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WO2012123273A1 - Revêtement antimicrobien - Google Patents

Revêtement antimicrobien Download PDF

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Publication number
WO2012123273A1
WO2012123273A1 PCT/EP2012/053698 EP2012053698W WO2012123273A1 WO 2012123273 A1 WO2012123273 A1 WO 2012123273A1 EP 2012053698 W EP2012053698 W EP 2012053698W WO 2012123273 A1 WO2012123273 A1 WO 2012123273A1
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WO
WIPO (PCT)
Prior art keywords
acid
antimicrobial
salts
diamine
polyamide copolymer
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Application number
PCT/EP2012/053698
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English (en)
Inventor
Marcus Fehr
Harald Keller
Catharina Hippius
Original Assignee
Basf Se
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Publication date
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Publication of WO2012123273A1 publication Critical patent/WO2012123273A1/fr

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    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
    • C08G69/00—Macromolecular compounds obtained by reactions forming a carboxylic amide link in the main chain of the macromolecule
    • 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
    • C09D177/00—Coating compositions based on polyamides obtained by reactions forming a carboxylic amide link in the main chain; Coating compositions based on derivatives of such polymers
    • 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
    • C08K3/01—Use of inorganic substances as compounding ingredients characterized by their specific function
    • C08K3/015—Biocides
    • 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
    • C08K5/0008—Organic ingredients according to more than one of the "one dot" groups of C08K5/01 - C08K5/59
    • C08K5/0058—Biocides

Definitions

  • the present invention relates to a process for coating the surface of a substrate with a biocidal substance, to substrates and articles with biocidal surfaces obtainable by this process, and to the use of certain copolyamides in combination with an antimicrobial agent for an antimicrobial surface finishing as well as for the reduction of microbial, especially bacterial, growth on such a surface, especially on the surface of a medical article.
  • WO 98/58690 proposes a coating comprising a hydrogel polymer and a bio- active agent entrapped in a flexible stabilizing polymer, which is mainly selected from crosslinkable acrylics.
  • WO 03/066721 discloses certain polyamide coatings which may be loaded with aque- ous solutions of some antimicrobials such as cetyl pyridinium chloride.
  • copolyamides are especially suitable as a carrier for an antimicrobial agent, and may be applied as a coating providing a slow and efficient release of said antimicrobial agent.
  • the invention thus primarily pertains to a composition comprising a film-forming polyamide copolymer and an antimicrobial agent, characterized in that the copolymer (i.e. generally the phase formed by the copolymer) takes up at least 2% by weight of water, if in contact with an aqueous phase, and further characterized in that the antimicrobial agent is, at least partly, water soluble.
  • the percentage of water uptake relates to the total weight of the swollen copolymer, the water content of which typically ranging from 2 to about 20% b.w..
  • Preferred copolyamides for use in the invention possess a capacity of water uptake, which is expressed by at least 3 % b.w.
  • Water uptake in the sense as noted above, is generally detectable by comparison of the weight of the dried copolymer with the same copolymer equilibrated with purified water at room temperature (drying may be effected, for exam- pie, by heating to 60-100 °C in air and/or drying under reduced pressure, e.g. 1 -100 mbar, until no further weight loss detectable).
  • Preferred copolymers are those, which are soluble in alcohol, or mixtures of alcohol containing up to 50% b.w. of water, and optionally up to 10% b.w. of further solvents.
  • examples are ethanol, propanol, especially in mixtures of lower (i.e. C1-C4-) alcohols in amounts of 70% b.w. or more, especially 80% b.w. or more, with water, a typical weight ratio being 8 : 2.
  • Further solvents may be selected e.g. from hydrocarbons such as toluene or especially non-aromatic hydrocarbons, they are preferably present in low amounts (e.g. up to 5, more preferably up to 2.5, especially up to 1 % b.w.), or not present at all. Examples for suitable polymers of this class, and solutions thereof, are given in WO 10/146054 or DE-A- 755617.
  • the invention further provides a coating formed by said composition, or an article comprising at least one surface covered with this coating.
  • Suitable polyamide copolymers are generally chosen from hydrophilic polyamides comprising a low ratio of (hydrophobic) methylene moieties CH2 to amide moieties CONH.
  • Typical polyamides for use in the present invention comprise, or consist of, monomers selected from C2-C15 dioic acids combined with one or more C2-C15 diamines and/or C4-C8 aminoacids, C4-C8 lactams; the monomer components are preferably aliphatic and/or cycloaliphatic.
  • dioic acids useful are aliphatic or cycloaliphatic ones like butane dioic acid, pentane dioic acid, hexane dioic acid, heptane dioic acid, octane dioic acid, cyclohexane dioic acid; preferred are straight-chain omega-dioic acids, or cyclohexane-1 ,4-dioic acid.
  • Diamine moieties are often straight- chain aliphatic omega-diamines and/or cycloaliphatic omega-diamines, especially mixtures thereof.
  • diamines useful are aliphatic diamines like butane diamine, pentane diamine, hexane diamine, heptane diamine, octane diamine, preferably straight-chain omega-diamines.
  • cycloaliphatic diamines are cyclohexane diamine, amino-(aminocyclohexyl)-cyclohexane, di(aminocyclohexyl)methane, di(aminocyclohexyl)ethane, di(aminocyclohexyl)propane, and especially those of formula
  • A is Ci-C4alkylene
  • D is Ci-C4alkylene, -0-, -S-, -SO-, -SO2-; and wherein the residues Ax-Nh preferably are in the positions 4,4'.
