Classifications

• • 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
  • C08G83/00—Macromolecular compounds not provided for in groups C08G2/00 - C08G81/00
  • C08G83/002—Dendritic macromolecules
  • C08G83/005—Hyperbranched macromolecules
• • 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
  • A01N33/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic nitrogen compounds
  • A01N33/02—Amines; Quaternary ammonium compounds
  • A01N33/12—Quaternary ammonium compounds
• • 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
  • A01N55/00—Biocides, pest repellants or attractants, or plant growth regulators, containing organic compounds containing elements other than carbon, hydrogen, halogen, oxygen, nitrogen and sulfur
• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
  • C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic Table
  • C07F7/02—Silicon compounds
  • C07F7/08—Compounds having one or more C—Si linkages
  • C07F7/18—Compounds having one or more C—Si linkages as well as one or more C—O—Si linkages
  • C07F7/1804—Compounds having Si-O-C linkages
• • 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
  • C08G83/00—Macromolecular compounds not provided for in groups C08G2/00 - C08G81/00
  • C08G83/002—Dendritic macromolecules
• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
  • C07B2200/00—Indexing scheme relating to specific properties of organic compounds
  • C07B2200/11—Compounds covalently bound to a solid support

Definitions

• the present invention relates to antimicrobial protection and, more particularly, to a quaternary ammonium anti-microbial finish incorporating dendrimer polymers applied as a thin film coating using a silane coupling agent, and methods of use therefore.
• biocidal metals have been successfully incorporated into engineering materials and woven into fabrics. Because many of these agents act intra-cellularly, the active agent must migrate from the matrix into the microorganism in order to be effective. This may also result in a broader environmental contamination by the active agent. Other approaches include the use of compounds that can release small quantities of chlorine. However, these systems must be periodically recharged using specific wash procedures, which is not practical for many applications. The level of cellular killing is also an important consideration. Biocides are compounds that kill microorganisms such as bacteria, viruses and molds. Many of the current approaches have limited activity against Gram negative bacteria in particular, and may thus be considered “biostats" rather than biocides.
• Biostatic agents may merely inhibit microbial proliferation, and their limited efficacy means that a significant proportion of cells remain viable, which can then be transferred to other surroundings.
• What is desirable is a localized biocidal action that does not migrate from a matrix or platform, and which does not require regeneration. This could improve the performance and lifetime of manufactured items and provide a means to prevent cross-contamination, achieve infection control, prevent biofilm formation, and prevent deterioration and/or degradation by microorganisms.
• Quaternary ammonium compounds are a well-known example of an antimicrobial compound and are currently widely used as disinfectants. They are surface- active, broad-spectrum antimicrobial agents in which nitrogen is surrounded by four alkyl groups forming a positively charged molecule. The antimicrobial activity of QACs is markedly improved if a large aliphatic residue is attached to the quaternary nitrogen atom. This cation forms a salt with halogens such as chlorine, bromine or iodine. The biocidal action for QACs relies on an alteration of cell permeability which results in cytolytic damage and subsequent cell death.
• Dendrimers are well defined, highly branched macromolecules that emanate from a central core.
• dendritic architecture brings a very high number of Junctional groups in a compact space.
• dendritic polymers can be used as thin film coatings.
• Subsequent research into dendrimers has endeavored to protect surfaces from soils, stains, ice, graffiti, insects, oils, corrosion and chemical and biological contaminants. For example, R. Mezzenga et al. (Compos. Sci. Technol.
• dendritic polymers as modifiers for epoxy resins.
• a growing community of researchers is exploring or developing a variety of uses for dendritic macromolecules. These include nanoscale catalysts and reaction vessels, micelle mimics, magnetic resonance imaging agents, immuno-diagnostics, agents for delivering drugs or genes into cells, chemical and biological sensors, information-processing materials, high- ' performance polymers, adhesives and coatings, separation media, and molecular antennae for absorbing light energy and funneling it to a central core (as occurs in photosynthetic systems). The potential of dendrimers as hosts for other molecules was demonstrated in 1994 by
• Dendrimers have also been used to deliver antimicrobials. For example, Balogh et al. synthesized dendrimer nanocomposites, dendrimers with inorganic silver or silver ions, and tested their antibacterial properties. Balogh, L. Proc. Am. Chem. Soc. Div. Coll. & Surf. Chem., 54. (1999). For these dendrimer nanocomposites, the dendrimer itself did not have any antibacterial property.
