US20070048249A1 - Hydrophilized bactericidal polymers - Google Patents
Hydrophilized bactericidal polymers Download PDFInfo
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- US20070048249A1 US20070048249A1 US11/509,915 US50991506A US2007048249A1 US 20070048249 A1 US20070048249 A1 US 20070048249A1 US 50991506 A US50991506 A US 50991506A US 2007048249 A1 US2007048249 A1 US 2007048249A1
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- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
- C08F220/00—Copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and only one being terminated by only one carboxyl radical or a salt, anhydride ester, amide, imide or nitrile thereof
- C08F220/02—Monocarboxylic acids having less than ten carbon atoms; Derivatives thereof
- C08F220/10—Esters
- C08F220/26—Esters containing oxygen in addition to the carboxy oxygen
- C08F220/28—Esters containing oxygen in addition to the carboxy oxygen containing no aromatic rings in the alcohol moiety
- C08F220/285—Esters containing oxygen in addition to the carboxy oxygen containing no aromatic rings in the alcohol moiety and containing a polyether chain in the alcohol moiety
- C08F220/286—Esters containing oxygen in addition to the carboxy oxygen containing no aromatic rings in the alcohol moiety and containing a polyether chain in the alcohol moiety and containing polyethylene oxide in the alcohol moiety, e.g. methoxy polyethylene glycol (meth)acrylate
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- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
- A01N43/34—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom
- A01N43/40—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom six-membered rings
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- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
- C08F226/00—Copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and at least one being terminated by a single or double bond to nitrogen or by a heterocyclic ring containing nitrogen
- C08F226/06—Copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and at least one being terminated by a single or double bond to nitrogen or by a heterocyclic ring containing nitrogen by a heterocyclic ring containing nitrogen
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- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
- C12Q1/02—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving viable microorganisms
- C12Q1/18—Testing for antimicrobial activity of a material
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- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
- C08F220/00—Copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and only one being terminated by only one carboxyl radical or a salt, anhydride ester, amide, imide or nitrile thereof
- C08F220/02—Monocarboxylic acids having less than ten carbon atoms; Derivatives thereof
- C08F220/10—Esters
- C08F220/26—Esters containing oxygen in addition to the carboxy oxygen
- C08F220/28—Esters containing oxygen in addition to the carboxy oxygen containing no aromatic rings in the alcohol moiety
- C08F220/281—Esters containing oxygen in addition to the carboxy oxygen containing no aromatic rings in the alcohol moiety and containing only one oxygen, e.g. furfuryl (meth)acrylate or 2-methoxyethyl (meth)acrylate
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- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
- C08F226/00—Copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and at least one being terminated by a single or double bond to nitrogen or by a heterocyclic ring containing nitrogen
- C08F226/06—Copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and at least one being terminated by a single or double bond to nitrogen or by a heterocyclic ring containing nitrogen by a heterocyclic ring containing nitrogen
- C08F226/08—N-Vinyl-pyrrolidine
Definitions
- bactericidal properties can be strongly influenced by whether the polycation or a composition containing the polycation is soluble. In some instances the bactericidal property is most apparent in an insoluble form, which is not particularly amenable to killing microorganisms. In other instances the bactericidal activity is lost when the polycation is cross-linked or otherwise rendered insoluble.
- Application of bactericidal polymers may also be limited by their use in brushes, their insolubility in solution, or by their unfavorable biocompatibility characteristics.
- bactericidal formulations possessing having improved bactericidal, hydrophilicity/wettability and biocompatibility characteristics suitable for rendering materials or areas bactericidal and for killing airborne and/or waterborne microorganisms.
- the present invention is directed to polymeric compositions providing improved bactericidal, hydrophilicity/wettability, and biocompatibility characteristics.
- the present invention provides a bactericidal composition, including a hydrophilic first comonomer polymerized to a second comonomer to form a polymeric composition, where the polymeric composition is more soluble and/or more bactericidal in an aqueous solution than either of the first comonomer or the second comonomer alone.
- the present invention provides a quaternized bactericidal composition, in which poly(4-vinylpyridine) (PVP) is copolymerized with hydroxyethylmethacrylate (HEMA) or poly(ethyleneglycol) methacrylate (PEGMA).
- PVP poly(4-vinylpyridine)
- HEMA hydroxyethylmethacrylate
- PEGMA poly(ethyleneglycol) methacrylate
- the present invention provides a method for rendering a material or area bactericidal in which a bactericidal composition of the present invention is applied to a medium or device in an amount suitable for killing or significantly reducing the number of bacteria in or on the treated medium or device compared to an untreated medium or device.
- the present invention provides a method for killing or significantly reducing the number of bacteria on a material or area treated with a bactericidal composition of the present invention.
- the present invention provides a method for identifying a polymer having suitable bactericidal activity in which a hydrophilic first comonomer is polymerized to a second comonomer to form a bactericidal polymeric composition, where the polymeric composition is determined to have suitable bactericidal activity if the polymeric composition has a higher bactericidal activity in an aqueous solution than either of the hydrophilic first comonomer or second comonomer alone (or treated similarly as the polymeric composition).
- compositions include their use in catheters, needles, sutures, stents and other implantable medical devices, contact lenses, root canal fillers, wound dressings, burn dressings, tissue culture plates, and the like.
- FIG. 1 is a schematic showing (A) the radical polymerization of P(VP-co-HEMA) and (B) quaternization of P(VP-co-HEMA)-HB.
- FIG. 2 is graph of bactericidal results for surface testing of P(VP-co-HEMA)-HB.
- FIG. 3 is a graph of advancing and receding contact angles for P(VP-co-HEMA).
- FIG. 4 is a graph of bactericidal results for testing of P(VP-co-PEGMA1100).
- the term “monomer” refers to a relatively simple compound, usually containing carbon and of low molecular weight, which can react to form a polymer by combining with itself or with other monomers.
- polymer and “polymeric composition” are used interchangeably to denote a product of a polymerization reaction, and are inclusive of homopolymers, copolymers, terpolymers, etc.
- polymerization and “polymerization reaction” are inclusive of homopolymerizations, copolymerizations, terpolymerizations, and the like, and include all types of copolymerizations such as random, graft, block, and the like.
- the polymers in the bactericidal composition on may be prepared in accordance with any suitable polymerization process, including slurry polymerization, solution polymerization, emulsion polymerization, gas phase polymerization, and high pressure polymerization and the like.
- nonomer refers to a monomer, copolymer, or polymer which can copolymerize with itself or with at least one different monomer, copolymer, or polymer in a copolymerization reaction, the result of which can be a polymer, copolymer or polymeric composition.
- copolymer refers to a polymer which can copolymerize with itself or with at least one different comonomer, polymer, or copolymer in a polymerization reaction or it can refer to a product resulting from a polymerization reaction of two comonomers.
- the copolymer may be identified or named in terms of the monomer(s) from which the copolymer is produced.
- corresponding comonomer “corresponding copolymer,” and “corresponding polymer” are used to relate comonomers, copolymers, or polymers, respectively, sharing a common set of monomeric units between e.g. distinct polymeric compositions.
- the common comonomers, copolymers, or polymer need not be identical in terms of the molecular weight(s) or molar ratio(s) of commonly shared monomeric units.
- corresponding molecular weight is used to relate molecular weight(s) of corresponding comonomers, copolymers, or polymers, respectively, in distinct polymeric compositions in which the common comonomers, copolymers, or polymers differ from one another by molecular weight(s) or commonly shared monomeric units within the corresponding comonomer, copolymer or polymer.
- corresponding molar ratio is used to relate molar ratio(s) of corresponding comonomers, copolymers, or polymers, respectively, in distinct polymeric compositions in which the common comonomers, copolymers, or polymers differ from one another by molar ratio(s) or commonly shared monomeric units within the corresponding comonomer, copolymer or polymer.
- bactericidal is used to interchangeably denote any one of the following: (i) a comonomer, polymer, copolymer, polymeric composition suitably formulated to kill, reduce the growth, number, viability and/or metabolic activity of one or more bacteria; (ii) a material, substance, medium, device, or area treated with a bactericidal comonomer, polymer, copolymer, polymeric composition so as to kill, reduce the growth, number, viability and/or metabolic activity of one or more bacteria.
- aqueous solution refers to a solution in which water is the solvent.
- a treatable medium refers to a treatable material, treatable substance, treatable device, or treatable area in which “treatable” refers to a capacity to be rendered bactericidal by a bactericidal comonomer, polymer, or copolymer.
- a treatable medium may have a defined physical form, but may include liquid (e.g., water, aqueous solution) or gaseous materials (e.g., air) also.
- the phrases “significantly reducing the growth of bacteria” and “significantly reducing bacterial growth” are used interchangeably to denote one or more of the following conditions, including (i) a condition in which the metabolic activity of at least 50% of the microorganisms of a particular type exposed to a treated medium is terminated or reduced compared to bacteria of that particular type exposed to an untreated medium over a fixed period of time; (ii) a condition where there is 50% or less of one or more bacterial types present in and/or on a treated medium compared to the number of bacteria exposed to an untreated medium; and/or (iii) a condition resulting when one or more types of bacteria adhere 50% less to a treated medium compared to an untreated medium.
- the degree of bacterial growth reduction with respective to conditions (i)-(iii) may range from 50% to greater 99.9%.
- significantly bactericidal denotes a comonomer, polymer, copolymer, composition, polymeric composition, material, substance or treated area in which the bactericidal comonomer, polymer, copolymer, composition, polymeric composition, material, substance or treated area is suitably formulated to significantly reduce the growth, number, viability and/or metabolic activity of bacteria by at least 50%.
- biocompatible refers to a material that is substantially non-toxic in the in vivo environment of its intended use, and that is not substantially rejected by the patient's physiological system (i.e., is non-antigenic). This can be gauged by the ability of a material to pass the biocompatibility tests set forth in International Standards Organization (ISO) Standard No. 10993 and/or the U.S. Pharmacopeia (USP) 23 and/or the U.S. Food and Drug Administration (FDA) blue book memorandum No.
- ISO International Standards Organization
- USP U.S. Pharmacopeia
- FDA U.S. Food and Drug Administration
- G95-1 entitled “Use of International Standard ISO-10993, Biological Evaluation of Medical Devices Part-1: Evaluation and Testing.” Typically, these tests measure a material's toxicity, infectivity, pyrogenicity, irritation potential, reactivity, hemolytic activity, carcinogenicity and/or immunogenicity.
- a biocompatible structure or material when introduced into a majority of patients, will not cause a significantly adverse, long-lived or escalating biological reaction or response, and is distinguished from a mild, transient inflammation which typically accompanies surgery or implantation of foreign objects into a living organism.
- a bactericidal polymeric composition of the present invention includes a hydrophilic first comonomer polymerized to a second comonomer, where the polymeric composition is more soluble and/or more bactericidal in an aqueous solution than either of the first comonomer or the second comonomer alone.
- the polymeric composition of the present invention were found to have unexpected hydophilizing and/or wettabiliy properties providing enhanced bactericidal activity compared to either comonomer alone.
- the second comonomer may be inherently bactericidal or it may be rendered bactericidal after a subsequent step (e.g., polymerization) and/or chemical modification (e.g., quaternization) of alkyl groups.
- a subsequent step e.g., polymerization
- chemical modification e.g., quaternization
- the polymeric composition is further modified by chemical modification, such as quaternization, preferably, the polymeric composition is more hydrophilic and/or bactericidal than a similarly modified (by e.g., quaternization) second comonomer alone.
- Bactericidal comonomers or those capable of being rendered bactericidal are copolymerized to a hydrophilizing comonomer.
- Exemplary second comonomers for polymerization to a hydrophilizing comonomer may include a variety of vinyl monomers capable of free radical polymerization and/or quaternization. Accordingly, these comonomers may include, but are not limited to, vinyl amines, such as N,N-dimethylvinylamine; allyl amines; vinyl esters, such as vinyl acetate; alkyl acrylates; and vinyl chloride.
- a pyridinium-type comonomer such as vinyl pyridine or 4-vinylpyridine, is quaternized after polymerization to a hydrophilizing comonomer.
- the second comonomer composition may include or be chemically linked to a suitable bactericidal moiety, including, but not limited to polycationic species, polycationic derivatives or combinations therefrom.
- Polycationic species may contain two or more quaternary ammonium groups with a molecular weight ranging from several hundred Daltons to a few hundred thousand Daltons.
- the quaternary ammonium groups may be part of a ring or they may be acyclic. Examples include but are not limited to: polyionenes, poly(diallyldimethylammonium chloride), dimethylamine-epichlorohydrin copolymers and imidazole-epichlorohydrin copolymers.
- Suitable bactericidal comonomers for use in the present invention may include the quaternary ammonium group-containing polymers disclosed in U.S. Pat. No. 4,482,680, which are incorporated by reference herein.
- Polycationic species may contain two or more amine groups.
- the amine groups can be primary, secondary, tertiary, or mixtures thereof.
- the amine groups may be part of a ring or they may be acyclic. Examples include but are not limited to: polyethyleneimines, polypropyleneimines, polyvinylamines, polyallylamines, polydiallylamines, polyamidoamines, polyaminoalkylmethacrylates, polylysines, and mixtures thereof.
- the polycationic species may also be a modified polyamine with at least one amine group substituted with at least one other functional group. Examples include ethoxylated and alkoxylated polyamines and alkylated polyamines. Other suitable bactericidal comonomers or those that may be rendered bactericidal may be identified and/or used in accordance with the applications and objectives set forth in the specification and claims.
- Quaternization may be carried out using alkylating agents, including but not limited to alkyl halides (such as hexyl bromide), alkyl sulfonates, alkyl mesylates, alkyl tosylates, or other alkylating agents possessing a suitable leaving group. Quaternization reduces self-polymerization of the bactericidal comonomer upon polymerization with the hydrophilizing comonomer. Quaternization may confer increased bactericidal activity and is typically carried out after polymerization, since quaternized polymers are unpolymerizable.
- alkylating agents including but not limited to alkyl halides (such as hexyl bromide), alkyl sulfonates, alkyl mesylates, alkyl tosylates, or other alkylating agents possessing a suitable leaving group. Quaternization reduces self-polymerization of the bactericidal comono
- Quaternized alkyl groups and/or other cationic chains may be attracted to and/or promote interaction and penetration negatively charged bacterial cell walls on account of their lipophilic nature.
- Alkyl chain lengths of quaternizing agents and overall hydrophilic/lipophilic balance may affect bactericidal activity of the polymeric compositions of the present invention. Accordingly, these variables may be modified to optimize or improve bactericidal activity of the polymeric compositions.
- Hydrophilizing comonomers of the present invention confer increased wettability or hydrophilicity to one or more surfaces of the polymeric composition in aqueous solutions, including water.
- the polymeric composition is more wettable than a bactericidal comonomer or a comonomer rendered bactericidal by quaternization, such as poly(4-vinylpyridine).
- Suitable hydrophilizing monomers or copolymers may include, but are not limited to, ethylene glycol (ethylyene oxide); polyethylene glycol derivatives, including poly(ethyleneglycol) methacrylate (PEGMA), poly(ethyleneglycol) acrylate, and vinyl polyethylene glycol; vinyl acetate; poly(vinyl alcohol); vinyl pyrrolidone and poly(vinyl pyrrolidone); vinyl pyrrolidinone and poly(vinyl pyrrolininone); vinyl oxazoline and poly(vinyl oxazoline); vinyl foramide and poly(vinyl foramide); hydroxyalkyl acrylates and hydroxyalkyl methacrylates, such as hydroxyethyl methacrylate (HEMA) and hydroxyethyl acrylate; methacrylamide; acrylamide and methacrylamide based monomers, such as acrylamide, N,N-dimethyl acrylamide, N-ethyl acrylamide, N-isoprop
- Hydrophilic polymeric compositions and methods for hydrophilizing polymeric materials, including the use of high energy treatments, are disclosed in U.S. Pat. Appl. No. 20050008839, the contents of which are expressly incorporated by reference in their entirety, also may be used.
- the hydrophilizing comonomer is biocompatible.
- Standard assays may be utilized to evaluate biocompatibility, including but not limited to viability/cytotoxicity mammalian cell assays and the like.
- Representative hydrophilizing comonomers or copolymers include hydroxyethylmethacrylate (HEMA) and poly(ethyleneglycol) methacrylate (PEGMA).
- HEMA is widely used in biomedical applications and devices, most prominently soft contact lenses. HEMA, with 37.8% water per weight, is typical of hydrogels. Preferably, the molar ratio of HEMA comonomer in the polymeric composition is equal to or greater than about 90 to 1.
- PEGMA is a biocompatible polymer which possesses several important properties, such as good solubility in both organic and aqueous media, low toxicity, immunogenicity and nonbiodegradability.
- the molar molecular weight of PEGMA comonomer in the bactericidal composition is equal to or greater than 300, more preferably between about 300 and about 2000, including but not limited to 1100.
- the molar ratio of PEGMA comonomer in the polymeric composition is equal to or less than about 10 to 1; equal to or less than about 25 to 1; equal to or greater than about 75 to 1; equal to or greater than about 95 to 1; equal to or greater than about 99 to 1.