  • D is preferably alkylene, especially methylene. A is preferably zero.
  • Preferred cycloaliphatic diamines include cyclohexane-1 ,4-diamine, 1 -amino-4-(4-aminocyclohexyl)-cyclohexane, di(4- aminocyclohexyl)methane, 1 , 1 -di(4-aminocyclohexyl)ethane, 2,2-di(4- aminocyclohexyl)propane.
  • aminoacids useful are aminoacetic acid (glycin), 3-aminopropanoic acid, 6-aminohexanoic acid, 5-aminopentanoic acid, 4-aminobutanoic acid.
  • lactams useful are those of 6-aminohexanoic acid, 5-aminopentanoic acid, 4-aminobutanoic acid.
  • polyamides and copolyamides are linear ho- mopolyamides and copolyamides which are prepared in a known manner from the bi- functional carboxylic acids and diamines and/or from omega-amino acids, lactams or suitable derivatives of these compounds, such as a polyamide obtained from
  • metaxylylenediamine and adipic acid or from trimethyl- or hexamethylenediamine or isophoronediamine and adipic acid; or a polyamide of epsilon-caprolactam/adipic acid/hexamethylenediamine/4,4-diaminodicyclohexylmethane, or of epsilon- caprolactam/adipic acid/hexamethylenediamine/polyethyleneglycoldiamine; or the N- methylol or N-alkoxymethyl derivatives of all these homopolyamides and copolyamides.
  • the molar amount of dioic acid in general, is roughly the same as the molar amounts of diamines (i.e. both components are present in equimolar amounts).
  • the present copolymer thus preferably consists essentially of monomer components
  • lactame / amino acid monomers are preferably selected from 6- aminohexanoic acid, 5-aminopentanoic acid, 4-aminobutanoic acid and lactames thereof, especially epsilon-caprolactam.
  • the aliphatic diamine of component B is preferably selected from n-butane-1 ,4- diamine, n-pentane-1 ,5-diamine, n-hexane-1 ,6-diamine, n-heptane-1 ,7-diamine, n- octane-1 ,8-diamine, and most preferably is n-hexane-1 ,6-diamine (i.e. hexamethylenediamine).
  • the dioic acid components B and C is preferably selected from succinic acid, glutaric acid, adipic acid, pimelic acid, suberic acid, azelaic acid, sebacic acid; most preferably, the dioic acid monomer is adipic acid.
  • the cycloaliphatic diamine of component C preferably is of the formula
  • the cycloaliphatic diamine monomer is 4,4'-diamino-dicyclohexylmethane.
  • copolymers comprising the following monomer composition:
  • components A, B and C adding up to 100%.
  • suitable copolymers in the present compositions are those containing 20-30 % b.w. of component A, 20-30 % b.w. of component B and 40-60 % b.w. of component C; furthermore preferred are those containing 20-30 % b.w. of component A, 20-27.5 % b.w. of component B and 45-55 % b.w. of component C; for example those containing 25 % b.w. of component A, 25 % b.w. of component B and 50 % b.w. of component C wherein each quantity may vary by +-20%, especially by +-
  • copolymers essentially consisting of
  • each quantity may vary e.g. by +-5%.
  • the molecular weight (Mn, as determined e.g. by GPC) of the polyamide copolymer is preferably from the range 5000 to 50000, especially 10000 to 30000.
  • the polydisper- sity of the polyamide copolymer is preferably ⁇ 5, especially ⁇ 4.5, especially ⁇ 4.
  • Especially useful copolyamides for the purpose of the invention include those of CA- Reg. Nos. 25053-13-8, 74083-22-0, 150747-01 -6, 25053-13-8, 73561 -43-0,
  • An especially preferred copolyamide is the one essentially consisting of the monomer units hexanedioic acid, hexahydro-2H-azepin-2-one, 1 ,6-hexanediamine and 4,4'- methylenebis[cyclohexanamine] in the ratio as defined above (CA-Reg. No. 25053-13- 8).
  • the above swellable copolyamides are suitable for systems based on water soluble antimicrobial actives.
  • the present copolyamides especially CA-Reg. No. 25053-13-8, are film-forming polyamides which form flexible, scratch-resistant coatings or tough, resilient, abrasion-resistant coverings on plastics, films, nonwovens, fabrics, leather, paper, wood, or metal. Most importantly, these materials are able to take up water (see above), which forms a liquid phase. It has been the finding of the present invention, that water-soluble actives can migrate within this phase to the polymer surface, thus leading to a water triggered release of the active component. Proper migration leads to bactericidal concentrations at the surface that efficiently kill adhering microorganisms.
  • Polyamides useful in the present invention are known compounds, many of them are items of commerce.
  • Examples for medical devices comprising the present composition are especially catheters, vascular shunts. Further, the present composition may be included in filter materials, dressing materials, syringes, suture materials, gloves, mattresses, packag- ing materials (for food, drugs, medical devices, cosmetics, e.g. in the form of boxes or films comprising paper, cardboard and/or plastics coated with the composition of the invention), hospital furniture and equipment, fabrics and water purification equipment.
