 4, wherein, described polymer backbone is selected from the group be made up of polystyrene and acrylic ester polymer.
6. the surface-coating compositions as described in as arbitrary in claim 1-5, wherein, described surface-coating compositions provides a kind of described left-handed dexmedetomidine of controllable release.
7. surface-coating compositions as claimed in claim 6, wherein, described left-handed dexmedetomidine is adsorbed in nano particle.
8. surface-coating compositions as claimed in claim 7, wherein, described nano particle is selected from the group be made up of the oxide compound of copper, zinc, titanium, aluminium, silicon and magnesium, is preferably copper (II) oxide compound and zinc (II) oxide compound.
9. surface-coating compositions as claimed in claim 7 or 8, wherein, the specific surface area of described nano particle is 10-50m 2/ g, preferred 20-30m 2/ g.
10. the surface-coating compositions as described in as arbitrary in claim 1-9, wherein, also comprises the stain control agent that at least one is additional.
11. surface-coating compositions as claimed in claim 10, wherein, described additional stain control agent is selected from the group be made up of algicide, mycocide, weedicide and general biocide.
12. surface-coating compositions as described in claim 10 or 11, wherein, described additional stain control agent is selected from by m-tetrachlorophthalodinitrile, Pecudin, 4,5-bis-chloro-2-n-octyl-3 (2H) isothiazoloness 2-methylthio group-4-TERTIARY BUTYL AMINE-6-cyclopropylamino-S-triazine 3-(3,4-dichlorophenyl)-1,1-dimethyl urea tolylfluanid, ZPT, pyrrole sulphur copper, dichlofluanid, zineb two (dimethyl-thiocarbamic acid) zinc ethylidene dithiocarbamate manganese quaternary ammonium compound, 2-(rubigan)-3-cyano group-4-bromo-5-trifluoromethyl the group of composition.
13. 1 kinds be coated with as arbitrary in claim 1-12 as described in the surface of surface-coating compositions.
14. surfaces as claimed in claim 13, wherein, described surface is the surface for being submerged in ocean environment.
15. surfaces as claimed in claim 14, wherein, described surface is a hull or a seawater pipe.
16. 1 kinds of dexmedetomidine or salt relative to dexmedetomidine with the left-handed dexmedetomidine of higher amount or solvated compounds are as the purposes of marine organisms stain control agent.
17. purposes as claimed in claim 16, wherein, described dexmedetomidine comprises the left-handed dexmedetomidine of more than 50%, such as comprises the left-handed dexmedetomidine of at least 60%, 70%, 80%, 90%, 99% or 100%.
18. purposes as described in claim 16 or 17, wherein, for suppressing barnacle cyprid larvae surface attachment.
19. as arbitrary in claim 16-18 as described in purposes, wherein, the marine organisms stain control agent additional with at least one combinationally uses.
20. purposes as claimed in claim 19, wherein, described additional stain control agent is selected from the group be made up of algicide, mycocide, weedicide and general biocide.
21. purposes as described in claim 19 or 20, wherein, described additional stain control agent is selected from by m-tetrachlorophthalodinitrile, Pecudin, 4,5-bis-chloro-2-n-octyl-3 (2H) isothiazoloness 2-methylthio group-4-TERTIARY BUTYL AMINE-6-cyclopropylamino-S-triazine 3-(3,4-dichlorophenyl)-1,1-dimethyl urea tolylfluanid, ZPT, pyrrole sulphur copper, dichlofluanid, zineb two (dimethyl-thiocarbamic acid) zinc ethylidene dithiocarbamate manganese quaternary ammonium compound, 2-(rubigan)-3-cyano group-4-bromo-5-trifluoromethyl the group of composition.
22. 1 kinds, for preventing the method for marine organisms surface attachment, comprise application and have the dexmedetomidine of the left-handed dexmedetomidine of higher amount or salt or solvate relative to dexmedetomidine.
23. methods as claimed in claim 22, wherein, described dexmedetomidine comprises the left-handed dexmedetomidine of more than 50%, such as comprises the left-handed dexmedetomidine of at least 60%, 70%, 80%, 90%, 99% or 100%.
24. methods as described in claim 22 or 23, wherein, for suppressing the surface attachment of barnacle cyprid larvae.
25. as arbitrary in claim 22-24 as described in method, wherein, also comprise application at least with a kind of additional marine organisms stain control agent on described surface.
26. methods as claimed in claim 25, wherein, described additional stain control agent is selected from the group be made up of algicide, mycocide, weedicide and general biocide.
27. methods as described in claim 25 or 26, wherein, described additional stain control agent is selected from by m-tetrachlorophthalodinitrile, Pecudin, 4,5-bis-chloro-2-n-octyl-3 (2H) isothiazoloness 2-methylthio group-4-TERTIARY BUTYL AMINE-6-cyclopropylamino-S-triazine 3-(3,4-dichlorophenyl)-1,1-dimethyl urea tolylfluanid, ZPT, pyrrole sulphur copper, dichlofluanid, zineb two (dimethyl-thiocarbamic acid) zinc ethylidene dithiocarbamate manganese quaternary ammonium compound, 2-(rubigan)-3-cyano group-4-bromo-5-trifluoromethyl the group of composition.
CN201480041073.3A 2013-07-24 2014-07-23 Use of the enantiomer levomedetomidine as inhibitor for marine biofouling of surfaces Pending CN105473669A (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US201361857910P 2013-07-24 2013-07-24
US61/857,910 2013-07-24
PCT/EP2014/065793 WO2015011177A1 (en) 2013-07-24 2014-07-23 Use of the enantiomer levomedetomidine as inhibitor for marine biofouling of surfaces