- Hydrophilicity or wettability can be evaluated by any suitable methodology known in the art, including contact angle testing and tensionometry testing.
- Contact angle testing of polymeric compositions may be carried out by dip coating microscope slides in solutions with copolymer dissolved in chloroform and methanol and obtaining contact angle measurements using e.g., a Ramé-Hart Advanced Goniometer.
- Contact angles may be characterized as advancing or receding, the difference being whether or not the angle is taken when moving onto a dry surface or moving off a wet surface. Advancing angles may be used for surface energy determinations, receding angles for characterizing other surface characteristics.
- the disclosed bactericidal compositions are suitably formulated to significantly reduce the growth, number, viability and/or metabolic activity of bacteria.
- a bactericidal composition may be formulated to significantly reduce bacterial growth from a treated medium by a factor of at least 50%. Further, a bactericidal composition may be formulated to significantly reduce bacterial growth from a treated medium by at least 60%, by at least 70%, by at least 80%, by at least 90%, by at least 95%, by at least 99%, or by at least 99.9%.
- the bactericidal composition may be applied as a coating to at least one portion or surface of a medium or medical device, including but not limited to catheters, needles, stents, and other implantable medical devices.
- a medium or medical device including but not limited to catheters, needles, stents, and other implantable medical devices.
- Various methods may be used to apply the comonomers or bactericidal polymers as a coating to the surface of the medical device. Suitable methods for applying coatings may include, but are not limited to the methods disclosed in U.S. Pat. No. 5,509,899 and U.S. Pat. No. 6,221,425, the contents of which are expressly incorporated by reference in their entirety.
- Comonomers may be applied to a surface and subsequently polymerized.
- the bactericidal polymer composition may be applied directly to the surface of the medical device.
- one or more comonomers or bactericidal polymers may be combined with water and sprayed onto the medical device.
- the medical device may be dipped into a solution containing the bactericidal polymer.
- the comonomer or bactericidal polymer may be present in the solution in an amount from about 50% to about 98% by weight, particularly from about 70% to about 90% by weight, and applied to the surface of the medical device.
- the viscosity of the monomeric or polymeric solution can be adjusted depending upon the particular application and circumstances. In general, when dipping the medical device into the solution, higher viscosities will cause more of the bactericidal polymer to remain on the surface of the device. Thus, if thicker coatings are desired, the viscosity can be increased. The viscosity of the solution can be increased by minimizing the amount of water in the solution. Additionally, thickeners, such as a polyacrylamide, can be added to the solution. The viscosity of the solution may also be increased by partially polymerizing the monomer.
- the present invention provides methods for rendering a material or area bactericidal. In a further example, the present invention provides a method for killing or significantly reducing the number of bacteria on a material or area treated with a bactericidal composition of the present invention.
- a bactericidal composition of the present invention is applied to a medium or medical device in an amount sufficient to kill or significantly reducing the number of bacteria in or on the treated medium compared to an untreated medium.
- a bactericidal composition according to the present invention is applied to a medium or medical device in an amount sufficient to kill at least one bacterium or significantly reduce bacterial growth compared to an untreated medium.
- the bacteria may be Gram-positive or Gram-negative.
- the bactericidal composition may be is included in or coated onto a catheter, stent, implantable medical device, contact lens, root canal filler, or wound dressing.
- the treated medium may include natural or synthetic materials, implantable devices, or bodily surfaces.
- the treated medium may be contact with an aqueous environment, such as water or the inside of a patient or other vertebrate organism.
- the treated medium may be contact with air or air and/or air borne bacteria in an external environment or an enclosed bodily organ, such as lung.
- Biocompatibility may be evaluated by any suitable methodology known in the art, including biocompatibility tests set forth in International Standards Organization (ISO) Standard No. 10993 and/or the U.S. Pharmacopeia (USP) 23 and/or the U.S. Food and Drug Administration (FDA) blue book memorandum No. G95-1, entitled “Use of International Standard ISO-10993, Biological Evaluation of Medical Devices Part-1: Evaluation and Testing.”
- ISO International Standards Organization
- USP U.S. Pharmacopeia
- FDA Food and Drug Administration
- G95-1 entitled “Use of International Standard ISO-10993, Biological Evaluation of Medical Devices Part-1: Evaluation and Testing.”
- any of the viability/cytotoxicity assays known to those of ordinary skill in the art may be used to evaluate lack of toxicity for normal human cells.
- the present invention provides a method for identifying a polymer having suitable bactericidal activity.
- a hydrophilizing first comonomer may be polymerized to a second comonomer and a bactericidal polymeric composition is formed.
- the bactericidal polymeric composition may be applied to a medium to form a first treated medium and the medium may be separately treated with the second comonomer used in the first treated medium.
- the first treated medium and the second treated medium may be separately contacted with a plurality of bacteria. Whether the first treated medium is more bactericidal than the second treated medium may be determined.
- a first polymeric composition and a second polymeric composition differing by molecular weight with regard to one or more corresponding comonomers may be separately applied to a medium and tested to identify a polymeric composition having improved bactericidal activity.
- a first polymeric composition and a second polymeric composition differing by molar ratio of their corresponding comonomers may be varied and may be separately applied to a medium and tested to identify a polymeric composition having improved bactericidal activity.
- a given polymeric composition may be rendered bactericidal by quaternization after polymerizing the hydrophilizing first comonomer to the second comonomer. Accordingly, the quaternized polymeric composition would be deemed suitable for use in a bactericidal composition if a medium containing or treated with the quaternized polymeric composition is more hydrophilic and/or bactericidal than the same medium containing or treated with the quaternized second comonomer alone.
- Bactericidal activity may be evaluated using any suitable testing methodology used in the art, including, but not limited to, luminescence, optical density, or microscopic evaluation of bacterial growth or viability of coated and/or stained microscopic slides, plates or cultures.
- Copolymers possessing suitable bactericidal properties and a suitable hydrophilicity/biocompatibility profile were obtained using a quaternized polymeric composition synthesized from 4-vinylpyridine and a biocompatible, hydrophilic comonomer, such as hydroxyethylmethacrylate (HEMA) or poly(ethyleneglycol) methacrylate.
- HEMA hydroxyethylmethacrylate
- poly(ethyleneglycol) methacrylate such as poly(ethyleneglycol) methacrylate.
- Copolymers were synthesized by radical copolymerization with AIBN as initiator. The reactants were stirred at 70° C. for 48 hours under flowing N 2 to prevent oxidation. As the monomer contents were varied, the AIBN proportion was held constant to a massic ratio VP+PEGMA:AIBN equal to 22:1. To investigate the effects of hydrophilization, seven different compositions of VP with PEGMA300, PEGMA 1100 and HEMA were synthesized, containing a molar percentage of VP of 10, 25, 50, 75, 90, 95 and 99.
- Copolymers were quaternized with a 3-fold excess of hexyl bromide (HB) in a mixture of chloroform and methanol by reflux for 48 hr. They were precipitated in hexane, recovered and dried under vacuum.
- HB hexyl bromide
- VP, HEMA and PEGMA were purchased from Sigma Aldrich Co. (Milwaukee, USA). To avoid polymerization through heat or light, these monomers were inhibited with hydroquinone (HQ), 4-Methoxyphenol (MEHQ), and 2,6-di-tert-butyl-4-methylphenol (BHT) respectively.
- HQ hydroquinone
- MEHQ 4-Methoxyphenol
- BHT 2,6-di-tert-butyl-4-methylphenol
- the HQ and MEHQ inhibitors were removed by means of trap to trap while BHT was purified from PEGMA by column chromatography on silica gel (70-270 mesh) stationary phase.
- Bactericidal tests were performed with a small quantity of the bacteria Escherichia coli O157:H7 in which the lux gene was added for luminescence, which provides a measure of metabolic growth or activity.
- a sample was taken from a culture and placed in contact with the coated slides, by means of a pipette. The intensity of the bioluminescence was recorded as a function of time for two hours with a photomultiplier tube. Reduced bioluminescence correlates with enhanced bactericidal activity.
- P(VP-co-HEMA)-HB 95/5 and P(VP-co-HEMA)-HB 90/10 exhibited enhanced bactericidal activity compared to PVP-HB alone.
- the luminescence recorded for P(VP-co-HEMA)-HB 99/1 is similar to, but slightly less than that observed for PVP-HB alone. Accordingly, this copolymer, having one molar percent HEMA, displays properties similar to PVP-HB alone. However, a slide coated with P(VP-co-HEMA)-HB 99/1 kills bacteria faster than one coated with PVP-HB.
- bactericidal activity in the polymer facilitates enhances bacterial killing, in part because of the water-loving nature of bacteria: a hydrophilic growth medium is better able to support uptake and killing by a hydrophilized bactericidal polymer compared to an unhydrophilized bactericidal polymer. Moreover, it is believed that the bactericidal polymers are electrostatically attracted to the bacterial cell wall whereby lipophilic side chains insert into the bacterial cell membrane, disrupting it so that holes form therein.
- P(VP-co-HEMA)-HB 90/10 the wettability effect is particularly evident.
- This polymer exhibits a more optimal bactericidal activity, reflected in the fact that all bacteria were killed in 30 minutes. This further illustrates that that a slide coated with P(VP-co-HEMA)-HB 90/10 copolymer is significantly more bactericidal than pure PVP-HB.
- P(VP-co-PEGMA1100)-HB 25/75 and 10/90 displayed a surprisingly high antibacterial activity. Although counterintuitive, this fact can have several explanations.
- the molecular weight of P(VP-co-PEGMA1100)-HB 10/90 is much higher than other copolymer formulations of this system. This could increase bactericidal activity, because the copolymer possesses more alkyl tails to traverse the bacterial membranes.
- the enhanced water wettability of the polymer may enable the polymer to better dissolve in and/or surround the bacteria in an aqueous medium, so as to facilitate more efficient bacterial killing.
- PPEGMA300 (graph not shown) alone does not kill bacteria and actually improves growth due to its biocompatibility and hydrophilicity.
- the improved biocompatibility and hydrophilicity is carried over into the P(VP-co-PEGMA300) copolymers with ratios from 0/100 to 50/50 thereby improving bacterial growth.
- ratios greater 50/50 bactericidal activity was observed.
- the optimum balance between spreading and VP content was found to be 75/25, in which half the bacteria were killed in the first 15 minutes. Overall, the bactericidal behavior of the PEGMA300 based polymers were reduced compared to PEGMA1100 based polymers.
- PEGMA1100 has a significantly larger PEG size than PEGMA300. A smaller fraction of PEGMA 1100 is thus necessary to hydrophilize P(VP-co-PEGMA 1100). However, even for some similarly hydrophilized polymers, the PEGMA 1100 materials exhibit superior bactericidal activity, possibly due to the enhanced protein resistance imparted by longer PEG chains in the polymers.
- the enhanced bactericidal activity exhibited by the HEMA and PEGMA copolymers appears to result from enhanced wettability in aqueous solutions, allowing the polymer to better surround and/or gain access to the bacteria, so as to enhance bacterial killing.
- FIG. 5 shows that an exemplary bactericidal PEGMA 1100 copolymer is non-toxic to mammalian cells.
- Corneal epithelial cells were seeded onto polystyrene culture plates in phosphobuffered saline solution (PBS; pH 7.2) at a density of 3,500 cells/cm 2 for 24 hrs at 37° C. The cells were co-incubated for 4 hrs. with quaternized P(VP-co-PEGMA 1100) copolymer or PPEGMA control polymer in PBS at a concentration of 2.5 mg/ml, along with a PBS negative control media.
- PBS phosphobuffered saline solution
- Live cells were distinguished from dead cells using a fluorescence-based LIVE/DEAD viability/cytotoxicity assay system (Molecular Probes, Invitrogen Detection Technologies).
- the assay system includes two probes, calcein AM, a fluorogenic esterase substrate producing a green fluorescent product in live cells having intracellular esterase activity, and ethidium homodimer-1, a high-affinity, red fluorescent dye only able to pass through and stain the compromised membranes of dead cells.
- FIG. 5 plots the fraction of dead epithelial cells as a function of added bactericidal polymer or polymer control. As shown in FIG. 5 , treatment of epithelial cells with the bactericidal P(VP-co-PEGMA) polymer did not exhibit a statistically significant level of epithelial cell killing over that of the PEGMA polymer or PBS negative controls.
Abstract
A bactericidal polymeric composition includes a hydrophilic first comonomer copolymerized to a second comonomer to produce a polymeric composition that is more hydrophilic or more bactericidal in an aqueous solution than either of the comonomers alone. Methods for identifying bactericidal polymers, methods for rendering materials bactericidal, and methods for using bactericidal compositions to kill or reduce bacterial growth are also described. Applications for the inventive compositions include their use in catheters, stents, medical devices, contact lenses; root canal fillers; and/or wound dressings.
Description
- This application claims the benefit of priority under 35 U.S.C. § 119(e) to U.S. Provisional Application No. 60/711,234, filed Aug. 24, 2005, which is hereby incorporated by reference in its entirety.
- There is an ever-growing demand for materials suitable for killing harmful microorganisms. Such materials could be used to coat surfaces of common objects touched by people to render them antiseptic so as to prevent transmission of bacterial infections or to facilitate the killing of microorganisms in solution.
- Various polycations are known to have bactericidal properties. However, their bactericidal properties can be strongly influenced by whether the polycation or a composition containing the polycation is soluble. In some instances the bactericidal property is most apparent in an insoluble form, which is not particularly amenable to killing microorganisms. In other instances the bactericidal activity is lost when the polycation is cross-linked or otherwise rendered insoluble. Application of bactericidal polymers may also be limited by their use in brushes, their insolubility in solution, or by their unfavorable biocompatibility characteristics. Accordingly, there is a need for bactericidal formulations possessing having improved bactericidal, hydrophilicity/wettability and biocompatibility characteristics suitable for rendering materials or areas bactericidal and for killing airborne and/or waterborne microorganisms.
- The present invention is directed to polymeric compositions providing improved bactericidal, hydrophilicity/wettability, and biocompatibility characteristics. In particular, the present invention provides a bactericidal composition, including a hydrophilic first comonomer polymerized to a second comonomer to form a polymeric composition, where the polymeric composition is more soluble and/or more bactericidal in an aqueous solution than either of the first comonomer or the second comonomer alone.
- In a particular example, the present invention provides a quaternized bactericidal composition, in which poly(4-vinylpyridine) (PVP) is copolymerized with hydroxyethylmethacrylate (HEMA) or poly(ethyleneglycol) methacrylate (PEGMA).
- In another example, the present invention provides a method for rendering a material or area bactericidal in which a bactericidal composition of the present invention is applied to a medium or device in an amount suitable for killing or significantly reducing the number of bacteria in or on the treated medium or device compared to an untreated medium or device.
- In another example, the present invention provides a method for killing or significantly reducing the number of bacteria on a material or area treated with a bactericidal composition of the present invention.
- In a further example, the present invention provides a method for identifying a polymer having suitable bactericidal activity in which a hydrophilic first comonomer is polymerized to a second comonomer to form a bactericidal polymeric composition, where the polymeric composition is determined to have suitable bactericidal activity if the polymeric composition has a higher bactericidal activity in an aqueous solution than either of the hydrophilic first comonomer or second comonomer alone (or treated similarly as the polymeric composition).
- Applications for the inventive compositions include their use in catheters, needles, sutures, stents and other implantable medical devices, contact lenses, root canal fillers, wound dressings, burn dressings, tissue culture plates, and the like.
-
FIG. 1 is a schematic showing (A) the radical polymerization of P(VP-co-HEMA) and (B) quaternization of P(VP-co-HEMA)-HB. -
FIG. 2 is graph of bactericidal results for surface testing of P(VP-co-HEMA)-HB. -
FIG. 3 is a graph of advancing and receding contact angles for P(VP-co-HEMA). -
FIG. 4 is a graph of bactericidal results for testing of P(VP-co-PEGMA1100). - In order to provide a more clear and consistent understanding of the specification and claims, the following definitions are provided. Unless defined otherwise, all technical and scientific terms have the same meaning as is commonly understood by one of skill in the art to which this invention belongs.
- The term “monomer” refers to a relatively simple compound, usually containing carbon and of low molecular weight, which can react to form a polymer by combining with itself or with other monomers.
- The terms “polymer” and “polymeric composition” are used interchangeably to denote a product of a polymerization reaction, and are inclusive of homopolymers, copolymers, terpolymers, etc.
- The terms “polymerization” and “polymerization reaction” are inclusive of homopolymerizations, copolymerizations, terpolymerizations, and the like, and include all types of copolymerizations such as random, graft, block, and the like. In general, the polymers in the bactericidal composition on may be prepared in accordance with any suitable polymerization process, including slurry polymerization, solution polymerization, emulsion polymerization, gas phase polymerization, and high pressure polymerization and the like.
- The term “comonomer” refers to a monomer, copolymer, or polymer which can copolymerize with itself or with at least one different monomer, copolymer, or polymer in a copolymerization reaction, the result of which can be a polymer, copolymer or polymeric composition.