• a quaternary ammonium functionalized dendrimer can be represented by D n -(W) 2 wherein the chemical structure of the chemical group W of a dendrimer (D) of
• quaternary ammonium generation n is terminated by a quaternary ammonium compound.
• Cooper et al.'s quaternary ammonium functionalized dendrimers derive antibacterial properties from the dendrimer itself (the surface groups of the dendrimers were transformed into quaternary ammonium groups).
• the quaternary ammonium functionalized dendrimers are much more effective against Gram-negative bacteria such as E. coli than comparable amounts of quaternary ammonium salt. Chen successfully immob ⁇ lized.these antimicrobial dendrimers onto a polyurethane in solution (post-polymerization) to create a non-leaching biocidal polymer (Chen, Z.C. Ph.D. Thesis, 2000, University of Delaware).
• Silane is a known coupling agent, but there is the potential for cross-reactions between the silane functionality and the amine groups in the backbone of polypropyleneimine (PPI) dendrimers as shown in Cooper et al.
• PPI polypropyleneimine
• silane-QAC-D silane-QAC-dendritic polymer
• the present invention provides a silane-
• the silane-QAC- D biocide generally comprises a riyperb ⁇ anched polymer modified to include functionalized quaternary ammonium for biocidal activity, and further modified to include a functionalized silane moiety to covalently attach the polymer biocide to a variety of substrates through hydrolysis.
• the dendritic polymer may be any one from among a group consisting of dendrimers, dendritic polymers, and hyperbranched polymers, and the functionalized silane moiety may be Siloxane (-Si (OR)3).
• the resulting surface treatment combines the demonstrated high potency of quaternary ammonium compound dendrimers and hyperbranched polymers with the well-established coupling chemistry of silane functional groups.
• silane groups such as methoxys ⁇ lane and ethoxysilane groups will couple to functional groups such as amines and hydroxyl groups, and covalently attach.
• a method of formulation is also disclosed. This approach provides an effective biocidal surface treatment for any substrates having exposed hydroxyl and/or amine groups and/or carbonyl groups, as well as a variety of other reactive groups or "surface activating" groups. Substrates that are usually considered non-reactive can be activated using etching (e.g. by plasma, acid etc.) or other surface activating techniques.
• FIG. 1 illustrates the products of the reaction between the quaternized hyperbranched polymer and 3-isocyanatopropyltriethoxysilane.
• FIG. 2 shows the Bioluminescence of 2* 10 9 cfu/ml E. coli in contact with polyurethane grafted with 3 rd generation PPl dendrimer containing CnQAC (Cl- couhteranion) (0.1% urethane substitution) (Chen and Cooper, Biomaterials, (2002) vol 23:3359-68).
• FIG. 3 illustrates the reaction of the siloxy groups condensing with each other to produce a cross-linked matrix at the surface.
• the present invention is a silane-QAC-dendritic polymer biocide compound in which quaternary ammonium compounds provide biocidal activity, while a silane moiety provides a means to covalently attach the biocide to a variety of substrates through hydrolysis.
• the invention is intended as a manufacturing and/or post-fabrication surface treatment by which antimicrobial agents are covalently bonded to various products, textiles, and fabrics etc. for use in various applications (to be described) where antimicrobial properties are advantageous.
• the antimicrobial agents are based on dendrimers, dendritic polymers and hyperbranched polymers that have been modified to immobilize quaternary ammonium compounds (quats, QACs) at the chain ends.
• Quats are broad spectrum antimicrobial compounds, and demonstrate very large improvements in effectiveness when present in high local concentrations such as those achieved by immobilization to dendrimers and dendritic and hyperbranched polymers.
• the present invention yields silane-QAC-Ds, i.e. dendrimers and other highly branched, high molecular weight polymers that have been modified to attach quaternary ammonium compounds at the outer boundary of the molecule.
• the resulting high local concentrations of quats account for the superior microbicidal properties of these compounds.
• substrate binding is achieved by silane coupling agents.
• Organofunctional silanes with a typical chemical structure of X-(CHa) n -Si(OR) 3 are the presently-preferred coupling agents.
• silanes excel in binding to glass, glass-fiber composites, wood, paper, leather, and synthetic fabrics etc.
