SOLID ORGANIC ANTIBACTERIAL MATERIAL

Description

TECHNICAL FIELD

[0001] This description relates to amphiphilic block copolymers of the methacrylic type and organic solid materials; their preparation process; and their use for antibacterial, antimicrobial, anti-inflammatory and / or antifungal applications. STATE OF THE ART

[0002] Antibiotic resistance to bacteria has become a public health issue. Certain antibiotics, such as methicillin and vancomycin, have become ineffective against infections caused by bacteria like methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Staphylococcus aureus (VRAS), respectively. Antibacterial materials can therefore play a role in combating bacterial infections, particularly in hospitals where infections are a leading cause of complications in intensive care units.

[0003] Various methods exist today for developing antibacterial materials: i) the inclusion of biocidal molecules (antibiotics or silver-based molecules for example) but which are released outside the material, leading to a loss of activity of the material, in some cases side effects and / or an exacerbation of the phenomenon of antimicrobial resistance; ii) the modification of the surface of the material by grafting or coupling, which is a long, expensive and multi-step method; iii) the use of antibacterial surfactants (at a level of about 10% by weight) to make antimicrobial films.

[0004] For several years, antimicrobial peptides (AMPs) have been the subject of numerous studies aimed at providing an alternative to current antibiotics. Unlike conventional antibiotics, AMPs have the advantage of not inducing resistance due to a different mechanism of action that primarily targets the bacterial membrane (Michl et al. Polym. Chem. 2014, 19, 5813). However, the main obstacle to the use of AMPs is their cost and limited production volume, as the peptides are either obtained by solid-phase peptide synthesis in the case of synthetic peptides or extracted from various natural sources such as venoms. To overcome these problems, various synthetic copolymers have been studied to mimic the antimicrobial activity of AMPs while being easily synthesized on a large scale.These copolymers, called SMAMPs for "synthetic mimic antimicrobial peptides," are generally amphiphilic copolymers with a hydrophilic, usually charged, portion that interacts with the bacterial membrane to bind to it, and a hydrophobic portion that destabilizes or penetrates the bacterial membrane (Kuroda et al. Nanomed. Nanobiotechnology 2013, 5, 49; Takahashi et al. Macromol. Biosci. 2013, 13, 1285). While the mode of action of SMAMPs mimics that of AMPs, their synthesis is much easier, as it is achieved through various polymerization techniques, particularly radical polymerization, which allows for very large-scale production.

[0005] Furthermore, Lenoir et al. (Biomacromolecules, 2006, 7, 2291) reported in 2006 the dispersion of dibloc poly(ethylene- co -butylene)-b-poly(2-( tert- butylamino)ethyl methacrylate) (PEB- b -PTBAEMA, Mn = 14000 g / mol) to impart antimicrobial properties to low-density polyethylene (LDPE) films. The copolymers were mixed into LDPE at a concentration of 10% by weight and showed activity against E. coli (Gram -). Zuo et al. (Journal of Applied Polymer Science, 2012, 125, 3537) reported the development of commercial poly(methyl methacrylate) (PMMA) rendered antibacterial by mixing with at least 10% by weight of poly(t ert- butylamino)ethyl methacrylate) (PTBAEMA, M w ≤ 10000 g / mol) to mount an activity against S. aureus (Gram +) and E. coli(Gram -). Finally, Li et al. (European Polymer Journal, 2014, 51, 120) showed that it was possible to prepare antibacterial polypropylene (PP) by supercritical CO2 grafting and reactive extrusion of poly(hexamethylenediamine-guanidinium chloride) chains. This complex process made it possible to develop PP-based materials active against bacteria of the type S. aureus And E. coli.

[0006] However, the copolymer used is typically of low molar mass (< 15,000 g / mol) to mimic the structure of natural antimicrobial peptides. According to the literature, a higher molar mass is also associated with an increase in the hemolytic character of the copolymer (Ganewatta et al. Polymer 2015, 63, A1). Furthermore, the amount of copolymer required to observe antimicrobial activity is high, around 10% by weight. Moreover, the reported activity only applies to model bacterial strains (typically S. aureusAnd E. coli These methods do not include pathogenic strains, which are nevertheless of crucial public health importance for the future. Furthermore, the various manufacturing processes mentioned above only allow for the production of antibacterial organic materials of a single chemical nature (HBPE, PMMA, or PP). A versatile process for incorporating the antimicrobial copolymer into organic matrices of different chemical compositions is therefore lacking. Consequently, there is a need for solid organic materials and their preparation processes that overcome some of the limitations mentioned above. SUMMARY

[0007] The purpose of this description is to provide amphiphilic block copolymers of the methacrylic type and organic solid materials with antibacterial, antimicrobial, anti-inflammatory and / or antifungal properties.

[0008] According to a first aspect, the aforementioned object, as well as other advantages, are obtained by an organic solid material comprising 0.02 to 2% by weight of at least one amphiphilic block copolymer of the methacrylic type, the block copolymer being dispersed in a polymeric matrix, the block copolymer having a number-average molar mass ( M n) greater than or equal to 20,000 g / mol. The block copolymer comprises at least one hydrophilic methacrylic block comprising at least one tertiary amine group and at least one quaternary ammonium ion group.

[0009] According to one or more embodiments, the block copolymer exhibits a M n less than or equal to 100,000 g / mol. According to one or more embodiments, the block copolymer has an average number-average molar mass (Mn)between 20,000 and 70,000 g / mol. Depending on one or more embodiments, the block copolymer has an average number-average molar mass (Mn) between 21,000 and 55,000 g / mol. Depending on one or more embodiments, the block copolymer has an average number-average molar mass (Mn) between 22,000 and 40,000 g / mol.

[0010] According to one or more embodiments, the block copolymer is a diblock polymer. i . e ., comprising two types of monomers.

[0011] The organic solid material comprises from 0.02 to 2 wt% of the block copolymer. In one or more embodiments, the organic solid material comprises from 0.1 to 2 wt% of the block copolymer. In one or more embodiments, the organic solid material comprises from 0.2 to 2 wt% of the block copolymer.

[0012] According to one or more embodiments, the block copolymer has at least one hydrophilic part, i . e ., at least one hydrophilic methacrylic block, and at least one hydrophobic part, i.e., at least one hydrophobic methacrylic block.

[0013] The term "hydrophilic" is synonymous with (meaning the same as) being capable of forming hydrogen bonds, such as with a polar solvent, such as water. The term "hydrophobic" is synonymous with (meaning the same as) being incapable of forming hydrogen bonds, such as with a polar solvent, such as water.

[0014] The hydrophilic methacrylic block comprises at least one tertiary amine group and at least one quaternary ammonium ion group.

[0015] According to one or more embodiments, the hydrophilic methacrylic monomer ( i.e.,hydrophilic repeating motif of the hydrophilic methacrylic block) is chosen from the group consisting of a methacrylate of N,N -(dialkylamino)alkyl, such as an N,N-(dialkylamino)ethyl methacrylate, and a quaternary ammonium ion thereof. According to one or more embodiments, at least one of the alkyl functions is a substituted or unsubstituted alkyl and / or comprises between 1 and 8 carbon atoms, such as between 2 and 6 carbon atoms.

[0016] The term "unsubstituted" is synonymous with (means the same as) unsubstituted of an atom other than one or more hydrogen atoms.

