Method for preparing a crosslinked copolymer and use thereof as a porous material

Abstract

The present invention relates to a method for manufacturing a crosslinked copolymer from at least one CO2-loaded polyamine and at least one polyelectrophilic monomer. The present invention also relates to a porous material consisting of the crosslinked copolymer that can be or is obtained by the claimed method, and to the use thereof in various applications, and in particular as a tissue adhesive foam.

Description

[0001] PROCESS FOR PREPARING A CROSSLINKED COPOLYMER AND ITS USE AS A POROUS MATERIAL

[0002] TECHNICAL FIELD OF THE INVENTION

[0003] The present invention relates to a method for manufacturing a crosslinked copolymer as well as a porous material consisting of the crosslinked copolymer obtained by the method of the invention and its uses.

[0004] STATE OF THE ART

[0005] Biocompatible adhesives can be used in a variety of applications, from surgery to food packaging to medical devices such as bandages.

[0006] Surgeries involve the use of invasive techniques such as sutures, clips, and staples to close tissues and control any bleeding resulting from the operation. These invasive techniques can cause tissue damage, infection, scarring, and / or additional bleeding.

[0007] To avoid such complications, tissue adhesives are increasingly used to close tissues after surgery. These tissue adhesives have the advantage of being easy to apply, more flexible, inexpensive, and less likely to cause damage than the aforementioned techniques.

[0008] Currently, tissue adhesives approved by European and American regulatory bodies are classified into two categories:

[0009] - adhesives obtained by a so-called "top-down" approach, from biomacromolecules derived from biological extracts (animal, plant, microbial). These macromolecules such as collagen, albumin, fibrin, can be post-functionalized and co-formulated. Fibrin-based tissue adhesives are widely used, particularly to control post-surgical bleeding (Beudert et al. ACS Biomater. Sci. Eng. 2022, 8, 2220-2231). These adhesives are biocompatible, biodegradable, and do not cause tissue necrosis or inflammation. However, since fibrin is an animal protein, there is a significant risk of viral transmission with these adhesives. In addition, they can degrade too quickly and have poor adhesion capabilities, limiting their use in the human body. This top-down approach is also limited by the high cost of the raw material.

[0010] - adhesives obtained by a so-called "bottom-up" approach, from monomers derived from fossil resources and impacting inputs, which are polymerized and then possibly post-functionalized by traditional chemical routes, leading to a product with low biocompatibility (Pascual, G. et al. PLOS ONE 11, e0157920 (2016)). Tissue adhesives based on polyurethane, particularly thermoplastic polyurethane (TPU), have been developed with improved adhesion to muscle tissue and skin (Mouren, A. and Avérous, L. Chem. Soc. Rev. 2023, 52, 277). These adhesives can notably be in the form of foam. However, it is necessary to couple TPU with other elements (xylose, rosin, hydroxyapatite nanocrystals) to obtain the desired adhesive performance (Bhagat et al. Biomacromolecules, 2017, 18, 3009-3039). These synthetic materials are petroleum-based, poorly biodegradable and poorly biocompatible.In addition, they pose risks of tissue inflammation.

[0011] Other types of bottom-up adhesives are cyanoacrylate-based and provide strong and long-lasting adhesion. In addition, they have inherent bactericidal properties. However, because cyanoacrylate degradation products are toxic, these adhesives are limited to topical application (Bhagat et al. Biomacromolecules, 2017, 18, 3009-3039). These adhesives also have the disadvantages of being non-biobased and non-biodegradable.

[0012] Recently, adhesive hydrogels based on supramolecular interactions have been described (Zhao et al. Chem. Rev. 2022, 122, 5604-5640). Such dynamic interactions make it possible to adapt to the complexity and diversity of biological tissues. These hydrogels are particularly interesting due to their adhesion capacity in a wet environment and their bottom-up approach using bio-sourced molecules. These materials also have the ability to encapsulate and deliver therapeutic substances. A progressive release of these substances makes it possible to reduce the administered quantity of active molecules during treatment and allows continuous care, greatly improving the effectiveness of treatments compared to conventional methods. However, their use is still limited by the biocompatibility of these new biopolymers, as well as their biodegradability.For example, catechol-based adhesive hydrogels generate H2O2, a by-product lethal to cells. They may also include metal ions as a complexing agent that can induce high toxicity. A simple-to-produce supramolecular hydrogel would address most of the aforementioned issues. The biodegradable polymeric hydrogels disclosed in WO201 1 / 111067 comprise a component A and a component B forming a B-aminoester bond such that the bond results in gelation, component A being a water-soluble polymer containing an acrylate functionality and component B being a water-soluble polymer containing an amine functionality. Component B is not loaded with CO2, and the resulting hydrogels are not in the form of a foam or porous material.

