Classifications

• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
  • A61L24/00—Surgical adhesives or cements; Adhesives for colostomy devices
  • A61L24/04—Surgical adhesives or cements; Adhesives for colostomy devices containing macromolecular materials
  • A61L24/043—Mixtures of macromolecular materials
• • 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
  • A01N47/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom not being member of a ring and having no bond to a carbon or hydrogen atom, e.g. derivatives of carbonic acid
  • A01N47/40—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom not being member of a ring and having no bond to a carbon or hydrogen atom, e.g. derivatives of carbonic acid the carbon atom having a double or triple bond to nitrogen, e.g. cyanates, cyanamides
  • A01N47/42—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom not being member of a ring and having no bond to a carbon or hydrogen atom, e.g. derivatives of carbonic acid the carbon atom having a double or triple bond to nitrogen, e.g. cyanates, cyanamides containing —N=CX2 groups, e.g. isothiourea
  • A01N47/44—Guanidine; Derivatives thereof
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
  • A61L24/00—Surgical adhesives or cements; Adhesives for colostomy devices
  • A61L24/001—Use of materials characterised by their function or physical properties
  • A61L24/0015—Medicaments; Biocides
• • C—CHEMISTRY; METALLURGY
  • C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
  • C09J—ADHESIVES; NON-MECHANICAL ASPECTS OF ADHESIVE PROCESSES IN GENERAL; ADHESIVE PROCESSES NOT PROVIDED FOR ELSEWHERE; USE OF MATERIALS AS ADHESIVES
  • C09J11/00—Features of adhesives not provided for in group C09J9/00, e.g. additives
  • C09J11/02—Non-macromolecular additives
  • C09J11/06—Non-macromolecular additives organic
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K9/00—Medicinal preparations characterised by special physical form
  • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
  • A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
  • A61L2300/20—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials
  • A61L2300/204—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials with nitrogen-containing functional groups, e.g. aminoxides, nitriles, guanidines
  • A61L2300/206—Biguanides, e.g. chlorohexidine
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
  • A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
  • A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
  • A61L2300/404—Biocides, antimicrobial agents, antiseptic agents

Definitions

• the present invention relates to methods for incorporating chlorhexidine salts and particularly chlorhexidine gluconate, into an adhesive; adhesives containing chlorhexidine salts; and products using such adhesive.
• a wide array of medical products use adhesive for affixing the product onto a user's skin.
• adhesive for affixing the product onto a user's skin.
• it is desirable to prevent or at least minimize microbial growth or reproduction along the interface of adhesive and skin, as such can readily lead to infection and other undesirable conditions.
• Chlorhexidine gluconate has a broad antimicrobial spectrum, is safe, and is well accepted in the market.
• chlorhexidine gluconate has never been incorporated into solvent based acrylic adhesives which are the standard for surgical applications due to their low cost and good adhesion on skin in dry and wet conditions.
• the present invention provides a method of forming chlorhexidine in solid form.
• the method comprises providing an aqueous solution of at least one chlorhexidine salt.
• the method also comprises actively drying the aqueous solution to thereby obtain the at least one chlorhexidine salt in solid form.
• the invention provides a method of forming an adhesive containing chlorhexidine.
• the method comprises providing an aqueous solution of at least one chlorhexidine salt and actively drying the aqueous solution to thereby obtain the at least one chlorhexidine salt in solid form.
• the method additionally comprises providing an adhesive component and providing a solvent compatible with the adhesive component.
• the method also comprises solubilizing the solid form chlorhexidine in the solvent to form a chlorhexidine solution.
• the method comprises combining the chlorhexidine solution with the adhesive component to thereby form an adhesive containing chlorhexidine.
• the invention provides an adhesive formulation including chlorhexidine.
• the adhesive formulation comprises an adhesive, and at least one chlorhexidine salt.
• the present invention provides a medical product having an adhesive with antimicrobial properties.
• the medical product comprises an adhesive formulation including chlorhexidine.
• Figure 1 is a graph illustrating antimicrobial efficacy of various adhesive samples described herein.
• Figure 2 is a graph illustrating antimicrobial efficacy of various adhesive samples described herein.
• chlorhexidine gluconate (CHG) into solvent based adhesives has not been achieved yet due to certain physical and chemical properties of chlorhexidine gluconate.
• chlorhexidine gluconate is strongly hydrophilic and is only soluble in methanol and acetone.
• chlorhexidine gluconate is typically commercially available as a 20% or 40% by weight in water formulation.
• Aqueous compositions can not be readily combined with solvent based adhesives.