[0017] The term "substituted" is synonymous with (means the same as) substituted with at least one element other than a hydrogen atom, for example substituted with at least one hydrocarbon substituent. According to one or more embodiments, the element is chosen from the group consisting of an alkyl, an alkenyl, an alkynyl, an aryl, a heteroaryl, an alkylalkenyl, an alkenylalkyl, an alkylalkynyl, an alkynylalkyl, an alkylaryl, an arylalkyl, an alkylheteroaryl, a heteroarylalkenyl, an alkenyllaryl, an alkenylheteroaryl, an arylalkynyl, a heteroarylalkynyl, an alkynyllaryl and an alkynylheteroaryl, the element comprising from 1 to 20 carbon atoms, such as from 2 to 18, 3 to 16, 4 to 14 or 5 to 12 carbon atoms; which element optionally comprises one or more heteroatoms, such as for example N, O, S, P, Si, Sn, Ge, As, F, Cl,Br and I; and / or which element optionally comprising one or more functional groups selected from the list consisting of an alkyl, an alkene, an alkyne, an aryl, a heteroaryl, an alcohol, a ketone, a benzoyl, an aldehyde, a carbonate, a carboxylic acid, a carboxylate, an ester, an ether, a heterocycle, an amine, an amide, an azo, a diazo, a diazoamino, an azide, a secondary imine, a hydrazine, a hydrazone, an amidine, a carbamate, a guanidine, a carbodiimide, a nitrile, an isonitrile, an imide, an azide, a diimide, a thiol, a thioether, a thioketone, a cyanate, a nitrate, a nitrite, a nitro, a nitroso, an oxime, a pyridyl, a thioether, a disulfide, a sulfinyl, a sulfonyl, a thiocyanate, an isothiocyanate, a thione, a phosphorane, a phosphine, a boronate, a borinate, a silane and a halogen, functional groups comprising from 0 to 20 carbon atoms, such as from 1 to 20, 2 to 18, 3 to 16,4 to 14 or 5 to 12 carbon atoms.

[0018] According to one or more embodiments, the hydrophilic methacrylic monomer is chosen from the group consisting of the methacrylate of N,N-(dimethylamino)ethyl (DMAEMA), the methacrylate of N , N -(diethylamino)ethyl (DEAEMA) and a quaternary ammonium ion of these.

[0019] According to one or more embodiments, the hydrophobic methacrylic monomer ( i.e., The hydrophobic repeating motif of the hydrophobic methacrylic block is chosen from the group consisting of a linear, branched, cyclic, or cyclic and branched alkyl methacrylate, having, for example, from 1 to 20 carbon atoms. According to one or more embodiments, the alkyl methacrylate is chosen from the group consisting of methyl methacrylate (MMA) and butyl methacrylate (BMA).

[0020] According to one or more embodiments, the hydrophilic methacrylic block and / or the hydrophobic methacrylic block further comprises at least one additional repeating motif as selected from the group consisting of styrene (S) and acrylonitrile (ACN).

[0021] In one or more embodiments, the block copolymer comprises at least one block selected from PBMA, PMMA, PDMAEMA, and PDEAEMA. In one or more embodiments, the block copolymer comprises at least one of the following formulations: PMMA- b -PDMAEMA, PMMA- b -PDEAEMA, PBMA- b- PDMAEMA, PBMA- b -PDEAEMA, P(MMA- Co -S)- b -PDMAEMA, P(MMA- Co -S)- b- PDEAEMA, P(BMA- Co -S)- b -PDMAEMA, P(BMA- Co -S)-b-PDEAEMA, P(MMA- Co- ACN)- b -PDMAEMA, P(MMA- Co -ACN)- b -PDEAEMA, P(BMA- Co -ACN)- b -PDMAEMA, P(BMA- Co-ACN)- b -PDEAEMA, PMMA- b -P(DMAEMA- Co -S), PMMA- b -P(DEAEMA- Co -S), PBMA- b -P(DMAEMA- Co -S), PBMA- b -P(DEAEMA- Co -S), PMMA- b -P(DMAEMA- Co -ACN), PMMA- b -P(DEAEMA- Co -ACN), PBMA- b -P(DMAEMA- Co -ACN), PBMA- b- P(DEAEMA- Co -ACN), P(MMA- Co -S)- b -P(DMAEMA- Co -S), P(MMA-Co-S)- b- P(DEAEMA- Co -S), P(BMA- C oS)-bP(DMAEMA- Co -S), P(BMA- Co -S)- b -P(DEAEMA- Co -S), P(MMA- Co -ACN)- b -P(DMAEMA- Co -ACN), P(MMA- Co -ACN)- b -P(DEAEMA- Co- ACN), P(BMA- Co -ACN)- b -P(DMAEMA- Co -ACN), P(BMA- Co -ACN)- b -P(DEAEMA- Co- ACN), P(MMA- Co -S)- b -P(DMAEMA- Co -ACN), P(MMA- Co -S)-b -P(DEAEMA- Co -ACN), P(BMA- Co -S)- b -P(DMAEMA- Co -ACN), P(BMA- Co -S)- b -P(DEAEMA- Co -ACN), P(MMA- Co -ACN)- b -P(DMAEMA- Co -S), P(MMA- Co -ACN)- b -P(DEAEMA- Co -S), P(BMA- Co -ACN)- b -P(DMAEMA- Co -S) and P(BMA- Co -ACN)- b -P(DEAEMA- Co -S). According to one or more embodiments, the block copolymer comprises one of the following formulations: P(BMA-Co-S)- b -P(DMAEMA-Co-S), and P(BMA- Co -ACN)- b -P(DMAEMA-Co-ACN).

[0022] In one or more embodiments, the block copolymer comprises 20 to 80 mol% of hydrophilic repeating units. In one or more embodiments, the block copolymer comprises 50 to 70 mol% of hydrophilic repeating units.

[0023] In one or more embodiments, the block copolymer comprises 20 to 80 mol% of hydrophobic repeating units. In one or more embodiments, the block copolymer comprises 30 to 50 mol% of hydrophobic repeating units.

[0024] In one or more embodiments, the block copolymer comprises 3 to 20 wt% of additional repeating units. In one or more embodiments, the block copolymer comprises 5 to 10 wt% of additional repeating units.

[0025] According to one or more embodiments, the hydrophobic methacrylic block has an average molar mass in number ( Mn ) between 4000 and 30000 g / mol. According to one or more embodiments, hydrophobic methacrylic block has an average molar mass in number ( Mn ) between 6000 and 20000 g / mol.

[0026] According to one or more embodiments, the block copolymer has a dispersity (D) between 1 and 2.0. According to one or more embodiments, the block copolymer has a dispersity (D) between 1.30 and 1.50.

[0027] According to one or more embodiments, the hydrophobic methacrylic block has a dispersity (D) between 1.20 and 1.50. According to one or more embodiments, the hydrophobic methacrylic block has a dispersity (D) between 1.30 and 1.40.

[0028] According to one or more embodiments, the polymer matrix comprises at least one repeating unit selected from the group consisting of polyethylene (PE), polypropylene (PP), polycarbonate (PC), polyamide (PA), polyester, polyurethane (PU), polystyrene (PS), poly(methyl methacrylate) (PMMA), poly(vinyl chloride) (PVC), acrylic resins, silicones, and thermosetting composites. Examples of polyesters include poly(lactic acid) and poly(ethylene terephthalate), etc.

[0029] According to one or more embodiments, the polymer matrix comprises at least one repeating motif selected from the group consisting of polystyrene (PS), poly(methyl methacrylate) (PMMA), polycarbonate (PC).

[0030] According to a second aspect, the aforementioned objects, as well as other advantages, are obtained by a process for manufacturing a solid organic material, such as the solid organic material according to the first aspect, the process comprising the dispersion of 0.02 to 2 wt% of at least one amphiphilic block copolymer of the methacrylic type in a polymeric matrix, wherein the block copolymer has a number-average molar mass ( M n) greater than or equal to 20,000 g / mol. The block copolymer comprises at least one hydrophilic methacrylic block comprising at least one tertiary amine group and at least one quaternary ammonium ion group.

[0031] According to one or more embodiments, the process includes the preparation of the block copolymer by controlled radical polymerization with nitroxides.

[0032] According to one or more embodiments, radical polymerization is carried out in the presence of nitroxideN -(2-methylpropyl)- N -(1-diethylphosphono-2,2-dimethylpropyl)-N-oxyl) called SG1.