• a functional silane group onto the present dendrimer, the net result is a silane-QAC- D biocide that can be used as a finishing treatment for a wide range of articles and finished goods to provide biocidal properties in a variety of performance, industrial or medical settings.
• the silane- QAC-D surface and finishing antimicrobial treatment offers distinct advantages compared with competing technologies in that activity is biocidal rather than biostatic, and since cell death is achieved by membrane disruption, they retain effectiveness when bound to a substrate and can also be non-leaching.
• the invention can also be used to treat other finished articles including filters, garments, woven and non-woven fabrics, pipes, storage vessels and medical devices for the control of microbial proliferation.
• the basic components and method of formulation will now be described. 1. Dendrimers, Dendritic Polymers and Hyperbranched Polymers
• the present invention makes use of any of the group of dendrimers, dendritic polymers and hyperbranched polymers (HPB). These are all generally characterized as highly branched, high molecular weight 3-D macromolecuies with branches that emanate from a central core. All dendritic structures inclusive of dendrimers, dendritic polymers; and hyperbranched polymer (having lower symmetry), all reflect a compact structure and a large number of reactive end groups that offer the potential to achieve high levels of potency and local concentration. Suitable dendrimers (a) are commercially produced by Dendritech Inc. (Midland, MI) and DSM (Geleen, Netherlands) and can be purchased from Sigma-Aldrich (Wl).
• Dendritic polymers are also three-dimensional structures, and can be considered as structurally imperfect dendrimers. Hyperbranched polymers also possess significant branching, but lack symmetry. These are also produced commercially, primarily for use as cross-linkers in polymers systems.
• the Boltorn series of dendritic polymers produced by Perstorp Polyols, Toledo, OH is well-suited. Boltorn is a polyester based dendritic molecule, with terminal hydroxyl groups. These structures can be produced more easily in commercial quantities, and hence are much less expensive.
• the present invention contemplates using any of the foregoing highly-branched 3-D macromolecuies that emanate from a central core.
• This may be any from the group consisting essentially of polyamidoamine, polylysine based dendrimers, polyethylene oxide based dendrimers, silicon based dendrimers, polypropylene imine dendrimers, polyether dendrimers, polyethylene oxide based hyperbranched polymers, polyglycerol based hyperbranched polymers, silicon based hyperbranched polymers, hyperbranched polyols and HybraneTM from DSM (Geleen, Netherlands).
• the present invention modifies the foregoing general dendrimer and hyperbranched polymer formula to immobilize quaternary ammonium compounds (quats, QACs) at the chain ends (at the outer boundary of the molecule), as follows:
• D is a dendrimer (any from the above group)
• n is the number of reactive terminal groups on the unmodified dendrimer or dendritic polymer
• X is an anion
• R is a linking group
• Y is an alkyl group or aryl group
• A is an alkyl group or aryl group
• B is an alkyl group or aryl group.
• the method of composing antimicrobial agents of the present invention in which high molecular weight polymers are modified to attach quaternary ammonium compounds at the outer boundary of the molecule include two steps: 1) Synthesis of Quaternary ammonium compounds dendrimers, followed by 2) inclusion of silane reactive end group for post- fabrication coupling. The method steps are detailed as follows:
• Step 1 Synthesis of Quaternary ammonium compounds dendrimers (QAC-Ds).
• QAC-Ds Quaternary ammonium compounds dendrimers
• This step essentially comprises the substeps of a) halogenation of the terminal amine groups, followed by b) quatern ⁇ zation with a tertiary amine.
• These sub-steps are detailed as follows: a. Halogenation is achieved through reaction with 2-chloroethylisocyanate. The isocyanate group reacts with the terminal hydroxyl groups on the hyperbranched polymer, to produce chlorinated chain ends.
• 3-5 grams of Perstorp Dendritic polymer Boltorn H40 are dissolved in 100 ml anhydrous N, N'dimethylacetamide (DMAc).
• a total of 60 ml of anhydrous toluene is divided equally into 3 portions and is used to strip moisture in the dendrimer or hyperbranched polymer solution using a rotary evaporator. Because isocyanate chemistry is moisture sensitive, stripping is repeated three or more times. An amount of the isocyanate (3-8 grams of 2-chloroethyl isocyanate, or 2-bromoethy! isocyanate) equivalent to 60-90% of the available reactive end groups is dissolved in a minimal amount of anhydrous DMAc (ca. 5 ml) and added dropwise to the solution at room temperature. The solution is stirred overnight at room temperature.