• Chlorhexidine gluconate is sensitive to high temperatures thereby limiting its subsequent processing as would otherwise likely be necessary in any adhesive incorporation. And, when dried by evaporation, the compound does not readily disperse in solvent. This presents another difficulty in attempting to incorporate this compound into a solvent based adhesive.
• the present invention provides a unique strategy for incorporating chlorhexidine gluconate into a solvent based adhesive such as solvent based acrylic adhesives which are widely used in medical and surgical applications.
• the new method incorporates chlorhexidine gluconate into a solvent based adhesive by an active drying operation and preferably by freeze drying or spray drying, chlorhexidine gluconate to obtain a powder.
• the powder is then dissolved in a solvent that is compatible with the adhesive of interest such as an acrylic adhesive.
• An example of a suitable solvent for a typical acrylic adhesive is methanol.
• Chlorhexidine is a chemical antiseptic and generally used as an antimicrobial agent. It is effective on both Gram-positive and Gram-negative bacteria, although it is less effective with some Gram-negative bacteria. It has both bactericidal as well as bacteriostatic mechanisms of action, the mechanism of action being membrane disruption and not ATPase inactivation as previously thought. It is also useful against fungi and enveloped viruses, though this has not been extensively investigated. Products containing chlorhexidine in high concentrations should be kept away from eyes and the ears, due to the risk of damage to those organs. However, chlorhexidine is safely used in very low concentrations, for example in some contact lens solutions.
• Chlorhexidine gluconate (also known as chlorhexidine digluconate) is a salt of chlorhexidine and gluconic acid.
• the structural formula of chlorhexidine gluconate is: m t m m
• chlorhexidine gluconate as used herein encompasses the digluconate compound. Also, the terms “chlorhexidine gluconate” and “chlorhexidine digluconate” are used interchangeably herein.
• chlorhexidine salts that may be used as antimicrobial agents according to the invention include, but are not limited to, chlorhexidine palmitate, chlorhexidine diphosphanilate, chlorhexidine dihydrochloride, chlorhexidine diacetate, and chlorhexidine digluconate.
• Chlorhexidine free base is a further example of an antimicrobial agent.
• the present invention provides methods for incorporating one or more chlorhexidine salts and particularly chlorhexidine gluconate in a solvent based adhesive such as an acrylic adhesive.
• a solvent based adhesive such as an acrylic adhesive.
• the present invention is particularly directed to the incorporation of chlorhexidine gluconate, the invention is applicable to other chlorhexidine salts and related compounds.
• any chlorhexidine salt that is generally provided or produced in an aqueous or liquid form is a candidate for the various preferred aspects of the invention as described herein.
• active drying refers to any operation in which liquid and typically water, is removed and separated from the chlorhexidine salt(s) besides passive evaporation of the liquid.
• Passive evaporation refers to evaporation of the liquid component(s) at ambient temperatures without any moving air streams or other flowing currents to aid in removal and separation of the liquid component(s) from the chlorhexidine salt(s).
• active drying refers to a wide array of liquid removal techniques such as but not limited to aggressive evaporation using airflows over the liquid also known as pneumatic drying, heating promoted evaporation in which thermal energy is supplied to the liquid also known as hot air drying, drying by exposure to electromagnetic radiation such as microwave energy, freeze drying, and spray drying for example. Combinations of these and other drying strategies can be utilized.
• active drying is performed by freeze drying or spray drying.
• Freeze drying is a dehydration process typically used to preserve a perishable material or render the material more convenient for transport. Freeze drying is typically performed by freezing the material and then reducing the surrounding pressure and adding sufficient heat to allow the frozen water in the material to sublime directly from the solid phase to the gas phase.
• a preferred method in accordance with the present invention is to freeze dry a 20% (all percentages are percentages by weight unless noted otherwise) chlorhexidine gluconate solution. Freeze drying may be performed in nearly any manner.
• the noted solution of 20% chlorhexidine gluconate and 80% water is fully frozen by subjecting the solution to a temperature of about -20°C and a pressure of about 0.180 bars, for a time period of about 24 hours. It will be appreciated that these temperature, pressure, and time values are merely representative.
• the invention includes a significantly broader range of freeze drying conditions.
• temperatures are within a range of from about -80°C (or less) to about 10°C (or more), and preferably from about -50°C to about 0°C.
• pressures are within a range of from about 0.01 bars to about 0.95 bars, and preferably from about 0.10 bars to about 0.50 bars.
• Typical time periods range from several seconds up to several days.