- The term “copolymer” refers to a polymer which can copolymerize with itself or with at least one different comonomer, polymer, or copolymer in a polymerization reaction or it can refer to a product resulting from a polymerization reaction of two comonomers. The copolymer may be identified or named in terms of the monomer(s) from which the copolymer is produced.
- The terms “corresponding comonomer,” “corresponding copolymer,” and “corresponding polymer” are used to relate comonomers, copolymers, or polymers, respectively, sharing a common set of monomeric units between e.g. distinct polymeric compositions. The common comonomers, copolymers, or polymer need not be identical in terms of the molecular weight(s) or molar ratio(s) of commonly shared monomeric units.
- The phrase “corresponding molecular weight” is used to relate molecular weight(s) of corresponding comonomers, copolymers, or polymers, respectively, in distinct polymeric compositions in which the common comonomers, copolymers, or polymers differ from one another by molecular weight(s) or commonly shared monomeric units within the corresponding comonomer, copolymer or polymer.
- The phrase “corresponding molar ratio” is used to relate molar ratio(s) of corresponding comonomers, copolymers, or polymers, respectively, in distinct polymeric compositions in which the common comonomers, copolymers, or polymers differ from one another by molar ratio(s) or commonly shared monomeric units within the corresponding comonomer, copolymer or polymer.
- The term “bactericidal” is used to interchangeably denote any one of the following: (i) a comonomer, polymer, copolymer, polymeric composition suitably formulated to kill, reduce the growth, number, viability and/or metabolic activity of one or more bacteria; (ii) a material, substance, medium, device, or area treated with a bactericidal comonomer, polymer, copolymer, polymeric composition so as to kill, reduce the growth, number, viability and/or metabolic activity of one or more bacteria.
- The term “aqueous solution” refers to a solution in which water is the solvent.
- The term “medium” refers to a treatable material, treatable substance, treatable device, or treatable area in which “treatable” refers to a capacity to be rendered bactericidal by a bactericidal comonomer, polymer, or copolymer. A treatable medium may have a defined physical form, but may include liquid (e.g., water, aqueous solution) or gaseous materials (e.g., air) also.
- The phrases “significantly reducing the growth of bacteria” and “significantly reducing bacterial growth” are used interchangeably to denote one or more of the following conditions, including (i) a condition in which the metabolic activity of at least 50% of the microorganisms of a particular type exposed to a treated medium is terminated or reduced compared to bacteria of that particular type exposed to an untreated medium over a fixed period of time; (ii) a condition where there is 50% or less of one or more bacterial types present in and/or on a treated medium compared to the number of bacteria exposed to an untreated medium; and/or (iii) a condition resulting when one or more types of bacteria adhere 50% less to a treated medium compared to an untreated medium. The degree of bacterial growth reduction with respective to conditions (i)-(iii) may range from 50% to greater 99.9%.
- The phrase “significantly bactericidal” denotes a comonomer, polymer, copolymer, composition, polymeric composition, material, substance or treated area in which the bactericidal comonomer, polymer, copolymer, composition, polymeric composition, material, substance or treated area is suitably formulated to significantly reduce the growth, number, viability and/or metabolic activity of bacteria by at least 50%.
- The term “biocompatible” refers to a material that is substantially non-toxic in the in vivo environment of its intended use, and that is not substantially rejected by the patient's physiological system (i.e., is non-antigenic). This can be gauged by the ability of a material to pass the biocompatibility tests set forth in International Standards Organization (ISO) Standard No. 10993 and/or the U.S. Pharmacopeia (USP) 23 and/or the U.S. Food and Drug Administration (FDA) blue book memorandum No. G95-1, entitled “Use of International Standard ISO-10993, Biological Evaluation of Medical Devices Part-1: Evaluation and Testing.” Typically, these tests measure a material's toxicity, infectivity, pyrogenicity, irritation potential, reactivity, hemolytic activity, carcinogenicity and/or immunogenicity. A biocompatible structure or material, when introduced into a majority of patients, will not cause a significantly adverse, long-lived or escalating biological reaction or response, and is distinguished from a mild, transient inflammation which typically accompanies surgery or implantation of foreign objects into a living organism.
- A bactericidal polymeric composition of the present invention includes a hydrophilic first comonomer polymerized to a second comonomer, where the polymeric composition is more soluble and/or more bactericidal in an aqueous solution than either of the first comonomer or the second comonomer alone. The polymeric composition of the present invention were found to have unexpected hydophilizing and/or wettabiliy properties providing enhanced bactericidal activity compared to either comonomer alone.
- The second comonomer may be inherently bactericidal or it may be rendered bactericidal after a subsequent step (e.g., polymerization) and/or chemical modification (e.g., quaternization) of alkyl groups. Where the polymeric composition is further modified by chemical modification, such as quaternization, preferably, the polymeric composition is more hydrophilic and/or bactericidal than a similarly modified (by e.g., quaternization) second comonomer alone.
- Bactericidal comonomers or those capable of being rendered bactericidal are copolymerized to a hydrophilizing comonomer. Exemplary second comonomers for polymerization to a hydrophilizing comonomer may include a variety of vinyl monomers capable of free radical polymerization and/or quaternization. Accordingly, these comonomers may include, but are not limited to, vinyl amines, such as N,N-dimethylvinylamine; allyl amines; vinyl esters, such as vinyl acetate; alkyl acrylates; and vinyl chloride. In a preferred embodiment, a pyridinium-type comonomer, such as vinyl pyridine or 4-vinylpyridine, is quaternized after polymerization to a hydrophilizing comonomer.
- The second comonomer composition may include or be chemically linked to a suitable bactericidal moiety, including, but not limited to polycationic species, polycationic derivatives or combinations therefrom. Polycationic species may contain two or more quaternary ammonium groups with a molecular weight ranging from several hundred Daltons to a few hundred thousand Daltons. The quaternary ammonium groups may be part of a ring or they may be acyclic. Examples include but are not limited to: polyionenes, poly(diallyldimethylammonium chloride), dimethylamine-epichlorohydrin copolymers and imidazole-epichlorohydrin copolymers. Suitable bactericidal comonomers for use in the present invention may include the quaternary ammonium group-containing polymers disclosed in U.S. Pat. No. 4,482,680, which are incorporated by reference herein.
- Polycationic species may contain two or more amine groups. The amine groups can be primary, secondary, tertiary, or mixtures thereof. The amine groups may be part of a ring or they may be acyclic. Examples include but are not limited to: polyethyleneimines, polypropyleneimines, polyvinylamines, polyallylamines, polydiallylamines, polyamidoamines, polyaminoalkylmethacrylates, polylysines, and mixtures thereof.
- The polycationic species may also be a modified polyamine with at least one amine group substituted with at least one other functional group. Examples include ethoxylated and alkoxylated polyamines and alkylated polyamines. Other suitable bactericidal comonomers or those that may be rendered bactericidal may be identified and/or used in accordance with the applications and objectives set forth in the specification and claims.
- Quaternization may be carried out using alkylating agents, including but not limited to alkyl halides (such as hexyl bromide), alkyl sulfonates, alkyl mesylates, alkyl tosylates, or other alkylating agents possessing a suitable leaving group. Quaternization reduces self-polymerization of the bactericidal comonomer upon polymerization with the hydrophilizing comonomer. Quaternization may confer increased bactericidal activity and is typically carried out after polymerization, since quaternized polymers are unpolymerizable.
- Quaternized alkyl groups and/or other cationic chains may be attracted to and/or promote interaction and penetration negatively charged bacterial cell walls on account of their lipophilic nature. Alkyl chain lengths of quaternizing agents and overall hydrophilic/lipophilic balance may affect bactericidal activity of the polymeric compositions of the present invention. Accordingly, these variables may be modified to optimize or improve bactericidal activity of the polymeric compositions.
- Hydrophilizing comonomers of the present invention confer increased wettability or hydrophilicity to one or more surfaces of the polymeric composition in aqueous solutions, including water. Preferably, the polymeric composition is more wettable than a bactericidal comonomer or a comonomer rendered bactericidal by quaternization, such as poly(4-vinylpyridine). Suitable hydrophilizing monomers or copolymers, may include, but are not limited to, ethylene glycol (ethylyene oxide); polyethylene glycol derivatives, including poly(ethyleneglycol) methacrylate (PEGMA), poly(ethyleneglycol) acrylate, and vinyl polyethylene glycol; vinyl acetate; poly(vinyl alcohol); vinyl pyrrolidone and poly(vinyl pyrrolidone); vinyl pyrrolidinone and poly(vinyl pyrrolininone); vinyl oxazoline and poly(vinyl oxazoline); vinyl foramide and poly(vinyl foramide); hydroxyalkyl acrylates and hydroxyalkyl methacrylates, such as hydroxyethyl methacrylate (HEMA) and hydroxyethyl acrylate; methacrylamide; acrylamide and methacrylamide based monomers, such as acrylamide, N,N-dimethyl acrylamide, N-ethyl acrylamide, N-isopropyl acrylamide, and hydroxymethyl acrylamide; monomers containing one or more of the following functional groups: hydroxy, amino, ammonium, ether, carboxylate, amide, and sulfoamide groups; and combinations or copolymers thereof. polyvinyloxazolines
- Hydrophilic polymeric compositions and methods for hydrophilizing polymeric materials, including the use of high energy treatments, are disclosed in U.S. Pat. Appl. No. 20050008839, the contents of which are expressly incorporated by reference in their entirety, also may be used.
- Preferably, the hydrophilizing comonomer is biocompatible. Standard assays may be utilized to evaluate biocompatibility, including but not limited to viability/cytotoxicity mammalian cell assays and the like. Representative hydrophilizing comonomers or copolymers include hydroxyethylmethacrylate (HEMA) and poly(ethyleneglycol) methacrylate (PEGMA).
- HEMA is widely used in biomedical applications and devices, most prominently soft contact lenses. HEMA, with 37.8% water per weight, is typical of hydrogels. Preferably, the molar ratio of HEMA comonomer in the polymeric composition is equal to or greater than about 90 to 1.
- PEGMA is a biocompatible polymer which possesses several important properties, such as good solubility in both organic and aqueous media, low toxicity, immunogenicity and nonbiodegradability.
- Preferably, the molar molecular weight of PEGMA comonomer in the bactericidal composition is equal to or greater than 300, more preferably between about 300 and about 2000, including but not limited to 1100. Preferably, the molar ratio of PEGMA comonomer in the polymeric composition is equal to or less than about 10 to 1; equal to or less than about 25 to 1; equal to or greater than about 75 to 1; equal to or greater than about 95 to 1; equal to or greater than about 99 to 1.
- Hydrophilicity or wettability can be evaluated by any suitable methodology known in the art, including contact angle testing and tensionometry testing. Contact angle testing of polymeric compositions may be carried out by dip coating microscope slides in solutions with copolymer dissolved in chloroform and methanol and obtaining contact angle measurements using e.g., a Ramé-Hart Advanced Goniometer. Contact angles may be characterized as advancing or receding, the difference being whether or not the angle is taken when moving onto a dry surface or moving off a wet surface. Advancing angles may be used for surface energy determinations, receding angles for characterizing other surface characteristics.
- Polymeric bactericidal compositions may be rendered hydrophilic by engineering them to have advancing contact angles with water of less than or equal to about 90 degrees, preferably less than or equal to about 45 degrees, more preferably less than or equal to about 30 degrees, less than or equal to 15 degrees after 30 seconds of spreading.
- The disclosed bactericidal compositions are suitably formulated to significantly reduce the growth, number, viability and/or metabolic activity of bacteria. A bactericidal composition may be formulated to significantly reduce bacterial growth from a treated medium by a factor of at least 50%. Further, a bactericidal composition may be formulated to significantly reduce bacterial growth from a treated medium by at least 60%, by at least 70%, by at least 80%, by at least 90%, by at least 95%, by at least 99%, or by at least 99.9%.
- The bactericidal composition may be applied as a coating to at least one portion or surface of a medium or medical device, including but not limited to catheters, needles, stents, and other implantable medical devices. Various methods may be used to apply the comonomers or bactericidal polymers as a coating to the surface of the medical device. Suitable methods for applying coatings may include, but are not limited to the methods disclosed in U.S. Pat. No. 5,509,899 and U.S. Pat. No. 6,221,425, the contents of which are expressly incorporated by reference in their entirety.
- Comonomers may be applied to a surface and subsequently polymerized. Alternatively, the bactericidal polymer composition may be applied directly to the surface of the medical device. In particular, one or more comonomers or bactericidal polymers may be combined with water and sprayed onto the medical device. Alternatively, the medical device may be dipped into a solution containing the bactericidal polymer. The comonomer or bactericidal polymer may be present in the solution in an amount from about 50% to about 98% by weight, particularly from about 70% to about 90% by weight, and applied to the surface of the medical device.
- The viscosity of the monomeric or polymeric solution can be adjusted depending upon the particular application and circumstances. In general, when dipping the medical device into the solution, higher viscosities will cause more of the bactericidal polymer to remain on the surface of the device. Thus, if thicker coatings are desired, the viscosity can be increased. The viscosity of the solution can be increased by minimizing the amount of water in the solution. Additionally, thickeners, such as a polyacrylamide, can be added to the solution. The viscosity of the solution may also be increased by partially polymerizing the monomer.
- In another example, the present invention provides methods for rendering a material or area bactericidal. In a further example, the present invention provides a method for killing or significantly reducing the number of bacteria on a material or area treated with a bactericidal composition of the present invention.
- Accordingly, in one example, a bactericidal composition of the present invention is applied to a medium or medical device in an amount sufficient to kill or significantly reducing the number of bacteria in or on the treated medium compared to an untreated medium. In a further example, a bactericidal composition according to the present invention is applied to a medium or medical device in an amount sufficient to kill at least one bacterium or significantly reduce bacterial growth compared to an untreated medium.
- The bacteria may be Gram-positive or Gram-negative. The bactericidal composition may be is included in or coated onto a catheter, stent, implantable medical device, contact lens, root canal filler, or wound dressing. The treated medium may include natural or synthetic materials, implantable devices, or bodily surfaces. The treated medium may be contact with an aqueous environment, such as water or the inside of a patient or other vertebrate organism. Alternatively, the treated medium may be contact with air or air and/or air borne bacteria in an external environment or an enclosed bodily organ, such as lung.
- Biocompatibility may be evaluated by any suitable methodology known in the art, including biocompatibility tests set forth in International Standards Organization (ISO) Standard No. 10993 and/or the U.S. Pharmacopeia (USP) 23 and/or the U.S. Food and Drug Administration (FDA) blue book memorandum No. G95-1, entitled “Use of International Standard ISO-10993, Biological Evaluation of Medical Devices Part-1: Evaluation and Testing.” In addition, any of the viability/cytotoxicity assays known to those of ordinary skill in the art may be used to evaluate lack of toxicity for normal human cells.
- In a further example, the present invention provides a method for identifying a polymer having suitable bactericidal activity. In this method, a hydrophilizing first comonomer may be polymerized to a second comonomer and a bactericidal polymeric composition is formed. The bactericidal polymeric composition may be applied to a medium to form a first treated medium and the medium may be separately treated with the second comonomer used in the first treated medium. The first treated medium and the second treated medium may be separately contacted with a plurality of bacteria. Whether the first treated medium is more bactericidal than the second treated medium may be determined.
- In a further example, a first polymeric composition and a second polymeric composition differing by molecular weight with regard to one or more corresponding comonomers may be separately applied to a medium and tested to identify a polymeric composition having improved bactericidal activity.
- Alternatively, a first polymeric composition and a second polymeric composition differing by molar ratio of their corresponding comonomers may be varied and may be separately applied to a medium and tested to identify a polymeric composition having improved bactericidal activity.
- In the above disclosed methods, a given polymeric composition may be rendered bactericidal by quaternization after polymerizing the hydrophilizing first comonomer to the second comonomer. Accordingly, the quaternized polymeric composition would be deemed suitable for use in a bactericidal composition if a medium containing or treated with the quaternized polymeric composition is more hydrophilic and/or bactericidal than the same medium containing or treated with the quaternized second comonomer alone.
- Bactericidal activity may be evaluated using any suitable testing methodology used in the art, including, but not limited to, luminescence, optical density, or microscopic evaluation of bacterial growth or viability of coated and/or stained microscopic slides, plates or cultures.
- The following examples illustrate features in accordance with the present invention, and are provided solely by way of illustration. They are not intended to limit the scope of the appended claims or their equivalents.
- 1. Radical Polymerization and Quaternization. Copolymers possessing suitable bactericidal properties and a suitable hydrophilicity/biocompatibility profile were obtained using a quaternized polymeric composition synthesized from 4-vinylpyridine and a biocompatible, hydrophilic comonomer, such as hydroxyethylmethacrylate (HEMA) or poly(ethyleneglycol) methacrylate.
