EP0858486A1 - Method for making bactericidal polymers, and resulting products - Google Patents

Method for making bactericidal polymers, and resulting products

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Publication number
EP0858486A1
EP0858486A1 EP97929350A EP97929350A EP0858486A1 EP 0858486 A1 EP0858486 A1 EP 0858486A1 EP 97929350 A EP97929350 A EP 97929350A EP 97929350 A EP97929350 A EP 97929350A EP 0858486 A1 EP0858486 A1 EP 0858486A1
Authority
EP
European Patent Office
Prior art keywords
photoinitiator
energy radiation
basic formulation
bactericidal agent
bactericidal
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Withdrawn
Application number
EP97929350A
Other languages
German (de)
French (fr)
Inventor
Raffaella Ciampa
Bernard Boutevin
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Merlin Jacques
Original Assignee
Merlin Jacques
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Filing date
Publication date
Application filed by Merlin Jacques filed Critical Merlin Jacques
Publication of EP0858486A1 publication Critical patent/EP0858486A1/en
Withdrawn legal-status Critical Current

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Classifications

    • 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
    • C08F290/00—Macromolecular compounds obtained by polymerising monomers on to polymers modified by introduction of aliphatic unsaturated end or side groups
    • C08F290/08—Macromolecular compounds obtained by polymerising monomers on to polymers modified by introduction of aliphatic unsaturated end or side groups on to polymers modified by introduction of unsaturated side groups
    • C08F290/14—Polymers provided for in subclass C08G
    • C08F290/147—Polyurethanes; Polyureas
    • 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
    • A01N25/00—Biocides, pest repellants or attractants, or plant growth regulators, characterised by their forms, or by their non-active ingredients or by their methods of application, e.g. seed treatment or sequential application; Substances for reducing the noxious effect of the active ingredients to organisms other than pests
    • A01N25/08—Biocides, pest repellants or attractants, or plant growth regulators, characterised by their forms, or by their non-active ingredients or by their methods of application, e.g. seed treatment or sequential application; Substances for reducing the noxious effect of the active ingredients to organisms other than pests containing solids as carriers or diluents
    • A01N25/10—Macromolecular compounds
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N25/00—Biocides, pest repellants or attractants, or plant growth regulators, characterised by their forms, or by their non-active ingredients or by their methods of application, e.g. seed treatment or sequential application; Substances for reducing the noxious effect of the active ingredients to organisms other than pests
    • A01N25/24—Biocides, pest repellants or attractants, or plant growth regulators, characterised by their forms, or by their non-active ingredients or by their methods of application, e.g. seed treatment or sequential application; Substances for reducing the noxious effect of the active ingredients to organisms other than pests containing ingredients to enhance the sticking of the active ingredients
    • 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
    • A01N37/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having three bonds to hetero atoms with at the most two bonds to halogen, e.g. carboxylic acids
    • A01N37/12—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having three bonds to hetero atoms with at the most two bonds to halogen, e.g. carboxylic acids containing the group, wherein Cn means a carbon skeleton not containing a ring; Thio analogues 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
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/28—Materials for coating prostheses
    • A61L27/34—Macromolecular 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
    • A61L29/00—Materials for catheters, medical tubing, cannulae, or endoscopes or for coating catheters
    • A61L29/08—Materials for coatings
    • A61L29/085—Macromolecular materials

