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WO2012013577A1 - Composition pour revêtement de dispositifs médicaux contenant lae et un polymère amphotère polycationique - Google Patents

Composition pour revêtement de dispositifs médicaux contenant lae et un polymère amphotère polycationique Download PDF

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Publication number
WO2012013577A1
WO2012013577A1 PCT/EP2011/062580 EP2011062580W WO2012013577A1 WO 2012013577 A1 WO2012013577 A1 WO 2012013577A1 EP 2011062580 W EP2011062580 W EP 2011062580W WO 2012013577 A1 WO2012013577 A1 WO 2012013577A1
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WO
WIPO (PCT)
Prior art keywords
lae
poly
polycationic
devices
medical devices
Prior art date
Application number
PCT/EP2011/062580
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English (en)
Inventor
Abdul Gaffar
Xavier Rocabayera Bonvila
Original Assignee
Laboratorios Miret, S.A.
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Publication date
Application filed by Laboratorios Miret, S.A. filed Critical Laboratorios Miret, S.A.
Publication of WO2012013577A1 publication Critical patent/WO2012013577A1/fr

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Classifications

    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N47/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom not being member of a ring and having no bond to a carbon or hydrogen atom, e.g. derivatives of carbonic acid
    • A01N47/40—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom not being member of a ring and having no bond to a carbon or hydrogen atom, e.g. derivatives of carbonic acid the carbon atom having a double or triple bond to nitrogen, e.g. cyanates, cyanamides
    • A01N47/42—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom not being member of a ring and having no bond to a carbon or hydrogen atom, e.g. derivatives of carbonic acid the carbon atom having a double or triple bond to nitrogen, e.g. cyanates, cyanamides containing —N=CX2 groups, e.g. isothiourea
    • A01N47/44—Guanidine; Derivatives thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L15/00—Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
    • A61L15/16—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
    • A61L15/42—Use of materials characterised by their function or physical properties
    • A61L15/46—Deodorants or malodour counteractants, e.g. to inhibit the formation of ammonia or bacteria
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L17/00—Materials for surgical sutures or for ligaturing blood vessels ; Materials for prostheses or catheters
    • A61L17/005—Materials for surgical sutures or for ligaturing blood vessels ; Materials for prostheses or catheters containing a biologically active substance, e.g. a medicament or a biocide
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L24/00—Surgical adhesives or cements; Adhesives for colostomy devices
    • A61L24/001—Use of materials characterised by their function or physical properties
    • A61L24/0015—Medicaments; Biocides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L29/00—Materials for catheters, medical tubing, cannulae, or endoscopes or for coating catheters
    • A61L29/14—Materials characterised by their function or physical properties, e.g. lubricating compositions
    • A61L29/16—Biologically active materials, e.g. therapeutic substances
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
    • A61L31/14—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/20—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials
    • A61L2300/216—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials with other specific functional groups, e.g. aldehydes, ketones, phenols, quaternary phosphonium groups
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
    • A61L2300/404—Biocides, antimicrobial agents, antiseptic agents