- Copolymers were synthesized by radical copolymerization with AIBN as initiator. The reactants were stirred at 70° C. for 48 hours under flowing N2 to prevent oxidation. As the monomer contents were varied, the AIBN proportion was held constant to a massic ratio VP+PEGMA:AIBN equal to 22:1. To investigate the effects of hydrophilization, seven different compositions of VP with PEGMA300, PEGMA 1100 and HEMA were synthesized, containing a molar percentage of VP of 10, 25, 50, 75, 90, 95 and 99.
- Copolymers were quaternized with a 3-fold excess of hexyl bromide (HB) in a mixture of chloroform and methanol by reflux for 48 hr. They were precipitated in hexane, recovered and dried under vacuum. A schematic of the radical polymerization and quaternization process can be seen in
FIG. 1 . - Synthesis of P(VP-co-HEMA), P(VP-co-PEGMA300) and P(VP-co-PEGMA 1100) was followed with FTIR and NMR. Spectroscopy showed that the synthesis was successful and that the quaternization went to near completion and that the resultant products were relatively pure after work-up.
- VP, HEMA and PEGMA were purchased from Sigma Aldrich Co. (Milwaukee, USA). To avoid polymerization through heat or light, these monomers were inhibited with hydroquinone (HQ), 4-Methoxyphenol (MEHQ), and 2,6-di-tert-butyl-4-methylphenol (BHT) respectively. The HQ and MEHQ inhibitors were removed by means of trap to trap while BHT was purified from PEGMA by column chromatography on silica gel (70-270 mesh) stationary phase.
- 2. Contact Angle and Bactericidal Testing. To evaluate wettability or hydrophilicity, contact angle tests were conducted by dip coating microscope slides in solutions with copolymer dissolved in chloroform and methanol. Contact angle measurements were obtained on a Ramé-Hart Advanced Goniometer.
- Bactericidal tests were performed with a small quantity of the bacteria Escherichia coli O157:H7 in which the lux gene was added for luminescence, which provides a measure of metabolic growth or activity. A sample was taken from a culture and placed in contact with the coated slides, by means of a pipette. The intensity of the bioluminescence was recorded as a function of time for two hours with a photomultiplier tube. Reduced bioluminescence correlates with enhanced bactericidal activity.
- 3. Bactericidal activity of P(VP-co-HEMA). The results of the bactericidal tests on quaternized copolymers of VP and HEMA are shown in
FIG. 2 . An initial increase of intensity is observed in the control, due to the fast growth of the bacteria, called blooming. After approximately 19 minutes, the intensity starts decreasing as the bacteria start to die. PVP-HB, known to kill bacteria, prevents blooming, as reflected by the fact that the intensity never increases by more than 1 percent. The intensity starts decreasing after only 7 minutes. Since this is much earlier than the control, the death of the bacteria can be attributed to the properties of the polymer. An uninterrupted blooming is observed for a slide coated with PHEMA, and the number of bacteria has quadrupled after two hours, following a lag-log behavior. This indicates that PHEMA by itself is not bactericidal. - P(VP-co-HEMA)-HB 95/5 and P(VP-co-HEMA)-HB 90/10 exhibited enhanced bactericidal activity compared to PVP-HB alone. The luminescence recorded for P(VP-co-HEMA)-HB 99/1, is similar to, but slightly less than that observed for PVP-HB alone. Accordingly, this copolymer, having one molar percent HEMA, displays properties similar to PVP-HB alone. However, a slide coated with P(VP-co-HEMA)-HB 99/1 kills bacteria faster than one coated with PVP-HB.
- The wettability of dry, vitreous HEMA-based materials was studied by contact angle measurements. The results for both advancing and receding angles are given in
FIG. 3 . Contact angle measurements showed an increase in hydrophilicity provoked by the copolymerization. The surface energy was found to be minimal for P(VP-co-HEMA) at 90/10 and slightly higher for P(VP-co-HEMA)-HB 99/1. This corresponds to the bactericidal behavior of the polymers and suggests that the wettability plays a significant role in the polymer's effectiveness. Being a hydrogel monomer, HEMA hydrophilizes the copolymer. - Although not wishing to be bound by theory, it is believed that coupling hydrophilization to bactericidal activity in the polymer facilitates enhances bacterial killing, in part because of the water-loving nature of bacteria: a hydrophilic growth medium is better able to support uptake and killing by a hydrophilized bactericidal polymer compared to an unhydrophilized bactericidal polymer. Moreover, it is believed that the bactericidal polymers are electrostatically attracted to the bacterial cell wall whereby lipophilic side chains insert into the bacterial cell membrane, disrupting it so that holes form therein.
- In P(VP-co-HEMA)-HB 90/10, the wettability effect is particularly evident. This polymer exhibits a more optimal bactericidal activity, reflected in the fact that all bacteria were killed in 30 minutes. This further illustrates that that a slide coated with P(VP-co-HEMA)-HB 90/10 copolymer is significantly more bactericidal than pure PVP-HB.
- 4. Bactericidal activity of P(VP-co-PEGMA). The bacterial growth behavior for copolymers with PEGMA1100 can be seen in
FIG. 4 . Comonomer ratios of 90/10, 25/75, and 10/90 exhibited enhanced bactericidal activity compared to PVP-HB alone. Extremely high bactericidal activity was seen with ratios of 99/1, presumably due to the large fraction of VP and improved wettability from PEGMA1100. Copolymers with ratios ranging from 95/5 to 50/50 displayed bacterial results similar to PVP-HB. - P(VP-co-PEGMA1100)-HB 25/75 and 10/90 displayed a surprisingly high antibacterial activity. Although counterintuitive, this fact can have several explanations. The molecular weight of P(VP-co-PEGMA1100)-HB 10/90 is much higher than other copolymer formulations of this system. This could increase bactericidal activity, because the copolymer possesses more alkyl tails to traverse the bacterial membranes. The enhanced water wettability of the polymer may enable the polymer to better dissolve in and/or surround the bacteria in an aqueous medium, so as to facilitate more efficient bacterial killing.
- PPEGMA300 (graph not shown) alone does not kill bacteria and actually improves growth due to its biocompatibility and hydrophilicity. The improved biocompatibility and hydrophilicity is carried over into the P(VP-co-PEGMA300) copolymers with ratios from 0/100 to 50/50 thereby improving bacterial growth. However, for ratios greater 50/50, bactericidal activity was observed. The optimum balance between spreading and VP content was found to be 75/25, in which half the bacteria were killed in the first 15 minutes. Overall, the bactericidal behavior of the PEGMA300 based polymers were reduced compared to PEGMA1100 based polymers.
- PEGMA1100 has a significantly larger PEG size than PEGMA300. A smaller fraction of PEGMA 1100 is thus necessary to hydrophilize P(VP-co-PEGMA 1100). However, even for some similarly hydrophilized polymers, the PEGMA 1100 materials exhibit superior bactericidal activity, possibly due to the enhanced protein resistance imparted by longer PEG chains in the polymers.
- The enhanced bactericidal activity exhibited by the HEMA and PEGMA copolymers appears to result from enhanced wettability in aqueous solutions, allowing the polymer to better surround and/or gain access to the bacteria, so as to enhance bacterial killing.
- 5. Cytotoxity of P(VP-co-PEGMA). A viability/cytotoxicity assay may be used to evaluate biocompatibility of the bactericidal polymers for mammalian cells. In particular,
FIG. 5 shows that an exemplary bactericidal PEGMA 1100 copolymer is non-toxic to mammalian cells. Corneal epithelial cells were seeded onto polystyrene culture plates in phosphobuffered saline solution (PBS; pH 7.2) at a density of 3,500 cells/cm2 for 24 hrs at 37° C. The cells were co-incubated for 4 hrs. with quaternized P(VP-co-PEGMA 1100) copolymer or PPEGMA control polymer in PBS at a concentration of 2.5 mg/ml, along with a PBS negative control media. - Live cells were distinguished from dead cells using a fluorescence-based LIVE/DEAD viability/cytotoxicity assay system (Molecular Probes, Invitrogen Detection Technologies). The assay system includes two probes, calcein AM, a fluorogenic esterase substrate producing a green fluorescent product in live cells having intracellular esterase activity, and ethidium homodimer-1, a high-affinity, red fluorescent dye only able to pass through and stain the compromised membranes of dead cells.
FIG. 5 plots the fraction of dead epithelial cells as a function of added bactericidal polymer or polymer control. As shown inFIG. 5 , treatment of epithelial cells with the bactericidal P(VP-co-PEGMA) polymer did not exhibit a statistically significant level of epithelial cell killing over that of the PEGMA polymer or PBS negative controls. - It is to be understood that the above-described polymers and methods for their use are merely representative embodiments illustrating the principles of this invention and that other variations in the polymers or methods, may be devised by those skilled in the art without departing from the spirit and scope of this invention. The foregoing detailed description and accompanying drawings have been provided solely by way of explanation and illustration, and are not intended to limit the scope of the appended claims. Many variations in the presently preferred embodiments illustrated herein will be apparent to one of ordinary skill in the art, and remain within the scope of the appended claims and their equivalents.
Claims (20)
1. A polymeric composition comprising:
a hydrophilic first comonomer polymerized to a second comonomer to form a polymeric composition, where the polymeric composition is more hydrophilic than either of the first comonomer or the second comonomer alone and/or where the polymeric composition is more bactericidal than either of the first comonomer or the second comonomer alone.
2. The composition of claim 1 , where the hydrophilic first comonomer comprises hydroxyethylmethacrylate.
3. The composition of claim 1 , where the hydrophilic first copolymer comprises poly(ethyleneglycol) methacrylate.
4. The composition of claim 1 , where the second comonomer comprises polycationic species, polycationic derivatives or combinations therefrom.
5. The composition of claim 1 , where the second comonomer comprises a plurality of quaternary ammonium groups.
6. The composition of claim 1 , where the second comonomer comprises quaternized poly(4-vinylpyridine).
7. A method for killing bacteria or rendering a medium bactericidal comprising:
providing a polymeric composition comprising a hydrophilic first comonomer polymerized to a second comonomer, where the polymeric composition is more hydrophilic than either of the first comonomer or the second comonomer alone and/or where the polymeric composition is more bactericidal than either of the first comonomer or the second comonomer alone;
applying the polymeric composition to a medium to form a treated medium, where the polymeric composition is applied in an amount sufficient to kill at least one bacterium or significantly reduce bacterial growth in or on the treated medium compared to an untreated medium.
8. The method of claim 7 , where the polymeric composition is applied as a coating to at least one surface of the medium.
9. The method of claim 7 , where the treated medium is in contact with an aqueous environment.
10. The method of claim 7 , where the treated medium is in contact with air.
11. The method of claim 7 , where the treated medium is included in or coated onto a catheter, stent, implantable medical device, contact lens, root canal filler, or wound dressing.
12. The method of claim 7 , further comprising the step of contacting the treated medium with bacteria, where the treated medium comprises the polymeric composition in an amount sufficient to kill at least one bacterium or significantly reduce bacterial growth in or on the treated medium compared to an untreated medium.
13. The method of claim 12 , where the treated medium is formulated to kill or significantly reduce the growth of Gram-positive bacteria.
14. The method of claim 12 , where the treated medium is suitably formulated to kill or significantly reduce the growth of Gram-negative bacteria.
15. A method of identifying a polymeric composition suitable for use in a bactericidal composition comprising:
a) providing a first comonomer, where the first comonomer is soluble in an aqueous solution;
b) providing a second comonomer, where the second comonomer is bactericidal or capable of being rendered bactericidal;
c) polymerizing the first comonomer in step (a) to the second comonomer in step (b) to form a polymeric composition;
d) treating or applying the polymeric composition in step (c) to a medium to form a first treated medium;
e) separately applying a comonomer from step (a) or step (b) to the medium of step (d) to form a second treated medium;
f) separately contacting the first treated medium and the second treated medium with a plurality of bacteria; and
g) determining whether the first treated medium is more bactericidal than the second treated medium, where the polymeric composition is suitable for use in a bactericidal composition if the first treated medium is more bactericidal than the second treated medium.
16. The method of claim 15 , where each comonomer from step (a) and step (b) is separately applied to the medium of step (d) to form a second treated medium and a third treated medium, respectively, where the polymeric composition is suitable for use in a bactericidal composition if the first treated medium is more bactericidal than each of the second and third treated mediums.
17. The method of claim 15 , where the molecular weight(s) of one or more more monomers in the first comonomer in the first polymeric composition of the first treated medium is modified compared to the corresponding molecular weight(s) of one or more monomers in a second polymeric composition of a fourth medium, such that the fourth treated medium is more bactericidal than the first treated medium.
18. The method of claim 15 , where a molar ratio(s) of one or one or more monomers in the first comonomer in the first polymeric composition in a first treated medium is modified compared to the corresponding molar ratio(s) of one or more monomers in a second polymeric composition of a fourth medium, such that the fourth treated medium is more bactericidal than the first treated medium.
19. The method of claim 15 , where the second comonomer is quaternized after the second comonomer is polymerized to the first comonomer.
20. The method of claim 15 , where step (g) comprises a luminescence assay, optical density determination or microscopic determination.