Definitions

  • the present invention relates to a process for manufacturing bactericidal polymers, as well as the products obtained by this process.
  • binders consist of the combination of a chlorinated vinylyque polymer with 10 to 20% by weight of a quaternary ammonium salt of which at least one substituent is chosen from the group comprising a hydrocarbon derivative with a long linear chain, aryl or alkyl .
  • the present invention makes it possible to obtain a plastic material which can be used for producing probes, catheters, or other instruments for medical use.
  • This product has biocidal properties whose role is to inhibit the formation of bacterial biofilm. Due to its low manufacturing cost and its ecological process (no solvent), it is easy to make this research industrializable.
  • the originality of the concept lies in the fact that the bactericidal agent enters directly into the final composition of the basic formulations.
  • the method according to the invention is based on the formation of a coating which has a covalent bond between a bactericidal agent and a three-dimensional network itself adhering to the base material consisting of a synthetic resin, said bond being obtained by exposure to energetic radiation, for example ultraviolet, gamma rays or electronic bombardments, of a formulation comprising three essential components consisting of at least one photoinitiator, at least one crosslinkable oligomer and at least one mono or multifunctional monomer, as well as various additives giving specific properties to the final product.
  • energetic radiation for example ultraviolet, gamma rays or electronic bombardments
  • One of the originalities comes from the synthesis of a monomer capable of acting as an antiseptic and of reacting with a polymer or an oligomer which is particularly active under energetic activation.
  • One of the processes used is that of photocrosslinking under ultraviolet radiation to create a coating having quaternary ammonium bonds, the basic formulation consisting of a mixture of photoinitiator (s), oligomers and monomer (s) mono or multifunctional (s).
  • the crosslinkable formulation by radical route is a mixture of compounds comprising at least one bactericidal agent with an unsaturated structure consisting of a multifunctional monomer formed of molecules having the following structure: 0
  • This molecule has the following peculiarities
  • the bactericidal effect is maximum, if and only if, the quaternary ammonium has an alkyl chain structure (R7) in C8hl7 ⁇ and a counterion X ⁇ .
  • This counterion is a bromide ion because the iodide ion would be too bulky and the divalent anion would induce conformation constraints and therefore a decrease in antimicrobial activity.
  • the reaction principle is based on a reaction between a tertiary amine and an alkyl halide in an acetone / dichloromethane mixture.
  • the quaternary ammonium monomer is cold precipitated in pentane, filtered and rinsed several times with pentane and dried under vacuum over phosphoric anhydride (P205).
  • the product thus obtained is a white salt which is characterized by infrared (IR), by (P205).
  • the product thus obtained is a white salt which is characterized by infrared (IR), by nuclear magnetic resonance (NMR 200 Mhz) and by elemental analysis (determination of nitrogen, oxygen and bromine).
  • the reaction resulting from the process according to the invention is that of a radical polymerization.
  • the polymerization rate will depend on the light intensity, the efficiency of the photoinitiator, the reactivity of the functional group and the viscosity of the medium.
  • the final polymerization rate and the physico-chemical properties of the photocrosslinked polymer will depend on the chemical structure and the functionality of the monomer and of the oligomer.
  • Crosslinkable oligomers are polymers or copolymers which are particularly active under energy radiation.
  • the subject of the present invention is a polymer material for medical use which is characterized in that it is based at least on a resin or a mixture of resins resulting from the combination of diol, diisocyanate and ether vinyl.
  • the mono or multifunctional monomers are for example reactive diluent monomers such as TGPDA, HDDA or HEA These compounds carrying two reactive functions chosen from epoxy, vinyl or hydroxy ether functions, combined or not, will affect the speed of polymerization, on the conversion rate and therefore on the physicochemical properties of the crosslinked polymer.
  • the basic formulation could have the following composition:
  • the material has a more or less significant antibacterial effect.
  • the basic formulation includes three essential components, namely one or more photoinitiator (s), one or more crosslinkable oligomer (s) and one or more mono or multifunctional monomer (s), as well as various additives intended to give the final product well-defined properties.
  • additives are in particular stabilizers, wetting agents, spreading agents, fillers, pigments, etc., provided that they are not themselves inhibitors of the polymerization.
  • the photocrosslinking process can be considered as the transition from an unactivated basic system to an activated system, then crosslinked.
  • the bactericidal product incorporated into the basic formulation resin (s) acrylate (s), photoinitiator (s), monomer (s) and additive (s) constitutes a more or less viscous mixture which is used to coat a synthetic material preferably made up a polyvinyl chloride, a polyurethane or a polycarbonate previously activated on the surface chemically and / or mechanically, the synthetic material once coated having passed under ultraviolet radiation.
  • the compositions thus formulated can be applied according to any known technique, for example spray gun, hardened or defiled.
  • the photoinitiator is not necessary for formulation, and activation of the material is then unnecessary.
  • Another more recent system consists of photo or cationic electropolymerization.
  • the monomers capable of reacting with such a system are vinyl ethers, epoxides but also derivatives of aromatic compounds such as styrene.
  • the photoinitiators used are very different from the previous ones, in the sense that these products decompose under ultraviolet radiation, forming Lewis acids. This will allow the polymerization, inter alia, of epoxides, vinyl ethers or other monomers and polymer (s) capable of reacting under radiative / cationic crosslinking.
  • the diaryliodonium salts [(Ar2I + , X ") j or bis (diodecylphenyl) iodonium [(C12H25Ar2r * * , X
  • X represents in all these compounds an anion of type PF6 “, BF4", AsF6 “ , SbF6 “ , FeC14 “ , SbC16 ⁇ , ...
  • aryl radicals are generally phenyl radicals. These aryl radicals are optionally substituted by a linear or branched alkyl radical having from 1 to 12 carbon atoms.
  • the bactericidal agent is introduced into the formulation as a reactive diluting agent.
  • the positioning of the various constituent elements gives the object of the invention a maximum of useful effects which had not, to date, been obtained by similar devices.

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  • Life Sciences & Earth Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Environmental Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Wood Science & Technology (AREA)
  • Zoology (AREA)
  • Agronomy & Crop Science (AREA)
  • Pest Control & Pesticides (AREA)
  • Plant Pathology (AREA)
  • Engineering & Computer Science (AREA)
  • Dentistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Medicinal Chemistry (AREA)
  • Toxicology (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Epidemiology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Transplantation (AREA)
  • Materials For Medical Uses (AREA)
  • Dermatology (AREA)
  • Oral & Maxillofacial Surgery (AREA)
  • Organic Chemistry (AREA)
  • Paints Or Removers (AREA)
  • Polymers & Plastics (AREA)

Abstract

A method for making bactericidal polymers, and the resulting products, are disclosed. The method is based on the formation of a coating having a covalent bond between a bactericidal agent and a three-dimensional network which is in turn adhered to the base material consisting of a synthetic resin, said bond being achieved by the exposure to energy radiation, e.g. ultraviolet radiation, gamma rays or electron bombardment, of a formulation comprising three essential components, i.e. at least one photoinitiator, at least one cross-linkable oligomer and at least one mono- or multifunctional monomer, as well as various additives conferring specific properties to the end product. Said method is particularly useful for producing medical instruments made of synthetic material, especially probes and catheters, but is also useful in numerous other fields.