  • Catheter associated urinary infections are among the most common and costly hospi- tal-acquired infections. Very often, these infections originate from biofilms that form on the abiotic catheter surfaces. To avoid or delay biofilm formation catheters with antimicrobial functionalities are required. Antimicrobial functionalities can be achieved by (i) permanently immobilizing antimicrobial actives on the catheter's surface or by (ii) compounding the antimicrobial actives into the polymer matrix or into a coating aiming at slow release. Surfaces with permanently immobilized actives are prone to inactivation by surface alterations such as protein film formation, adsorption of dead bacteria and aging.
  • antimicrobial surface functionalities based on the slow release of actives are more resistant to these processes since their activity is not solely dependent on the properties of the outermost layer.
  • slow release approaches often suffer from poor migration of the antimicrobial actives.
  • poor migration leads to low and often sub-lethal concentrations of antimicrobial actives on the surfaces.
  • Sublethal concentrations lead to incomplete inactivation of microorganisms and promote the formation of resistances.
  • an antimicrobial coating is required that efficiently kills adhering microorganisms by ensuring proper migration of the antimicrobial active.
  • the antimicrobial agent (antimicrobial active) contained in the present composition generally is water soluble, at least to an extent necessary to provide the desired antim- icrobial effect.
  • the antimicrobial agent may be selected from suitable biocides, antibiotics and/or complexing agents.
  • Complexing agents are usually selected from suitable mono- or especially multidentate components (also denoted as chelators) containing bonding sites e.g. selected from sulfur, oxygen, aminic nitrogen, hydroxamate, carboxylate, examples are polycarbox- ylic acids and hydroxy acids including their salts like citrate, lactate, maleate, ethyl- enediaminetetraacetate (EDTA), ethyleneglycol-bis ⁇ -aminoethylether)-N ,N ,N',N'- tetraacetate (EGTA), diethylene triamine pentaacetate (DTPA), N ,N'-ethylene-bis-(o- hydroxyphenyl-glycine) (EH PG), deferasirox, deferiprone (3-hydroxy-1 ,2- dimethylpyridin-4(1 H)-one); amino acids and their salts; polythiocarboxylic acids and their salts like dimercaptosuccinic acid; peptides and proteins such
  • Biocides for use as the water soluble antimicrobial active are, for example, antimicrobial oligomers or polymers, such as oligomers or polymers comprising quaternary ammonium moieties or guanidine moieties, or are antimicrobial peptides or proteins with antimicrobial effect.
  • Preferred agents of this class are polyhexamethylene biguanide (PH M B)
  • PH M B and properties when applied in aqueous environment, is disclosed e.g. in US- 4758595; see especially col. 3, line 12, to column 4, line 50, whose contents is hereby incorporated by reference.
  • antimicrobial peptides are the first line of defense against pathogenic microorganisms that try to attack mucous membranes.
  • Antimicrobial peptides are synthesized by mucous membranes and secreted to the surface. The peptides kill pathogenic bacteria before they can attach and colonize the surface.
  • PH M B belongs to the large class of cationic/hydrophobic antimicrobials (like quaternary ammonium compounds).
  • Antimicrobial peptides and cati- onic/hydrophobic antimicrobials kill bacteria by interacting with the poly- anionic/hydrophobic bacterial envelope (cell wall and plasma membrane). The interaction with the cell envelope leads to the disruption of membrane gradients and finally to the death of the microorganisms.
  • antimicrobial peptides useful in combination with the present copolymer in the present invention are disclosed, for example, at http://aps.unmc.edu/AP/main.php; Wang et al., Nucleic Acids Res. 2004 January 1 ; 32(Database issue): D590-D592.
  • any other antimicrobial active belonging to the large class of cationic antimicrobials can be used such as:
  • Quarternary ammonium compounds (Benzylalkyldimethyl (Alkyl from C8- C22, saturated and non-saturated, coco- and soy alkylic) chloride, bromide or hydroxide)
  • Quarternary ammonium compounds (Benzylalkyldimethyl (Alkyl from C8- C22, saturated and non-saturated, coco- and soy alkylic) chloride, bromide oder methylsulphate)
  • Quarternary ammonium compounds (Alkyltri methyl (Alkylkyl)
  • Benzalkonium chloride Alkyl-dimethyl-benzyl-ammoniumchloride
  • Alkyl-didecyl-polyoxethyl-ammoniumpropionate Alkyl-dimethyl- compounds alkylbenzyl-ammoniumchlorid, Alkyl-dimethyl-ethyl-ammoniumchloride,
  • Cocos-dimethylbenzyl-ammoniumchloride Cocos-dimethylbenzyl-ammoniumchloride
  • N-alkyl polyethylenimines N-alkyl polyethylenimines
  • oligodynamic metals or their compounds, especially particles containing silver: Zeolite supported silver is disclosed in U.S. Pat. Nos. 4,775,585; 4,91 1 ,898; 4,91 1 ,899, 6,071 ,542, U.S. Pat. No. 6,585,989. Glass supported silver is disclosed for example in published U.S. app. No. 2005/0233888. Antibacterial micro- or nanosilver is disclosed inter alia in US-6720006, US-6822034, US-2006-018943, US-2010-136073, US-2008-306183, and literature cited therein. Also useful as biocidal agents are silver compounds like silver chloride, silver oxides, silver carboxylates like silver citrate.