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US12/549,004 US8343473B2 (en) | 2005-08-24 | 2009-08-27 | Hydrophilized antimicrobial polymers |
US13/682,159 US20130079481A1 (en) | 2005-08-24 | 2012-11-20 | Hydrophilized antimicrobial polymers |
US13/748,290 US20130136783A1 (en) | 2005-08-24 | 2013-01-23 | Hydrophilized antimicrobial polymers |
US14/087,188 US20140080977A1 (en) | 2005-08-24 | 2013-11-22 | Hydrophilized antimicrobial polymers |
US14/837,900 US20160053038A1 (en) | 2005-08-24 | 2015-08-27 | Hydrophilized bactericidal polymers |
US15/163,285 US11134684B2 (en) | 2005-08-24 | 2016-05-24 | Method of using hydrophilized bactericidal polymers |
US17/115,709 US11459415B2 (en) | 2005-08-24 | 2020-12-08 | Method of using hydrophilized bactericidal polymers |
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Cited By (25)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20070254006A1 (en) * | 2006-02-15 | 2007-11-01 | Massachusetts Institute Of Technology | Medical Devices and Coatings with Non-Leaching Antimicrobial Peptides |
US20090155335A1 (en) * | 2007-12-05 | 2009-06-18 | Semprus Biosciences Corp. | Non-leaching non-fouling antimicrobial coatings |
US20090295004A1 (en) * | 2008-06-02 | 2009-12-03 | Pinsly Jeremy B | Silicone hydrogel contact lenses displaying reduced protein uptake |
US20100145286A1 (en) * | 2008-12-05 | 2010-06-10 | Semprus Biosciences Corp. | Layered non-fouling, antimicrobial antithrombogenic coatings |
US20100152708A1 (en) * | 2008-12-05 | 2010-06-17 | Semprus Biosciences Corp. | Non-fouling, anti-microbial, anti-thrombogenic graft-from compositions |
US20110062410A1 (en) * | 2009-09-11 | 2011-03-17 | Ivanov Ilia N | Method for morphological control and encapsulation of materials for electronics and energy applications |
US8101913B2 (en) | 2009-09-11 | 2012-01-24 | Ut-Battelle, Llc | Method of making large area conformable shape structures for detector/sensor applications using glass drawing technique and postprocessing |
US8208136B2 (en) | 2009-09-11 | 2012-06-26 | Ut-Battelle, Llc | Large area substrate for surface enhanced Raman spectroscopy (SERS) using glass-drawing technique |
US8574660B2 (en) | 2010-06-09 | 2013-11-05 | Semprus Biosciences Corporation | Articles having non-fouling surfaces and processes for preparing the same without altering bulk physical properties |
US8709466B2 (en) | 2011-03-31 | 2014-04-29 | International Business Machines Corporation | Cationic polymers for antimicrobial applications and delivery of bioactive materials |
WO2014096851A2 (en) | 2012-12-21 | 2014-06-26 | Coopervision International Holding Company, Lp | Silicone hydrogel contact lenses for sustained release of beneficial polymers |
US8870372B2 (en) | 2011-12-14 | 2014-10-28 | Semprus Biosciences Corporation | Silicone hydrogel contact lens modified using lanthanide or transition metal oxidants |
US9000063B2 (en) | 2011-12-14 | 2015-04-07 | Semprus Biosciences Corporation | Multistep UV process to create surface modified contact lenses |
US9006359B2 (en) | 2011-12-14 | 2015-04-14 | Semprus Biosciences Corporation | Imbibing process for contact lens surface modification |
US9004682B2 (en) | 2011-12-14 | 2015-04-14 | Semprus Biosciences Corporation | Surface modified contact lenses |
US9096703B2 (en) | 2010-06-09 | 2015-08-04 | Semprus Biosciences Corporation | Non-fouling, anti-microbial, anti-thrombogenic graft-from compositions |
US9120119B2 (en) | 2011-12-14 | 2015-09-01 | Semprus Biosciences Corporation | Redox processes for contact lens modification |
US9147505B2 (en) | 2011-11-02 | 2015-09-29 | Ut-Battelle, Llc | Large area controlled assembly of transparent conductive networks |
WO2016182444A1 (en) * | 2015-05-12 | 2016-11-17 | Rijksuniversiteit Groningen | 3d-printable antimicrobial composite resins, methods for manufacturing the same |
US9758607B2 (en) | 2013-10-10 | 2017-09-12 | Research Foundation Of The City University Of New York | Polymer with antibacterial activity |
US10016532B2 (en) | 2010-06-09 | 2018-07-10 | Arrow International, Inc. | Non-fouling, anti-microbial, anti-thrombogenic graft compositions |
US11134684B2 (en) | 2005-08-24 | 2021-10-05 | Purdue Research Foundation | Method of using hydrophilized bactericidal polymers |
US11167064B2 (en) | 2016-07-14 | 2021-11-09 | Hollister Incorporated | Hygienic medical devices having hydrophilic coating |
US11421084B2 (en) | 2017-05-27 | 2022-08-23 | Poly Group LLC | Dispersible antimicrobial complex and coatings therefrom |
US11680116B2 (en) | 2017-06-16 | 2023-06-20 | Poly Group LLC | Polymeric antimicrobial surfactant |
Citations (32)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4414353A (en) * | 1977-06-03 | 1983-11-08 | Hercules Incorporated | Organic pigments |
US4459289A (en) * | 1980-06-18 | 1984-07-10 | Texcontor - Anstalt | Copolymers having bactericidal activity, process for the preparation thereof and pharmaceutical compositions therefrom |
US4482680A (en) * | 1981-09-15 | 1984-11-13 | Dynapol | Quaternary ammonium group-containing polymers having antimicrobial activity |
US4931522A (en) * | 1989-07-11 | 1990-06-05 | Robert Catena | Copolymers of polyalkylene glycol acrylate and a salt of a quarternized acrylate |
US5317063A (en) * | 1989-09-06 | 1994-05-31 | Lion Corporation | Water-soluble polymer sensitive to salt |
US5509899A (en) * | 1994-09-22 | 1996-04-23 | Boston Scientific Corp. | Medical device with lubricious coating |
US6221425B1 (en) * | 1998-01-30 | 2001-04-24 | Advanced Cardiovascular Systems, Inc. | Lubricious hydrophilic coating for an intracorporeal medical device |
US20010044482A1 (en) * | 1998-07-08 | 2001-11-22 | Hopin Hu | Interpenetrating polymer network hydrophilic hydrogels for contact lens |
US6358557B1 (en) * | 1999-09-10 | 2002-03-19 | Sts Biopolymers, Inc. | Graft polymerization of substrate surfaces |
US20020086160A1 (en) * | 2000-08-24 | 2002-07-04 | Yongxing Qiu | Process for surface modifying substrates and modified substrates resulting therefrom |
US6537663B1 (en) * | 2000-05-04 | 2003-03-25 | Kimberly-Clark Worldwide, Inc. | Ion-sensitive hard water dispersible polymers and applications therefor |
US6559116B1 (en) * | 1999-09-27 | 2003-05-06 | The Procter & Gamble Company | Antimicrobial compositions for hard surfaces |
US20030091641A1 (en) * | 2001-04-23 | 2003-05-15 | Tiller Joerg C. | Antimicrobial polymeric surfaces |
US20030161804A1 (en) * | 2001-12-20 | 2003-08-28 | Beatrice Perron | Self-adhesive cationic or amphoteric free-radical polymers and cosmetic use thereof |
US20030229185A1 (en) * | 2002-02-05 | 2003-12-11 | Daoyong Chen | Method for preparation of block copolymeric nanoparticles |
US20030236376A1 (en) * | 2002-03-11 | 2003-12-25 | Ture Kindt-Larsen | Low polydispersity poly-HEMA compositions |
US20040009136A1 (en) * | 2002-05-31 | 2004-01-15 | L'oreal | Aqueous hair treatment compositions, thickened with an amphiphilic linear block copolymer |
US6689856B2 (en) * | 2001-05-16 | 2004-02-10 | L'oreal | Water-soluble polymers with a water-soluble backbone and side units with a lower critical solution temperature, process for preparing them, aqueous compositions containing them and cosmetic use thereof |
US20040135967A1 (en) * | 2002-12-03 | 2004-07-15 | Carney Fiona Patricia | Medical devices having antimicrobial coatings thereon |
US20040202639A1 (en) * | 2001-03-08 | 2004-10-14 | Degrado William F. | Facially amphiphilic polymers as anti-infective agents |
US6815502B1 (en) * | 2000-05-04 | 2004-11-09 | Kimberly-Clark Worldwide, Inc. | Ion-sensitive, water-dispersable polymers, a method of making same and items using same |
US6815074B2 (en) * | 2001-05-30 | 2004-11-09 | Novartis Ag | Polymeric materials for making contact lenses |
US20050008839A1 (en) * | 2002-01-30 | 2005-01-13 | Cramer Ronald Dean | Method for hydrophilizing materials using hydrophilic polymeric materials with discrete charges |
US20050008876A1 (en) * | 2001-11-08 | 2005-01-13 | Toyoyuki Teranishi | Ultra-water-repellent substrate |
US20050013842A1 (en) * | 2003-07-16 | 2005-01-20 | Yongxing Qiu | Antimicrobial medical devices |
US6852353B2 (en) * | 2000-08-24 | 2005-02-08 | Novartis Ag | Process for surface modifying substrates and modified substrates resulting therefrom |
US20050032931A1 (en) * | 2003-07-18 | 2005-02-10 | Naisby Andrew S. | Ink jet recording medium |
US20050053569A1 (en) * | 2001-12-12 | 2005-03-10 | Bruno Bavouzet | Use of cationic block copolymers to assist the deposition of simple or multiple emulsions |
US20050058844A1 (en) * | 2002-12-19 | 2005-03-17 | Rubner Michael F. | Method for making medical devices having antimicrobial coatings thereon |
US20050101740A1 (en) * | 2003-09-01 | 2005-05-12 | Nathalie Mougin | Block ethylenic copolymers comprising a vinyllactam block, cosmetic compositions containing them and cosmetic use of these copolymers |
US20060057209A1 (en) * | 2004-09-16 | 2006-03-16 | Predicant Biosciences, Inc. | Methods, compositions and devices, including microfluidic devices, comprising coated hydrophobic surfaces |
US7112559B1 (en) * | 2005-03-14 | 2006-09-26 | Ecolab Inc. | Thickened quaternary ammonium compound sanitizer |
Family Cites Families (309)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US2717887A (en) | 1952-12-02 | 1955-09-13 | Du Pont | Salts of vinylpyridine polymers with anionic soap-forming sulfuric and sulfonic acids of high molecular weight |
US2882157A (en) | 1955-08-19 | 1959-04-14 | Eastman Kodak Co | Treatment of photographic film for static resistance |
US2972537A (en) | 1957-09-03 | 1961-02-21 | Eastman Kodak Co | Condensation products of polyvinylketones with hydrazides containing quaternary nitrogen groups |
US3140227A (en) | 1961-02-14 | 1964-07-07 | American Cyanamid Co | Durable germicidal finish for hydrophobic polyamide textile materials |
US3296167A (en) | 1962-02-02 | 1967-01-03 | Morton Int Inc | Process for polymerizing an ethylenically unsaturated amine-containing monomeric mixture |
BE633443A (en) | 1962-06-12 | 1900-01-01 | ||
US3227672A (en) | 1962-12-12 | 1966-01-04 | Nat Starch Chem Corp | Water soluble cationic copolymers of beta-hydroxyalkyl ethlenically unsaturated ester with vinyl tertiary amine |
DE1244398B (en) | 1963-07-11 | 1967-07-13 | Bayer Ag | Antistatic thermoplastic molding compounds |
US3296196A (en) | 1964-06-01 | 1967-01-03 | Gen Electric | Siloxane polymers containing allylcinnamate groups |
US3328328A (en) | 1964-07-09 | 1967-06-27 | American Cyanamid Co | Water-insolubilized floor wax composition containing alkali metal aluminate and method for preparing same |
US3619200A (en) | 1966-06-21 | 1971-11-09 | Commw Scient Ind Res Org | Method and food composition for feeding ruminants |
US3597313A (en) | 1968-09-23 | 1971-08-03 | American Cyanamid Co | Polyaldehyde crosslinked aliphatic alcohol resins and a process of making temporary wet strength paper and paper made therefrom |
US3592805A (en) | 1969-02-17 | 1971-07-13 | Stauffer Chemical Co | Complex of organic amine with a completely halogenated acetone and method of preparation |
GB1299012A (en) | 1969-02-25 | 1972-12-06 | Mitsubishi Gas Chemical Co | Process for producing cationic synthetic latices |
JPS5343533B2 (en) | 1970-06-23 | 1978-11-21 | ||
US3754055A (en) | 1970-12-28 | 1973-08-21 | California Inst Of Techn | Cationic vinyl-pyridine copolymers and products thereof |
US4029694A (en) | 1971-09-01 | 1977-06-14 | Basf Wyandotte Corporation | Antistatic agents for melt-formed polymers |
US4093676A (en) | 1971-09-01 | 1978-06-06 | Basf Wyandotte Corporation | Antistatic agents for melt-formed polymers |
US3753716A (en) | 1972-02-04 | 1973-08-21 | Konishiroku Photo Ind | Method for antistatic treatment of plastic films |
US3872128A (en) | 1972-03-08 | 1975-03-18 | Union Carbide Corp | Antimicrobial hydroxy quinoline, ethylene-acrylic polymer compositions |
US3975350A (en) | 1972-08-02 | 1976-08-17 | Princeton Polymer Laboratories, Incorporated | Hydrophilic or hydrogel carrier systems such as coatings, body implants and other articles |
US3898188A (en) | 1972-08-14 | 1975-08-05 | California Inst Of Techn | Novel polyelectrolytes |
US4017440A (en) | 1973-10-10 | 1977-04-12 | Rohm And Haas Company | Polymers stabilized with polymerizable vinylbenzyltrialkyl ammonium salt surfactant |
US4234381A (en) | 1973-10-10 | 1980-11-18 | Rohm And Haas Company | Fibrous material made with polymers stabilized by polymerizable vinyl benzyltrialkyl ammonium salt surfactant |
US3871376A (en) | 1974-03-13 | 1975-03-18 | Union Carbide Corp | Combination absorbent dressing and flexible cooling device |
US3929741A (en) | 1974-07-16 | 1975-12-30 | Datascope Corp | Hydrophilic acrylamido polymers |
US4181752A (en) | 1974-09-03 | 1980-01-01 | Minnesota Mining And Manufacturing Company | Acrylic-type pressure sensitive adhesives by means of ultraviolet radiation curing |
US4011178A (en) | 1974-12-23 | 1977-03-08 | The Goodyear Tire & Rubber Company | Resins and polymer mixtures thereof |
JPS51146586A (en) | 1975-06-12 | 1976-12-16 | Toyo Soda Mfg Co Ltd | Preparation of polymer emulsions |
DE2529939C3 (en) | 1975-07-04 | 1980-10-09 | Chemische Fabrik Stockhausen & Cie, 4150 Krefeld | Antistatic preparation for coating masses of textile fabrics |
US4045510A (en) | 1975-09-24 | 1977-08-30 | Basf Wyandotte Corporation | Method for providing polymers with durable improved properties |
USRE31454E (en) | 1975-11-25 | 1983-12-06 | Lectec Corporation | Monitoring and stimulation electrode |
US4125110A (en) | 1975-11-25 | 1978-11-14 | Hymes Alan C | Monitoring and stimulation electrode |
US4026941A (en) | 1975-11-28 | 1977-05-31 | Basf Wyandotte Corporation | Polyoxyalkylated polyol polyesters having improved antistatic properties |
US4070189A (en) | 1976-10-04 | 1978-01-24 | Eastman Kodak Company | Silver halide element with an antistatic layer |
DE2650306A1 (en) | 1976-11-02 | 1978-05-03 | Merck Patent Gmbh | ANTIBACTERIAL DRESSING AND METHOD OF ITS MANUFACTURING |
US4080315A (en) | 1976-11-08 | 1978-03-21 | Basf Wyandotte Corporation | Polyesters of N,N-bis(hydroxyalkyl) taurine salts as antistatic agents for synthetic polymers |
US4229554A (en) | 1976-12-02 | 1980-10-21 | Basf Wyandotte Corporation | Flame retardant antistatic additives and antistatic fibers |
JPS5378288A (en) | 1976-12-22 | 1978-07-11 | Sanyo Chem Ind Ltd | Preparation of water in oil type polymer emulsion having improved flowability |
US4104443A (en) | 1977-05-06 | 1978-08-01 | J. P. Stevens & Co., Inc. | Antistatic finish for textiles material |
AU3747378A (en) | 1977-06-27 | 1980-02-21 | Univ Melbourne | Amphoteric latices |
US4147550A (en) | 1977-07-15 | 1979-04-03 | Eastman Kodak Company | Photographic silver halide element with a layer of sulfonated polymer |
US4119094A (en) | 1977-08-08 | 1978-10-10 | Biosearch Medical Products Inc. | Coated substrate having a low coefficient of friction hydrophilic coating and a method of making the same |
JPS5837439B2 (en) | 1978-01-27 | 1983-08-16 | 花王株式会社 | fiber sizing agent |
JPS5536237A (en) | 1978-09-06 | 1980-03-13 | Kureha Chem Ind Co Ltd | Antistatic resin composition |
US4416668A (en) | 1978-10-25 | 1983-11-22 | Petrolite Corporation | Antistatic agents for organic liquids |
US4259411A (en) | 1978-11-15 | 1981-03-31 | Calgon Corporation | Electroconductive coating formulations |