Description

PROCÉDÉ DE FABRICATION DE POLYMERES BACTÉRICIDES ET PRODUITS OBTENUS PAR CE PROCÉDÉ PROCESS FOR PRODUCING BACTERICIDAL POLYMERS AND PRODUCTS OBTAINED THEREBY
La présente invention a pour objet un procédé de fabrication de polymères bactéricides, ainsi que les produits obtenus par ce procédé.The present invention relates to a process for manufacturing bactericidal polymers, as well as the products obtained by this process.
Ces polymères sont essentiellement destinés à la réalisation d'instruments en matière synthétique pour usage médical, tels que sondes et cathéters en particulier, mais peuvent trouver des applications dans de nombreux autres domaines.These polymers are essentially intended for the production of plastic instruments for medical use, such as probes and catheters in particular, but can find applications in many other fields.
Les problèmes d'infections par cathéters et autres instruments en matériaux plastiques constituent actuellement un problème majeur dans les milieux hospitaliers. Malgé les précautions prises aussi bien lors du conditionnement de ces articles afin d'assurer leur stérilité au moment de leur emploi, que lors de leur élimination, ils sont souvent la cause d'infection ou de transmission d'infection chez les personnes hospitalisées. C'est pourquoi un certain nombre de laboratoires et de sociétés s'investissent depuis quelques temps dans la recherche de matériaux bactéricides afin d'empêcher les possibles contaminations microbiennes, et ceci quelle qu'en soit l'origine.The problems of infections by catheters and other plastic instruments are currently a major problem in hospital settings. Despite the precautions taken both when packaging these items to ensure their sterility at the time of use, and when disposing of them, they are often the cause of infection or transmission of infection in hospitalized people. This is why a certain number of laboratories and companies have been investing for some time in the research of bactericidal materials in order to prevent possible microbial contamination, and this whatever its origin.
Dans le brevet européen N° EP 0 270 465, déposé par l'Université de Provence à MarseilleIn European patent N ° EP 0 270 465, filed by the University of Provence in Marseille
(Inventeurs : MM Alain PERICHAUD et Georges SAUVET) , est décrit un procédé permettant d'obtenir des liants résistant aux salissures et micro-organismes présents en milieu aqueux, et destinés en particulier à la réalisation de peintures marines "anti fooling". Ces liants sont constitués de l'assiociation d'un polymère vinylyque chloré avec 10 à 20 % en poids d'un sel d'ammonium quaternaire dont au moins un substituant est choisi dans le groupe comprenant un dérivé hydrocarboné à longue chaîne linéaire, aryle ou alkyle.(Inventors: MM Alain PERICHAUD and Georges SAUVET), a process is described making it possible to obtain binders resistant to soiling and microorganisms present in an aqueous medium, and intended in particular for the production of "anti fooling" marine paints. These binders consist of the combination of a chlorinated vinylyque polymer with 10 to 20% by weight of a quaternary ammonium salt of which at least one substituent is chosen from the group comprising a hydrocarbon derivative with a long linear chain, aryl or alkyl .
La substitution des atomes de chlore dudit polymères par une aminé tertiaire conduit à créer une liaison covalente non hydrolysable de type ammonium quaternaire. Malgré de bons résultats bactériologiques, ce procédé reste sur un plan industriel difficilement réalisable et ne répond que partiellement au cahier des charges applicable à des instruments à usage médical. C'est pourquoi, nous nous sommes intéressés à une technique de réticulation radiative de monomères en particulier acryliques et vinyliques (développée dans l'équipe du professeur B. BOUTEVIN du CNRS de Montpellier) dans lesquels le revêtement adhère fortement au matériau de base, ce matériau pouvant être de nature très variée, on peut citer entre autres le polychlorure de vinyle, le polyuréthane ou les silicones.The substitution of the chlorine atoms of said polymers by a tertiary amine leads to the creation of a non-hydrolysable covalent bond of the quaternary ammonium type. Despite good bacteriological results, this process remains difficult on an industrial level and only partially meets the specifications applicable to instruments for medical use. This is why, we are interested in a radiative crosslinking technique of monomers in particular acrylic and vinyl (developed in the team of professor B. BOUTEVIN of the CNRS of Montpellier) in which the coating adheres strongly to the base material, this material which can be of very varied nature, one can quote inter alia polyvinyl chloride, polyurethane or silicones.
La présente invention permet d'obtenir un matériau plastique utilisable pour la réalisation de sondes, cathéters, ou autres instruments à usage médical. Ce produit présente des propriétés biocides ayant pour rôle d'inhiber la formation du biofilm bactérien. De par son coût de fabrication peu élevé et son procédé écologique (inexistence de solvant), il est facile de rendre cette recherche industrialisable. L'originalité du concept réside dans le fait que l'agent bactéricide entre directement dans la composition finale des formulations de base. Le procédé selon l'invention est basé sur la formation d'un revêtement qui présente une liaison covalente entre un agent bactéricide et un réseau tridimensionnel lui-même adhérent au matériau de base constitué d'une résine synthétique, ladite liaison étant obtenue par exposition à un rayonnement énergétique, par exemple ultraviolets, rayons gammas ou bombardements électroniques, d'une formulation comportant trois composants essentiels constitués d'au moins un photoamorceur, d'au moins un oligomère réticulable et d'au moins un monomère mono ou multifonctionnel, ainsi que divers additifs conférant