  • any other water soluble antimicrobial active, biocide, antibiotic can be used with this system: such other biocides include, for example, benzoic acid, its salts and esters; propionic acid and its salts; salicylic acid and its salts; sorbic acid and its salts; formaldehyde; paraformaldehyde; o-phenylphenol and its salts; inorganic sulphites and hydrogen sulphites; sodium iodate; chlorobutanol; 4-hydroxybenzoic acid and its salts and esters; 3-acetyl-6-methylpyran-2,4 (3H)-dione; formic acid; sodium formiate; di- bromohexamidine and its salts; undec-10-enoic acid and salts; hexetidine; 5-bromo-5- nitro-1 ,3-dioxane; bronopol; 2,4-dichlorobenzyl alcohol; triclocarban; 2.4.4'-trichloro
  • Antibiotics include: Aminoglycosides (Amikacin, Gentamicin, Kanamycin, Neomycin, Netilmicin, Tobramycin, Paromomycin), Ansamycins (Geldanamycin, )Herbimy-cin), Carbacephem (Loracarbef), Carbapenems (Ertapenem, Doripenem, Imipe- nem/Cilastatin, Meropenem), Cephalosporins (Cefadroxil, Cefazolin, Cefalotin or Cefa- lothin, Cefalexin, Cefaclor, Cefamandole, Cefoxitin, Cefprozil, Cefuroxime), Cefixime, Cefdinir, Cefditoren, Cefoperazone, Cefotaxime, Cefpodoxime, Cef-tazidime, Ceftibu- ten, Ceftizoxime, Ceftriaxone, Cefepime
  • Sulfadiazine Silver sulfadiazine, Sulfamethizole, Sulfamethoxazole, Sul- fanilimide , Sulfasalazine, Sulfisoxazole, Trimethoprim, Tri-methoprim-
  • Tetracyclines Desmeclocycline, Doxycycline, Mino-cycline, Oxytet- racycline, Tetracycline
  • Others Arsphenamine, Chloramphenicol, Fosfomycin, Fusidic acid, Linezolid, Metronidazole, Mupirocin, Platensimycin, Quinupristin/Dalfopristin, Ri- faximin, Thiamphenicol, Tinidazole).
  • antimicrobial surface functionality is not limited to catheters but can be applied for all applications that require antimicrobial surface functionality.
  • compositions of the invention antimicrobial coatings on plastics, films, nonwovens, fabrics, leather, paper, wood, ceramics or metal can be achieved.
  • the substrate can be a two-dimensional object such as a sheet or a film, or any three dimensional object; it can be transparent or opaque.
  • plastics or films examples are polymers such as acrylic polymers, styrene polymers and hydrogenated products thereof, vinyl polymers and derivatives thereof, polyolefins and hydrogenated or epoxidized products thereof, aldehyde polymers, epoxide polymers, polyamides, polyesters, polyurethanes, polycarbonates, silicones, sulfone-based polymers and natural polymers and derivatives thereof.
  • Acrylic polymers can be polymers formed from at least one acrylic monomer or from at least one acrylic monomer and at least one other ethylenically unsaturated monomer such as a styrene monomer, vinyl monomer, olefin monomer or maleic monomer.
  • acrylic monomers are (meth)acrylic acid, (meth)acrylamide,
  • (meth)acrylonitrile ethyl (meth)acrylate, butyl (meth)acrylate, hexyl (meth)acrylate, 2- ethylhexyl (meth)acrylate, glycidyl methacrylate, acetoacetoxyethyl methacrylate, di- methylaminoethyl acrylate and diethylaminoethyl acrylate.
  • styrene monomers are styrene, 4-methylstyrene and 4-vinylbiphenyl.
  • vinyl monomers are vinyl alcohol, vinyl chloride, vinylidene chloride, vinyl isobutyl ether and vinyl acetate.
  • olefin monomers are ethylene, propylene, butadiene and isoprene and chlorinated or fluorinated derivatives thereof such as tetrafluroethylene.
  • maleic monomers are maleic acid, maleic anhydride and maleimide.
  • acrylic polymers are poly(methyl methacrylate) (PMMA), poly(butyl methacrylate), polyacrylonitrile (PAN), polyacrylic acid, styrene/2-ethylhexyl acrylate copolymer, styrene/acrylic acid copolymer.
  • Styrene polymers can be polymers formed from at least one styrene monomer or from at least one styrene monomer and at least one vinyl monomer, olefin monomer and/or maleic monomer.
  • styrene polymers are polystyrene (PS), styrene butadiene styrene block polymers, styrene ethylene butadiene block polymers, styrene ethylene propylene styrene block polymers and styrene-maleic anhydride copolymers.
  • Vinyl polymers can be polymers formed from at least one vinyl monomer or from at least one vinyl monomer and at least one olefin monomer or maleic monomer.
  • vinyl polymers are polyvinyl chloride (PVC), polyvinylidenfluoride (PVDF), poly- vinylalcohol, polyvinylacetate, partially hydrolysed polyvinyl acetate and methyl vinyl ether-maleic anhydride copolymers.
  • PVDF polyvinylidenfluoride
  • derivatives thereof are carboxy- modified polyvinyl alcohol, acetoacetyl-modified polyvinyl alcohol, diacetone-modified polyvinyl alcohol and silicon-modified polyvinyl alcohol.
  • Polyolefins can be polymers formed from at least one olefin monomer or from at least one olefin monomer and maleic monomer.
  • polyolefines are low-density polyethylene (LDPE), high-density polyethylene (HDPE), polypropylene (PP), biaxially orientated polypropylene (BOPP), polybutadiene, polytetrafluoroethylene (Teflon- PTFE), chlorinated polyethylene and isopropylene-maleic anhydride copolymer.