CA1153427A (en) | 1978-12-11 | 1983-09-06 | Patrick T. Cahalan | Tape electrode |
US4226232A (en) | 1979-04-09 | 1980-10-07 | Spenco Medical Corporation | Wound dressing |
US4361623A (en) | 1979-11-13 | 1982-11-30 | Basf Wyandotte Corporation | Flame retardant antistatic additives and antistatic fibers |
US4318947A (en) | 1979-12-26 | 1982-03-09 | The Kendall Company | Polymer coating and curing process for catheters |
US4539996A (en) | 1980-01-23 | 1985-09-10 | Minnesota Mining And Manufacturing Company | Conductive adhesive and biomedical electrode |
US4581821A (en) | 1980-02-14 | 1986-04-15 | Medtronic, Inc. | Method of preparing tape electrode |
US4393048A (en) | 1980-02-15 | 1983-07-12 | The United States Of America As Represented By The Secretary Of The Army | Protective gel composition for wounds |
JPS5933361Y2 (en) | 1980-03-14 | 1984-09-18 | 日東電工株式会社 | electrode pad |
US4306996A (en) | 1980-05-05 | 1981-12-22 | Calgon Corporation | Electroconductive polymer composition |
JPS573809A (en) | 1980-06-10 | 1982-01-09 | Kureha Chem Ind Co Ltd | Multilayer antistatic resin and its composition |
US4377667A (en) | 1980-06-13 | 1983-03-22 | Asahi Kasei Kogyo Kabushiki Kaisha | Polyacetal and process of producing same |
US4304703A (en) | 1980-06-23 | 1981-12-08 | Ppg Industries, Inc. | Cationic polymer dispersions and their method of preparation |
US4379869A (en) | 1981-01-15 | 1983-04-12 | W. R. Grace & Co. | Cationic latices and their electrodeposition |
US4768523A (en) | 1981-04-29 | 1988-09-06 | Lifecore Biomedical, Inc. | Hydrogel adhesive |
US4373009A (en) | 1981-05-18 | 1983-02-08 | International Silicone Corporation | Method of forming a hydrophilic coating on a substrate |
US4366238A (en) | 1981-06-25 | 1982-12-28 | Fuji Photo Film Co., Ltd. | Silver halide photographic materials |
US4500517A (en) | 1981-12-07 | 1985-02-19 | H. B. Fuller Co. | Antimicrobial composition for a semipermeable membrane |
US4515593A (en) | 1981-12-31 | 1985-05-07 | C. R. Bard, Inc. | Medical tubing having exterior hydrophilic coating for microbiocide absorption therein and method for using same |
DE3363213D1 (en) | 1982-01-18 | 1986-06-05 | Medtronic Inc | Electrically conductive compositions and electrodes utilizing same |
US4699146A (en) | 1982-02-25 | 1987-10-13 | Valleylab, Inc. | Hydrophilic, elastomeric, pressure-sensitive adhesive |
US4570629A (en) | 1982-03-17 | 1986-02-18 | University Of Illinois Foundation | Hydrophilic biopolymeric copolyelectrolytes, and biodegradable wound dressing comprising same |
GB2122900A (en) | 1982-07-01 | 1984-01-25 | Surgikos Inc | Disinfectant compositions having residual biocidal activity and wipes and sprays containing them |
DE3371914D1 (en) | 1982-07-16 | 1987-07-09 | Mitsui Petrochemical Ind | Hot-melt adhesive composition |
US4506070A (en) | 1982-07-26 | 1985-03-19 | E. I. Du Pont De Nemours And Company | Antistatic composition and polyester fiber containing same |
US4769013A (en) | 1982-09-13 | 1988-09-06 | Hydromer, Inc. | Bio-effecting medical material and device |
US5512329A (en) | 1982-09-29 | 1996-04-30 | Bsi Corporation | Substrate surface preparation |
AU562370B2 (en) | 1982-10-02 | 1987-06-11 | Smith & Nephew Associated Companies Plc | Moisture vapour permeable adhesive surgical dressing |
DE3339662C2 (en) | 1982-11-04 | 1986-10-30 | Mitsubishi Paper Mills, Ltd., Tokio/Tokyo | Process for the production of an electrophotographic suspension developer and its use for the production of electrophotographic printing plates |
FR2540123A1 (en) | 1983-01-28 | 1984-08-03 | Rhone Poulenc Spec Chim | STABLE AQUEOUS DISPERSIONS AND AMPHOTERIES OF SYNTHETIC POLYMERS |
US4791063A (en) | 1983-02-14 | 1988-12-13 | Cuno Incorporated | Polyionene transformed modified polysaccharide supports |
DE3305964A1 (en) | 1983-02-21 | 1984-08-23 | Henkel KGaA, 4000 Düsseldorf | USE OF CATIONIC POLYMERS AS ANTISTATIC ADDITIVES TO HAIR TREATMENT AGENTS |
US4480075A (en) | 1983-06-24 | 1984-10-30 | Shell Oil Company | Block copolymers of Ziegler-Natta polymerized and anionically polymerized monomers |
US4563184A (en) | 1983-10-17 | 1986-01-07 | Bernard Korol | Synthetic resin wound dressing and method of treatment using same |
US4675347A (en) | 1983-10-29 | 1987-06-23 | Unitika Ltd. | Antimicrobial latex composition |
JPS60130640A (en) | 1983-12-16 | 1985-07-12 | Dainippon Ink & Chem Inc | Preparation of aqueous dispersion of vinyl copolymer resin |
US5024840A (en) | 1984-03-08 | 1991-06-18 | Interface, Inc. | Antimicrobial carpet and carpet tile |
JPS60210613A (en) | 1984-04-03 | 1985-10-23 | Fuji Photo Film Co Ltd | Photosensitive material |
US4617343A (en) | 1984-04-23 | 1986-10-14 | National Starch And Chemical Corporation | Laminating adhesives containing polymerized surfactant |
US4546140A (en) | 1984-08-02 | 1985-10-08 | National Starch And Chemical Corporation | One-package aqueous latices containing alkaline-curable self-crosslinking polymers |
US4632881A (en) | 1984-10-12 | 1986-12-30 | Olin Corporation | Pyrithione-containing bioactive polymers and their use in paint and wood perservative products |
US4668748A (en) | 1984-10-19 | 1987-05-26 | E. I. Du Pont De Nemours And Company | Crosslinkable antistatic polymers and their manufacture |
US4543390A (en) | 1984-12-20 | 1985-09-24 | Toray Industries, Inc. | Antistatic resinous compositions |
US4842768A (en) | 1985-01-16 | 1989-06-27 | Kyowa Gas Chemical Industry Co., Ltd. | Electrically conductive adhesive |
US4708870A (en) | 1985-06-03 | 1987-11-24 | E. I. Du Pont De Nemours And Company | Method for imparting antimicrobial activity from acrylics |
EP0208367B1 (en) | 1985-07-05 | 1989-05-03 | Akzo N.V. | Process for coating an electrically conductive substrate and an aqueous coating composition based on a cationic binder |
US4810567A (en) | 1985-08-21 | 1989-03-07 | Uop | Antimicrobial fabrics utilizing graft copolymers |
GB2191941B (en) | 1985-08-27 | 1990-03-14 | Glyzinc Pharma Ltd | Zinc glycerolate complex and additions for pharmaceutical applications |
US4705709A (en) | 1985-09-25 | 1987-11-10 | Sherwood Medical Company | Lubricant composition, method of coating and a coated intubation device |
US4816508A (en) | 1985-11-07 | 1989-03-28 | Calgon Corporation | Stabilized cationic acrylate or methacrylate polymer admixtures |
US4674512A (en) | 1986-02-03 | 1987-06-23 | Lectec Corporation | Medical electrode for monitoring and diagnostic use |
US4722965A (en) | 1986-02-24 | 1988-02-02 | Reichhold Chemicals, Inc. | Chalk adhesion polymer composition and method of preparation |
JPS62235305A (en) | 1986-04-04 | 1987-10-15 | Dai Ichi Kogyo Seiyaku Co Ltd | Production of high-molecular-weight acrylic polymer |
US5338795A (en) | 1986-04-14 | 1994-08-16 | Toray Industries, Inc. | Housing and thermoplastic resin compositions including polyether ester amide, styrene based resin and vinyl copolymer |
US5081182A (en) | 1986-05-19 | 1992-01-14 | Exxon Chemical Patents Inc. | Cationic monomer delayed addition process |
JPH0689323B2 (en) | 1986-06-13 | 1994-11-09 | 第一工業製薬株式会社 | Antistatic agent |
US4777954A (en) | 1986-06-30 | 1988-10-18 | Nepera Inc. | Conductive adhesive medical electrode assemblies |
US4728323A (en) | 1986-07-24 | 1988-03-01 | Minnesota Mining And Manufacturing Company | Antimicrobial wound dressings |
US4859727A (en) | 1986-08-22 | 1989-08-22 | Mitsubishi Rayon Company Ltd. | Antistatic thermoplastic resin composition |
US4848353A (en) | 1986-09-05 | 1989-07-18 | Minnesota Mining And Manufacturing Company | Electrically-conductive, pressure-sensitive adhesive and biomedical electrodes |
JPH0764940B2 (en) | 1986-09-16 | 1995-07-12 | 三菱レイヨン株式会社 | Manufacturing method of synthetic resin moldings with excellent antistatic properties |
US5055171A (en) | 1986-10-06 | 1991-10-08 | T And G Corporation | Ionic semiconductor materials and applications thereof |
DE3776776D1 (en) | 1986-12-06 | 1992-03-26 | Lion Corp | POLYMER LATEX WITH ULTRA FINE PARTICLES AND COMPOSITIONS CONTAINING THEM. |
PH23983A (en) | 1986-12-23 | 1990-02-09 | Biopolymers Ltd | Biostatic and biocidal composition |
DE3704486A1 (en) | 1987-02-13 | 1988-08-25 | Bayer Ag | ANTISTATIC, THERMOPLASTIC MOLDING MATERIALS BASED ON VINYLAROMATE POLYMERISATES II |
US4931506A (en) | 1987-03-20 | 1990-06-05 | The B. F. Goodrich Company | Ethylene oxide/epihalohydrin copolymer antistatic additive for chlorine-containing polymers |
US5153321A (en) | 1987-04-03 | 1992-10-06 | Ciba-Geigy Corporation | Antistatic and electrically conducting polymers and moulding materials |
DE3711680A1 (en) | 1987-04-07 | 1988-10-27 | Hoechst Ag | AQUEOUS BIOCIDES CATIONIC PLASTIC DISPERSIONS AND THE USE THEREOF AS FUNGICIDES, BACTERICIDES AND ALGICIDES EQUIPMENT |
ES2031948T3 (en) | 1987-04-17 | 1993-01-01 | Bayer Ag | FIRE-FIGHTING ANTI-STATIC POLYCARBONATE MOLDING MASSES. |
CA1318740C (en) | 1987-04-17 | 1993-06-01 | Simon Hsiao-Pao Yu | Copolymers of ethylene oxide as antistatic additives |
AU605217B2 (en) | 1987-05-12 | 1991-01-10 | Ecolab Inc. | Disinfectant polymeric coatings for hard surfaces |
US4857590A (en) | 1987-06-08 | 1989-08-15 | Ge Chemicals, Inc. | Polymer blend compositions |
US4948720A (en) | 1987-08-20 | 1990-08-14 | Eastman Kodak Company | Photographic element containing polyphosphazene antistatic composition |
US5057560A (en) | 1987-10-05 | 1991-10-15 | Ciba-Geigy Corporation | Thermotropic copolymer hydrogels from N,N-dimethylacrylamide and methoxy-ethyl (meth) acrylate |
US4841021A (en) | 1987-11-30 | 1989-06-20 | Minnesota Mining And Manufacturing Company | Polypyridinium |
US5019096A (en) | 1988-02-11 | 1991-05-28 | Trustees Of Columbia University In The City Of New York | Infection-resistant compositions, medical devices and surfaces and methods for preparing and using same |
US5082697A (en) | 1988-02-17 | 1992-01-21 | The Dow Chemical Company | Polymer salt complex for fiber or fabric treatment |
US5330527A (en) | 1988-03-25 | 1994-07-19 | Lec Tec Corporation | Multipurpose medical electrode |
US5205297A (en) | 1988-03-25 | 1993-04-27 | Lectec Corporation | Multipurpose medical stimulation electrode |
JP2595678B2 (en) | 1988-04-15 | 1997-04-02 | ダイキン工業株式会社 | Antifouling paint composition and coated product |
US5043195A (en) | 1988-10-28 | 1991-08-27 | Minnesota Mining & Manufacturing Company | Static shielding film |
GB8829835D0 (en) | 1988-12-21 | 1989-02-15 | Smith Kline French Lab | Compounds |
US4898908A (en) | 1989-01-26 | 1990-02-06 | Kuwait Institute For Scientific Research | Anionic polymer hydrogels and a process for making the same |
DE3905919A1 (en) | 1989-02-25 | 1990-08-30 | Degussa | MIXTURES CONTAINING ORGANOSILICIUM COMPOUNDS AND THE USE THEREOF FOR HYDROPHOBIC AND ANTIMICROBIAL IMPREGNATION |
US5432000A (en) | 1989-03-20 | 1995-07-11 | Weyerhaeuser Company | Binder coated discontinuous fibers with adhered particulate materials |
US5498478A (en) | 1989-03-20 | 1996-03-12 | Weyerhaeuser Company | Polyethylene glycol as a binder material for fibers |
US5143071A (en) | 1989-03-30 | 1992-09-01 | Nepera, Inc. | Non-stringy adhesive hydrophilic gels |
US4981936A (en) | 1989-04-14 | 1991-01-01 | Polypure, Inc. | Terpolymer of oxyalkyene acrylates, acrylamides and quaternary monomers |
US4997697A (en) | 1989-06-29 | 1991-03-05 | Xerox Corporation | Transparencies |
US4954636A (en) | 1989-07-03 | 1990-09-04 | Gaf Chemicals Corporation | Antimicrobial polymeric bisbiguanides |
US5312863A (en) | 1989-07-05 | 1994-05-17 | Rohm And Haas Company | Cationic latex coatings |
US5271943A (en) | 1989-10-27 | 1993-12-21 | Scott Health Care | Wound gel compositions containing sodium chloride and method of using them |
US5006267A (en) | 1989-11-08 | 1991-04-09 | The Dow Chemical Company | Biocidal fluid filters |
US4957908A (en) | 1990-01-08 | 1990-09-18 | Olin Corporation | Chitosan pyrithione as antimicrobial agent useful in personal care products |
US5269770A (en) | 1990-01-10 | 1993-12-14 | Rochester Medical Corporation | Microcidal agent releasing catheter with balloon |
US5261896A (en) | 1990-01-10 | 1993-11-16 | Rochester Medical Corporation | Sustained release bactericidal cannula |
US5124076A (en) | 1990-01-19 | 1992-06-23 | Contour Electrodes, Inc. | Rapid, curing, electrically conductive adhesive |
WO1991012282A1 (en) | 1990-02-14 | 1991-08-22 | H.B. Fuller Licensing & Financing Inc. | Copolymers with inherent antimicrobial action |
US5059629A (en) | 1990-02-16 | 1991-10-22 | The Dow Chemical Company | Biocidal foams |
US5004760A (en) | 1990-02-16 | 1991-04-02 | The Dow Chemical Company | Biocidal foams |
US5069907A (en) | 1990-03-23 | 1991-12-03 | Phoenix Medical Technology | Surgical drape having incorporated therein a broad spectrum antimicrobial agent |
JP3740549B2 (en) | 1990-03-30 | 2006-02-01 | アルザ・コーポレーション | Apparatus and method for drug administration by ion permeation therapy |
US5142010A (en) | 1990-05-10 | 1992-08-25 | H. B. Fuller Licensing & Financing Inc. | Polymeric biocidal agents |
US5080097A (en) | 1990-05-14 | 1992-01-14 | Boston University | Combination pacer defibrillator electrodes and pacer-defibrillator and method for use therewith |
US5183576A (en) | 1990-06-06 | 1993-02-02 | Betz Laboratories, Inc. | Cationic polymers for sludge dewatering |
FR2665450B1 (en) | 1990-08-01 | 1994-04-08 | Rhone Poulenc Chimie | PROCESS FOR THE PREPARATION OF AQUEOUS COPOLYMER DISPERSIONS. |
US5175059A (en) | 1990-09-05 | 1992-12-29 | Mitsubishi Rayon Company Ltd. | Synthetic resin molded article having good antistatic property and process for preparation thereof |
US5369179A (en) | 1990-09-07 | 1994-11-29 | W. R. Grace & Co.-Conn. | Inherently antistatic thermoplastic polyamide-polyether films |
JPH06501239A (en) | 1990-10-12 | 1994-02-10 | ザ ダウ ケミカル カンパニー | antibacterial hydrogel |
US5314959A (en) | 1991-03-06 | 1994-05-24 | Minnesota Mining And Manufacturing Company | Graft copolymers containing fluoroaliphatic groups |
EP0537774B1 (en) | 1991-10-18 | 1998-01-07 | Kuraray Co., Ltd. | Antimicrobial polymerizable composition, the polymer and article obtained from the same |
AU652494B2 (en) | 1991-11-15 | 1994-08-25 | Minnesota Mining And Manufacturing Company | Solid state conductive polymer compositions, biomedical electrodes containing such compositions, and method of preparing same |
IT1252628B (en) | 1991-12-06 | 1995-06-19 | Pier Giorgio Righetti | FORMULATIONS FOR POLYACRYLAMIDIC MATRICES IN ELECTROKINETIC METHODS |
FR2686088B1 (en) | 1992-01-10 | 1995-06-23 | Atochem Elf Sa | PROCESS FOR THE MANUFACTURE OF MULTI-SEQUENCE POLYCONDENSATES, IN STAR OR IN NETWORKS BY COUPLING USING DI- OR MULTI-ALDEHYDES, AND POLYCONDENSATES OBTAINED THEREBY. |
DE4201604A1 (en) | 1992-01-22 | 1993-07-29 | Bayer Ag | FLUORINE COPOLYMERISATE AND AQUEOUS DISPERSIONS MADE THEREOF |
DE69328523T2 (en) | 1992-02-13 | 2000-09-21 | Surmodics Inc | IMMOBILIZATION OF A CHEMICAL SPECIES IN A NETWORKED MATRIX |
US5264249A (en) | 1992-03-20 | 1993-11-23 | Medtronic, Inc. | Method for making a conductive coated product |
DE4211461A1 (en) | 1992-04-06 | 1993-10-07 | Agfa Gevaert Ag | Antistatic plastic parts |
JPH05286811A (en) | 1992-04-07 | 1993-11-02 | Sunstar Inc | Microorganism adsorbing material |
DE4216167A1 (en) | 1992-05-18 | 1993-11-25 | Roehm Gmbh | Water soluble polymer dispersions |