[0013] Many other biocompatible adhesives have been tested in recent years (based on polysaccharides, PEG, peptides, etc.) without, however, providing satisfactory performance in terms of strength and speed of adhesion, degradability, stability and ease of processing. In this regard, we can notably mention document US2024 / 018304, which describes biodegradable alkoxylated polyamine polymers, useful in many technical fields; however, the polyamine used to prepare these alkoxylated polyamines is not loaded with CO2, and the polymers obtained are not in the form of foam or porous material. Thus, adhesion in a humid environment represents a real challenge.

[0014] Transdermal patches (TDDS) adhere and deliver the therapeutic substance through a layer of pressure-sensitive adhesives (PSAs). Among commercial PSAs, those based on poly(isobutylene) (PIB) (Estraderm®) are suitable for the delivery of low-polar therapeutic molecules. PIBs have low adhesiveness and also a low free volume, limiting the diffusion of target molecules (Benedek et al. Marcel Dekker, 1997). These polymers are also petroleum-based.

[0015] Silicone-based PSAs (Neupro®), including a poly(dimethylsiloxane) and silicate resin blend, are biocompatible, easy to produce, and have high diffusivity. However, the majority of therapeutic molecules are insoluble in this type of PSA (Pfister et al. Pharm. Technol. 1992, 16, 42-58). Silicones are petroleum-based and therefore have limited use in sustainable development. Another type of commercial PSA used in TDDS is poly(acrylate) (BuTrans®). This PSA family is biocompatible, exhibits good adhesion and diffusion properties, and a wide range of compatibility with excipients or therapeutic molecules. However, the release of the monomers used and the detachment of the TDDS can lead to skin irritation (Lobo et al. Therapeutic Delivery, 2016, 7(1), 33-48).

[0016] A bio-sourced ASP, capable of adhering to the skin and delivering therapeutic substances without tissue irritation, is therefore sought in the context of TDDS.

[0017] Flexible multi-layer packaging materials account for 10% of plastic packaging. Their properties allow for a 10% lower carbon footprint compared to food packaging products (Bauer et al. Foods. 2021, 10, 2702-2719). Multi-layer packaging materials are mainly produced by co-extrusion, lamination, or coating.

[0018] The different layers are linked either by binder layers, generally poly(ethylene) polymers or copolymers grafted with maleic anhydrides, acid, ester or alcohol functions (Maes et al. Polymer Reviews, 2018, 58(2), 209-246), or by adhesives such as ethylene vinyl acetate, poly(urethane), acrylates or poly(vinyl alcohols) (Aznar et al. Journal of Materials Chemistry, 2011, 21(12), 4358-4370). The difficulty of separating the different layers and the thermal incompatibility of the polymers used make flexible multilayer packaging materials considered non-recyclable.

[0019] One solution to increase recyclability and maintain the barrier and mechanical properties of the material would be to integrate a reversible and bio-sourced glue between the different layers, simplifying their separation and therefore their recycling (Anukiruthika et al. Comprehensive Reviews in Food Science and Food Safety. 2020, 19(3), 1156-1186).

[0020] A need therefore remains for the provision of a biocompatible material, preferably biosourced, having adhesive properties, which can thus be useful in various applications, in particular as a tissue adhesive for surgery, as a pressure-sensitive adhesive or as a glue for recyclable food packaging, which makes it possible to overcome the aforementioned drawbacks and which is obtained by a process which is easy to implement.