au produit final des propriétés spécifiques.The present invention makes it possible to obtain a plastic material which can be used for producing probes, catheters, or other instruments for medical use. This product has biocidal properties whose role is to inhibit the formation of bacterial biofilm. Due to its low manufacturing cost and its ecological process (no solvent), it is easy to make this research industrializable. The originality of the concept lies in the fact that the bactericidal agent enters directly into the final composition of the basic formulations. The method according to the invention is based on the formation of a coating which has a covalent bond between a bactericidal agent and a three-dimensional network itself adhering to the base material consisting of a synthetic resin, said bond being obtained by exposure to energetic radiation, for example ultraviolet, gamma rays or electronic bombardments, of a formulation comprising three essential components consisting of at least one photoinitiator, at least one crosslinkable oligomer and at least one mono or multifunctional monomer, as well as various additives giving specific properties to the final product.
La description détaillée ci-après se rapporte à des exemples non limitatifs de formes de réalisation de l'objet de l'invention.The detailed description below relates to nonlimiting examples of embodiments of the subject of the invention.
Une des originalités provient de la synthèse d'un monomère capable d'agir comme antiseptique et de réagir avec un polymère ou un oligomère particulièrement actif sous activation énergétique.One of the originalities comes from the synthesis of a monomer capable of acting as an antiseptic and of reacting with a polymer or an oligomer which is particularly active under energetic activation.
Un des processus utilisés est celui de la photoréticulation sous rayonnement ultraviolet pour créer un revêtement présentant des liaisons ammonium quaternaire, la formulation de base étant constituée d'un mélange de photoamorceur(s) , d'oligomères et de monomère(s) mono ou multifonctionnel(s) .One of the processes used is that of photocrosslinking under ultraviolet radiation to create a coating having quaternary ammonium bonds, the basic formulation consisting of a mixture of photoinitiator (s), oligomers and monomer (s) mono or multifunctional (s).
La formulation réticulable par voie radicalaire est un mélange de composés comprenant au moins un agent bactéricide à structure insaturée constitué d'un monomère multifonctionnel formé de molécules ayant la structure suivante: 0The crosslinkable formulation by radical route is a mixture of compounds comprising at least one bactericidal agent with an unsaturated structure consisting of a multifunctional monomer formed of molecules having the following structure: 0
H2C=CR3-C-0-R4 où R3 = H ou CH3 et R4 = CyH2y+l-N*-R5R6R7 , X" H2C = CR3-C-0-R4 where R3 = H or CH3 and R4 = CyH2y + lN * -R5R6R7, X "
Cette molécule présente les particularités ci- aprèsThis molecule has the following peculiarities
- structure acrylique et non vinylique, les composés acryliques étant plus réactifs que les composés vinyliques en polymérisation radicalaire,- acrylic and non-vinyl structure, acrylic compounds being more reactive than vinyl compounds in radical polymerization,
- présence d'une chaîne alkyle CyH2y+l avec y = 2 ou 5, permettant de séparer la fonction insaturée de la fonction ammonium quaternaire et donc de laisser une certaine mobilité à l'ammonium quaternaire vis-à-vis de la cellule bactérienne,- presence of an CyH2y + l alkyl chain with y = 2 or 5, making it possible to separate the unsaturated function from the quaternary ammonium function and therefore to leave a certain mobility for the quaternary ammonium with respect to the bacterial cell,
- R5 et/ou R6 sont des groupements méthyles,- R5 and / or R6 are methyl groups,
- R7 = CxH2x+l avec x = 6 ou 16 ; ou R7 = C6H5. L'effet bactéricide est maximal, si et seulement si, l'ammonium quaternaire présente une structure à chaîne alkyle (R7) en C8hl7~ et un contre-ion XΛ . Ce contre-ion est un ion de bromure car l'ion iodure serait trop encombrant et l'anion divalent induirait des contraintes de conformation et donc une diminution de l'activité antimicrobienne.- R7 = CxH2x + 1 with x = 6 or 16; or R7 = C6H5. The bactericidal effect is maximum, if and only if, the quaternary ammonium has an alkyl chain structure (R7) in C8hl7 ~ and a counterion X Λ . This counterion is a bromide ion because the iodide ion would be too bulky and the divalent anion would induce conformation constraints and therefore a decrease in antimicrobial activity.
Le principe réactionnel est basé sur une réaction entre une aminé tertiaire et un halogénure d'alkyle dans un mélange acétone/dichlorométhane.The reaction principle is based on a reaction between a tertiary amine and an alkyl halide in an acetone / dichloromethane mixture.
Le monomère amonium quaternaire est précipité à froid dans du pentane, filtré et rincé plusieurs fois au pentane et séché sous vide sur anhydride phosphorique (P205). Le produit ainsi obtenu est un sel de couleur blanche qui est caractérisé par infrarouge (I.R.), par (P205). Le produit ainsi obtenu est un sel de couleur blanche qui est caractérisé par infrarouge (I.R.), par résonnance magnétique nucléaire (RMN 200 Mhz) et par analyse élémentaire (dosage de l'azote, de l'oxygène et du brome) .The quaternary ammonium monomer is cold precipitated in pentane, filtered and rinsed several times with pentane and dried under vacuum over phosphoric anhydride (P205). The product thus obtained is a white salt which is characterized by infrared (IR), by (P205). The product thus obtained is a white salt which is characterized by infrared (IR), by nuclear magnetic resonance (NMR 200 Mhz) and by elemental analysis (determination of nitrogen, oxygen and bromine).