US5263481A (en) | 1992-05-21 | 1993-11-23 | Jens Axelgaard | Electrode system with disposable gel |
TW259806B (en) | 1992-09-16 | 1995-10-11 | Sekisui Plastics | |
US5984102A (en) | 1992-09-24 | 1999-11-16 | Survivalink Corporation | Medical electrode packaging technology |
US5402884A (en) | 1992-09-24 | 1995-04-04 | Surviva Link Corporation | Medical electrode packaging technology |
US5597661A (en) | 1992-10-23 | 1997-01-28 | Showa Denko K.K. | Solid polymer electrolyte, battery and solid-state electric double layer capacitor using the same as well as processes for the manufacture thereof |
GB2272376B (en) | 1992-11-13 | 1996-07-24 | Eric Thomas Mcadams | A multifunction multielectrode device |
US5622168A (en) | 1992-11-18 | 1997-04-22 | John L. Essmyer | Conductive hydrogels and physiological electrodes and electrode assemblies therefrom |
US5429590A (en) | 1992-12-01 | 1995-07-04 | Nitto Denko Corporation | Medical water-absorptive polymer and dressing for wound and medical bandage using the same |
DK0604103T3 (en) | 1992-12-15 | 1999-09-27 | Johnson & Johnson Consumer | Hydrogel laminate, compounds and materials, and processes for their preparation |
TW228529B (en) | 1992-12-23 | 1994-08-21 | Ciba Geigy | |
DE4301459A1 (en) | 1993-01-20 | 1994-07-21 | Huels Chemische Werke Ag | Aqueous fabric softener for the treatment of textiles |
US5255979A (en) | 1993-02-01 | 1993-10-26 | Ferrari R Keith | Medical temperature probe cover |
TW243455B (en) | 1993-02-09 | 1995-03-21 | Ciba Geigy | |
US5652326A (en) | 1993-03-03 | 1997-07-29 | Sanyo Chemical Industries, Ltd. | Polyetheresteramide and antistatic resin composition |
DE19709075A1 (en) | 1997-03-06 | 1998-09-10 | Huels Chemische Werke Ag | Process for the production of antimicrobial plastics |
US5403587A (en) | 1993-04-22 | 1995-04-04 | Eastman Kodak Company | Disinfectant and sanitizing compositions based on essential oils |
US5340583A (en) | 1993-05-06 | 1994-08-23 | Allergan, Inc. | Antimicrobial lenses and lens care systems |
US5665490A (en) | 1993-06-03 | 1997-09-09 | Showa Denko K.K. | Solid polymer electrolyte, battery and solid-state electric double layer capacitor using the same as well as processes for the manufacture thereof |
DE69413790T2 (en) | 1993-07-14 | 1999-02-25 | Nippon Chemical Ind | ANTIBACTERIAL POLYMER, CONTACT LENS AND CONTACT LENS CARE PRODUCT |
US5489437A (en) | 1993-08-17 | 1996-02-06 | Applied Extrusion Technologies, Inc. | Hydrogel products and methods of producing same |
US5403640A (en) | 1993-08-27 | 1995-04-04 | Reichhold Chemicals, Inc. | Textile coating and method of using the same |
US5533971A (en) | 1993-09-03 | 1996-07-09 | Alza Corporation | Reduction of skin irritation during electrotransport |
DE69316005T2 (en) | 1993-09-17 | 1998-07-16 | Agfa Gevaert Nv | Photographic light-sensitive material with preserved antistatic properties |
US5314924A (en) | 1993-10-12 | 1994-05-24 | Sealed Air Corporation | Antistatic polyolefin composition |
GB9322132D0 (en) | 1993-10-27 | 1993-12-15 | Zeneca Ltd | Antimicrobial treatment of textile materials |
US5608021A (en) | 1993-11-29 | 1997-03-04 | Osaka Yuki Kagaku Kogyo Kabushiki Kaisha | Cationic polymer thickener and process for preparing the same |
US5420197A (en) | 1994-01-13 | 1995-05-30 | Hydromer, Inc. | Gels formed by the interaction of polyvinylpyrrolidone with chitosan derivatives |
US5670557A (en) | 1994-01-28 | 1997-09-23 | Minnesota Mining And Manufacturing Company | Polymerized microemulsion pressure sensitive adhesive compositions and methods of preparing and using same |
TW369558B (en) | 1994-01-28 | 1999-09-11 | Minnesota Mining & Mfg | Polymerized microemulsion pressure sensitive adhesive compositions and methods of preparing and using same |
US5618586A (en) | 1994-03-29 | 1997-04-08 | Ppg Industries, Inc. | N-alkoxymethyl (meth)acrylamide functional polymers and their use in self-crosslinkable coating compositions |
US5474065A (en) | 1994-04-04 | 1995-12-12 | Graphic Controls Corporation | Non-invasive fetal probe |
US5614586A (en) | 1994-04-06 | 1997-03-25 | Graphic Controls Corporation | Polyacrylate and Polymethacrylate ester based hydrogel adhesives |
US5674275A (en) | 1994-04-06 | 1997-10-07 | Graphic Controls Corporation | Polyacrylate and polymethacrylate ester based hydrogel adhesives |
AU2286995A (en) | 1994-04-08 | 1995-10-30 | Alza Corporation | Electrotransport system with ion exchange competitive ion capture |
UA10911C2 (en) | 1994-08-10 | 1996-12-25 | Мале Впроваджувальне Підприємство "Іhтерфалл" | Biocompatible hydrogel |
US5536494A (en) | 1994-10-04 | 1996-07-16 | Alcon Laboratories, Inc. | Polyethylene oxide-containing quaternary ammunium polymers and pharmaceutical compositions containing an antimicrobial amount of same |
US5518788A (en) | 1994-11-14 | 1996-05-21 | Minnesota Mining And Manufacturing Company | Antistatic hard coat incorporating a polymer comprising pendant fluorinated groups |
US5614538A (en) | 1994-12-05 | 1997-03-25 | Olin Corporation | Synergistic antimicrobial composition containing pyrithione and alcohol |
DE19507025A1 (en) | 1995-03-01 | 1996-09-05 | Huels Chemische Werke Ag | Multi-layer pipe with an electrically conductive inner layer |
US5591799A (en) | 1995-03-03 | 1997-01-07 | Air Products And Chemicals, Inc. | Aqueous emulsion materials containing copolymerized vinyl amide monomers and hydrolysis products thereof |
US5667913A (en) | 1995-03-23 | 1997-09-16 | National Science Council | Electroconductive polymer composites as positive electrode active materials in secondary batteries |
US5725789A (en) | 1995-03-31 | 1998-03-10 | Minnesota Mining And Manufacturing Company | Aqueous oil and water repellent compositions |
US5624704A (en) | 1995-04-24 | 1997-04-29 | Baylor College Of Medicine | Antimicrobial impregnated catheters and other medical implants and method for impregnating catheters and other medical implants with an antimicrobial agent |
US5688855A (en) | 1995-05-01 | 1997-11-18 | S.K.Y. Polymers, Inc. | Thin film hydrophilic coatings |
DE19519481A1 (en) | 1995-05-27 | 1996-11-28 | Huels Chemische Werke Ag | Multi-layer plastic fuel filter with antistatic properties |
US5962580A (en) | 1995-06-07 | 1999-10-05 | Rohm And Haas Company | Method for providing a waterborne coating composition with improved color acceptance |
US5654369A (en) | 1995-07-25 | 1997-08-05 | Dai-Ichi Kogyo Seiyaku Co., Ltd. | Antistatic thermoplastic resin composition |
JP3398809B2 (en) | 1995-07-27 | 2003-04-21 | 日本光電工業株式会社 | Method for producing conductive composition for bioelectrode |
US6024895A (en) | 1995-08-11 | 2000-02-15 | Mitsubishi Rayon Co., Ltd. | Cross-linkable, electrically conductive composition, electric conductor and process for forming the same |
US5849822A (en) | 1995-08-17 | 1998-12-15 | Teijin Limited | Thermoplastic resin composition superior in transparency and antistatic property |
US5773507A (en) | 1995-08-25 | 1998-06-30 | Henkel Corporation | Anti-static composition and process for making same |
US5646197A (en) | 1995-10-16 | 1997-07-08 | Martin; Howard | Antimicrobial root canal sealer |
GB9521253D0 (en) | 1995-10-17 | 1995-12-20 | Luthra Ajay K | Biocompatible lubricious hydrophilic materials for medical devices |
US5830934A (en) | 1995-10-27 | 1998-11-03 | Reichhold Chemicals, Inc. | Colloidally stabilized emulsion polymer |
EP0780594A1 (en) | 1995-12-21 | 1997-06-25 | Elf Atochem S.A. | Antistatic belts |
US5985990A (en) | 1995-12-29 | 1999-11-16 | 3M Innovative Properties Company | Use of pendant free-radically polymerizable moieties with polar polymers to prepare hydrophilic pressure sensitive adhesive compositions |
BR9708281A (en) | 1996-03-27 | 1999-08-03 | Procter & Gamble | Conditioning containing polyalphaolefins conditioner |
US6280509B1 (en) | 1996-05-09 | 2001-08-28 | Alistagen Corporation | Biocidal coating compositions and method |
EP0846418B1 (en) | 1996-05-10 | 2006-08-16 | Toyo Boseki Kabushiki Kaisha | Antimicrobial composition and antimicrobial laminate |
DE69715404T2 (en) | 1996-05-28 | 2003-01-09 | Eastman Chem Co | SURFACE-ACTIVE AGENT-CONTAINING ACETOACETOXY FUNCTIONAL AND ENAMINE FUNCTIONAL POLYMERS |
JP3193300B2 (en) | 1996-07-12 | 2001-07-30 | 帝人株式会社 | Antistatic polyester film |
EP0952168A4 (en) | 1996-07-16 | 2000-05-24 | Toray Industries | Graft polymer and moldings thereof for medical supply |
JPH10104692A (en) | 1996-09-30 | 1998-04-24 | Minolta Co Ltd | Static-proof finder |
US5645968A (en) | 1996-10-07 | 1997-07-08 | Xerox Corporation | Cationic Toner processes |
US6039940A (en) | 1996-10-28 | 2000-03-21 | Ballard Medical Products | Inherently antimicrobial quaternary amine hydrogel wound dressings |
US6800278B1 (en) | 1996-10-28 | 2004-10-05 | Ballard Medical Products, Inc. | Inherently antimicrobial quaternary amine hydrogel wound dressings |
US5800685A (en) | 1996-10-28 | 1998-09-01 | Cardiotronics Systems, Inc. | Electrically conductive adhesive hydrogels |
DE19654897A1 (en) | 1996-11-14 | 1998-06-04 | Roehm Gmbh | Monomers for polymers with antimicrobial properties |
FR2757866B1 (en) | 1996-12-30 | 2004-12-17 | Catalyse | POLYMERS COMPRISING QUATERNARY AMMONIUM GROUPS, THEIR USE FOR THE MANUFACTURE OF AN ANTIBACTERIAL PROPERTY MATERIAL AND THEIR PREPARATION METHODS |
US6218492B1 (en) | 1997-01-03 | 2001-04-17 | Huels Aktiengesellschaft | Water insoluble bacteriophobic polymers containing carboxyl and sulfonic acid groups |
EP0860213A3 (en) | 1997-01-03 | 2002-10-16 | Therapol SA | Bioactive coating on surfaces |
ES2227799T3 (en) | 1997-01-06 | 2005-04-01 | Arkema | ANTISTATIC FILM FOR THE PACKAGING OF MATERIALS THAT DISSEMINATE VOLATILE PRODUCTS. |
US6242526B1 (en) | 1997-01-28 | 2001-06-05 | Stepan Company | Antimicrobial polymer latexes derived from unsaturated quaternary ammonium compounds and antimicrobial coatings, sealants, adhesives and elastomers produced from such latexes |
US5907017A (en) | 1997-01-31 | 1999-05-25 | Cornell Research Foundation, Inc. | Semifluorinated side chain-containing polymers |
DE19705579A1 (en) | 1997-02-14 | 1998-08-20 | Huels Chemische Werke Ag | An article with microorganism repellent coating, its preparation and use |
GB2322300A (en) | 1997-02-20 | 1998-08-26 | Reckitt & Colman Inc | Miticidal and disinfectant composition |
BR9805903A (en) | 1997-02-25 | 1999-08-24 | Amoco Corp | Copolymer process to prepare the same and structure in several layers |
DE19709076A1 (en) | 1997-03-06 | 1998-09-10 | Huels Chemische Werke Ag | Process for the production of antimicrobial plastics |
DE19716606A1 (en) | 1997-04-21 | 1998-10-22 | Huels Chemische Werke Ag | Bacteria-repellent and blood-compatible modified surfaces |
US5900451A (en) | 1997-05-15 | 1999-05-04 | Reichhold Chemicals, Inc. | Collaidally stabilized butadiene emulsions |
EP0893165A3 (en) | 1997-06-28 | 2000-09-20 | Degussa-Hüls Aktiengesellschaft | Bioactive coating of surfaces using macroinitiators |
DE19728489A1 (en) | 1997-07-03 | 1999-01-07 | Huels Chemische Werke Ag | Medical device for improving the skin fixation of indwelling catheters and other transcutaneous implants with a reduced risk of infection |
KR20010023208A (en) | 1997-08-28 | 2001-03-26 | 브루스, 제임스 에이취 | Chemical and Pharmacological Standardization of Herbal Extracts |
US6015836A (en) | 1997-10-28 | 2000-01-18 | Martin; Howard | Chemical disinfectant employing dual chain quaternary ammonium compounds with iodine |
US6063745A (en) | 1997-11-26 | 2000-05-16 | Allergan | Mutli-purpose contact lens care compositions |
US6197322B1 (en) | 1997-12-23 | 2001-03-06 | Kimberly-Clark Worldwide, Inc. | Antimicrobial structures |
US6038464A (en) | 1998-02-09 | 2000-03-14 | Axelgaard Manufacturing Co., Ltd. | Medical electrode |
BR9908386A (en) | 1998-07-17 | 2000-10-31 | Chemeq Ltd | Method of preparing polymeric compositions, microbicidal, dermatological and / or feed additive compositions and their uses |
DE19833066A1 (en) | 1998-07-22 | 2000-02-03 | Elotex Ag Sempach Station | Process for the preparation of aqueous dispersions of (co) polymers, the dispersions obtainable thereafter, redispersible powders obtainable from the dispersions and their use |
DE19833062A1 (en) | 1998-07-22 | 2000-02-03 | Elotex Ag Sempach Station | Redispersible powder and its aqueous dispersion, process for its preparation and use |
AU5547299A (en) | 1998-08-07 | 2000-02-28 | Reichhold, Inc. | Novel latex compositions for deposition on various substrates |
DE19854819A1 (en) | 1998-11-27 | 2000-05-31 | Degussa | Hollow article with antistatic properties |
US7709694B2 (en) | 1998-12-08 | 2010-05-04 | Quick-Med Technologies, Inc. | Materials with covalently-bonded, nonleachable, polymeric antimicrobial surfaces |
FR2789574B1 (en) | 1999-02-16 | 2001-03-30 | Oreal | DETERGENT COSMETIC COMPOSITIONS CONTAINING ANIONIC HYDROXYALKYLETHER SURFACTANT AND CATIONIC POLYMER AND USES THEREOF |
DE19910811C2 (en) | 1999-03-11 | 2002-11-14 | Sunyx Surface Nanotechnologies | Hydrophilizable block copolymers |
ATE410455T1 (en) | 1999-05-26 | 2008-10-15 | Rhodia | BLOCK POLYMERS, COMPOSITIONS AND METHODS FOR USE IN FOAM, DETERGENT, SHOWER CLEANER AND COAGULANT |
US20050065284A1 (en) | 1999-08-06 | 2005-03-24 | Venkataram Krishnan | Novel latex compositions for deposition on various substrates |
EP1144505A3 (en) | 1999-09-09 | 2002-02-20 | Atofina | Antistatic acrylic polymer compositions |
US6207361B1 (en) | 1999-12-27 | 2001-03-27 | Eastman Kodak Company | Photographic film with base containing polymeric antistatic material |
DE10025707A1 (en) | 2000-05-26 | 2001-11-29 | Degussa | Multi-layer, reinforced plastic connection element with antistatic properties |
US6500981B1 (en) | 2000-08-02 | 2002-12-31 | Ethox Chemicals Llc | Hydroxy and sulfonic acid substituted alkenes and salts |
US6797743B2 (en) | 2000-09-27 | 2004-09-28 | Michigan Biotechnology Institute | Antimicrobial polymer |
JP2002105152A (en) | 2000-09-29 | 2002-04-10 | Nof Corp | Fluorine-containing block copolymer for fluorocoating |
US7264638B2 (en) | 2000-12-21 | 2007-09-04 | John William Artley | Polyethylene glycol saturated substrate and method of making |
WO2002066530A1 (en) | 2001-01-05 | 2002-08-29 | Cornell Research Foundation, Inc. | Polymer material with stable non-wetting surface |
JP3434800B2 (en) | 2001-01-31 | 2003-08-11 | 海洋科学技術センター | Crust core sample collection method, and antibacterial polymer gel and gel material used for the method |
US6821943B2 (en) | 2001-03-13 | 2004-11-23 | S. C. Johnson & Son, Inc. | Hard surface antimicrobial cleaner with residual antimicrobial effect comprising an organosilane |
US6686890B2 (en) * | 2001-04-19 | 2004-02-03 | Fox Broadcasting Company | Slot-array antennas with shaped radiation patterns and a method for the design thereof |
DE10122149A1 (en) | 2001-05-08 | 2002-11-14 | Creavis Tech & Innovation Gmbh | Process for the antimicrobial finishing of porous materials |
US7081139B2 (en) | 2001-05-11 | 2006-07-25 | E. I. Du Pont De Nemours And Company | Antimicrobial polyester-containing articles and process for their preparation |
DE10131484A1 (en) | 2001-06-29 | 2003-01-09 | Creavis Tech & Innovation Gmbh | Antimicrobial polymer foams with amino alcohols |
DE10135667A1 (en) | 2001-07-21 | 2003-02-06 | Creavis Tech & Innovation Gmbh | Microbicidal wallpaper |