• the isocyanate group reacts with the terminal hydroxyl groups on the dendritic polymer, to produce chlorinated chain ends.
• the reaction between hydroxyl groups and isocyanates can be catalyzed by selected tin compounds and can be used to promote complete reaction. Gentle heating may also be applied to the reaction vessel to promote reaction. Approximately 60-90 % of the hydroxyl groups are reacted, leaving some free hydroxyl groups for subsequent silanization (described below). b. Quaternization with a tertiary amine occurs next.
• the chlorinated ends of the hyperbranched polymer are then quaternized with stoichiometric amounts of a tertiary amine, such as N 3 N dimethyloctylamine to generate the quaternary ammonium compounds at the chain ends.
• a tertiary amine such as N 3 N dimethyloctylamine
• the solution is slowly brought up to 80 degrees C and is stirred for at least 72 hours. Quaternization of the halogenated chain ends is the desired end point.
• Quaternary ammonium compounds are usually synthesized by the addition of an alkyl halide to a tertiary amine. It has been shown that quaternary ammonium salts are most effective when one constituent is an alkyl chain with at least eight carbon atoms. Rahn, O.; Van Wseltine, W. Annual Review of Microbiology 1947, 1, 173. The issue of alkyl chain length was considered again when Cutler et al. studied how size affects the antimicrobial activity of a homologous series of alkyldimethylbenzyl ammonium chlorides. They found out that the highest potency is achieved when the alkyl chain has 14 carbons. Block, S. Disinfection, Sterilization and Preservation; 3rd ed.; Lea & Febiger: Philadelphia (1983). Step 2: Synthesis of QAC-dendrimer with silane reactive end group for substrate coupling.
• Organofunctional silanes with a typical chemical structure of OCN-(CH 2 ) n -Si(OR)3 are suitable coupling agents.
• QAC- dendrimers and hyperbranched polymers can be used as a finishing treatment for textiles, or a surface treatment for other finished goods and hard surfaces to provide biocidal properties for use in a variety of settings.
• the quaternized hyperbranched polymer formed as above is reacted overnight with a slight excess compared to the unreacted terminal hydroxyl groups of 3-isocyanatopropyltriethoxysilane as shown by the reaction of FIG. 1.
• the large excluded volume of the silane group helps to ensure that the isocyanate group is the one that is presented to the unreacted hydroxyl groups on the hyperbranched polymer, and should prevent condensation between unreacted hydroxyl groups on the hyperbranched polymer and the silane from occurring. This also contributes to the stability of the compound in storage.
• Siloxane (-Si(OR) 3 ) groups hydrolyze in the presence of moisture, a reaction that is catalyzed by acids, and will condense onto the surface, and will react with hydroxyl groups, amines, carbonyls, etc., to form a covalent bond with the substrate.
• the siloxy groups may condense with each other to produce a cross-linked matrix at the surface, as shown in FlG. 3.
• a covalent bond is formed as a result of the hydrolysis of the methoxy or ethoxy group, (methanol or ethanol is liberated) linking the desired molecule to the substrate.
• the length of the silane compound should be similar to, or slightly exceed the length of the alkylating chain to ensure that the silane group is unhindered for subsequent coupling reactions. It is practice to remove moisture in all solvents and reagents when preparing QAC- dendrimers and hyperbranched polymers, and to keep all the reagents dry to avoid side reactions with isocyanates. The absence of water will also prevent hydrolysis of the silane group during preparation of the siloxy/QAC dendrimer moiety. To help achieve uniform distribution, dilution of reagents and vigorous stirring should be used during all steps of synthesis. It has been found that no gelation or precipitation occurred when using the hyperbranched polymers in this reaction scheme, suggesting that cross-linking was not a competing side reaction.
• the siloxy/QAC dendrimer is precipitated in hexane and dried by rotary evaporation.
• a semi-continuous process called diaf ⁇ ltration, a combination of dialysis and ultrafiltration, can be used for further purification.
• the diafiltration usually takes 2-3 days.
• the diafiltration may be stopped when the exit stream does not contain any tertiary amine or other small molecules detectable by a gas chromatography-mass spectrometer (GC-MS).