[0033] According to one or more embodiments, radical polymerization is carried out in the presence of alkoxyamine ( N -(2-methylpropyl)- N -(1-diethylphosphono-2,2-dimethylpropyl)-O-(2-carboxylprop-2-yl) marketed by Arkema under the name BlocBuilder MA.

[0034] According to one or more embodiments, the preparation of the methacrylic-type amphiphilic block copolymer comprises: the polymerization of one of the hydrophilic or hydrophobic monomers (optionally in the presence of an additional repeating motif) to form a first hydrophilic or hydrophobic block respectively; then the extension of this first block by the polymerization of the other hydrophobic or hydrophilic monomer (optionally in the presence of an additional repeating motif) to form the hydrophilic-block-hydrophobic or hydrophobic-block-hydrophilic amphiphilic block copolymer.

[0035] According to one or more embodiments, polymerization is carried out by heating the monomers, preferably under an inert atmosphere (e.g. under nitrogen or argon), in the presence of a polymerization initiator (BlocBuilder MA or macroalkoxyamine forming the first block of the copolymer) and free nitroxide SG1.

[0036] According to one or more embodiments, polymerization is carried out at a temperature between 80°C and 130°C. According to one or more embodiments, polymerization is carried out at a temperature of 90°C.

[0037] According to one or more embodiments, the polymerization is carried out for a period of between 4 and 15 hours. According to one or more embodiments, the polymerization is carried out for a period of between 4 and 10 hours, such as 5 hours 30 minutes.

[0038] In one or more embodiments, polymerization is carried out until a conversion of between 30 and 80% is achieved for each block (hydrophilic and hydrophobic). In one or more embodiments, polymerization is carried out until a conversion of between 40 and 60% is achieved, such as between 45 and 50% for each block (hydrophilic and hydrophobic).

[0039] According to one or more embodiments, the dispersion of the amphiphilic block copolymer of the methacrylic type in a polymeric matrix comprises: the preparation of a solution comprising a solvent (e.g. THF) and the polymeric matrix (e.g. PS or PMMA), the addition of the block copolymer (quaternized or not) to the solution, and the evaporation of the solvent to obtain the organic solid material.

[0040] According to one or more embodiments, the process comprises the quaternization of the tertiary amine. According to one or more embodiments, the quaternization is carried out using methyl iodide (MeI). According to one or more embodiments, the percentage of quaternization of the tertiary amine is from 2.0 mol% (relative to the polymer chains) to 100%, the value 100% not being part of the claimed subject matter.

[0041] According to a third aspect, the aforementioned objects, as well as other advantages, are obtained by using a solid organic material according to any of the embodiments of the first aspect for non-therapeutic applications, whether antibacterial and / or antimicrobial and / or antifungal.

[0042] According to a fourth aspect, the aforementioned objects, as well as other advantages, are obtained by a device comprising an organic solid material according to any of the embodiments of the first aspect.

[0043] According to one or more embodiments, the device is chosen from the group constituted by a catheter.

[0044] According to a further aspect, the aforementioned objects, as well as other advantages, are obtained by an amphiphilic block copolymer of the methacrylic type having an average molar mass in number (Mn)greater than or equal to 20,000 g / mol, for example, for antibacterial and / or antimicrobial and / or anti-inflammatory and / or antifungal applications. The amphiphilic block copolymer of the methacrylic type exhibits the characteristics defined above when forming part of the organic solid material. In particular, the block copolymer comprises at least one hydrophilic methacrylic block including at least one tertiary amine group and at least one quaternary ammonium ion group. It is also envisaged that the amphiphilic block copolymer of the methacrylic type may be used as a medicinal product.

[0045] According to a further aspect, the aforementioned objects, as well as other advantages, are obtained from an organic material according to any of the embodiments of the first aspect for its use as a medicinal product, for example antibacterial and / or antifungal and / or anti-inflammatory.

[0046] Embodiments according to the aspects referenced above, as well as additional advantages, will become apparent from the description illustrated by the following Figures and the attached claims. BRIEF DESCRIPTION OF THE DRAWINGS

[0047] THE Figures 1 to 4 represent diagrams illustrating the antibacterial activity and hemolytic character of solid materials according to examples of embodiments of this description. The P18 polymer mentioned in the Figure 4 , as well as the material incorporating it, are not part of the claimed subject matter. DETAILED DESCRIPTION

[0048] In the following detailed description of embodiments of this description, many specific details are set forth to provide a more thorough understanding of the present description. However, it will be apparent to a person skilled in the art that this description can be implemented without these specific details. In other cases, well-known features have not been described in detail to avoid unnecessarily complicating the description.

[0049] In what follows, the term "include" is synonymous with (means the same as) "include" or "contain," and is inclusive or open-ended, not excluding other elements not described or depicted. Furthermore, in this description, the terms "approximately" and "about" are synonymous with (means the same as) a margin of error of 10% or more of the respective value.

[0050] This description relates to an organic solid material. The organic solid material comprises at least one amphiphilic block copolymer of the methacrylic type, the block copolymer being dispersed in a polymeric matrix, the block copolymer having a number-average molar mass (Mn) greater than or equal to 20,000 g / mol. The block copolymer comprises at least one hydrophilic methacrylic block comprising at least one tertiary amine group and at least one quaternary ammonium ion group.

[0051] According to one or more embodiments, the solid organic material possesses antibacterial, antimicrobial, anti-inflammatory and / or antifungal properties.

[0052] According to one or more embodiments, an improved dispersion of the block copolymer in the polymer matrix is ​​obtained without increasing the toxicity of the organic solid material or decreasing the antibacterial, antimicrobial, anti-inflammatory and / or antifungal activity.

[0053] According to one or more embodiments, solid organic materials are particularly active against Gram + and Gram - type bacteria and pathogens.

[0054] According to one or more embodiments, the solid organic materials do not lose their activity over time and do not need to be replaced in case of prolonged use or deterioration.

[0055] According to one or more embodiments, solid organic materials do not release biocidal compounds into the environment.

[0056] According to one or more embodiments, the solid organic material is adapted to avoid the release of molecules and therefore the loss of activity over time, the problems of side effects and contamination of the patient and / or the environment.

[0057] According to one or more embodiments, the solid organic material is entirely antibacterial, and not just the surface of the material, an important advantage in case of degradation of said material.

[0058] This description also relates to a process for manufacturing an organic solid material, such as the organic solid material according to the first aspect, the process comprising dispersing 0.02 to 2% of at least one amphiphilic block copolymer of the methacrylic type in a polymeric matrix, wherein the block copolymer has a number-average molar mass (Mn)greater than or equal to 20,000 g / mol, and wherein the block copolymer comprises at least one hydrophilic methacrylic block comprising at least one tertiary amine group and at least one quaternary ammonium ion group.

[0059] According to one or more embodiments, the process according to the second aspect is a simple, versatile process, suitable for a wide range of polymer matrices (e.g., PS, PMMA, PVC, silicones and thermosetting composites) and scalable to large scale, allowing for the imparting of permanent antibacterial and antimicrobial properties against different strains of bacteria (Gram + ( B. subtilis ) and Gram - ( E. coli )) to conventional polymer matrices. In addition, these organic solid materials may be of interest as antifungal, antiviral and anti-inflammatory materials.

[0060] According to one or more embodiments, the process allows the development of solid organic materials according to the first aspect by simple dispersion, in conventional polymeric matrices (e.g. PS, PVC, PMMA), of quantities, preferably small (e.g. < 10% by weight), of amphiphilic block copolymers of the methacrylic type, the copolymer being able to be used as an additive at a low percentage by weight.

[0061] According to one or more embodiments, amphiphilic block copolymers of the methacrylic type are able to self-organize in different matrices ensuring homogeneous dispersion in the organic solid material.