• the aqueous chlorhexidine gluconate solution is preferably placed in a vessel that increases the surface area of the solution. As will be appreciated, increasing the solution surface area promotes heat transfer and thus reduces the time period necessary to freeze the aqueous chlorhexidine gluconate solution. Increasing the surface area also promotes migration and sublimation of water from the frozen mass to thereby leave a remaining component of chlorhexidine gluconate.
• chlorhexidine gluconate is also typically available as a 40% aqueous solution and so such may be freeze dried as described herein. It is contemplated that a range of aqueous solutions having concentrations of from about 1% up to the solubility limit of the compound could be used. Typically for many chlorhexidine salts, they are commercially available in an aqueous solution and in a concentration of from about 1% to about 60%.
• freeze drying After initially freezing the aqueous solution to form a solid, at least a portion of the water is removed from the solid by sublimation.
• the present invention includes operations in which the water component is partially removed by other techniques or practices besides freeze drying. However, preferably at least a majority and most preferably all of the water is removed via freeze drying.
• Spray drying is a method of producing a dry powder from a liquid or slurry by rapidly drying with a hot gas. This is the preferred method of drying of many thermally sensitive materials such as foods and pharmaceuticals. A consistent particle size distribution is a reason for spray drying some industrial products such as catalysts. Air is typically the heated drying media. However, if the liquid is a flammable solvent or the product is oxygen-sensitive then nitrogen can be used. [0030] All spray dryers use some type of atomizer or spray nozzle to disperse the liquid or slurry into a controlled drop size spray. The most common of these are rotary nozzles and single fluid pressure swirl nozzles.
• two-fluid or ultrasonic nozzles are used.
• drop sizes from 10 to 500 micrometers can be achieved with the appropriate nozzle selection.
• the most common drop sizes are in the 100 to 200 micrometer diameter range.
• the resulting dry powder is often free-flowing.
• the hot drying gas can be passed as a co-current or counter-current flow to the atomizer direction.
• a co-current flow enables the particles to have a lower residence time within the system and the particle separator (typically a cyclone device) operates more efficiently.
• the counter- current flow method enables a greater residence time of the particles in the chamber and usually is paired with a fluidized bed system.
• Additional techniques and/or alternative active drying operations can include for example combinations of spray drying and freeze drying.
• the powder can be readily solubilized by adding the chlorhexidine gluconate in particulate form to one or more suitable solvent(s) such as methanol.
• suitable solvent(s) such as methanol.
• the chlorhexidine gluconate is added to the solvent in an amount such that the compound readily dissolves in the solvent.
• methanol a concentration of chlorhexidine gluconate in a range from about 15% to about 20% has been found acceptable.
• concentrations greater than and less than these values are examples of concentrations greater than and less than these values.
• the chlorhexidine gluconate solution is incorporated into a solvent based adhesive. Typically, this is performed by adding or otherwise incorporating the solution directly into an adhesive component or adhesive formulation.
• the adhesive containing chlorhexidine salt is then incorporated in a product or used as desired.
• conventional coating and drying operations can be performed to form an adhesive layer on a medical product.
• medical products include surgical goods such as incise films, and device fixation products; wound care products; and ostomy pouches.
• the adhesive can be covered with a carrier, preferably a polyurethane film or any alternative material.
• the methods of the invention can be used to incorporate chlorhexidine salts such as chlorhexidine gluconate, into a wide array of adhesives, and preferably a solvent based adhesive.
• Non limiting adhesives include acrylic adhesives, rubber adhesives, silicone adhesives, polyurethane adhesives, and variants and combinations thereof.
• the resulting chlorhexidine salt which is preferably chlorhexidine gluconate, can be incorporated into nearly any non-aqueous based adhesive.
• the adhesive is a solvent based adhesive. More preferably, the adhesive is a solvent based acrylic adhesive.
• the present invention also includes combining chlorhexidine powder produced by the methods described herein, with an adhesive component such as an adhesive ingredient and/or an adhesive premix.
• This strategy provides an alternative approach for subsequent formation of a chlorhexidine containing adhesive.
• one or more chlorhexidine salts can be incorporated into an adhesive by combining a liquid solution, mixture or dispersion containing chlorhexidine salt(s) into an adhesive formulation or an adhesive intermediate and then subjecting the resulting mixture to one or more drying operations to thereby remove the liquid component(s) from the mixture of adhesive and chlorhexidine salt(s).
• chlorhexidine is in a particle form
• another advantage results when the particles are incorporated into a hydrophobic adhesive matrix. Due to its hydrophilic properties, chlorhexidine and particularly chlorhexidine gluconate, will easily release from a hydrophobic adhesive matrix.
• One or more additional additives can be incorporated into the adhesive and chlorhexidine formulation.