Definitions

  • the present invention relates to novel combinations for the treatment of medical devices. BACKGROUND ART
  • a large number of medical devices such as urinary catheters, endotracheal tubes, central venous catheters are used in patient care and are a leading cause of hospital-acquired infections in high risk patients.
  • Such high-risk patients include critically ill patients admitted to intensive care units (ICU), cancer patients and patients with chronic diseases requiring long term care, such as those on total parenteral nutrition.
  • Anti-infective devices coated with antimicrobial agents have been shown to significantly decrease the risk of device-related and hospital- acquired infections. Most nosocomial (hospital-acquired) infections are caused by contamination of medical devices.
  • patients undergo a vast number of surgical procedures in the United States. Current data show 27 million procedures performed per year and post-surgical site infections occur in approximately 2-3 % of these cases. Whenever medical devices are used in surgical settings the risk of infection is increased.
  • US 2006/ 02633404A1 provides an assembly of preparations of medical devices having a porous coating comprising hydrogen peroxide for catheters, such as urinary catheters, endoscopes, laryngoscopes, tubes for feeding, tubes for drainage, guidewires, condoms, urisheets, barrier coatings, for example gloves, stents and other implants, extracorporeal blood conduits, membranes, for example for dialysis, blood filters, devices for circulatory assistance, dressings for wound care and ostomy bags.
  • catheters such as urinary catheters, endoscopes, laryngoscopes, tubes for feeding, tubes for drainage, guidewires, condoms, urisheets, barrier coatings, for example gloves, stents and other implants, extracorporeal blood conduits, membranes, for example for dialysis, blood filters, devices for circulatory assistance, dressings for wound care and ostomy bags.
  • WO2007/062330682 discloses methods for coatings or impregnating surfaces with antimicrobial agents that involve coating the surface with a composition including antimicrobial agents and solvents, in curing surfaces by applying heat.
  • W01 /95876 teaches the coating of medical devices with antibiotics and quaternary ammonium compounds to prevent bacteria from growing on the devices.
  • European Patent Application 0590348A1 teaches the coating of venous catheters with lipodalbahepatide antibiotics for preventing development of catheter-related infections.
  • WO2007/050565A2 relates to the coating of medical devices with bactericidal and bacteriostatic coatings to prevent infection.
  • US Patent 5752941 discloses central venous polyurethane catheters with a thin hydrophilic coating loaded with antibiotics to prevent catheter related infection.
  • US 2008/0020127A1 describes the coating using the bridged polycyclic compounds with quaternary ammonium moieties to prevent infection.
  • US2008/026080482A1 provides a composition containing polyquat to coat medical devices preferably contact lens to prevent bacterial infection.
  • US2006/0263444A1 describes compositions containing cationic surfactants lauric arginate and antimicrobial metals such as silver and silver compounds for coating medical devices.
  • US2007/02252220A1 discloses compositions containing cationic surfactants lauric arginate and antibiotics for coating medical devices.
  • PROBLEMS TO BE SOLVED BY THE INVENTION As indicated above the prior art does not cover multiple problems such as infection, formation of thrombi, biofilm formation proliferation and bacterial toxins left over by the antibacterial action on the devices.
  • most antibacterial coatings disclosed in the prior art teach the use of antibiotics and metals, which tend to form resistant microorganisms which could lead to serious infections.
  • This invention relates to a multifunctional coating of medical devices to provide control of bacterial infection, prevention of the formation of biofilms, to inhibit local thrombosis and to bind and neutralize toxins.
  • Cationic surfactants are known as preservatives used in food, cosmetic and pharmaceutical industry. Cationic surfactants have turned out to be highly effective against microbial proliferation and at the same time safe for intake in humans and mammals in general. For all of this, cationic surfactants are an attractive tool in the industry.
  • X " is a counter ion derived from an organic or inorganic acid, preferably Br “ , CI “ or HS0 4 " , or an anion on the basis of a phenolic compound;
  • R-i is a straight a Iky I chain from a saturated fatty acid or hydroxy I acid having from 8 to 14 atoms linked to the a-amino acid group via an amidic bond;
  • R 2 is a straight or branched a Iky I chain from 1 to 18 carbon atoms or an aromatic group
  • R 3 is
  • n is from 0 to 4.
  • the organic acids which may be the source of the counter ion X " can be citric acid, lactic acid, acetic acid, fumaric acid, maleic acid, gluconic acid, propionic acid, sorbic acid, benzoic acid, carbonic acid, glutamic acid or other amino acids, lauric acid and fatty acids such as oleic acid and linoleic acid, whereas the inorganic acids can be phosphoric acid, nitric acid and thiocyanic acid.
  • the phenolic compound which may be the basis of the anion X " is for instance butylated hydroxyanisole (BHA) and the related butylated hydroxytoluene, tertiary butyl hydroquinone and parabens such as methylparaben, ethylparaben, propylparaben and butylparaben.
  • BHA butylated hydroxyanisole
  • parabens such as methylparaben, ethylparaben, propylparaben and butylparaben.