[0021] SUMMARY OF THE INVENTION

[0022] The invention relates to a method for manufacturing a crosslinked copolymer comprising the following steps: a) Providing:

[0023] - a polyelectrophilic monomer, and

[0024] - a polyamine loaded with CO2 obtained by reaction between a gaseous mixture comprising CO2 and a polyamine of formula (I):

[0025] [Chem 1] in which

[0026] R 2 independently represents a hydrogen atom, a C1-C6 alkyl, or a C1-C6 alkyl substituted in the terminal position by an NR group 5 R 6

[0027] R 1 , R 3 , R 4 , R 5 and R 6 are independently a hydrogen atom or a C1-C6 alkyl,

[0028] R is a hydrogen atom or a carboxylic acid function, m is 1, 2, 3, 4, 5, 6, 7 or 8, and each n is independently 0, 1, 2, 3, 4 or 5, b) Reaction between the CO2-charged polyamine and the polyelectrophilic monomer provided in step a), preferably at a temperature below 70°C, preferably in an aqueous medium, leading to the formation of the crosslinked copolymer.

[0029] According to certain variants, in formula (I):

[0030] R 1 , R 2 , R 3 and R 4 are independently a hydrogen atom or a C1-C6 alkyl,

[0031] R is a hydrogen atom or a carboxylic acid function, m is 1, 2, 3, 4, 5, 6, 7 or 8, and n is 0, 1, 2, 3, 4 or 5.

[0032] The present invention also relates to a porous material consisting of a crosslinked copolymer obtained or capable of being obtained by the process according to the invention.

[0033] The present invention also relates to the use of such a porous material as a tissue adhesive.

[0034] Finally, the present invention relates to an article comprising such a porous material.

[0035] Other aspects of the invention are as described below.

[0036] DETAILED DESCRIPTION OF THE INVENTION

[0037] Definitions

[0038] The term "biocompatible" refers to a material that does not produce adverse effects when in contact with a living system, particularly a human being.

[0039] The term "foam" refers to any material in which gas, in the form of gas bubbles, is dispersed to form pores. The average pore diameter is generally greater than 10 μm, typically determined by X-ray tomography on a CT scanner, such as a GE Phoenix v|tome|x s240 CT scanner with a Varian Paxscan detector.

[0040] The term "carbamate function" is understood in this description as the carbamate anion of formula It is understood that the carbamate anion represented in its charged form in the present description is associated with a positively charged counterion, for example a metallic counterion, preferably chosen from lithium ions (Li + ), sodium (Na + ), magnesium (Mg 2+ ), calcium (Ca 2+ ) and potassium (K + ), or an ammonium ion as defined below, although this counterion is not systematically represented.

[0041] The term "ammonium bicarbonate function" refers to a functional group of formula

[0042] The term "copolymer" refers to a polymer comprising at least two different repeating units. A repeating unit is a group of atoms repeated several times in the polymer to form a polymer chain.

[0043] The term "alternating copolymer" refers to a copolymer whose different repeating units systematically alternate with each other so that a repeating unit is never linked to another identical repeating unit. For example, an alternating copolymer comprising repeating units A and B will have the following structure: AB AB AB AB AB AB AB AB AB .

[0044] The term "alternating crosslinked copolymer" means an alternating copolymer as defined above comprising crosslinking points between the copolymer chains so as to form a three-dimensional network. These crosslinking points may be covalent and optionally non-covalent bonds, for example hydrogen bonds, 7t-7t interactions, Van der Waals bonds, dipole-dipole interactions or ionic interactions.

[0045] The term “diamino acid” refers to an amino acid comprising two amine functions and at least one carboxylic acid function.

[0046] In the present description, the “carboxylic acid” functions are equivalently represented in their neutral form -COOH, in their charged form -COO' or in their charged form in the presence of a metal counterion -C00M, M being an alkali metal preferably chosen from lithium (Li), sodium (Na), magnesium (Mg), calcium (Ca) and potassium (K).

[0047] An "ammonium function" corresponds to a positively charged primary, secondary, or tertiary amine function. The ammonium function can, for example, be of the formula -NH2 + -, -NH3 + , -NHR a+ -, -NH2R a+ , -N(R a )2 + - or -NH(R a )2 + , R a being a C1-C6 alkyl group.

[0048] Process for manufacturing a crosslinked copolymer

[0049] The inventors have developed a process for obtaining a porous polymeric material that meets the requirements expressed in terms of biocompatibility, biodegradability and adhesiveness. The process uses bio-sourced materials and is carried out under very mild solvent and temperature conditions. Indeed, the polyelectrophilic monomer and the polyamine of formula (I) are mainly bio-sourced.