La réaction résultant du processus selon l'invention est celui d'une polymérisation radicalaire. La vitesse de polymérisation va dépendre de l'intensité lumineuse, de l'efficacité du photoamorceur, de la réactivité du groupement fonctionnel et de la viscosité du milieu. Le taux de polymérisation final et les propriétés physico-chimiques du polymère photoréticulé vont dépendre de la structure chimique et de la fonctionalité du monomère et de 1Oligomère.The reaction resulting from the process according to the invention is that of a radical polymerization. The polymerization rate will depend on the light intensity, the efficiency of the photoinitiator, the reactivity of the functional group and the viscosity of the medium. The final polymerization rate and the physico-chemical properties of the photocrosslinked polymer will depend on the chemical structure and the functionality of the monomer and of the oligomer.
C'est en raison de l'effet inhibiteur de l'oxygène dans les polymérisations radicalaires (il réagit très facilement avec des radicaux alkyles) qu'il sera nécessaire d'ajouter à la formulation de base des aminés tertiaires (molécules donneuses de protons).It is because of the inhibitory effect of oxygen in radical polymerizations (it reacts very easily with alkyl radicals) that it will be necessary to add to the basic formulation of tertiary amines (proton donor molecules) .
Les oligomères réticulables sont des polymères ou copolymères particulièrement actifs sous rayonnement énergétique. La présente invention a pour objet un matériau polymère à usage médical qui se caractérise par le fait qu'il est à base au moins d'une résine ou d'un mélange de résines résultant de la combinaison de diol, de diisocyanate et d'éther vinylique.Crosslinkable oligomers are polymers or copolymers which are particularly active under energy radiation. The subject of the present invention is a polymer material for medical use which is characterized in that it is based at least on a resin or a mixture of resins resulting from the combination of diol, diisocyanate and ether vinyl.
Les monomères mono ou multifonctionnels sont par exemple des monomères diluants réactifs tels que le T.G.P.D.A., le H.D.D.A. ou le H.E.A. Ces composés porteurs de deux fonctions réactives choisies parmi les fonctions époxy, éther vynilique ou hydroxy combinées ou non entre elles, vont jouer sur la vitesse de polymérisation, sur le taux de conversion et donc sur les propriétés physico-chimiques du polymère réticulé. La structure générale de ce composé est A-B-A ou A-B-C, avec A et C pouvant représenter des groupes réactifs hydroxyles (-0H), des groupes éthers vinyliques (-0- CH=CH2) , voire des groupemeents époxydes.The mono or multifunctional monomers are for example reactive diluent monomers such as TGPDA, HDDA or HEA These compounds carrying two reactive functions chosen from epoxy, vinyl or hydroxy ether functions, combined or not, will affect the speed of polymerization, on the conversion rate and therefore on the physicochemical properties of the crosslinked polymer. The general structure of this compound is ABA or ABC, with A and C possibly representing hydroxyl reactive groups (-0H), vinyl ether groups (-0- CH = CH2), or even epoxy groups.
D'autre part, ce sont des monomères réactifs "fonctionnels" dans le sens ou ces monomères vont conférer au matériau la propriété souhaitée.On the other hand, they are reactive "functional" monomers in the sense that these monomers will give the material the desired property.
A titre d'exemple, la formulation de base pourra avoir la composition suivante :As an example, the basic formulation could have the following composition:
- 15 à 35 % d'ammonium quaternaire- 15 to 35% of quaternary ammonium
- 40 à 65 % de polyuréthane diacrylate (PUDA)- 40 to 65% polyurethane diacrylate (PUDA)
- 20 à 30 % de monomères réactifs et diluants - 2 à 10 % de photoamorceur(s) + amorceur thermique + additif(s).- 20 to 30% of reactive and diluent monomers - 2 to 10% of photoinitiator (s) + thermal initiator + additive (s).
Suivant les caractéristiques demandées, il est possible de faire varier la composition et la nature des composants, résines et photoamorceurs. Suivant la teneur en ammonium quaternaire, le matériau a un effet antibactérien plus ou moins important.Depending on the characteristics requested, it is possible to vary the composition and the nature of the components, resins and photoinitiators. Depending on the quaternary ammonium content, the material has a more or less significant antibacterial effect.
Par ailleurs, il est bon de rappeler que toutes les réactions ne se font pas à 100 % de conversion, même si les paramètres fixés tendent vers cette valeur. C'est pourquoi, afin de palier à ce défaut éventuel, nous avons rajouté à notre formulation de base un amorceur thermique, il va permettre de terminer la polymérisation de monomères ou d'oligomères susceptibles encore de réagir.Furthermore, it is worth remembering that not all reactions are done at 100% conversion, even if the parameters set tend towards this value. This is why, in order to overcome this possible defect, we have added to our basic formulation a thermal initiator, it will allow the polymerization of monomers or oligomers which are still liable to react to be completed.
Des essais menés en laboratoire permettent de dire que le temps de photoréticulation doit être supérieur ou égal à 70 secondes, que le temps de cuisson, ou postcure, doit être de plus de 24 heures pour un conditionnement dans une étuve à 60 °C et que les produits doivent subir un lavage à l'eau afin d'éliminer tous produits résiduels.Tests conducted in the laboratory make it possible to say that the photocrosslinking time must be greater than or equal to 70 seconds, that the cooking time, or aftercare, must be more than 24 hours for conditioning in an oven at 60 ° C and the products must undergo washing with water in order to remove any residual products.