• GC-MS gas chromatography-mass spectrometer
• silanes to surfaces through hydrolysis Siloxane (-Si(OR)3) groups hydrolyze in the presence of moisture and condense onto the surface, and will react with hydroxyl groups, amines, carbonyls etc. to form a covalent bond with the substrate.
• the siloxy groups may condense with each other to produce a cross-linked matrix at the surface (see Figure 1).
• a covalent bond is formed as a result of the hydrolysis of the methoxy or ethoxy group, (methanol or ethanol is liberated) linking the desired organic group to the substrate.
• Initial application of the silane-QAC-Ds may be by incubating in a bath, by screen application, or by atomized or aerosol spray. Examples are as follows: Example 1 : Coupling to Glass
• Silanes were deposited from a dilute solution of alcohol (e.g. 1% of reagent in 50/50 water/methanol). A drop of sulfuric acid was added as a catalyst. Hydrolysis occurs, forming a covalent bond between the siloxy group and surface hydroxyl groups, in this case with the elimination of ethanol. Curing of the surface by exposure to heat follows, for example, the treated slides are cured at 80 degrees C for 24 hours. Successful coupling of the silane resulted in a more hydrophobic surface, causing water to bead up at the surface. The presence of quats at the surface was demonstrated by staining with bromophenol blue solution.
• Cotton is a cellulosic fiber.
• Several cellulose chains are held together by hydrogen bonds in close alignment to form crystalline microfibrils.
• the microfibrils in turn align themselves into larger organizational units, or fibrils. These fibrils are usually laid down in a helical fashion. Void and amorphous (unordered) regions exist between crystalline regions. Untreated cotton is thought to be about 70% crystalline.
• Untreated cotton is thought to be about 70% crystalline.
• the fiber is subjected to a number of chemical and physical processes.
• Mercerization of cotton refers to the treatment of cotton with a caustic solution (typically 15- 25% sodium hydroxide) to induce a diametric swelling of the fiber, associated with longitudinal shrinkage. If the fabric is held under tension while being treated, shrinkage is controlled, and a high luster on the fabric is produced. Mercerization is irreversible, and reduces the degree of crystallinity of cotton from 70% to about 50%. The size of crystallites is also reduced. Of greater importance is the observed increase in absorption of moisture and dyes into the fibers following the mercerization process. This is believed to arise from the increased number and availability of hydroxyl groups in the amorphous regions that are available for chemical reaction or cross-linking. These cellulosic OH groups will undergo chemical reactions typical of other hydroxyl groups and have been used in cross-linking reactions when applying finishes to cottons, or applying dyes including reactive dyes.
• a caustic solution typically 15- 25% sodium hydroxide
• the foregoing coupling of the QAC-silane compounds can be applied to broad range of substrates, and particularly any substrates having exposed hydroxyl and/or amine groups such as fabric and flooring, polymers, glass, metal, fabrics, polyamides, polyalcohols, plastic, ceramic and cotton ceramics, polyaramids, diene rubbers, PVC, polyurethane, polycarbonate, carbon, polyurethane and other substrates.
• substrates and particularly any substrates having exposed hydroxyl and/or amine groups such as fabric and flooring, polymers, glass, metal, fabrics, polyamides, polyalcohols, plastic, ceramic and cotton ceramics, polyaramids, diene rubbers, PVC, polyurethane, polycarbonate, carbon, polyurethane and other substrates.
• the invention can also be used to treat a variety of finished articles including fluid (e.g. air and water) filters, garments, woven and non-woven fabrics, glass screens, ductwork, pipes, storage vessels, computer keyboards, instrument panels and medical devices for the control of microbial proliferation.
• fluid e.g. air and water
• the present coupling method is not intended to be limited solely to amine or hydroxyl surfaces, and may be effective on other surfaces as well.
• textile finishing e.g. clothing
• protective and performance apparel e.g. carpets, flooring, household finishing, bedding
• touch- screens e.g. screens used to place food orders at restaurants and automated teller machines
• medical textiles e.g. from privacy curtains to wound dressings
• medical devices e.g. from privacy curtains to wound dressings
• fluid filters e.g. from privacy curtains to wound dressings
• medical devices e.g. from privacy curtains to wound dressings
• fluid filters e.g. from privacy curtains to wound dressings
• medical devices e.g. from privacy curtains to wound dressings
• fluid filters e.g. from privacy curtains to wound dressings
• medical devices e.g. from privacy curtains to wound dressings
• fluid filters e.g. from privacy curtains to wound dressings
• medical devices e.g. from privacy curtains to wound dressings
• fluid filters e.g. from privacy curtains to wound dressings
• medical devices e.g. from privacy curtains to wound dressings
• fluid filters e.g. from
• the functionalized silane-QAC-Ds are also intended for industrial as well as medical and home use applications including but not limited to elements of protective coatings such as paints, hand-wash formulations, ointments and related topical applications, cosmetics, cleaning and/or disinfectant/sanitation products, and sanitation of recreational water such as swimming pools and spas.