  • Aldehyde polymers can be polymers formed from at least one aldehyde monomer or polymer and at least one alcohol monomer or polymer, amine monomer or polymer and/or urea monomer or polymer.
  • aldehyde monomers are formaldehyde, furfural and butyral.
  • alcohol monomers are phenol, cresol, resorcinol and xylenol.
  • An example of a polyalcohol is polyvinyl alcohol.
  • amine monomers are aniline and melamine.
  • urea monomers are urea, thiurea and dicyandiamide.
  • aldehyde polymer polyvinyl butyral formed from butyral and polyvi- nylalcohol.
  • Epoxide polymers can be polymers formed from at least one epoxide monomer and at least one alcohol monomer and/or amine monomer.
  • epoxide monomers are epichlorohydrine and glycidol.
  • alcohol monomers are phenol, cresol, resorcinol, xylenol, bisphenol A and glycol.
  • An example of epoxide polymer is phenoxy resin, which is formed from epichlorihydrin and bisphenol A.
  • Polyamides can be polymers formed from at least one monomer having an amide group or an amino as well as a carboxy group or from at least one monomer having two amino groups and at least one monomer having two carboxy groups.
  • An example of a monomer having an amide group is caprolactam.
  • An example of a diamine is 1 ,6- diaminohexane.
  • dicarboxylic acids are adipic acid, terephthalic acid, isophthalic acid and 1 ,4-naphthalenedicarboxylic acid.
  • polyamides are polyhexamethylene adipamide and polycaprolactam.
  • Polyesters can be polymers formed from at least one monomer having a hydroxy as well as a carboxy group or from at least one monomer having two hydroxy groups and at least one monomer having two carboxy groups or a lactone group.
  • An example of a monomer having a hydroxy as well as a carboxy group is adipic acid.
  • An example of a diol is ethylene glycol.
  • An example of a monomer having a lactone group is carprolac- tone.
  • dicarboxylic acids are terephthalic acid, isophthalic acid and 1 ,4- naphthalenedicarboxylic acid.
  • An example of a polyester is polyethylene terephthalate (PET). So-called alkyd resins are also regarded to belong to polyester polymers.
  • Polyurethane can be polymers formed from at least one diisocyanate monomer and at least one polyol monomer and/or polyamine monomer.
  • diisocyanate monomers are hexamethylene diisocyanate, toluene diisiocyanate, isophorone diisocyanate and diphenylmethane diisocyanate.
  • polycarbonates examples include poly(aromatic carbonates) and poly(aliphatic carbonates).
  • Poly(aliphatic carbonates) can be formed from carbon dioxide and at least one epoxide.
  • sulfone-based polymers examples include polyarylsulfone, polyethersulfone (PES), poly- phenylsulfone (PPS) and polysulfone (PSF).
  • PES polyethersulfone
  • PPS poly- phenylsulfone
  • PSF polysulfone
  • Polysulfone (PSF) is a polymer formed from 4,4-dichlorodiphenyl sulfone and bisphenol A.
  • Examples of natural polymers are starch, cellulose, gelatine, caesin and natural rubber.
  • Examples of derivatives are oxidised starch, starch-vinyl acetate graft copolymers, hy- droxyethyl cellulose, hydroxypropyl cellulose, methyl cellulose, nitryl cellulose, ethyl cellulose, carboxymethyl cellulose and acetyl cellulose.
  • Fabrics can be made from natural fibres such as fibres from animal or plant origin, or from synthetic fibres.
  • natural fibres from animal origin are wool and silk.
  • natural fibres from plant origin are cotton, flax and jute.
  • synthetic textiles are polyester, polyacrylamide, polyolefins such as polyethylene and poly- propylene and polyamides such as nylon and lycra.
  • Ceramics are products made primarily from clay, for example bricks, tiles and porcelain, as well as technical ceramics.
  • Technical ceramics can be oxides such as aluminium oxide, zirconium dioxide, titanium oxide and barium titanate, carbides such as sodium, silicon or boron carbide, borides such as titanium boride, nitrides such as titanium or boron nitride and silicides such as sodium or titanium silicide.
  • metals examples include iron, nickel, palladium platin, copper, silver, gold, zinc and aluminium and alloys such as steel, brass, bronze and duralumin.
  • the invention further pertains to a process for applying an antimicrobial coating, and to the use of the composition of the invention for achieving an antimicrobial, preserving and/or sterilizing effect, especially on the surface of an article, such as a medical article, like those described above.
  • the invention opens a way to provide an article equipped with an antimicrobial surface by carrying out the following steps: i) preparing a solution or dispersion of a polyamide copolymer as described above and the antimicrobial agent as described above, in a suitable solvent,
  • the solvent in step (i) is preferably selected from aliphatic C1 -C6 alcohols, phenols, benzyl alcohol, and mixtures thereof with up to 50% b.w. of water; especially selected from methanol, ethanol, propanol and mixtures thereof with water.
  • the composition can be applied, for example, using a wire bar or by dipping or spraying.
  • Drying (step iii) may be effected, for example, by heating to 60-100 °C in air and/or drying under reduced pressure, e.g. 1 -100 mbar.
  • the dry coating layer can have a thickness in the range of from 0.1 to 1000 ⁇ , preferably from 1 to 100 ⁇ .
  • the amount of antimicrobial agent usually ranges from 1 to 100 parts by weight, relative to 100 parts by weight of the educt polyamide copolymer.
  • the solution or dispersion of step (i) may comprise one or more quarternary ammonium compounds, other biocides and/or additional components such as surfactants, de-foamers.