Publications (1)

Publication Number Publication Date
CN105473669A true CN105473669A (en) 2016-04-06

Family

ID=51292926

Family Applications (1)

Application Number Title Priority Date Filing Date
CN201480041073.3A Pending CN105473669A (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 (en)
KR (1) KR101831536B1 (en)
CN (1) CN105473669A (en)
SG (1) SG11201510548VA (en)
WO (1) WO2015011177A1 (en)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN108218909A (en) * 2016-12-22 2018-06-29 赢创德固赛有限公司 For the compound based on the adduct with isocyanates of coating composition

Families Citing this family (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2015011177A1 (en) * 2013-07-24 2015-01-29 I-Tech Ab Use of the enantiomer levomedetomidine as inhibitor for marine biofouling of surfaces
AU2016257388A1 (en) * 2015-05-06 2017-11-23 I-Tech Ab Medetomidine for use in controlling parasitic crustaceans on fish
JP6887783B2 (en) * 2016-11-17 2021-06-16 中国塗料株式会社 Antifouling paint compositions, antifouling coatings and their uses
DE202018001813U1 (en) 2018-04-09 2018-05-22 I-Tech Ab Soluble container for coating components
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
US10519327B2 (en) 2018-04-20 2019-12-31 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
WO2024047144A1 (en) * 2022-09-01 2024-03-07 I-Tech Ab Composition protecting wood against marine woodborers

Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH07315282A (en) * 1994-05-26 1995-12-05 Daikyo Manabu Antifouling painting method for frp hull and antifouling frp hull
CN101137725A (en) * 2005-03-11 2008-03-05 I-技术有限公司 Method and use of acidified modified polymers to bind biocides in paints
CN101166797A (en) * 2005-03-11 2008-04-23 I-技术有限公司 Method and use of nanoparticles to bind biocides in paints
CN101671305A (en) * 2009-09-29 2010-03-17 北京华禧联合科技发展有限公司 Method for resolution of levorotatory enantiomer and dexiotropic enantiomer of medetomidine
CN102257077A (en) * 2008-12-19 2011-11-23 Ppg有限责任公司 Resin composition, antifouling coating comprising barnacle antifoulant and processes of production thereof
CN102791812A (en) * 2010-03-23 2012-11-21 中国涂料株式会社 Antifouling coating composition and use for same