• the additional additives include medicinal compounds.
• Such medicinal compounds include, but are not limited to, antimicrobials, antibiotics, antifungal agents, antiviral agents, antithrombogenic agents, anesthetics, anti-inflammatory agents, analgesics, anticancer agents, vasodilation substances, wound healing agents, angiogenic agents, angiostatic agents, immune boosting agents, growth factors, and other biological agents.
• Suitable antimicrobial agents include, but are not limited to, biguanide compounds; triclosan; penicillins; tetracyclines; aminoglycosides, such as gentamicin and TobramycinTM; polymyxins; rifampicins; bacitracins; erythromycins; vancomycins; neomycins; chloramphenicols; miconazole; quinolones, such as oxolinic acid, norfloxacin, nalidixic acid, pefloxacin, enoxacin, and ciprofloxacin; sulfonamides; nonoxynol 9; fusidic acid; cephalosporins; and combinations of such compounds and similar compounds.
• the adhesive composition may comprise one or more absorbents.
• a suitable absorbent is a hydrocolloid agent.
• the hydrocolloid may be linear or crosslinked.
• Suitable hydrocolloids include synthetic hydrocolloids such as sodium carboxymethyl cellulose, and natural products such as gelatin, pectin, guar gum, locust bean gum, tragacanth gum, gum karaya, starches, gum arabic, alginic acid and its sodium and/or calcium salts.
• hydrocolloids such as polyvinyl alcohol, polyvinyl acetate, polyvinyl pyrollidone, polyacrylic acid, polyhydroxyalkyl acrylates, polyacrylamides, high molecular weight polyethylene glycols and polypropylene glycols are useful.
• Others hydrocolloids include crosslinked or crystalline sodium carboxymethyl cellulose, crosslinked dextran and starch-acrylonitrile graft copolymer.
• the adhesive compositions included an adhesive component, an absorbent agent, and an antimicrobial agent.
• the 1807 adhesive is an acrylic adhesive commercially available from Avery Dennison.
• the AVC-12363 adhesive is also available from Avery Dennison and is a solvent acrylic adhesive suitable for medical applications such as for adhesive dressings, securement devices, incise films, etc.
• Samples of the composition were prepared as follows. 20% chlorhexidine water based solution was freeze dried. Wet adhesive was weighted and added into a breaker. A800 carboxymethyl cellulose (particle size less than 75 ⁇ ) was added directly into the adhesive under mixing at 800 rpm.
• Adhesives were then coated at 100 gsm onto a BG684 release liner. Coating speed used was 4 m/min.
• Med5575A was manually laminated on top of the coating as carrier.
• T06/022 procedure corresponds to EN13726. Details as to T04/001 and T04/095 are as follows:
• the tack property of a pressure sensitive material is the force required to separate a loop of material which has been brought into contact with a specified area of a standard surface instantly (or substantially so), using no external pressure to secure more thorough contact.
• Tack is a measure of a tape's ability to adhere instantly with a minimum of pressure.
• Test specimen The test specimens had a width of 25 mm and a length of 150 mm. The test specimen was cut with a suitable cutter, normally in the machine direction.
• Equipment A flat "Float Process" glass plate with a minimum thickness of 3.0 mm was used. A metal peg was attached at the center of the plate. The dimensions of the peg should be such that the peg can be clamped in the lower jaw of an adhesion tester. 37 micron polyester film is used.
• Test method Prior to testing, the glass panels were cleaned. To determine the tack, the side of the glass not to be tested was covered with 37 micron polyester film. The test strips were 25 mm wide and 150 mm long. The cuts should be clean and straight. The backing paper from each strip was removed immediately prior to the test being carried out. The test samples were positioned as follows. The two ends of the sample were held and formed into a loop, with the adhesive surface directed outward, by bringing the two ends together. The free ends were covered with polyester to protect the jaws of the adhesion tester from the adhesive coating. The polyester-protected ends of the sample were placed in between the jaws in such a way that a loop of 150 mm was formed.
• the tester was started and the loop was brought into contact with the glass plate at a speed of 300 mm per minute.
• the direction of the tester was immediately reversed thereby allowing separation to take place at a speed of 300 mm per minute. It is important that delay in reversing direction is kept to a minimum. The maximum force necessary to separate the loop completely from the glass plate was recorded.
• the tack report includes the tack value in Newton per meter width (N/m). If other than 25 mm widths are tested, Newton per meter values are obtained by dividing the observed value by the width of the specimen. Report which side of the tape the values represent (laminating or mounting), and if the value is obtained from a deviating test width, then this specific width should also be mentioned. The rigidity of the specimen affects the results and must be considered when comparing different adhesives on different carriers. Report the tack value in Newton per meter width (N/m).