  • biocides are 5-chloro-2-(2,4-dichlorophenoxy)phenol, which is sold, for example, under the tradename Ciba® Irgasan® DP300, N'-ferf-butyl-N-cyclopropyl- 6-(methylthio)-1 ,3,5-triazine-2,4-diamine, which is sold under the tradename Ciba® Irgarol® 1051 , 2-thiazol-4-yl-1 H-benzoimidazole, which is sold under the tradename Ciba® Irgaguard® F3000, chlorhexidine, gallic acid, mucobromic acid, itaconic acid and 3-iodo-2-propynyl butyl carbamate, which is sold under the tradename Ma- guardTM 1-100.
  • Ciba® Irgasan® DP300 N'-ferf-butyl-N-cyclopropyl- 6-(methylthio)-1 ,3,5-triazine-2,4
  • surfactants examples include anionic surfactants such as sodium dodecyl sulfate or ammonium lauryl sulfate, cationic surfactants such as cetyl trimethylammonium bromide or cetyl pyridinium chloride, amphoteric surfactants such as dodecyl betaine and nonionic surfactants such as copolymers of poly(ethylene oxide) and poly(propylene oxide).
  • anionic surfactants such as sodium dodecyl sulfate or ammonium lauryl sulfate
  • cationic surfactants such as cetyl trimethylammonium bromide or cetyl pyridinium chloride
  • amphoteric surfactants such as dodecyl betaine
  • nonionic surfactants such as copolymers of poly(ethylene oxide) and poly(propylene oxide).
  • defoamers are mineral oil preparations such as the defoamer sold under the tradename Ciba® EFKA® 2526 and polyether functionalzed polysiloxanes such as the defoamer sold under the tradename Ciba® EFKA® 2550
  • the composition can comprise 0 to 50% by weight of the additional components based on the weight of the composition. Preferably, it comprises 0.001 to 10% by weight of additional components and more preferably 0.01 to 5% by weight.
  • the antimicrobial article of the invention thus comprises a substrate material having at least one surface formed by plastics, films, nonwovens, fabrics, leather, paper, wood, glass or metal, which is covered by the antimicrobial composition described above.
  • the antimicrobial article preferably is a medical device, a filter pad, a dressing, a syringe, a suture, a glove, a mattress, especially a catheter or a vascular shunt.
  • medical articles are wound care bandages, catheters, implants, artificial organs, artificial joints, artificial blood vessels and medicinal devices such as medical instruments and tools, stethoscopes, tubes, syringes and needles.
  • TSBY growth medium for bacteria Peptone from casein 17.0 g , peptone from soymeal 3.0 g, D(+)-Glucose 2.5 g, NaCI 5.0 g , K2HP04 2.5 g, distilled water 1000.0 ml , adjust pH to 7.3)
  • a copolyamide (CA-Reg. No. 25053-13-8) consisting of equal amounts by weight of the monomer components epsilon-caprolactam (component A), equimolar mixture of hexamethylenediamine and adipic acid (component B), and equimolar mixture of 4,4'- diamino-dicyclohexylmethane and adipic acid (component C), together with an antimicrobial agent (P18 or PHMB), is dissolved in a mixture of n-propanol (80%) and water (20%).
  • PHM B is supplied by Arch Chemicals
  • P18 is supplied by custom peptide synthesis, Bachem (Switzerland).
  • Silicone rubber discs are coated using the resulting vis- cous solution. After evaporation of the solvents, the films are washed to mimic leaching of the antimicrobials in a continuous-flow of a urinary catheter.
  • the antimicrobials are added to 1.5 ml of a mixture of 80% n-propanol and 20% water to a final concentration of 10% relative to the copolyamide. The mixture is heated to 85°C and stirred until the antimicrobials are completely dissolved and a homogenous, viscous and clear solution is obtained. The viscous and clear solution is used to cast films on silicone rubber discs.
  • PHMB is compounded into the copolyamide of CA-Reg. No. 25053-13-8 (example 1 ) and films are casted as described in example 1 on PVC foil (backing film).
  • the PHMB content is 10% (w/w) relative to the copolymer.
  • the coated films are incubated in 100 ml of ultra-pure water. Every 60 min the film is transferred into a new container with 100 ml of water.
  • the PHMB content in the water is analyzed by competition with Nioxime for NiCI2.
  • Nioxime forms a red complex with NiCI2.
  • PHMB forms a more stable and colorless complex with NiCI2.
  • the increase in PHMB is determined by the decrease in red color using a calibration curve.
  • NiCI2-solution 3.37 mM
  • Nioxime solution 28.14 mM
  • the sample is sonicated for 5 min and incubated for 1 h.
  • the red color intensity is determined by measuring the ab- sorption at 550 nm.
  • Figure 1 shows rapid and substantial release of PH MB within the first 10 h.
  • the release rate decreases with increasing time and decreasing concentration of PH MB within the polymer. Still, within 190 h more than 85% of the PHM B is released, arguing for proper migration of PHM B inside the water phase of the present coating.
  • Example 3 Analysis of Antimicrobial Activity
  • a static biofilm assay in 24-well plates is developed for Staphylococcus epidermidis, Escherichia coli and Proteus mirabilis.
  • the biofilm is grown on silicone rubber discs that are reversibly attached to the bottom of the wells.
  • Surface colonization and biofilm formation are analyzed 1 h and 24h after addition of the bacteria.