• protective coatings such as paints, hand-wash formulations, ointments and related topical applications, cosmetics, cleaning and/or disinfectant/sanitation products, and sanitation of recreational water such as swimming pools and spas.
• S 1 High Performance Fabrics Performance apparel represents one of the most dynamic sectors of the international textile and clothing industry.
• T-shirts incorporating antimicrobial agents are purported to provide odor control through the control of odor-generating bacteria.
• Antimicrobial finishes can also be used to increase the level of protection offered by protective garments.
• Tents and shelter fabrics are subjected to microbial degradation in use and in storage. Effective, long-lasting b ⁇ ocidal fabric treatments can be applied to prevent mildew formation and odor. It is estimated that the coated fabrics market will be driven by demand in protective clothing, awnings and tents (among others). These fabrics include cotton, polyester and other synthetics.
• the functional ized silane-QAC-dendrimers of the present invention may be applied to fabrics by bath during the production process, or by spray (aerosol or atomizer) as a post-fabrication treatment. In both cases the silane-QAC- dendrimers are immobilized on the fabric by covalent bonding as cross-linked (cured) networks or as interpenetrating networks.
• Viable bacteria can still be transferred and proliferate in more friendly surroundings. Since the present biocidal agent by definition kills the cell, it is the most effective way to minimize cross-contamination.
• Medical textiles can be classified in three categories: surgical, extracorporeal, and healthcare/hygiene. Further classifications of medical textiles can be made, depending on whether one considers the physical form of the textile (woven, filamentous etc.), or implantability.
• the functionalized silane-QAC-dendrimers of the present invention can increase the infection control properties of medical textiles, without significantly adding to the weight, or reducing comfort when applied to garments.
• the functionalized silane-QAC- dendrimers of the present invention may be grafted directly to these and other fabrics on a large scale, using a bath or vat process, or may be applied to only one side of the textile by spray-on. In both cases the treatment will confer biocidal properties to the textile, rather than being merely bacteriostatic. The potential for cross-contamination and transmission of infections from patient to patient, and the health risks to the wearer will be significantly reduced.
• the functionalized dendrimers can also be immobilized on the surface of solid materials to create efficient antimicrobial environments in a wide variety of applications including polymers, glass, and metals.
• One promising application is thin film (TFT) display screens, and especially touch-screen displays, which are normally used by many different people and are seldom if ever cleaned. Touch screens at fast food restaurants are not treated at all today, and yet pose a significant health hazard and liability issue.
• the functionalized silane-QAC-dendrimers of the present invention create a new application here because they can be applied in a microscopically-thin layer by spray, and remain clear so as not to affect the visibility of the screen. The treatment confers lasting biocidal properties, to prevent the transmission of bacteria amongst users of the TFT through contact with the TFT screen.
• the functionalized silane-QAC-dendrimers may also be an additive to protective coatings such as paints, handwash formulations, ointments and related topical applications, cosmetics, cleaning and/or disinfectant/sanitation products, and sanitation of recreational water such as swimming pools and spas.
• the functionalized silane-QAC-dendrimers may also be used to treat disposable apparel such as the garments used to protect personnel during the clean up and decontamination of areas contaminated with hazardous or biological waste.
• FTIR spectroscopy has been used to determine the presence of methoxy groups, siloxy groups, and quaternary ammonium groups (key markers for interpretation of spectra) in the isolated product.
• Nuclear Magnetic Resonance (NMR) could allow a more powerful determination of ratios of silane groups to quaternary ammonium groups, and can be used if further characterization is required.