• Peel adhesion onto polyethylene is the force (average) required to remove a pressure sensitive tape from a test panel at a specified angle and speed using a defined pressure to establish contact.
• Equipment The following equipment was used for this evaluation:
• Polyethylene foil (25 ⁇ ) (standard PE testing side is typically an interior face of the roll) Supplier ACE
• Test material and polyethylene test substrates were conditioned for 24 hours at a temperature of 23 ⁇ 2°C and at a relative humidity at that temperature of 50 ⁇ 2%.
• a DC-tape was laminated onto the aluminum panel.
• the untreated side of the polyethylene foil was laminated onto the self-adhesive aluminum panel with a hard rubber roller.
• the polyethylene foil was protected with a clean unlacquered paper.
• the test specimens had a width of 25 mm and a length of approximately 150 mm.
• the test specimens were cut with a suitable cutter, in the machine direction. At the edge a paper strip was laminated with overlapping of ⁇ 1 cm.
• 90° peel is the averaged force required to remove the test specimen from the test substrate (N/25 mm).
• Prototypes were prepared based on two adhesives. 1807 was chosen for its well known application in negative pressure wound therapy (NPWT) (long term application on skin). AVC12363 was selected for its polymer structure. AVC-12363 does not contain any -COOH functional groups.
• Tables 3 and 4 summarize the performance and characteristics of multilayer assemblies formed using the adhesive compositions described herein.
• the designation "FD CHG” in the column “Antimicrobial” refers to freeze dried chlorhexidine gluconate as described herein.
• the term “AMX” refers to antimicrobial efficacy.
• PAPE refers to adhesion on polyethylene.
• FHC refers to fluid handling capacity.
• NT refers to not nested.
• Antimicrobial efficacy evaluation was performed following ASTM 2180 initially on both adhesive samples with and without carboxymethyl cellulose. The rational for this choice was based upon the following. 1807 with its high concentration of -COOH functional groups might inhibit the release of the positively charged chlorhexidine gluconate. And, carboxymethyl cellulose is an anionic polymer and could retain the chlorhexidine gluconate.
• Figures 1 and 2 Antimicrobial efficacy of the various samples are illustrated in Figures 1 and 2. The data in the referenced figures was based upon all adhesives coated at 100 gsm. Figure 1 represents antimicrobial efficacy following ASTM2180 without re-inoculation. Figure 2 represents antimicrobial efficacy following ASTM2180.
• antimicrobial efficacy of the prototypes made with 1807 or AVC-12363 with or without carboxymethyl cellulose (A800) exhibited similar antimicrobial efficacy (see Figures 1 and 2) at high chlorhexidine gluconate concentration. Neither the carboxymethyl cellulose nor the - COOH functional group of the 1807 adhesive appeared to inhibit the antimicrobial efficacy.

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• Health & Medical Sciences (AREA)
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• General Health & Medical Sciences (AREA)
• Engineering & Computer Science (AREA)
• Chemical & Material Sciences (AREA)
• Veterinary Medicine (AREA)
• Surgery (AREA)
• Public Health (AREA)
• Animal Behavior & Ethology (AREA)
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• Pest Control & Pesticides (AREA)
• Agronomy & Crop Science (AREA)
• Organic Chemistry (AREA)
• Materials Engineering (AREA)
• Materials For Medical Uses (AREA)
• Adhesives Or Adhesive Processes (AREA)
• Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
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• 2012
  • 2012-01-23 DK DK12702693.8T patent/DK2665363T3/da active
  • 2012-01-23 ES ES12702693T patent/ES2767278T3/es active Active
  • 2012-01-23 WO PCT/US2012/022162 patent/WO2012100244A2/en not_active Ceased
  • 2012-01-23 US US13/980,592 patent/US9346981B2/en active Active
  • 2012-01-23 PL PL12702693T patent/PL2665363T3/pl unknown
  • 2012-01-23 JP JP2013550654A patent/JP2014510038A/ja active Pending
  • 2012-01-23 BR BR112013018616-0A patent/BR112013018616B1/pt active IP Right Grant
  • 2012-01-23 EP EP12702693.8A patent/EP2665363B1/en active Active
  • 2012-01-23 CN CN2012800139761A patent/CN103442572A/zh active Pending
  • 2012-01-23 CN CN201711155286.0A patent/CN107890583A/zh active Pending
  • 2012-01-23 HU HUE12702693A patent/HUE048016T2/hu unknown
• 2016
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• 2018
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