[0062] According to one or more embodiments, the manufacturing process also has the advantage of avoiding the release of molecules and therefore the loss of activity over time, the problems of side effects and contamination of the patient and / or the environment.

[0063] According to one or more embodiments, the manufacturing process ensures that the entire material is antibacterial, an important advantage in case of material degradation.

[0064] This description also applies to devices comprising an organic solid material as described in the first aspect. Indeed, the organic solid materials described here are suitable for developing antibacterial and / or antimicrobial devices, such as (venous) catheters, which no longer require regular replacement (approximately every 3 weeks) in the case of prolonged use. These devices may also be of interest as antifungal and anti-inflammatory materials.

[0065] This description also applies to amphiphilic block copolymers of the methacrylic type considered alone. Specifically, this description applies to a methacrylic block amphiphilic copolymer with a number-average molar mass (Mn) greater than or equal to 20,000 g / mol, for example for antibacterial and / or antimicrobial, anti-inflammatory and / or antifungal application, the block copolymer comprising at least one hydrophilic methacrylic block comprising at least one tertiary amine group and at least one quaternary ammonium ion group.

[0066] Examples of amphiphilic block copolymers of the methacrylic type, organic solid materials and manufacturing processes according to the aforementioned aspects are described below. Synthesis and characterization of amphiphilic diblock copolymers PBMA-b-PDMAEMA

[0067] A series of amphiphilic diblock copolymers PBMA- b-PDMAEMAs were prepared by nitroxide-controlled radical polymerization (NMP) using alkoxyamine BlocBuilder MA as a initiator and adding a comonomer for molar mass control and molar mass distribution. In these examples, 10 mol% styrene (S) or acrylonitrile (ACN) was used. The dibloc copolymers have the following structure: where n and m are the degree of polymerization of each block, and R is styrene or acrylonitrile. In these examples, the percentage of hydrophobic group and the molecular weight of the amphiphilic diblock copolymer were varied.

[0068] The synthesis of (PBMA 7000 - b -PDMAEMA 45800 ) ( P8The following is presented here as an example of a manufacturing process according to the second aspect. This synthesis is applicable to all block copolymers as described herein. BMA (hydrophobic monomer, 50 g, 0.35 mol), styrene (3.66 g, 0.035 mol), BlocBuilder MA (1.27 g, 3.33 mmol), and SG1 (nitroxide) are heated to 90°C under a nitrogen atmosphere. N -(2-methylpropyl)- N -(1-diethylphosphono-2,2-dimethylpropyl)- N-oxyl), 100 mg, 0.33 mmol). Samples are taken periodically to monitor conversion and molar mass. The reaction is stopped when conversion reaches 45% (e.g., 2 hours). Conversion is determined by 1< H NMR (Bruker 300 MHz spectrometer, CDCl3) by comparing the peaks of the -CH2- groups near the ester function of the monomer (δ = 4.11 ppm) and the polymer (δ = 3.91 ppm). PBMA is then recovered by precipitation in a cold MeOH / H2O mixture (4:1 by volume) and analyzed by SEC / DMF (size exclusion chromatography PL120 (Polymer Laboratories, England) with DMF as the eluent) to obtain the number-average molar mass values ​​( Mn ) and dispersity (Ð ; Mw / Mn ) ( Mn = 7000 g.mol⁻¹, D = 1.41). After drying for 24 hours under vacuum, PBMA is used to initiate the polymerization of the hydrophilic monomer (DMAEMA) and obtain the PBMA- diblock copolymer. b-PDMAEMA corresponding. To do this, PBMA (1 g), styrene (662 mg, 6.36 mmols), DMAEMA (10 g, 63.6 mmols), 1,4-dioxane (5 ml), and SG1 (4 mg, 0.0125 mmol) are heated to 90°C under a nitrogen atmosphere. Samples are taken periodically to monitor the conversion by 1H NMR (Bruker CDCl3 spectrometer, 400 MHz) and the value of the Mn is determined by SEC / DMF. The reaction is stopped when the conversion is close to 50%. The PBMA- diblock copolymer b -Final PDMAEMA is then isolated by precipitation in cold pentane. The resulting P8 copolymer is analyzed by 1H NMR and SEC / DMF to obtain a composition with an FDMAEMA = 0.60 (molar ratio of DMAEMA in the final copolymer), a Mn = 45800 g.mol -1< and a D = 1.37. Synthesis and characterization of amphiphilic PMMA-b-PDMAEMA diblock copolymers

[0069] A series of amphiphilic PMMA- diblock copolymers b-PDMAEMAs were prepared by nitroxide-controlled radical polymerization (NMP) using alkoxyamine BlocBuilder MA as a initiator and adding a comonomer for molar mass control and molar mass distribution. In these examples, 10 mol% styrene (S) or acrylonitrile (ACN) was used. The dibloc copolymers have the following structure: in which n and m are the degree of polymerization of each block, and R is styrene or acrylonitrile.

[0070] The synthesis of (PMMA 9300 - b -PDMAEMA 40000 ) ( P1This is presented here as an example of a manufacturing process according to the second aspect. This synthesis is applicable to all block copolymers as described herein. MMA (methyl methacrylate, 50 g, 0.50 mol), styrene (5.2 g, 0.05 mol), BlocBuilder MA (954 mg, 2.5 mmol), and SG1 (74 mg, 0.25 mmol) are heated to 90°C under a nitrogen atmosphere. Samples are taken periodically to monitor the conversion and molar mass. The reaction is stopped when the conversion reaches 45% (e.g., 2 hours). The conversion is determined by 1H NMR (Bruker 300 MHz spectrometer, CDCl3) by comparing the peaks of the -CH3- groups near the ester function of the monomer (δ = 4.11 ppm) and the polymer (δ = 3.91 ppm). The PMMA is then recovered by precipitation in a cold MeOH / H₂O mixture (4:1 by volume) and analyzed by SEC / DMF to obtain the number-average molar mass values (Mn) and dispersity (D) ( Mn= 9300 g.mol⁻¹, D = 1.30). After drying for 24 hours under vacuum, PMMA is used to initiate the polymerization of DMAEMA and obtain the PMMA- diblock copolymer. b -PDMAEMA corresponding. To do this, PMMA (1 g), styrene (662 mg, 6.37 mmols), DMAEMA (10 g, 63.6 mmols), 1,4-dioxane (5 ml), and SG1 (4 mg, 0.0125 mmol) are heated to 90°C under a nitrogen atmosphere. Samples are taken periodically to monitor the conversion by 1H NMR (Bruker CDCl3 spectrometer, 400 MHz) and the value of the Mn is determined by SEC / DMF. The reaction is stopped when the conversion is close to 50%. The PMMA- diblock copolymer b The final PDMAEMA is then isolated by cold precipitation in pentane. The resulting copolymer P1 is analyzed by 1< H NMR and SEC / DMF to obtain a composition having an F DMAEMA = 0.74, a Mn = 40000 g.mol -1< and a D = 1.46. Synthesis and characterization of amphiphilic PMMA-b-PDEAEMA diblock copolymers

[0071] A series of amphiphilic PMMA- diblock copolymers b -PDEAEMAs were prepared by nitroxide-controlled radical polymerization (NMP) using alkoxyamine BlocBuilder MA as a initiator and adding a comonomer for molar mass control and molar mass distribution. In these examples, 10 mol% styrene (S) or acrylonitrile (ACN) was used. The dibloc copolymers have the following structure: in which n and m are the degree of polymerization of each block, and R is styrene or acrylonitrile.