  • the most preferred compound of the above class of compounds is the ethyl ester of the lauramide of the arginine monohydrochloride, hereafter referred to as LAE (CAS No. 60372-77-2). This compound is now well-known for its use as an antimicrobial agent. In practical use LAE turned out to be well tolerated and to display a very low toxicity to human beings. LAE has the chemical structure of formula (2) displayed here
  • the compound LAE is remarkable for its activity against different micro-organisms, like bacteria, moulds and yeasts which can be present in food products (WO 03/034842) and also in cosmetic formulations and preparations (WO 03/013453, WO 03/013454 and WO 03/043593).
  • the compound has been furthermore described for its effect on parasites in fish, such as on the larvae of Anisakis or other species (European application 07 382 004.5). Its preservative action is particularly pronounced in a combination with a polyene fungicide such as natamycin (PCT/EP2007/060598). It has furthermore been shown to be effective for killing endospores and for having an effect in virus infections (European application 08 382 025.8). The specific use for the protection of teeth against dental erosion has been described (European application 08 382 007.6).
  • LAE also known as lauric arginate
  • LAMIRSA LAMIRSA, Spain
  • Lauric arginate is listed by the FDA (Food and Drug Administration) as being a GRAS substance (Generally Recognized As Safe) under GRN 000164.
  • the USDA United States Department of Agriculture
  • FSIS Directive 7120.1 has approved its use in meat and poultry products (FSIS Directive 7120.1 ) and also as a processing aid for fresh meat and poultry products.
  • LAE is completely harmless to animals and humans. Therefore, LAE and related compounds are particularly suitable to be used in the preservation of all perishable food products. LAE and related compounds are equally suitable for use in cosmetic or medical products and in medical devices where growth of microorganisms is common. As has been remarked above, the cationic surfactants are remarkable for their inhibitory action over the proliferation of different microorganisms, such as bacteria, fungi and yeasts.
  • the minimum inhibitory concentrations of LAE are shown in the following table 1 . Table 1
  • Lactobacillus delbrueckii ssp 1 act is CECT 372 16
  • the compound directly before use in one of the following preferred solvents of food grade: water, ethanol, propylene glycol, isopropyl alcohol, other glycols, mixtures of glycols and mixtures of glycols and water, diacetin, triacetin, glycerol, sorbitol, mannitol and xylitol. If the treatment shall be performed at a specific pH value the use of a corresponding buffer solution may be recommendable. On the other hand the compound can be easily used in its solid form or formulated with solid carriers such as salt, sugar, maltodextrine, hydrocolloids and sorbitol.
  • the compound LAE has been proven to be highly suitable for the coating of surfaces.
  • the anti-attachment mechanism in the oral cavity provides a non-specific protection against bacterial adhesion. It is an advantage of this approach, that there is no risk, that the bacteria will become resistant. Measurement of the contact angle of sessile drops from liquids with a range of polarities was used to determine the polar component of the surface energy, y s p .
  • y s is reduced to 1 1 .5 dynes/cm on an LAE-coated surface, less than half of the original y s p of 23 dynes/cm on a bare or saliva-coated substrate (fig. 1 ). This reduction is expected to make the surface more resistant to bacterial attachment.
  • MIC values minimum inhibitory concentrations for susceptible and resistant strains were the same.
  • MRSA methicillin resistance Staphylococcus aureus
  • MRSA Staphylococcus aureus
  • MRSA Acinetobacter Baumanii
  • polycationic materials used in the present invention with LAE have a plurality of positively charged groups along a polymer chain.
  • suitable examples of such polycationic materials include, but are not limited to,
  • PAH poly(allylamine hydrochloride)
  • PAI poly(ethyleneimine)
  • PVBT poly(vinylbenzyltrimethylamine)
  • PAN polyaniline
  • PAN polypyrrole
  • Other cationic polymers include poly quaternium-6 and polyquaternium-7.
  • an amphoteric polymer having positive and negative charges such as Amphomer®, octylacrylamide/acrylates/butylaminoethyl methylacrylate polymer, is a preferred embodiment.
  • a preferred combination is the combination of LAE with Amphomer ® at 0.2%.
  • Preparations for the treatment of the medical devices are usually solutions containing LAE and the polycationic material, such as for instance poly(allylamine hydrochloride) (PAH), poly(ethyleneimine) (PAI), poly(vinylbenzyltrimethylamine) (PVBT), polyaniline (PAN), polypyrrole and poly(pyridinium acetylene).
  • the solution usually contains LAE in a concentration within the range of 0.0001 to 5% and the polycationic material in a concentration range of 0.1 to 10% .
  • a preferred range for the concentration of LAE is 0.005 to 1 %.
  • a preferred range for the concentration of the polycationic material is 0.005 to 1 % .
  • the solution shall contain the two components in a ratio of 2.5 : 1 .
  • an auxiliary material from the group consisting of cationic and amphoteric surfactants is present.
  • Suitable cationic surfactants to be added as auxiliary material may be selected from quaternary ammonium salts, amines with amide linkages, polyoxyethylene a Iky I amines, polyoxyethylene alicyclic amines, N , N , N ' , N '-tetrakis-su bstituted ethylenediamines and 2-alkyl-1 -hydroxyethyl-2-imidazoles.
  • Suitable amphoteric surfactants to be added as auxiliary material may be selected from glycinates, betaines and propionates or dipropionates.