Family Cites Families (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB9521680D0 (en) 1995-10-23 1996-01-03 Orion Yhtymo Oy New use of imidazole derivatives
AR015744A1 (en) 1998-04-01 2001-05-16 Orion Corp USE OF DEXMEDETOMIDINE FOR SEDATION IN INTENSIVE THERAPY
US20060189686A1 (en) * 2005-01-27 2006-08-24 Lena Martensson Use of a combination of substances to prevent biofouling organisms
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
WO2011070069A1 (en) * 2009-12-09 2011-06-16 I-Tech Ab Process for preparation of medetomidine
WO2012176809A1 (en) * 2011-06-23 2012-12-27 中国塗料株式会社 Two-component hydrolysis-type antifouling paint composition, antifouling coating film, and method for producing antifouling substrate
WO2015011177A1 (en) * 2013-07-24 2015-01-29 I-Tech Ab Use of the enantiomer levomedetomidine as inhibitor for marine biofouling of surfaces

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH07315282A (en) * 1994-05-26 1995-12-05 Daikyo Manabu Antifouling painting method for frp hull and antifouling frp hull
CN101137725A (en) * 2005-03-11 2008-03-05 I-技术有限公司 Method and use of acidified modified polymers to bind biocides in paints
CN101166797A (en) * 2005-03-11 2008-04-23 I-技术有限公司 Method and use of nanoparticles to bind biocides in paints
CN102257077A (en) * 2008-12-19 2011-11-23 Ppg有限责任公司 Resin composition, antifouling coating comprising barnacle antifoulant and processes of production thereof
CN101671305A (en) * 2009-09-29 2010-03-17 北京华禧联合科技发展有限公司 Method for resolution of levorotatory enantiomer and dexiotropic enantiomer of medetomidine
CN102791812A (en) * 2010-03-23 2012-11-21 中国涂料株式会社 Antifouling coating composition and use for same

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN108218909A (en) * 2016-12-22 2018-06-29 赢创德固赛有限公司 For the compound based on the adduct with isocyanates of coating composition

Also Published As

Publication number Publication date
SG11201510548VA (en) 2016-02-26
JP6621407B2 (en) 2019-12-18
WO2015011177A1 (en) 2015-01-29
KR20160034311A (en) 2016-03-29
JP2018158932A (en) 2018-10-11
KR101831536B1 (en) 2018-04-04
JP2016527243A (en) 2016-09-08

Similar Documents

Publication Publication Date Title
CN105473669A (en) Use of the enantiomer levomedetomidine as inhibitor for marine biofouling of surfaces
CN105531330A (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
TWI352106B (en) Antifouling compositions comprising a polymer with
CN102300944B (en) Marine organism anti-fouling paint and preparing method and use thereof
US20080095737A1 (en) Non-toxic coating composition, methods of use thereof and articles protected from attachment of biofouling organisms
WO2006096129A1 (en) Method and use of acidified modified polymers to bind biocides in paints
AU2001275527A1 (en) Non-toxic coating composition, methods of use thereof and articles protected from attachment of biofouling organisms
CN1299589A (en) 5-acylamilino-chloroalkyl thiazole as anti-microbe agent and sea anti-fouling agent
US20060217456A1 (en) Non-toxic coating composition, methods of use thereof and articles protected from attachment of biofouling organisms
CN1266130C (en) Ester derivative of indole, its preparation method and application
EP2285914A1 (en) Novel environmental friendly anti-microbial adhesion agents for anti-fouling paints and anti-fouling paints containing them
US20020022044A1 (en) Non-toxic coating composition, methods of use thereof and articles protected from attachment of biofouling organisms
TW200923035A (en) Method and use of nanoparticles to bind biocides in paints
JPH1192308A (en) Antifouling agent
JPH11302113A (en) Antimicrobial, antifungal, algicidal and antifouling agent for industrial purpose containing pyridazinotrizine

Legal Events

Date Code Title Description
C06 Publication
PB01 Publication
C10 Entry into substantive examination
SE01 Entry into force of request for substantive examination
RJ01 Rejection of invention patent application after publication

Application publication date: 20160406

RJ01 Rejection of invention patent application after publication