  • the surfaces are removed from the plate, rinsed and the attached bacteria are removed by sonication.
  • the resulting suspensions are diluted and plated on agar plates.
  • the number of living bacteria on the silicone rubber surface is determined by counting the colonies after overnight incubation of the agar plates.
  • biofilm formation is triggered by adding 105 colony forming units (cfu, number living bacteria) at high salinity to each well.
  • a pre-culture in a 100 ml shake-flask is started from an overnight culture by diluting into TSBY medium to yield a final optical density (OD 600 nm) of 0.1 .
  • the pre-culture is shaken at 37°C until the logarithmic growth phase with an OD 600 nm of ⁇ 3 is reached.
  • the pre-culture is diluted to a final concentration of ⁇ 10E5 cfu/ml (OD 600 nm of ⁇ 0.0004) in 5% TSBY in saline (0,9% NaCI in water).
  • PHMB is compounded into the copolyamide of CA-Reg. No. 25053-13-8 as described in example 1 .
  • the anti-biofilm activity of the coated silicone rubber discs is analyzed against S. epidermidis, E. coli and P. mirabilis as in example 3.
  • the protocols include repeated washing cycles with 1 ml of saline (10x) and incubation in large volumes of saline for 1 h and 24h.
  • the antimicrobial peptide P18 is used as antimicrobial active.
  • P18 is compounded into the copolyamide of CA-Reg. No. 25053-13- 8 as described in example 1.
  • the anti-biofilm activity of the coated silicone rubber discs is analyzed against S. epidermidis, E. coli and P. mirabilis as in example 3.
  • the surfaces are washed prior to the biofilm assay.
  • the protocols include repeated washing cycles with 1 ml of saline (10x) and incubation in large volumes of saline for 1 h and 24h.
  • Figure 1 shows the release of PHMB from the copolyamide as of example 1 (backing film/ultrapure water; cumulated release of PHMB in percent as a function of time).
  • Figure 2 shows the anti-biofilm activity of silicone rubber surfaces after coating according to example 4; Control (C, silicone rubber without antimicrobial surface functionaliza- tion), and Silicone rubber with coating containing 10 % PHM B after 10x washes and 24h in saline (A, B).

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  • Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Polymers & Plastics (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Materials Engineering (AREA)
  • Wood Science & Technology (AREA)
  • Agricultural Chemicals And Associated Chemicals (AREA)

Abstract

L'invention concerne des compositions combinant certains copolyamides gonflant dans l'eau avec des agents antimicrobiens qui sont solubles dans l'eau ou au moins partiellement solubles dans l'eau, lesdites compositions étant bien adaptées en tant que matières de revêtement, en particulier pour des dispositifs médicaux tels que des cathéters ou des shunts vasculaires.
PCT/EP2012/053698 2011-03-11 2012-03-05 Revêtement antimicrobien WO2012123273A1 (fr)

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Cited By (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8728455B2 (en) 2012-01-27 2014-05-20 Basf Se Radiation-curable antimicrobial coatings
CN106496430A (zh) * 2016-10-21 2017-03-15 克灵美（天津）生物科技有限公司 具有生物相容性的抗微生物高分子
EP3324739A4 (fr) * 2015-07-24 2019-02-13 Teleflex Medical Incorporated Compositions antimicrobiennes destinées à des applications chirurgicales
US10440950B2 (en) 2015-09-17 2019-10-15 Ecolab Usa Inc. Methods of making triamine solids
US10463041B2 (en) 2015-09-17 2019-11-05 Ecolab Usa Inc. Triamine solidification using diacids
WO2020057845A1 (fr) * 2018-09-17 2020-03-26 Unilever Plc Composition
CN112852043A (zh) * 2021-01-11 2021-05-28 华东理工大学 一种浓缩长效抗菌抗污聚烯烃母粒及其制备方法
CN115605238A (zh) * 2020-04-03 2023-01-13 特拉克特维斯有限公司（Es） 用于装置的涂层

Citations (15)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE755617C (de) 1941-05-23 1953-05-26 Ig Farbenindustrie Ag Verfahren zur Herstellung von Kondensationsprodukten
US4758595A (en) 1984-12-11 1988-07-19 Bausch & Lomb Incorporated Disinfecting and preserving systems and methods of use
US4775585A (en) 1983-01-21 1988-10-04 Kanebo Ltd./Kanto Chemical Co. Polymer article having an antibacterial property containing zeolite particles therein and the processes for producing same
WO1994013870A1 (fr) * 1992-12-04 1994-06-23 Warner-Lambert Company Monofilament antimicrobien pour brosse a dents
WO1998058690A2 (fr) 1997-06-23 1998-12-30 Sts Biopolymers, Inc. Hydrogel souple adhesif et revetements medicamenteux
US6071542A (en) 1995-03-16 2000-06-06 Kanebo Ltd. Antibacterial zeolite causing little discoloration and method of the production thereof