[0072] The synthesis of (PMMA 9300 - b -PDEAEMA 25500 ) ( P2This is presented here as an example of a manufacturing process according to the second aspect. This synthesis is applicable to all block copolymers as described herein. MMA (methyl methacrylate, 50 g, 0.50 mol), styrene (5.2 g, 0.05 mol), BlocBuilder MA (954 mg, 2.5 mmol), and SG1 (74 mg, 0.25 mmol) are heated to 90°C under a nitrogen atmosphere. Samples are taken periodically to monitor the conversion and molar mass. The reaction is stopped when the conversion reaches 45% (e.g., 2 hours). The conversion is determined by 1H NMR (Bruker 300 MHz spectrometer, CDCl3) by comparing the peaks of the -CH3- groups near the ester function of the monomer (δ = 4.11 ppm) and the polymer (δ = 3.91 ppm). The PMMA is then recovered by precipitation in a cold MeOH / H₂O mixture (4:1 by volume) and analyzed by SEC / DMF to obtain the number-average molar mass values (Mn) and dispersity (Ð) ( Mn= 9300 g.mol⁻¹, D = 1.30). After drying for 24 hours under vacuum, PMMA is used to initiate the polymerization of the hydrophilic monomer of 2-(diethylamino)ethyl methacrylate (DEAEMA) and obtain the PMMA- diblock copolymer. b -corresponding PDEAEMA. To do this, PMMA (1.3 g), styrene (562 mg, 5.4 mmols), DEAEMA (10 g, 54 mmols), 1,4-dioxane (5 ml), and SG1 (3 mg, 0.01 mmol) are heated to 90°C under a nitrogen atmosphere. Samples are taken periodically to monitor the conversion by 1H NMR (Bruker CDCl3 spectrometer, 400 MHz) and the value of the Mn is determined by SEC / DMF. The reaction is stopped when the conversion is close to 50%. The PMMA- diblock copolymer b -The final PDEAEMA is then isolated by precipitation in cold pentane. The resulting copolymer P2 is analyzed by 1< H NMR and SEC / DMF to obtain a composition having an F DMAEMA = 0.58, a Mn = 25500 g.mol -1< and a D = 1.30. Synthesis and characterization of amphiphilic diblock copolymers PBMA-b-PDEAEMA

[0073] A series of amphiphilic diblock copolymers PBMA- b -PDEAEMAs were prepared by nitroxide-controlled radical polymerization (NMP) using alkoxyamine BlocBuilder MA as a initiator and adding a comonomer for molar mass control and molar mass distribution. In these examples, 10 mol% styrene (S) or acrylonitrile (ACN) was used. The dibloc copolymers have the following structure: where n and m are the degree of polymerization of each block, and R is styrene or acrylonitrile. In these examples, the percentage of hydrophobic group and the molecular weight of the amphiphilic diblock copolymer were varied.

[0074] The synthesis of (PBMA 9300 - b -PDEAEMA 18000 ) ( P4This is presented here as an example of a manufacturing process according to the second aspect. This synthesis is applicable to all block copolymers as described herein. BMA (hydrophobic monomer, 50 g, 0.35 mol), styrene (3.66 g, 0.035 mol), BlocBuilder MA (952 g, 2.49 mmol), and SG1 (73 mg, 0.25 mmol) are heated to 90°C under a nitrogen atmosphere. Samples are taken periodically to monitor the conversion and molar mass. The reaction is stopped when the conversion reaches 45% (e.g., 2 hours). The conversion is determined by 1H NMR (Bruker 300 MHz spectrometer, CDCl3) by comparing the peaks of the -CH2- groups near the ester function of the monomer (δ = 4.11 ppm) and the polymer (δ = 3.91 ppm). The PBMA is then recovered by precipitation in a cold MeOH / H₂O mixture (4:1 by volume) and analyzed by SEC / DMF to obtain the number-average molar mass values (Mn) and dispersity (Ð ; Mw / Mn ) ( Mn = 9300 g.mol⁻¹, D = 1.24). After drying for 24 hours under vacuum, PBMA is used to initiate the polymerization of the hydrophilic monomer (DMAEMA) and obtain the PBMA- diblock copolymer. b -PDEAEMA corresponding. To do this, PBMA (1.5 g), styrene (562 mg, 5.4 mmols), DEAEMA (10 g, 54 mmols), 1,4-dioxane (5 ml), and SG1 (4 mg, 0.0125 mmol) are heated to 90°C under a nitrogen atmosphere. Samples are taken periodically to monitor the conversion by 1H NMR (Bruker CDCl3 spectrometer, 400 MHz) and the value of the Mn is determined by SEC / DMF. The reaction is stopped when the conversion is close to 50%. The PBMA- diblock copolymer b -The final PDEAEMA is then isolated by precipitation in cold pentane. The resulting copolymer P4 is analyzed by 1< H NMR and SEC / DMF to obtain a composition having an F DMAEMA = 0.31, a Mn = 18000 g.mol -1< and a D = 1.52. Ouaternization of block copolymers

[0075] The quaternization of the diblock copolymer examples was carried out by modifying the amine group of DMAEMA or DEAEMA with methyl iodide (MeI). Different quaternization yields were targeted, such as 0% (i.e., no quaternization, therefore not part of the claimed subject matter), 2%, and 100% (i.e., quaternization of all amine groups, therefore not part of the claimed subject matter). The diblock copolymer is solubilized in a solvent (e.g., 1 g of copolymer in 10 mL of DMF), and MeI is added to the solution, for example, slowly at room temperature. After 24 hours of stirring, the quaternized copolymer is dialyzed against ultrapure water (e.g. Milli-Q® water) for 3 days and then lyophilized before analysis by 1H NMR. Table 1: Amphibious block copolymer of the methacrylic type P1 to P18 (with 10 mole percent of styrene or acrylonitrile per methacrylic monomer) # block copolymer S or ACN % of the hydrophilic block % quat. Mel Mn (g / mol) Mn of the hydrophobic block (g / mol) Ð P1 PMMA- b- PDMAEMA S 74% 2 mol% 40 000 9 300 1.46 P2 PM MA- b- PDEAEMA S 58% 2 mol% 25 500 9 300 1.30 P3 PBMA- b- PDMAEMA S 49% 2 mol% 35 200 9 300 1.28 P4 PBMA- b- PDEAEMA S 31% 2 mol% 18 000 9 300 1.52 P5 PBMA- b- PDMAEMA S 46% 2 mol% 61 600 20 200 1.60 P6 PBMA- b- PDMAEMA S 1-9% 2 mol% 28 700 20 200 1.24 P7 PBMA- b - S 38% 2 mol% 17 700 7 000 1.38 PDMAEMA P8 PBMA- b- PDMAEMA S 60% 2 mol% 45 800 7 000 1.37 P9 PBMA- b- PDMAEMA S 40% 2 mol% 22 900 9 300 1.24 P10 PBMA- b- PDMAEMA S 37% 2 mol% 22 600 9 300 1.27 P11 PBMA- b- DMAEMA S 42% 2 mol% 22 100 7 000 1.26 P12 PBMA- b- PDMAEMA S 62% 2 mol% 52 800 7 000 1.26 P13 PBMA- b- PDMAEMA ACN 35% 2 mol% 22 400 12 800 1.32 P14 * PBMA- b- PDMAEMA S 73% 0 mol% 31 300 6 400 1.54 P15 * PBMA- b- PDMAEMA ACN 64% 0 mol% 20 500 9 300 1.34 P16 * PBMA- b- PDMAEMA S 73% 100 mol% 31 300 6 400 1.54 P17 * PBMA- b- PDMAEMA ACN 64% 100 mol% 20 500 9 300 1.34 P18 * PBMA- b- PDMAEMA ACN 72% 100 mol% 20500 9 000 1.45 * not part of the claimed subject matter Antimicrobial activities of methacrylic-type amphiphilic block copolymers in solution