[0050] The process for manufacturing a crosslinked copolymer thus comprises the reaction between a polyamine charged with CO2 and a polyelectrophilic monomer, preferably at a temperature below 70°C, preferably in an aqueous medium, leading to the formation of the crosslinked copolymer.

[0051] The reagents and method are as described below.

[0052] Polyamine loaded with COg

[0053] The CO2-charged polyamine useful in the context of the process of the invention is obtained by reaction between a gaseous mixture comprising CO2 and a polyamine of formula (I): [Chem 2] in which

[0054] R 2 independently represents a hydrogen atom, a C1-C6 alkyl, or a C1-C6 alkyl substituted in the terminal position by an NR group 5 R 6

[0055] R 1 , R 3 , R 4 , R 5 and R 6 are independently hydrogen or C 1 -C 6 alkyl, R is hydrogen or a carboxylic acid function, m is 1, 2, 3, 4, 5, 6, 7 or 8, and each n is independently 0, 1, 2, 3, 4 or 5.

[0056] According to certain variants, in formula (I):

[0057] R 1 , R 2 , R 3 and R 4 are independently a hydrogen atom or a C1-C6 alkyl,

[0058] R is a hydrogen atom or a carboxylic acid function, m is 1, 2, 3, 4, 5, 6, 7 or 8, and n is 0, 1, 2, 3, 4 or 5. Advantageously, m is 1 or 2, and each n is independently 0, 1, 2, 3 or 4.

[0059] Preferably, R 1 , R 3 , R 4 , R 5 and R 6 all represent a hydrogen atom

[0060] This reaction involves at least one amine function of the polyamine of formula (I) reacting with a CO2 molecule and transforming into an ammonium bicarbonate function or a carbamate function, it being understood that only the primary and secondary amine functions can transform into a carbamate function. In preferred embodiments, each of the amine functions of the polyamine of formula (I) transforms into an ammonium bicarbonate function or a carbamate function during the reaction, it being understood that only the primary and secondary amine functions can transform into a carbamate function.

[0061] Thus, unlike a polyamine not loaded with CO2, such as for example a polyamine which has not been brought into contact with gaseous CO2 or dissolved in water, a polyamine, in particular a polyamine of formula (I) as defined above, when loaded with CO2, comprises at least one ammonium bicarbonate function or one carbamate function, advantageously it comprises at least one carbamate function, and optionally at least one ammonium bicarbonate function.

[0062] In preferred embodiments, the polyamine, in particular the polyamine of formula (I) as defined above, when it is charged with CO2, comprises exclusively ammonium bicarbonate functions and / or carbamate functions, advantageously it comprises at least one carbamate function. It is understood that the CO2-charged polyamine of formula (II) can carry one or more positive charge(s) via the presence of one or more ammonium functions and / or one or more negative charges via the presence of one or more carbamate functions. Although not systematically represented, each of these charged functions is associated with a counterion so that the CO2-charged polyamines are electrically neutral. Thus, an ammonium function is in particular associated with a bicarbonate anion of formula HCCh' or with a carbamate function, for example carried by another CO2-charged polyamine molecule.Similarly, a carbamate function present on the molecule is associated with a metal cation or an ammonium function, for example carried by another CO2-charged polyamine molecule. Thus, the CO2-charged polyamine provided in step a) is typically of the following formula (II):.

[0063] [Chem 3] in which each X independently represents an NR grouping 2 , NR 2a or an ammonium group NHR 2a+ ,

[0064] Y represents an NR group 3 , NR 3a or an ammonium group NHR 3a+ ,

[0065] R 2 independently represents a hydrogen atom, a C1-C6 alkyl, or a C1-C6 alkyl substituted in the terminal position by an NR group 5 R 6

[0066] R 1 , R 3 , R 4 , R 5 and R 6 are independently hydrogen or C1-C6 alkyl, R 2aindependently represents a hydrogen atom, a C1-C6 alkyl, or a C1-C6 alkyl substituted in the terminal position by an NR group 5a R 6a or a carboxylic acid function,

[0067] R 3a , R 5a and R 6a are independently a hydrogen atom, a C1-C6 alkyl or a carboxylic acid function,

[0068] R is a hydrogen atom or a carboxylic acid function, m is 1, 2, 3, 4, 5, 6, 7 or 8, and n is 0, 1, 2, 3, 4 or 5, it being understood that Y represents an NR group 3a or an ammonium group NHR 3a+ , or at least one X represents an NR group 2a or an ammonium group NHR 2a+ .