La formulation de base inclut trois composants essentiels, à savoir un ou plusieurs photoamorceur(s) , un ou plusieurs oligomère(s) réticulable(s) et un ou plusieurs monomère(s) mono ou multifonctionnel(s) , ainsi que divers additifs destinés à conférer au produit final des propriétés bien déterminées. Ces additifs sont en particulier des stabilisants, des agents mouillants, des agents d'étalement, des charges, des pigments, etc.. à condition qu'ils ne soient pas eux-mêmes inhibiteurs de la polymérisation.The basic formulation includes three essential components, namely one or more photoinitiator (s), one or more crosslinkable oligomer (s) and one or more mono or multifunctional monomer (s), as well as various additives intended to give the final product well-defined properties. These additives are in particular stabilizers, wetting agents, spreading agents, fillers, pigments, etc., provided that they are not themselves inhibitors of the polymerization.
Le processus de photoréticulation peut être considéré comme le passage d'un système de base non activé en un système activé, puis réticulé.The photocrosslinking process can be considered as the transition from an unactivated basic system to an activated system, then crosslinked.
Le produit bactéricide incorporé à la formulation de base résine(s) acrylate(s), photoamorceur(s) , monomère(s) et additif(s) constitue un mélange plus ou moins visqueux qui est utilisée pour enduire un matériau synthétique constitué de préférence d'un polychlorure de vinyle, d'un polyuréthane ou d'un polycarbonate préalablement activé en surface chimiquement et/ou mécaniquement, le matériau synthétique une fois revêtu étant passé sous rayonnement ultraviolet. Les compositions ainsi formulées peuvent être appliquées selon toute technique connue par exemple pistolet, trempé ou défilé.The bactericidal product incorporated into the basic formulation resin (s) acrylate (s), photoinitiator (s), monomer (s) and additive (s) constitutes a more or less viscous mixture which is used to coat a synthetic material preferably made up a polyvinyl chloride, a polyurethane or a polycarbonate previously activated on the surface chemically and / or mechanically, the synthetic material once coated having passed under ultraviolet radiation. The compositions thus formulated can be applied according to any known technique, for example spray gun, hardened or defiled.
Dans le cas où la réticulation se fait par bombardement électronique, le photoamorceur n'est pas nécessaire à la formulation, et l'activation du matériau est alors inutile.In the case where crosslinking is done by electronic bombardment, the photoinitiator is not necessary for formulation, and activation of the material is then unnecessary.
Un autre système plus récent consiste en la photo ou électropolymérisation par voie cationique. Ici, les monomères susceptibles de réagir par un tel système sont des éthers vinvyliques, des époxydes mais aussi des dérivés de composés aromatiques tel que le styrène. Les photoamorceurs utilisés sont très différents des précédents, dans le sens où ces produits se décomposent sous rayonnement ultraviolet en formant des acides de Lewis. Cela va permettre la polymérisation, entre autres, des époxydes, des vinyls-éthers ou autres monomères et polymère(s) susceptibles de réagir sous réticulation radiative/cationique.Another more recent system consists of photo or cationic electropolymerization. Here, the monomers capable of reacting with such a system are vinyl ethers, epoxides but also derivatives of aromatic compounds such as styrene. The photoinitiators used are very different from the previous ones, in the sense that these products decompose under ultraviolet radiation, forming Lewis acids. This will allow the polymerization, inter alia, of epoxides, vinyl ethers or other monomers and polymer (s) capable of reacting under radiative / cationic crosslinking.
Parmi les photoamorceurs les plus efficaces peuvent être cités les sels d'onium et en particulier les sels d'aryldiazonium [ (Ar-N≈N)^" ,X~] Ar étant un radical aryl, les sels de diaryliodonium [(Ar2I+ ,X")j ou le bis(diodécylphényl) iodonium [ (C12H25Ar2r**,X" ) ] les sels de sulfonium tels que le triarylsulfonium hexafluoroantimonate et le triarylsulfonium hexafluorophosphate, les sels triarylsélénium [ (Ar3Se'*' ,X~ ) ] , Ar étant un radical aryl éventuellement substitué.Among the most effective photoinitiators may be mentioned the onium salts and in particular the aryldiazonium salts [(Ar-N≈N) ^ ", X ~] Ar being an aryl radical, the diaryliodonium salts [(Ar2I + , X ") j or bis (diodecylphenyl) iodonium [(C12H25Ar2r * * , X")] sulfonium salts such as triarylsulfonium hexafluoroantimonate and triarylsulfonium hexafluorophosphate, triarylselenium salts [(Ar3Se ' *', X ~)] , Ar being an optionally substituted aryl radical.
X représente dans tous ces composés un anion de type PF6", BF4", AsF6", SbF6 ", FeC14" , SbC16~, ...X represents in all these compounds an anion of type PF6 ", BF4", AsF6 " , SbF6 " , FeC14 " , SbC16 ~, ...
Les radicaux aryl précédents sont généralement des radicaux phényl. Ces radicaux aryl sont éventuellement substitués par un radical alkyl linéaire ou ramifié possédant de 1 à 12 atomes de carbone.The preceding aryl radicals are generally phenyl radicals. These aryl radicals are optionally substituted by a linear or branched alkyl radical having from 1 to 12 carbon atoms.
Comme dans le cas cité précédemment, l'agent bactéricide est introduit dans la formulation comme un agent diluant réactif. Le positionnement des divers éléments constitutifs donne à l'objet de l'invention un maximum d'effets utiles qui n'avaient pas été, à ce jour, obtenus par des dispositifs similaires. As in the case cited above, the bactericidal agent is introduced into the formulation as a reactive diluting agent. The positioning of the various constituent elements gives the object of the invention a maximum of useful effects which had not, to date, been obtained by similar devices.