  • Suitable products are N-coco-3-aminopropionic acid or its sodium salt, N-tallow-3-iminodipropionic acid or its disodium salt, and N-carboxymethyl-N-dimethyl-N-9-octadecenyl ammonium hydroxide and N-cocoamidethyl-N-hydroxyethylglycine or its sodium salt.
  • the amount of the auxiliary material in the antimicrobial composition is between 0 and 10 parts by weight relative to 100 parts by weight of the antimicrobial composition, preferably between 0.1 and 5 parts by weight per 100 parts by weight of the antimicrobial composition, more preferably between 0.5 and 2.0 parts by weight per 100 parts by weight of the antimicrobial composition.
  • the manner of treatment of the medical devices is usually the application of a LAE solution (0.1 to 10%) for 1 to 5 minutes for killing bacteria, pathogenic fungi and viruses on hard surfaces.
  • Medical devices which have been treated in this manner shall normally be kept in a dry and cool place. Under such circumstances the treated medical devices maintain their activity for at least 12 months.
  • the novel and unobvious utility of this coating for multifunctional coating of medical devices will be obvious from the examples given below.
  • DFR Drip-Flow Reactor
  • E. coli BDH 6057 and P. aeruginosa BDH 5990 were both isolated by Bozeman Deaconess Hospital from urine and are maintained at - 80°C as frozen stock cultures by the Medical Biofilms Laboratory at the CBE. The test organisms were cultured overnight from frozen stocks at 37°C in the test medium.
  • the DFRs were run in a 37°C incubator under aerobic conditions.
  • sterile medium was dripped-in and allowed to collect over coupons to form conditioning layer on the surface of HA- coated glass surfaces because biofilms are better retained on the slide surfaces for treatment and analysis.
  • Each of the channel reactor was then inoculated with 1 .0 ml of an overnight culture. DFR was maintained in a horizontal position for two hours with no flow to enable bacterial attachment to the substratum. The reactor was set at 10 degree angle and sterile medium dripped through the reactor at 40 ml/hr, total 10 ml/hr per coupon. Initially the reactor was run for 3 days, this was reduced to one day. For urinary biofilm E. coli in artificial urine medium was used. For venous catheters P. aeruginosa in 10% brain heart infusion was used.
  • Polymixin B is a well known deactivator of endotoxins used clinically. Therefore, it was of interest to see how LAE compares with Polymixin B. Data from binding studies showed, that LAE was as effective as Polymixin B, already proven to be an inactivator of endotoxin, in deactivating endotoxins.
  • a multi-species biofilm model (Guggenheim, J. Dental Res. 2001 ; 80, 363-370) was used to assess the effect of LAE in combinations with polycationic polymers to prevent growth and proliferation of microbial biofilms.
  • This model simulated conditions in vivo of biofilms on protein coated surfaces in the human body.
  • multi-species of bacteria and yeast were used in batch culture process, with multiple exposures to microbes and treatment.
  • the organisms used were Streptococcus oralis, Streptococcus sobrinus, Actinomyces naeslundii, Veillonelia dispar, Fusobacterium nucleatum and Candida albicans.
  • the substrate used for the biofilm formation consisted of hydroxyapatite (bone mineral) disc coated with saliva proteins to simulate body fluids like saliva and serum. Organisms were maintained alive by adding 100% saliva and bacteria growth medium. The sampling was done at 30 min, 16.5 hrs, 40.5 hrs and 65.5 hrs.
  • composition of the film was analyzed by culture technique, dead/live bacteria by Sytox stain and automated image analyses (IBES) of immunofluorescence.
  • the solutions tested were control (vehicle), LAE combined with polycationic materials which included poly(allylamine hydrochloride) (PAH), poly(ethyleneimine) (PAI),
  • PVBT poly(vinylbenzyltrimethylamine)
  • PAN polyaniline
  • PAN polypyrrole
  • the other cationic polymers included poly quaternium- 6 and polyquaternium-7.
  • an amphoteric polymer having positive and negative charges such as octylacrylamide/acrylates/-butylaminoethyl
  • the coating was accomplished via several ways.
  • One coating process embodiment involved solely dip-coating and dip-rinsing steps.
  • Another embodiment of coating process was by spray-coating and spray rinsing steps.
  • a number of alternatives which involves various combinations of spraying and dip-coating and rinsing steps may be designed by a person ordinarily skilled in the art.
  • One dip-coating alternative involved steps applying polycationic material to the material of the medical device by immersing said device in a solution of a polycationic material, optionally drying, followed by coating with LAE solutions. This bi-layered process can be repeated to achieve the desired film thickness of LAE on the surfaces.
  • LAE plus polycationics for coating medical devices provides antimicrobial activity, prevents proliferation and growth of biofilms, kills antibiotic resistant organisms, inactivates bacterial toxins and prevent thrombi when the devices are exposed to blood.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • General Health & Medical Sciences (AREA)
  • Epidemiology (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • Chemical & Material Sciences (AREA)
  • Materials Engineering (AREA)
  • Surgery (AREA)
  • Vascular Medicine (AREA)
  • Molecular Biology (AREA)
  • Biomedical Technology (AREA)
  • Plant Pathology (AREA)
  • Pest Control & Pesticides (AREA)
  • Agronomy & Crop Science (AREA)
  • Dentistry (AREA)
  • Wood Science & Technology (AREA)
  • Zoology (AREA)
  • Environmental Sciences (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Medicinal Chemistry (AREA)
  • Hematology (AREA)
  • Materials For Medical Uses (AREA)