• the antibacterial properties of the QAC-terminated dendrimers have been tested using Gram- positive bacteria ⁇ Staphylococcus aureus), and Gram-negative bacteria ⁇ Escherichia coli) and were found to be highly toxic against both organisms. Lower effective concentrations were required to achieve the same kill rate (at approx. 100 ug/ml), and at lower concentrations
• the QAC dendrimers had a much more marked effect on cell viability (as measured by optical density) than the free quat salt.
• Solution tests performed using Pseudomonas aeruginosa showed susceptibility of the organisms to the QAC dendrimers, whereas the free quat salt was ineffective against the bacteria.
• Staphylococcus aureus were also tested. Pseudomonas aeruginosa was resistant to most of the samples tested, following incubation for 24 hours.
• FIG. 2 shows the Bioluminescence of 2*109 cfu/ml E. coli in contact with polyurethane grafted with 3 rd generation PPI dendrimer containing C 12 QAC (Cl- counteranion) (0.1% urethane substitution). Data were confirmed by employing traditional plating methods, with wild type bacteria (i.e. not genetically modified). The negative control (unmodified polymer) showed an increase in the number of viable cells with time, implying that cells were able to reproduce.
• the immobilized QAC-dendrimer D3C1NC12 was able to exert a toxic effect on both S. aureus and E. coll. 99% reduction in E. coli was achieved after approx. 2 hours.
• polyurethane derivatized with QAC alone was able to kill S. aureus but not E. coli. Only a small loss in mechanical properties of the base polymer was observed (Chen and Cooper, Biomaterials, 23 (16): 3359-68). Studies comparing the efficacy of modified and unmodified polyurethanes were completed. Test organisms (S.
• TAB Trypticase Soy Broth
• PBS Phosphate Buffered Saline
• TSA Trypticase Soy Agar
• Ten ⁇ l aliquots were removed from the appropriate dilutions to yield ⁇ l,000 and 10,000 organisms and applied to coated and uncoated (control) slides.
• ten ⁇ l aliquots of PBS were applied to test and control slides. The slides were then put into individual Petri plates which were placed in gasketed containers containing water filled beakers to maintain humidity during the two hour incubation period at 37° C.
• the present invention provides a silane-QAC- hyperbranched polymer biocide coating based on polyester based hyperbranched polymers, in which functionalized quaternary ammonium provides biocidal activity, while a stlane moiety provides a means to covalently attach the biocide to a variety of substrates through hydrolysis.
• Silane is a known coupling agent, but there is the potential for cross-reactions between the silane functionality and the amine groups in the backbone of polypropylene ⁇ mine (PPI) dendr ⁇ mers as shown in Cooper et al., Thus, even if a silane-QAC- dendrimer could be isolated, the potential for cross-linking may result in a limited shelf life.
• PPI polypropylene ⁇ mine
• the present invention avoids this problem by derivatizing polyester-based hyperbranched (dendritic) polymers to attach both quaternary ammonium compounds (quats) and a hydrolysable silane moiety.
• the quaternary ammonium provides biocidal activity, while the silane moiety provides a means to covalently attach the biocide to a variety of substrates through hydrolysis.
• the result is a surface treatment that combines the demonstrated high potency of quaternary ammonium compound dendrimers and hyperbranched polymers with the well-established coupling chemistry of silane functional groups.
• methoxy- and ethoxy-silane groups will couple to functional groups such as amines and hydroxyl groups, and covalently attach.
• Silane coupling agents are used as surface modifiers to improve the compatibility between glass or any other substrates having exposed hydroxyl groups, and the surrounding matrix in glass fiber composites. Adhesion between the silane modified substrate and the matrix material is greatly improved, and is reflected in superior physical properties.
• glass and other substrates such as cotton that have exposed hydroxyl groups, or other reactive groups including amines, can be treated with silane-QAC-Ds to permanently attach biocides to the surface, and make them resist growth of microorganisms, in textiles, filters, clothing, shelters etc.
• textile finishing e.g. clothing
• carpets carpets, flooring, household finishing, bedding
• touch-screens e.g.
• the dendrimer biocides of the present invention are non-reactive and are virtually nontoxic to human skin, are non-leaching and do not require recharging, yet demonstrate superior b ⁇ ocidal activity over traditional bacteriostatic linear quat salts. These qualities ensure a more robust and durable b ⁇ ocidal treatment that is perfectly safe for human contact, thereby increasing industrial demand.

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• 2006
  • 2006-02-17 US US11/357,257 patent/US8790672B2/en not_active Expired - Fee Related
• 2007
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