[0069] Typically, in formula (II): each X independently represents an NR group 2 , NR 2a or an ammonium group NHR 2a+ ,

[0070] Y represents an NR group 3 , NR 3aor an ammonium group NHR 3a+ ,

[0071] R 1 , R 2 , R 3 , R 4 are independently a hydrogen atom or a C1-C6 alkyl,

[0072] R 2a and R 3a are independently a hydrogen atom, a C1-C6 alkyl or a carboxylic acid function, R is a hydrogen atom or a carboxylic acid function, m is 1, 2, 3, 4, 5, 6, 7 or 8, and each n is independently 0, 1, 2, 3, 4 or 5. provided that Y represents an NR group 3a or an ammonium group NHR 3a+ , or at least one X represents an NR group 2a or an ammonium group NHR 2a+ .

[0073] Advantageously, in formula (II): each X independently represents an NR group 2a or an ammonium group NHR 2a+ ,

[0074] Y represents an NR group 3a or an ammonium group NHR 3a+ ,

[0075] R 1 and R 4 are independently a hydrogen atom or a C1-C6 alkyl,

[0076] R 2a independently represents a hydrogen atom, a C1-C6 alkyl, or a C1-C6 alkyl substituted in the terminal position by an NR group 5a R 6a or a carboxylic acid function,

[0077] R 3a , R 5a and R 6a are independently a hydrogen atom, a C1-C6 alkyl OR a carboxylic acid function, m is 1, 2, 3, 4, 5, 6, 7 or 8, and n is 0, 1, 2, 3, 4 or 5, provided that

[0078] Y represents at least one NR group 3a in which R 3a is a carboxylic acid function, or an ammonium group NHR 3a+ , or at least one X represents an ammonium group NHR 2a+ , an NR group 2a in which R 2a is a carboxylic acid function in which R 2ais a C1-C6 alkyl substituted in the terminal position by an NR group 5a R 6a in which R 5a or R 6a is a carboxylic acid function.

[0079] Advantageously, m is 1 or 2, and each n is independently 0, 1, 2, 3 or 4.

[0080] Preferably, R 1 and R 4 are a hydrogen atom, and R 3a , R 5a and R 6a are independently a hydrogen atom or a carboxylic acid function. In particular embodiments, in formula (II):

[0081] X represents an NR group 2a or an ammonium group NHR 2a+ ,

[0082] Y represents an NR group 3a or an ammonium group NHR 3a+ ,

[0083] R 1 and R 4 are independently a hydrogen atom or a C1-C6 alkyl,

[0084] R 2a and R 3aare independently a hydrogen atom, a C1-C6 alkyl or a carboxylic acid function,

[0085] R is a hydrogen atom or a carboxylic acid function, m is 1, 2, 3, 4, 5, 6, 7 or 8, preferably 1 or 2, and n is 0, 1, 2, 3, 4 or 5, preferably 1, 2, 3 or 4, it being understood that

[0086] Y represents at least one NR group 3a in which R 3a is a carboxylic acid function, or an ammonium group NHR 3a+ , or at least one X represents an ammonium group NHR 2a+ , an NR group 2a in which R 2a is a carboxylic acid function.

[0087] In particular embodiments, in formula (II):

[0088] X represents an NR group 2a or an ammonium group NHR 2a+ ,

[0089] Y represents an NR group 3a or an ammonium group NHR 3a+ ,

[0090] R1 and R 4 are independently a hydrogen atom or a C1-C6 alkyl,

[0091] R 2a and R 3a are independently a hydrogen atom, a C1-C6 alkyl or a carboxylic acid function,

[0092] R is a hydrogen atom or a carboxylic acid function, m is 1, 2, 3, 4, 5, 6, 7 or 8, and n is 0, 1, 2, 3, 4 or 5.