WO2002080939A2 (fr) * 2001-01-18 2002-10-17 Genzyme Corporation Polymeres d'ionene et leur utilisation en tant qu'agents antimicrobiens
US6585989B2 (en) 2000-09-21 2003-07-01 Ciba Specialty Chemicals Corporation Mixtures of phenolic and inorganic materials with antimicrobial activity
WO2003066721A1 (fr) 2002-02-05 2003-08-14 Michigan Biotechnology Institute Polymere antimicrobien
US6720006B2 (en) 1999-06-17 2004-04-13 Bernhard Hanke Anti-microbial body care product
US20050233888A1 (en) 2004-03-08 2005-10-20 Schott Spezialglas Gmbh Antimicrobial phosphate glass with adapted refractive index
US20060018943A1 (en) 2000-08-31 2006-01-26 Bio-Gate Bioinnovative Materials Gmbh Antimicrobial material for implanting in bones
US20080306183A1 (en) 2007-06-11 2008-12-11 Joerg Leukel Antimicrobial polyolefin and polyester compositions
US20100136073A1 (en) 2007-04-18 2010-06-03 Ciba Corporation Antimicrobial plastics and coatings
WO2010146054A1 (fr) 2009-06-19 2010-12-23 Basf Se Copolyamide

Patent Citations (18)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE755617C (de) 1941-05-23 1953-05-26 Ig Farbenindustrie Ag Verfahren zur Herstellung von Kondensationsprodukten
US4775585A (en) 1983-01-21 1988-10-04 Kanebo Ltd./Kanto Chemical Co. Polymer article having an antibacterial property containing zeolite particles therein and the processes for producing same
US4911898A (en) 1983-01-21 1990-03-27 Kanebo Limited Zeolite particles retaining silver ions having antibacterial properties
US4911899A (en) 1983-01-21 1990-03-27 Kanebo Limited Zeolite particles having bacteriocidal properties
US4758595A (en) 1984-12-11 1988-07-19 Bausch & Lomb Incorporated Disinfecting and preserving systems and methods of use
WO1994013870A1 (fr) * 1992-12-04 1994-06-23 Warner-Lambert Company Monofilament antimicrobien pour brosse a dents
US6071542A (en) 1995-03-16 2000-06-06 Kanebo Ltd. Antibacterial zeolite causing little discoloration and method of the production thereof
WO1998058690A2 (fr) 1997-06-23 1998-12-30 Sts Biopolymers, Inc. Hydrogel souple adhesif et revetements medicamenteux
US6822034B2 (en) 1999-06-17 2004-11-23 Bernhard Hanke Anti-microbial silicone rubber composition and method for making same
US6720006B2 (en) 1999-06-17 2004-04-13 Bernhard Hanke Anti-microbial body care product
US20060018943A1 (en) 2000-08-31 2006-01-26 Bio-Gate Bioinnovative Materials Gmbh Antimicrobial material for implanting in bones
US6585989B2 (en) 2000-09-21 2003-07-01 Ciba Specialty Chemicals Corporation Mixtures of phenolic and inorganic materials with antimicrobial activity
WO2002080939A2 (fr) * 2001-01-18 2002-10-17 Genzyme Corporation Polymeres d'ionene et leur utilisation en tant qu'agents antimicrobiens
WO2003066721A1 (fr) 2002-02-05 2003-08-14 Michigan Biotechnology Institute Polymere antimicrobien
US20050233888A1 (en) 2004-03-08 2005-10-20 Schott Spezialglas Gmbh Antimicrobial phosphate glass with adapted refractive index
US20100136073A1 (en) 2007-04-18 2010-06-03 Ciba Corporation Antimicrobial plastics and coatings
US20080306183A1 (en) 2007-06-11 2008-12-11 Joerg Leukel Antimicrobial polyolefin and polyester compositions
WO2010146054A1 (fr) 2009-06-19 2010-12-23 Basf Se Copolyamide

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
ISSAM ET AL.: "The role of chelators is preventing biofilms formation and catheter- related bloodstream infections", CURRENT OPINION IN INFECTIOUS DISEASES, vol. 21, 2008, pages 385 - 392, XP008150471, DOI: doi:10.1097/QCO.0b013e32830634d8
KENAWY ET AL., THE CHEMISTRY AND APPLICATIONS OF ANTIMICROBIAL POLYMERS: A STATE-OF-THE-ART REVIEW, 2007
WANG ET AL., NUCLEIC ACIDS RES., vol. 32, 1 January 2004 (2004-01-01), pages D590 - D592

Cited By (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8728455B2 (en) 2012-01-27 2014-05-20 Basf Se Radiation-curable antimicrobial coatings
EP3324739A4 (fr) * 2015-07-24 2019-02-13 Teleflex Medical Incorporated Compositions antimicrobiennes destinées à des applications chirurgicales
US10440950B2 (en) 2015-09-17 2019-10-15 Ecolab Usa Inc. Methods of making triamine solids
US10463041B2 (en) 2015-09-17 2019-11-05 Ecolab Usa Inc. Triamine solidification using diacids
US11051512B2 (en) 2015-09-17 2021-07-06 Ecolab Usa Inc. Triamine solidification using diacids
US11730167B2 (en) 2015-09-17 2023-08-22 Ecolab Usa Inc. Triamine solidification using diacids
CN106496430A (zh) * 2016-10-21 2017-03-15 克灵美（天津）生物科技有限公司 具有生物相容性的抗微生物高分子
WO2020057845A1 (fr) * 2018-09-17 2020-03-26 Unilever Plc Composition
US20210348086A1 (en) * 2018-09-17 2021-11-11 Conopco Inc., D/B/A Unilever Composition
CN115605238A (zh) * 2020-04-03 2023-01-13 特拉克特维斯有限公司（Es） 用于装置的涂层
CN112852043A (zh) * 2021-01-11 2021-05-28 华东理工大学 一种浓缩长效抗菌抗污聚烯烃母粒及其制备方法

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