Abstract

L'invention concerne des compositions antimicrobiennes contenant LAE, un matériau polymère polycationique ou amphotère et facultativement un matériau auxiliaire dans le groupe constitué de tensioactifs cationiques et amphotères. La composition antimicrobienne contient de préférence un matériau polymère polycationique ou amphotère qui est choisi dans le groupe constitué des poly(chlorhydrate d'allylamine) (PAH), poly(éthylèneimine) (PAI), poly(vinylbenzyltriméthylamine) (PVBT), polyaniline (PAN), polypyrrole et poly(pyridinium acétylène)) pour le polymère polycationique et octylacrylamide/acrylates/méthylacrylate de butylaminoéthyle (Amphomer®).
PCT/EP2011/062580 2010-07-26 2011-07-21 Composition pour revêtement de dispositifs médicaux contenant lae et un polymère amphotère polycationique WO2012013577A1 (fr)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
EP10382206 2010-07-26
EP10382206.0 2010-07-26
US38709810P 2010-09-28 2010-09-28
US61/387,098 2010-09-28

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US10111679B2 (en) 2014-09-05 2018-10-30 Ethicon Llc Circuitry and sensors for powered medical device
US10117653B2 (en) 2014-03-26 2018-11-06 Ethicon Llc Systems and methods for controlling a segmented circuit
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US10206605B2 (en) 2015-03-06 2019-02-19 Ethicon Llc Time dependent evaluation of sensor data to determine stability, creep, and viscoelastic elements of measures
US10213201B2 (en) 2015-03-31 2019-02-26 Ethicon Llc Stapling end effector configured to compensate for an uneven gap between a first jaw and a second jaw
US10213262B2 (en) 2006-03-23 2019-02-26 Ethicon Llc Manipulatable surgical systems with selectively articulatable fastening device
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