[0076] The antimicrobial activity of P1-P18 copolymers was tested. Various Gram-negative strains were used: Escherichia coli (ATCC 8739), Pseudomonas aeruginosa (ATCC CRM-9027), and FQR (fluoroquinolone-resistant) P. aeruginosa (CIP 107398). Gram-positive strains were also used: Staphylococcus aureus (ATCC CRM-6538P) and methicillin-resistant Staphylococcus aureus (MRSA USA300) (ATCC BAA-1717 USA 300 CA-MRSA). The antimicrobial activity of the block copolymers was evaluated by determining the minimum inhibitory concentration (MIC). The ICD was determined using serial dilutions by two of antimicrobial agents in bacterial liquid media as described by the National Committee on Clinical Laboratory Standards (NCCLS) (NCCLS, 1997).In short, individual colonies of different bacterial strains cultured on Luria-Bertani (LB) agar plates are used to inoculate liquid bacterial culture medium (LB or Mueller-Hinton (MH)). The tubes are incubated overnight at 37°C with shaking (200 rpm). The following day, the bacterial suspensions (optical density OD > 1.0) are diluted 1 / 100 in 3 ml of fresh MH or LB medium and incubated at 37°C, 200 rpm until the bacteria reach the logarithmic growth phase (OD approximately 0.6). The bacteria are then diluted in MH or LB medium to achieve a bacterial density around 105 bacteria / ml. 135 µl of bacterial suspension are then added to each of the 96 wells of a sterile polypropylene microplate (Greiner BioOne) already containing 15 µl of serially diluted antimicrobial (1:2 in distilled water).The plates are incubated at 37°C for 18–24 h before measuring the OD at 600 nm using a microplate reader. The IMC is defined as the lowest concentration of antimicrobial that inhibits visible organism growth (99% inhibition). The results are described in Tables 2 and 3, where NS stands for insoluble. Table 2 block copolymer CIM (µM) in LB medium E. coli B subtilis S aureus P aeruginosa P1 PMMA- b -PDMAEMA 2,6 1,3 > 21 2,6 P2 PMMA- b -PDEAEMA 9,35 9,35 > 37 9,35 P3 PBMA- b -PDMAEMA 5,75 2,88 > 23 2,88 P4 PBMA- b -PDEAEMA 10 5 > 40 10,00 P5 PBMA- b -PDMAEMA 4,77 2,37 > 38 5 P6 PBMA- b -PDMAEMA NS NS NS NS P7 PBMA- b -PDMAEMA 5 >20 P8 PBMA- b -PDMAEMA 0,98 1 > 15,8 1 P9 PBMA- b -PDMAEMA 5 3 P10 PBMA- b -PDMAEMA 3 1 P11 PBMA- b -DMAEMA 20 20 P12 PBMA- b -PDMAEMA 1 1 P13 PBMA- b -PDMAEMA 20 10 P14* PBMA- b -PDMAEMA 2,5 P15* PBMA- b -PDMAEMA 10 P16* PBMA- b -PDMAEMA >20 P17* PBMA- b -PDMAEMA 5 * not part of the claimed subject matter Table 3 block copolymer CIM (µM) in MH medium E. coli B subtilis S aureus Pseudomonas FQR MRSA E faecalis VER P1 PMMA- b -PDMAEMA 5,250 0,660 21,300 2,6 2,6 >21,3 P2 PMMA- b -PDEAEMA > 37 >37 > 37 9,35 >37 >37,4 P3 PBMA- b -PDMAEMA 5,750 0,360 23,100 1,4 2,8 >23,1 P4 PBMA- b -PDEAEMA > 40 20,000 > 40 10 5 >40,2 P5 PBMA- b -PDMAEMA 9,550 1,180 19,100 2,4 4,75 38,2 P6 PBMA- b -PDMAEMA NS NS NS NS NS NS P7 PBMA- b -PDMAEMA >20 >20 6,5 >20 >26,1 P8 PBMA- b -PDMAEMA 1,975 0,490 7,900 0,98 0,98 15,8 P9 PBMA- b -PDMAEMA 1,250 0,313 2,5 5 20 P10 PBMA- b -PDMAEMA 1,250 0,625 2,5 5 >20 P11 PBMA- b -DMAEMA >20 0,625 20 1,25 1,25 P12 PBMA- b -PDMAEMA 0,625 0,150 2,5 1,25 20 P13 PBMA- b -PDMAEMA 20,000 10,000 20 1,25 2,5 P14* PBMA- b -PDMAEMA 0,6 0,3 0,3 0,6 P15* PBMA- b -PDMAEMA 0,6 0,3 2.5 1,25 P16* PBMA- b -PDMAEMA 0,6 0,6 1,25 0,15 P17* PBMA- b -PDMAEMA 0,6 0,15 0,6 0,07 P18* PBMA- b -PDMAEMA 2,5 0,31 5,0 0,31 * not part of the claimed subject matter Hemolytic properties of amphiphilic block copolymers of the methacrylic type in solution

[0077] The hemolytic nature of copolymers P1-P17was tested in solution. Specifically, hemolytic activity was determined by the loss of hemoglobin from human erythrocytes (obtained from Divbioscience, NL). Human erythrocytes were washed three times with phosphate-buffered saline (PBS) and concentrated by centrifugation at 800 g for 5 min. The human erythrocytes were then resuspended in PBS to a final concentration of 8%. 135 µl of human erythrocytes were then added to each of the 96 wells of a sterile microplate containing 15 µl of diluted antimicrobial (1:2 in distilled water). After 1 h at 37°C, the microplate was centrifuged at 800 g for 5 min. 100 µl were then carefully collected and transferred into a new 96-well microplate and the OD was measured at 405 nm.Hemolysis induced by the copolymers was expressed as a percentage of hemolysis, with Triton-X100 at 0.1% (v:v) used as a positive control, resulting in 100% hemolysis. The results are described in Table 4.

[0078] Tables 2-4: Antibacterial activities and hemolytic properties of diblock copolymers solution (HMC represents the concentration causing 100% hemolysis and HC50 the concentration causing 50% hemolysis; hRBC and sRBC are for "human red blood cell" and "sheep red blood cell", respectively). Table 4 block copolymer HMC (µM) HC50 (µM) hRBC sRBC hRBC sRBC P1 PMMA- b -PDMAEMA 10,6 > 21,3 2,6-5,3 > 21,3 P2 PMMA- b -PDEAEMA <0,36 <0,36 <0,36 <0,36 P3 PBMA- b -PDMAEMA 5,75 >23,1 1,4-2,8 >23,1 P4 PBMA- b -PDEAEMA <0,39 <0,39 <0,39 <0,39 P5 PBMA- b -PDMAEMA 5 >38 0,59-1,19 >38 P6 PBMA- b -PDMAEMA NS NS NS NS P7 PBMA- b -PDMAEMA <0,3 <0,3 <0,3 <0,3 P8 PBMA- b -PDMAEMA 1 2 0,24-0,49 0,47-0,9 P9 PBMA- b -PDMAEMA <0,3 <0,3 <0,3 <0,3 P10 PBMA- b -PDMAEMA <0,3 <0,3 <0,3 <0,3 P11 PBMA- b -DMAEMA >20 >20 1,25 20,00 P12 PBMA- b -PDMAEMA <0,3 20,00 <0,3 1,25 P13 PBMA- b -PDMAEMA >20 >20 >20 >20 P14* PBMA- b -PDMAEMA 0,039 P15* PBMA- b -PDMAEMA >20 P16* PBMA- b -PDMAEMA >20 P17* PBMA- b -PDMAEMA >20 * not part of the claimed subject matter Antifungal activity of an exemplary amphiphilic block copolymer of the methacrylic type in solution