US20030049437A1 (en) | 2001-08-03 | 2003-03-13 | Devaney Laura C. | Flexible carrier tape having high clarity and conductivity |
US7030203B2 (en) | 2001-09-28 | 2006-04-18 | 3M Innovative Properties Company | Water-in-oil emulsions with ethylene oxide groups, compositions, and methods |
DE10149973A1 (en) | 2001-10-10 | 2003-04-17 | Creavis Tech & Innovation Gmbh | Extraction stable polymer coatings useful for coating he inner surfaces of pipes, and for coating cooling equipment, air conditioning control panels, glass and synthetic resin surfaces, solar equipment, roof coating, window glass |
MXPA04003543A (en) | 2001-10-18 | 2004-07-22 | Procter & Gamble | Shampoo compositions with anionic surfactants, amphoteric surfactants and cationic polymers. |
US20050010174A1 (en) * | 2002-06-04 | 2005-01-13 | Berman Irwin R. | Applicator and methods of applying a substance |
WO2003104583A1 (en) | 2002-06-07 | 2003-12-18 | Microban Products Company | Antimicrobial wallboard |
MY134362A (en) | 2002-11-20 | 2007-12-31 | Efka Additives B V | Aqueous emulsion polymer as dipersant |
US7981946B2 (en) | 2003-07-03 | 2011-07-19 | Mallard Creek Polymers, Inc. | Antimicrobial and antistatic polymers and methods of using such polymers on various substrates |
US7781498B2 (en) | 2003-07-03 | 2010-08-24 | Mallard Creek Polymers, Inc. | Cationic latex as a carrier for bioactive ingredients and methods for making and using the same |
US7491753B2 (en) | 2003-07-03 | 2009-02-17 | Mallard Creek Polymers, Inc. | Antimicrobial and antistatic polymers and methods of using such polymers on various substrates |
JP4285481B2 (en) * | 2003-07-23 | 2009-06-24 | 東亞合成株式会社 | Water-based ink |
US7763687B2 (en) | 2004-02-20 | 2010-07-27 | Cornell Research Foundation, Inc. | Polymers containing quaternized nitrogen |
US7887790B2 (en) | 2004-02-20 | 2011-02-15 | Cornell Research Foundation, Inc. | Polymers and polymer coatings |
US7709055B2 (en) | 2004-02-20 | 2010-05-04 | Cornell Research Foundation, Inc. | Polymers with ether containing side chains and compositions thereof |
EP1809264B1 (en) | 2004-09-20 | 2016-04-13 | Avent, Inc. | Antimicrobial amorphous compositions |
EP1866166B1 (en) | 2005-03-31 | 2012-10-24 | Fujifilm Corporation | Ink set for ink jet recording, ink for ink jet recording, and ink jet image recording method |
US8343473B2 (en) | 2005-08-24 | 2013-01-01 | Purdue Research Foundation | Hydrophilized antimicrobial polymers |
US20070048249A1 (en) | 2005-08-24 | 2007-03-01 | Purdue Research Foundation | Hydrophilized bactericidal polymers |
US8349300B2 (en) | 2007-04-19 | 2013-01-08 | The Procter & Gamble Company | Personal care compositions containing at least two cationic polymers and an anionic surfactant |
US8673277B2 (en) | 2010-07-09 | 2014-03-18 | Lubrizol Advanced Materials, Inc. | Structured acrylate copolymer thickeners |
US20120046378A1 (en) | 2010-08-20 | 2012-02-23 | Sloan Donald D | Water-Based Digital Ink |
US9131683B2 (en) | 2011-09-30 | 2015-09-15 | The Sherwin-Williams Company | High quality antimicrobial paint composition |
US9663683B2 (en) | 2011-10-31 | 2017-05-30 | S. C. Johnson & Son, Inc. | Polish composition |
US9560849B2 (en) | 2012-06-09 | 2017-02-07 | The University Of Toledo | Antibacterial surfactant/microgel formulations, methods of making and methods of using the same |
NZ707855A (en) | 2012-11-06 | 2018-11-30 | Rochal Ind Llc | Delivery of biologically-active agents using volatile, hydrophobic solvents |
WO2016127387A1 (en) | 2015-02-13 | 2016-08-18 | The Procter & Gamble Company | Cleaning compositions containing alkyl sulfate surfactants and cationic polymer for holistic improvement of sudsing profile |
EP3316855B1 (en) | 2015-07-01 | 2020-09-23 | 3M Innovative Properties Company | Compositions for spore removal |
US20180237686A1 (en) | 2015-08-31 | 2018-08-23 | Halliburton Energy Services, Inc. | Method for stimulation treatment using polymer-surfactant combination |
US10159638B2 (en) | 2016-06-21 | 2018-12-25 | Johnson & Johnson Consumer Inc. | Personal care compositions containing complexing polyelectrolytes |
WO2018222622A1 (en) | 2017-05-27 | 2018-12-06 | Poly Group LLC | Dispersible antimicrobial complex and coatings therefrom |
US20180362678A1 (en) | 2017-06-16 | 2018-12-20 | Poly Group LLC | Polymeric antimicrobial surfactant |
-
2006
- 2006-08-24 US US11/509,915 patent/US20070048249A1/en not_active Abandoned
-
2015
- 2015-08-27 US US14/837,900 patent/US20160053038A1/en not_active Abandoned
-
2016
- 2016-05-24 US US15/163,285 patent/US11134684B2/en active Active
-
2020
- 2020-12-08 US US17/115,709 patent/US11459415B2/en active Active
Patent Citations (32)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4414353A (en) * | 1977-06-03 | 1983-11-08 | Hercules Incorporated | Organic pigments |
US4459289A (en) * | 1980-06-18 | 1984-07-10 | Texcontor - Anstalt | Copolymers having bactericidal activity, process for the preparation thereof and pharmaceutical compositions therefrom |
US4482680A (en) * | 1981-09-15 | 1984-11-13 | Dynapol | Quaternary ammonium group-containing polymers having antimicrobial activity |
US4931522A (en) * | 1989-07-11 | 1990-06-05 | Robert Catena | Copolymers of polyalkylene glycol acrylate and a salt of a quarternized acrylate |
US5317063A (en) * | 1989-09-06 | 1994-05-31 | Lion Corporation | Water-soluble polymer sensitive to salt |
US5509899A (en) * | 1994-09-22 | 1996-04-23 | Boston Scientific Corp. | Medical device with lubricious coating |
US6221425B1 (en) * | 1998-01-30 | 2001-04-24 | Advanced Cardiovascular Systems, Inc. | Lubricious hydrophilic coating for an intracorporeal medical device |
US20010044482A1 (en) * | 1998-07-08 | 2001-11-22 | Hopin Hu | Interpenetrating polymer network hydrophilic hydrogels for contact lens |
US6358557B1 (en) * | 1999-09-10 | 2002-03-19 | Sts Biopolymers, Inc. | Graft polymerization of substrate surfaces |
US6559116B1 (en) * | 1999-09-27 | 2003-05-06 | The Procter & Gamble Company | Antimicrobial compositions for hard surfaces |
US6537663B1 (en) * | 2000-05-04 | 2003-03-25 | Kimberly-Clark Worldwide, Inc. | Ion-sensitive hard water dispersible polymers and applications therefor |
US6815502B1 (en) * | 2000-05-04 | 2004-11-09 | Kimberly-Clark Worldwide, Inc. | Ion-sensitive, water-dispersable polymers, a method of making same and items using same |
US20020086160A1 (en) * | 2000-08-24 | 2002-07-04 | Yongxing Qiu | Process for surface modifying substrates and modified substrates resulting therefrom |
US6852353B2 (en) * | 2000-08-24 | 2005-02-08 | Novartis Ag | Process for surface modifying substrates and modified substrates resulting therefrom |
US20040202639A1 (en) * | 2001-03-08 | 2004-10-14 | Degrado William F. | Facially amphiphilic polymers as anti-infective agents |
US20030091641A1 (en) * | 2001-04-23 | 2003-05-15 | Tiller Joerg C. | Antimicrobial polymeric surfaces |
US6689856B2 (en) * | 2001-05-16 | 2004-02-10 | L'oreal | Water-soluble polymers with a water-soluble backbone and side units with a lower critical solution temperature, process for preparing them, aqueous compositions containing them and cosmetic use thereof |
US6815074B2 (en) * | 2001-05-30 | 2004-11-09 | Novartis Ag | Polymeric materials for making contact lenses |
US20050008876A1 (en) * | 2001-11-08 | 2005-01-13 | Toyoyuki Teranishi | Ultra-water-repellent substrate |
US20050053569A1 (en) * | 2001-12-12 | 2005-03-10 | Bruno Bavouzet | Use of cationic block copolymers to assist the deposition of simple or multiple emulsions |
US20030161804A1 (en) * | 2001-12-20 | 2003-08-28 | Beatrice Perron | Self-adhesive cationic or amphoteric free-radical polymers and cosmetic use thereof |
US20050008839A1 (en) * | 2002-01-30 | 2005-01-13 | Cramer Ronald Dean | Method for hydrophilizing materials using hydrophilic polymeric materials with discrete charges |
US20030229185A1 (en) * | 2002-02-05 | 2003-12-11 | Daoyong Chen | Method for preparation of block copolymeric nanoparticles |
US20030236376A1 (en) * | 2002-03-11 | 2003-12-25 | Ture Kindt-Larsen | Low polydispersity poly-HEMA compositions |
US20040009136A1 (en) * | 2002-05-31 | 2004-01-15 | L'oreal | Aqueous hair treatment compositions, thickened with an amphiphilic linear block copolymer |
US20040135967A1 (en) * | 2002-12-03 | 2004-07-15 | Carney Fiona Patricia | Medical devices having antimicrobial coatings thereon |
US20050058844A1 (en) * | 2002-12-19 | 2005-03-17 | Rubner Michael F. | Method for making medical devices having antimicrobial coatings thereon |
US20050013842A1 (en) * | 2003-07-16 | 2005-01-20 | Yongxing Qiu | Antimicrobial medical devices |
US20050032931A1 (en) * | 2003-07-18 | 2005-02-10 | Naisby Andrew S. | Ink jet recording medium |
US20050101740A1 (en) * | 2003-09-01 | 2005-05-12 | Nathalie Mougin | Block ethylenic copolymers comprising a vinyllactam block, cosmetic compositions containing them and cosmetic use of these copolymers |
US20060057209A1 (en) * | 2004-09-16 | 2006-03-16 | Predicant Biosciences, Inc. | Methods, compositions and devices, including microfluidic devices, comprising coated hydrophobic surfaces |
US7112559B1 (en) * | 2005-03-14 | 2006-09-26 | Ecolab Inc. | Thickened quaternary ammonium compound sanitizer |
Cited By (38)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US11459415B2 (en) | 2005-08-24 | 2022-10-04 | Purdue Research Foundation | Method of using hydrophilized bactericidal polymers |
US11134684B2 (en) | 2005-08-24 | 2021-10-05 | Purdue Research Foundation | Method of using hydrophilized bactericidal polymers |
US20070254006A1 (en) * | 2006-02-15 | 2007-11-01 | Massachusetts Institute Of Technology | Medical Devices and Coatings with Non-Leaching Antimicrobial Peptides |
US20090155335A1 (en) * | 2007-12-05 | 2009-06-18 | Semprus Biosciences Corp. | Non-leaching non-fouling antimicrobial coatings |
WO2009149022A3 (en) * | 2008-06-02 | 2010-02-25 | Johnson & Johnson Vision Care, Inc. | Silicone hydrogel contact lenses displaying reduced protein uptake |
WO2009149022A2 (en) * | 2008-06-02 | 2009-12-10 | Johnson & Johnson Vision Care, Inc. | Silicone hydrogel contact lenses displaying reduced protein uptake |
US20090295004A1 (en) * | 2008-06-02 | 2009-12-03 | Pinsly Jeremy B | Silicone hydrogel contact lenses displaying reduced protein uptake |
US20100145286A1 (en) * | 2008-12-05 | 2010-06-10 | Semprus Biosciences Corp. | Layered non-fouling, antimicrobial antithrombogenic coatings |
US20100152708A1 (en) * | 2008-12-05 | 2010-06-17 | Semprus Biosciences Corp. | Non-fouling, anti-microbial, anti-thrombogenic graft-from compositions |
US8308699B2 (en) | 2008-12-05 | 2012-11-13 | Semprus Biosciences Corp. | Layered non-fouling, antimicrobial antithrombogenic coatings |
US9358326B2 (en) | 2008-12-05 | 2016-06-07 | Arrow International, Inc. | Layered non-fouling, antimicrobial antithrombogenic coatings |
US9895470B2 (en) | 2008-12-05 | 2018-02-20 | Semprus Biosciences Corp. | Non-fouling, anti-microbial, anti-thrombogenic graft—from compositions |
US20110062410A1 (en) * | 2009-09-11 | 2011-03-17 | Ivanov Ilia N | Method for morphological control and encapsulation of materials for electronics and energy applications |
US8101913B2 (en) | 2009-09-11 | 2012-01-24 | Ut-Battelle, Llc | Method of making large area conformable shape structures for detector/sensor applications using glass drawing technique and postprocessing |
US8208136B2 (en) | 2009-09-11 | 2012-06-26 | Ut-Battelle, Llc | Large area substrate for surface enhanced Raman spectroscopy (SERS) using glass-drawing technique |
US8461600B2 (en) | 2009-09-11 | 2013-06-11 | Ut-Battelle, Llc | Method for morphological control and encapsulation of materials for electronics and energy applications |
US9895469B2 (en) | 2010-06-09 | 2018-02-20 | Arrow International, Inc. | Articles having non-fouling surfaces and processes for preparing the same including applying a primer coat |
US9764069B2 (en) | 2010-06-09 | 2017-09-19 | Semprus Biosciences Corporation | Articles having non-fouling surfaces and processes for preparing the same including pretreatment of articles |
US8574660B2 (en) | 2010-06-09 | 2013-11-05 | Semprus Biosciences Corporation | Articles having non-fouling surfaces and processes for preparing the same without altering bulk physical properties |
US8632838B2 (en) | 2010-06-09 | 2014-01-21 | Semprus Biosciences Corporation | Articles having non-fouling surfaces and processes for preparing the same including pretreatment of articles |
US9096703B2 (en) | 2010-06-09 | 2015-08-04 | Semprus Biosciences Corporation | Non-fouling, anti-microbial, anti-thrombogenic graft-from compositions |
US10117974B2 (en) | 2010-06-09 | 2018-11-06 | Arrow International, Inc. | Non-fouling, anti-microbial, anti-thrombogenic graft-from compositions |
US10016532B2 (en) | 2010-06-09 | 2018-07-10 | Arrow International, Inc. | Non-fouling, anti-microbial, anti-thrombogenic graft compositions |
US9974303B2 (en) | 2011-03-31 | 2018-05-22 | International Business Machines Corporation | Cationic polymers for antimicrobial applications and delivery of bioactive materials |
US8709466B2 (en) | 2011-03-31 | 2014-04-29 | International Business Machines Corporation | Cationic polymers for antimicrobial applications and delivery of bioactive materials |
US9147505B2 (en) | 2011-11-02 | 2015-09-29 | Ut-Battelle, Llc | Large area controlled assembly of transparent conductive networks |
US8870372B2 (en) | 2011-12-14 | 2014-10-28 | Semprus Biosciences Corporation | Silicone hydrogel contact lens modified using lanthanide or transition metal oxidants |
US9000063B2 (en) | 2011-12-14 | 2015-04-07 | Semprus Biosciences Corporation | Multistep UV process to create surface modified contact lenses |
US9120119B2 (en) | 2011-12-14 | 2015-09-01 | Semprus Biosciences Corporation | Redox processes for contact lens modification |
US9004682B2 (en) | 2011-12-14 | 2015-04-14 | Semprus Biosciences Corporation | Surface modified contact lenses |
US9006359B2 (en) | 2011-12-14 | 2015-04-14 | Semprus Biosciences Corporation | Imbibing process for contact lens surface modification |
WO2014096851A2 (en) | 2012-12-21 | 2014-06-26 | Coopervision International Holding Company, Lp | Silicone hydrogel contact lenses for sustained release of beneficial polymers |
US9758607B2 (en) | 2013-10-10 | 2017-09-12 | Research Foundation Of The City University Of New York | Polymer with antibacterial activity |
WO2016182444A1 (en) * | 2015-05-12 | 2016-11-17 | Rijksuniversiteit Groningen | 3d-printable antimicrobial composite resins, methods for manufacturing the same |
US11167064B2 (en) | 2016-07-14 | 2021-11-09 | Hollister Incorporated | Hygienic medical devices having hydrophilic coating |
US11421084B2 (en) | 2017-05-27 | 2022-08-23 | Poly Group LLC | Dispersible antimicrobial complex and coatings therefrom |
US11760844B2 (en) | 2017-05-27 | 2023-09-19 | Poly Group LLC | Dispersible antimicrobial complex and coatings therefrom |
US11680116B2 (en) | 2017-06-16 | 2023-06-20 | Poly Group LLC | Polymeric antimicrobial surfactant |
Also Published As
Publication number | Publication date |
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US20210084898A1 (en) | 2021-03-25 |
US20160262392A1 (en) | 2016-09-15 |
US20160053038A1 (en) | 2016-02-25 |
US11134684B2 (en) | 2021-10-05 |
US11459415B2 (en) | 2022-10-04 |
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