Claims

REVENDICATIONS
1°. Procédé de fabrication de polymères bactéricides à usage médical, essentiellement destinés à la réalisation d'instruments en matière synthétique, tels que sondes, raccords ou tuyauteries, caractérisé en ce qu'un agent bactéricide à structure insaturée est incorporé à une formulation de base composée d'au moins une résine réactive sous rayonnement énergétique fonctionnelle, d'au moins un monomère monofonctionnel ou multifonctionnel et d'éventuels additifs, ladite formulation de base étant déposée sur une résine synthétique activé en surface chimiquement et/ou mécaniquement et exposée à un rayonnement énergétique de manière à réaliser un revêtement sur lequel un agent bactéricide est lié de façon covalente.1 °. Process for the manufacture of bactericidal polymers for medical use, essentially intended for the production of plastic instruments, such as probes, fittings or pipes, characterized in that a bactericidal agent with an unsaturated structure is incorporated into a basic formulation composed of '' at least one reactive resin under functional energy radiation, at least one monofunctional or multifunctional monomer and any additives, said base formulation being deposited on a synthetic resin activated on the surface chemically and / or mechanically and exposed to energy radiation so as to produce a coating on which a bactericidal agent is covalently bonded.
2°. Procédé selon la revendication 1, se caractérisant par le fait que le rayonnement énergétique est constitué de rayons ultraviolets provoquant une photoréticulation.2 °. Method according to Claim 1, characterized in that the energy radiation consists of ultraviolet rays causing photocrosslinking.
3°. Procédé selon la revendication 2, se caractérisant par le fait que la formulation de base comporte au moins un photoamorceur.3 °. Method according to claim 2, characterized in that the basic formulation comprises at least one photoinitiator.
4°. Procédé selon les revendications 1, 2 et 3, se caractérisant par le fait que la formulation de base subit une photo ou électropolymérisation par voie cationique, le photoamorceur étant spécifique à ce type de réaction. 5°. Procédé selon la revendication 1, se caractérisant par le fait que le rayonnement énergétique est constitué de rayons gammas.4 °. Process according to Claims 1, 2 and 3, characterized in that the basic formulation undergoes a photo or electropolymerization by the cationic route, the photoinitiator being specific to this type of reaction. 5 °. Method according to claim 1, characterized in that the energy radiation consists of gamma rays.
6°. Procédé selon la revendication 1, se caractérisant par le fait que le rayonnement énergétique est constitué d'un bombardement électronique.6 °. Method according to claim 1, characterized in that the energy radiation consists of electronic bombardment.
7°. Procédé selon la revendication 1, se caractérisant par le fait que la formulation de base comporte au moins une résine acrylate, vinylique et/ou époxy.7 °. Method according to claim 1, characterized in that the basic formulation comprises at least one acrylate, vinyl and / or epoxy resin.
8°. Procédé selon l'une quelconque des revendications précédentes, se caractérisant par le fait que l'agent bactéricide est une molécule à structure acrylique comportant une chaîne alkyle CnH2n+l avec n = 2 ou 5, et se présentant sous la forme suivante : 0 |8 °. Process according to any one of the preceding claims, characterized in that the bactericidal agent is a molecule with an acrylic structure comprising an alkyl chain CnH2n + 1 with n = 2 or 5, and having the following form: 0 |
H2C=CR3-C-0-R4 dans laquelle :H2C = CR3-C-0-R4 in which:
R3 = CxH2x+l où particulièrement x=l R4 = CyH2y+l-N -R5R6R7,X R5 et/ou R6 sont des groupements méthyles,R3 = CxH2x + l where particularly x = l R4 = CyH2y + l-N -R5R6R7, X R5 and / or R6 are methyl groups,
R7 = Cn'H2n'+l avec n' = 6 ou 16, ou R7 = C6H12.R7 = Cn'H2n '+ l with n' = 6 or 16, or R7 = C6H12.
9°. Procédé selon l'une quelconque des revendications précédente, se caractérisant par le fait que la formulation de base est composée de :9 °. Method according to any one of the preceding claims, characterized in that the basic formulation is composed of:
- 15 à 35 % d'ammonium quaternaire- 15 to 35% of quaternary ammonium
- 40 à 65 % de polyuréthanne diacrylate (PUDA)- 40 to 65% polyurethane diacrylate (PUDA)
- 20 à 30 % de monomères réactifs et diluants- 20 to 30% of reactive and diluent monomers
2 à 10 % de photoamorceur(s) et/ou d'additif(s) . 2 à 10 % de photoamorceur(s) et/ou d'additif(s) .2 to 10% of photoinitiator (s) and / or additive (s). 2 to 10% of photoinitiator (s) and / or additive (s).
10°. Procédé selon l'une quelconque des revendications précédentes, se caractérisant par le fait que la formulation de base comporte un ou plusieurs monomères mono ou multifonctionnels consistant en monomères diluants réactifs tels que le T.G.P.D.A., le H.D.D.A. ou le H.E.A.10 °. Method according to any one of the preceding claims, characterized in that the basic formulation comprises one or more mono or multifunctional monomers consisting of reactive diluent monomers such as T.G.P.D.A., H.D.D.A. or the H.E.A.
11°. Procédé selon l'une quelconque des revendications précédentes, se caractérisant par le fait que la résine synthétique sur laquelle est déposée la formulation de base est constituée de polychlorure de vinyle, de polyuréthane ou de polycarbonate.11 °. Method according to any one of the preceding claims, characterized in that the synthetic resin on which the base formulation is deposited consists of polyvinyl chloride, polyurethane or polycarbonate.
12°. Instrument à usage médical réalisé au moyen du procédé selon les revendications précédentes, caractérisé en ce qu'il est constitué de résine synthétique comportant un revêtement sur lequel un agent bactéricide, l'ammonium quaternaire est lié de façon covalente de manière à ce que ses propriétés bactéricides soient respectées. 12 °. Instrument for medical use produced by the method according to the preceding claims, characterized in that it consists of synthetic resin comprising a coating on which a bactericidal agent, quaternary ammonium is covalently bonded so that its properties bactericides are met.
EP97929350A 1996-06-13 1997-06-13 Method for making bactericidal polymers, and resulting products Withdrawn EP0858486A1 (en)

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FR9607579A FR2749854A1 (en) 1996-06-13 1996-06-13 PROCESS FOR MANUFACTURING BACTERICIDAL POLYMERS AND PRODUCTS OBTAINED BY THIS PROCESS
FR9607579 1996-06-13
PCT/FR1997/001072 WO1997047696A1 (en) 1996-06-13 1997-06-13 Method for making bactericidal polymers, and resulting products

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FR2846970B1 (en) * 2002-11-08 2006-08-11 Desarrollo Del Grafting S L METHOD FOR SURFACE TREATMENT BY PHOTOPOLYMERIZATION TO OBTAIN BIOCIDAL PROPERTIES
US20080139441A1 (en) * 2006-10-31 2008-06-12 Huining Xiao Antimicrobial and bacteriostatic-modified polymers for cellulose fibres
FR3090271B1 (en) * 2018-12-19 2021-03-05 Commissariat A L’Energie Atomique Et Aux Energies Alternatives Cea PROCESS FOR THE PREPARATION OF A BIOCIDAL, BACTERICIDAL AND / OR BACTERIOSTATIC MATERIAL

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US4810567A (en) * 1985-08-21 1989-03-07 Uop Antimicrobial fabrics utilizing graft copolymers
JPH04110356A (en) * 1990-08-31 1992-04-10 Dainippon Ink & Chem Inc Actinic radiation-curable coating material
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