[0079] Antifungal tests were performed on two strains: Aspergillus niger and Candida albicans. Aspergillus niger was inoculated onto PDA agar plates and incubated at 35°C until sporulation (72 h). Once sporulation was reached, 1 ml of 0.85% saline buffer containing Tween 20 was added to facilitate mycelial dissociation. After filtering through sterile gauze, the spores were counted and diluted in PD medium to achieve a concentration close to 5 x 10⁴ CFU / ml. The spores were then added to the diluted compounds in 96-well plates and incubated for 48 h at 35°C. Candida albicans was inoculated onto LB agar plates and incubated overnight at 35°C. The following day, five colonies are collected from the dish and added to 5 ml of saline buffer. After reading the optical density at 600 nm (1 unit equivalent to 10⁷ CFU / ml), the yeasts are diluted in RPMI + MOPS medium to achieve a concentration of 10³ CFU / ml.Yeast cultures are then added to a 96-well plate in the presence of increasing concentrations of compounds and incubated for 48 h at 35°C. MICs are determined for Aspergillus niger and Candida albicans, with the lowest compound concentration resulting in no fungal growth assessed by measuring the absorbance of the wells at 600 nm. Tests show that compound P14 has a MIC of 40 µM on the fungi. Anti-inflammatory activity of amphiphilic block copolymers of the methacrylic type in solution

[0080] The anti-inflammatory activity of the compounds was tested on human monocytes (THP-1 cells) stimulated with lipopolysaccharide (LPS) (extracted from E. coli and used at a final concentration of 100 ng / ml). THP-1 cells were seeded in 96-well plates at a density of 10⁴ cells per well. The cells were then treated with LPS (at 100 ng / ml) in the presence or absence of the compounds, with increasing concentrations. After 6 h of incubation, the culture supernatant was collected before measuring the concentration of TNF-alpha, a cytokine marker of inflammation induced by LPS. Polymyxin B, an agent inhibiting the effect of LPS, was used as a positive control. The cell viability of the THP-1 cells was also measured using the Alamar blue assay. The inhibitory concentrations 50 (IC50) causing 50% inhibition of TNF-alpha production or cell viability were determined visually (Table 5).The "safety factor" was determined by dividing the IC50 for TNF-alpha production by the IC50 for viability. The results are described in Table 5. Table 5 block copolymer IC50 inflammation (µM) HC50 viability (µM) Safety Factor P14* PBMA- b -PDMAEMA 0,019 20 1000 P15* PBMA- b -PDMAEMA 0,15 >20 >100 P16* PBMA- b -PDMAEMA 0,039 >20 >500 P17* PBMA- b -PDMAEMA 0,078 >20 >250 * not part of the claimed subject matter Process for manufacturing solid organic material by solvent evaporation

[0081] Following biological tests in solution of the prepared copolymers, various solid organic materials by solvent evaporation PS and PMMA based products containing different amounts of butyl methacrylate (BMA) and N,N-dimethyl-amino ethyl methacrylate (DMAEMA) (quaternized or not) copolymers were prepared and tested.

[0082] The PS and PMMA-based polymer matrices were prepared by the same solvent evaporation method. For example, in the case of PS, a 20 wt% PS stock solution in THF is prepared. 226 mg of PX copolymer ( i.e.,P1-P17) are dissolved in 5 mL of the 20% PS / THF solution to give a 17% wt. copolymer / PS solution. The same procedure is used to prepare a 2% wt. copolymer / PS solution using 22.6 mg of copolymer and 5 mL of the 20% PS / THF solution. 500 µL of the 2% wt. copolymer / PS solution are then diluted with 4.5 mL of the 20% PS / THF solution to give a 0.2% wt. copolymer / PS solution. The same procedure is used to prepare 0.02% wt. copolymer / PS solutions. After 1 hour of stirring at room temperature, 150 µL of each solution are dispensed into each of the 96 wells of a sterile polypropylene microplate (Greiner BioOne). One line of the microplate is dedicated to each of the different copolymer concentrations and one line is filled with only a PS20% / THF solution as a blank test.After 2 days of THF evaporation at room temperature, the resulting copolymer / PS films are then tested in terms of hemolysis and antimicrobial activity against . E. coli And B. subtilis. Antimicrobial activities of a series of prepared organic solid materials about solvent evaporation

[0083] The antimicrobial activity of organic solid materials prepared by solvent evaporation containing dibloc copolymers P5, P8 And P12were tested. Antimicrobial activity was evaluated according to an adapted ISO 22196 procedure. The polymeric matrix (PS or PMMA) containing the dibloc copolymer is introduced into sterile 96-well polypropylene microplates (Greiner BioOne). Bacterial suspensions are prepared as performed for CIM assays, except that the bacterial suspension in the logarithmic growth phase (OD600 nm approximately 0.6) is centrifuged at 6,000 rpm for 10 min at 4°C. The bacterial pellets are washed with 10 ml of sterile phosphate-buffered saline (PBS) and centrifuged (6,000 rpm, 10 min, 4°C). The bacteria are then diluted in sterile PBS to achieve a bacterial density of approximately 1010 bacteria / ml. 10 µl of these suspensions (corresponding to 1,000 bacteria) are added to the surface of polymerized copolymers.Negative controls were obtained by adding 10 µl of the bacterial suspension directly onto the surface of the control polymer without the addition of block copolymer (PMMA or PS). After 60 minutes of incubation at room temperature, bacteria were collected by adding 90 µl of sterile PBS to the surface and repeating the pipetting up and down. The bacteria were then serially diluted (1:10 dilution) in sterile PBS before spreading 10 µl of the bacterial suspension onto LB agar plates. After overnight incubation at 37°C, the plates were observed and colonies were counted. The number of viable bacteria was expressed as a function of the number of colony-forming units (CFU) observed. The experiments were performed in three independent sets (n = 3). The results of the antimicrobial tests performed on the organic solid materials are presented in the [reference to relevant section]. Figures 1 to 3 . Hemolytic properties of a series of organic solid materials

[0084] The hemolytic character of organic solid materials containing dibloc copolymers P5, P8 And P12 were tested. 10 µl of human erythrocyte suspension (8% in PBS) was added to each of 96 wells of a microplate containing organic solids (PS or PMMA with a dibloc copolymer). After 60 minutes of incubation at room temperature, 90 µl of PBS was added, and the microplate was centrifuged at 800 g for 5 min. 50 µl were then carefully collected from the wells and transferred to a new 96-well microplate, and the OD was measured at 405 nm. Hemolysis induced by the copolymers is expressed as a percentage of hemolysis, with Triton-X100 used as a positive control. The results of the hemolytic tests performed on the organic solids are presented in the Figures 1 to 3 .

[0085] As shown on the Figures 1 to 3 , the tests carried out on E. coli And B. subtilisshow that the prepared organic solid materials are active up to 2 wt% and without hemolytic character (tests on human red blood cells, RBC).

[0086] Although the embodiments of this description mentioned above are described in detail, it is understood that other embodiments may be considered. Thus, for example, polymeric matrices other than PMMA or PS may be considered to obtain an organic solid material according to the first aspect; methacrylates other than DMAEMA or DEAEMA may be considered to obtain an organic solid material according to the first aspect; copolymers based on compounds other than MMA, BMA, S and / or ACN may be considered to obtain an organic solid material according to the first aspect. Process for manufacturing solid organic material by extrusion

[0087] Various organic solid materials based on PS, PMMA and PC (polycarbonate (CALIBRE 201-15 from TRINSEO)) containing different amounts of butyl methacrylate (BMA)-based copolymers and N , N -dimethyl-amino ethyl methacrylate (DMAEMA) (quaternized or not) were prepared by extrusion.

[0088] Copolymer dispersions P18 (not part of the claimed subject matter) in solid organic materials were carried out using a Thermo Scientific conical twin-screw mini extruder (Haake MiniLab II). The temperature and screw rotation speed were adapted to each die and are reported in Table 6. Table 6 Polymeric Matrix Supplier Mw (g / mol) Extrusion Temperature (°C) Screw rotation speed (rpm) PS Aldrich 192000 180 30 PMMA Aldrich 120000 200 100 PC TRINSEO - 220 30

[0089] Before extrusion, the solid organic materials were ground into a fine powder and then mixed with 0.5% by weight / matrix of the copolymer. P18.5 g of each mixture was manually introduced into the extruder in recirculation mode (1 to 2 min). After 2 min in recirculation mode, the mixture was extruded and recovered in the form of a rod.

[0090] Films of solid organic materials were prepared using a Specac Hydraulic press. The extruded mixtures (rods) were cut into small pieces and then pressed between two metal discs covered with an aluminum film. The pressure was set at 1 ton and the temperatures were the same as those used in extrusion. The resulting films have an average thickness of 330 µm. Antimicrobial activities of a series of organic solid materials prepared by extrusion

[0091] The antimicrobial activity of organic solid materials (not part of the claimed subject matter) prepared by extrusion containing a diblock copolymer P18was tested. Antimicrobial activity was evaluated according to an adapted ISO 22196 procedure. The polymeric matrix (PS, PMMA, Polycarbonate) containing the dibloc copolymer is introduced into sterile 96-well polypropylene microplates (Greiner BioOne). Bacterial suspensions are prepared as performed for CIM assays, except that the bacterial suspension in the logarithmic growth phase (OD600 nm approximately 0.6) is centrifuged at 6,000 rpm for 10 min at 4°C. The bacterial pellets are washed with 10 ml of sterile phosphate-buffered saline (PBS) and centrifuged (6,000 rpm, 10 min, 4°C). The bacteria are then diluted in sterile PBS to achieve a bacterial density of approximately 1010 bacteria / ml. 10 µl of these suspensions (corresponding to 1,000 bacteria) are added to the surface of polymerized copolymers.Negative controls are obtained by adding the 10 µl bacterial suspension directly or into a control well not containing film (sample "no film", . Figure 4 ), or on a film of the extruded organic solid material not containing the P18 copolymer (sample "no polymer", Figure 4After 60 minutes of incubation at room temperature, the bacteria were collected by adding 90 µl of sterile PBS to the surface and repeating the pipetting up and down. The bacteria were then serially diluted (1:10 dilution) in sterile PBS before spreading 10 µl of the bacterial suspension onto LB agar plates. After overnight incubation at 37°C, the plates were observed and the colonies were counted. The number of viable bacteria was expressed as a function of the number of colony-forming units (CFU) observed. The experiments were performed in three independent copies (n = 3). The results of the antimicrobial tests performed on the extruded organic solid materials are presented in the Figure 4 .

Claims

1. A solid organic material comprising from 0.02 to 2 wt% of at least one amphiphilic block copolymer of the methacrylic type, the block copolymer being dispersed in a polymer matrix, the block copolymer having a number-average molar mass (Mn) greater than or equal to 20 000 g / mol, wherein the block copolymer comprises at least one hydrophilic methacrylic block comprising at least one tertiary amine group and at least one quaternary ammonium ion.

2. The solid organic material as claimed in claim 1, wherein the block copolymer has a number-average molar mass (Mn) less than or equal to 100 000 g / mol.

3. The solid organic material as claimed in claim 1, wherein the hydrophilic methacrylic block comprises a hydrophilic repeating unit selected from the group consisting of N,N-(dialkylamino)alkyl methacrylate and a quaternary ammonium ion of the latter.

4. The solid organic material as claimed in any one of the preceding claims, wherein the block copolymer comprises at least one hydrophobic methacrylic block.

5. The solid organic material as claimed in claim 4, wherein the hydrophobic methacrylic block comprises a hydrophobic repeating unit selected from the group consisting of a linear, branched, cyclic or cyclic and branched alkyl methacrylate.

6. The solid organic material as claimed in claim 5, wherein the alkyl methacrylate is selected from the group consisting of methyl methacrylate (MMA) and butyl methacrylate (BMA).

7. The solid organic material as claimed in any one of the preceding claims, comprising one of the following formulations: PMMA-b-PDMAEMA, PMMA-b-PDEAEMA, PBMA-b-PDMAEMA, PBMA-b-PDEAEMA, P(MMA-Co-S)-b-PDMAEMA, P(MMA-CoS)-b-PDEAEMA, P(BMA-Co-S)-b-PDMAEMA, P(BMA-Co-S)-b-PDEAEMA, P(MMA-Co-ACN)-b-PDMAEMA, P(MMA-Co-ACN)-b-PDEAEMA, P(BMA-Co-ACN)-b-PDMAEMA, P(BMA-Co-ACN)-b-PDEAEMA, PMMA-b-P(DMAEMA-Co-S), PMMA-b-P(DEAEMA-Co-S), PBMA-b-P(DMAEMA-Co-S), PBMA-b-P(DEAEMA-Co-S), PMMA-b-P(DMAEMA-Co-ACN), PMMA-b-P(DEAEMA-Co-ACN), PBMA-b-P(DMAEMA-Co-ACN), PBMA-b-P(DEAEMA-Co-ACN), P(MMA-Co-S)-b-P(DMAEMA-Co-S), P(MMA-Co-S)-b-P(DEAEMA-Co-S), P(BMA-Co-S)-b-P(DMAEMA-Co-S), P(BMA-Co-S)-b-P(DEAEMA-Co-S), P(MMA-Co-ACN)-b-P(DMAEMA-Co-ACN), P(MMA-Co-ACN)-b-P(DEAEMA-Co-ACN), P(BMA-Co-ACN)-b-P(DMAEMA-Co-ACN), P(BMA-Co-ACN)-b-P(DEAEMA-Co-ACN), P(MMA-Co-S)-b-P(DMAEMA-Co-ACN), P(MMA-Co-S)-b-P(DEAEMA-Co-ACN), P(BMA-Co-S)-b-P(DMAEMA-Co-ACN), P(BMA-Co-S)-b-P(DEAEMA-Co-ACN), P(MMA-Co-ACN)-b-P(DMAEMA-Co-S), P(MMA-Co-ACN)-b-P(DEAEMA-Co-S), P(BMA-Co-ACN)-b-P(DMAEMA-Co-S) and P(BMA-Co-ACN)-b-P(DEAEMA-Co-S).

8. A method for preparing a solid organic material comprising dispersing from 0.02 to 2 wt% of at least one amphiphilic block copolymer of the methacrylic type in a polymer matrix, wherein the block copolymer has a number-average molar mass (Mn) greater than or equal to 20 000 g / mol, wherein the block copolymer comprises at least one hydrophilic methacrylic block comprising at least one tertiary amine group and at least one quaternary ammonium ion.

9. The method as claimed in claim 8, comprising preparing the block copolymer by nitroxide-mediated radical polymerization.

10. The method as claimed in claim 8 or claim 9, comprising quaternization of the tertiary amine.

11. Use of the solid organic material as claimed in any one of claims 1 to 7 for nontherapeutic antibacterial, antimicrobial, and / or antifungal applications.

12. A medical device comprising a solid organic material as claimed in any one of claims 1 to 7.

13. The medical device as claimed in claim 12, selected from the group consisting of a catheter.

14. An amphiphilic block copolymer of the methacrylic type for use thereof as a medicament in a solid organic material at a concentration of from 0.02 to 2 wt%, the block copolymer having a number-average molar mass (Mn) greater than or equal to 20 000 g / mol, wherein the block copolymer comprises at least one hydrophilic methacrylic block comprising at least one tertiary amine group and at least one quaternary ammonium ion.

15. An amphiphilic block copolymer of the methacrylic type for use thereof as an antibacterial, antifungal and / or anti-inflammatory medicament in a solid organic material at a concentration of from 0.02 to 2 wt%, the block copolymer having a number-average molar mass (Mn) greater than or equal to 20 000 g / mol, wherein the block copolymer comprises at least one hydrophilic methacrylic block comprising at least one tertiary amine group and at least one quaternary ammonium ion.

16. The solid organic material as claimed in any one of claims 1 to 7 for use as an antibacterial, antimicrobial, antifungal and / or anti-inflammatory medicament.