[0093] It is understood that the CO2-charged polyamine of formula (II) may carry one or more positive charges via the presence of one or more ammonium functions and / or one or more negative charges via the presence of one or more carbamate functions. Although not systematically represented, each of these charged functions is associated with a counterion so that the CO2-charged polyamines are electrically neutral. Thus, an ammonium function is in particular associated with a bicarbonate anion of formula HCCh' or with a carbamate function, for example carried by another CO2-charged polyamine molecule. In the same way, a carbamate function present on the molecule is associated with a metal cation or with an ammonium function, for example carried by another CO2-charged polyamine molecule.

[0094] In some preferred embodiments, m is 1 or 2, especially 1.

[0095] When R 1 and / or R 4is a C1-C6 alkyl, preferably methyl, ethyl or propyl, especially methyl. The same applies to R 3 , R 4 and R 5 .

[0096] The polyamine of formula (I) is preferably chosen from the following polyamines: [Chem 4]

[0097] M being an alkali metal preferably chosen from lithium (Li), sodium (Na), magnesium (Mg), calcium (Ca) and potassium (K). Advantageously, the polyamine of formula (I) is preferably chosen from polyamines Pib, Pic, PI d, Pie, P2b, P2c, P2d, P2e, P2f and P2g, M being an alkali metal preferably chosen from lithium (Li), sodium (Na), magnesium (Mg), calcium (Ca) and potassium (K).

[0098] More preferably, the polyamine of formula (I) is preferably chosen from polyamines P1, P2c and P2e, M being an alkali metal preferably chosen from lithium (Li), sodium (Na), magnesium (Mg), calcium (Ca) and potassium (K), in particular M is K.

[0099] The polyamine can also be tris(2-aminoethyl)amine.

[0100] In certain preferred embodiments, the polyamine of formula (I) is a diamino acid, for example chosen from the compounds Pib, Pic, Pld and Pie represented above.

[0101] In certain particularly preferred embodiments, the CO2-charged polyamine of formula (II) corresponds to one or more of the following formulas:

[0102] [Chem 5] in which M is as defined above, n is as defined above, x is equal to 2 or 3, y is equal to x-2, it being understood that each polyamine is associated with an adequate counterion if necessary to be electrically neutral.

[0103] More preferably, the polyamine of formula (I) is a lysine (Pie compound). The lysine used is in particular derived from biological fermentation, therefore entirely biosourced. The reaction between a gas mixture comprising CO2 and lysine then leads to a lysine loaded with CO2 corresponding to one or more of the following formulas: [Chem 6] in which A is an NH2 or NILC group, M is an alkali metal preferably chosen from lithium (Li), sodium (Na), magnesium (Mg), calcium (Ca) and potassium (K), it being understood that each polyamine is associated with an adequate counterion if necessary to be electrically neutral.

[0104] The different forms of the CO2-charged polyamine of formula (II) are generally found as a mixture in the reaction medium resulting from step a) and can exchange with each other (the CO2-charged polyamines of formula (II) can pass from one form to another). For example, when the polyamine of formula (I) is lysine, the reaction medium resulting from step a) comprises as a mixture the different forms L1 to L4 as described above.

[0105] The CO2-loaded polyamine useful in the context of the process of the invention can be obtained by reaction between a gaseous mixture comprising CO2 and a polyamine of formula (I) according to the following steps: i) dissolution of a polyamine of formula (I) in an appropriate solvent leading to the production of a solution of polyamine of formula (I), ii) bubbling of a gaseous mixture comprising CO2 into the solution of polyamine of formula (I), iii) recovery of the corresponding CO2-loaded polyamine.

[0106] Advantageously, the CO2 load rate, noted aN, varies from 10 to 70%, in particular from 20 to 65%.

[0107] The CO2 loading rate, denoted aN, is a dimensionless number, typically measured by NMR spectroscopy 13 C quantitative (NMR 13Cq), where appropriate supplemented by 2D HMBC or HSQC NMR spectra analyses to assign the different peaks unambiguously. The loading rate is calculated according to the following equation: aN =ncO2 / (nAmine*NNHx) in which nco2 represents the quantity of material in moles of CO2 in the loaded amine (i.e. in the form of ammonium bicarbonate function or carbamate function); represents the quantity of material in moles of amine functions, whatever their form (free amine function, carbamate or ammonium bicarbonate) and NNHX is the number of NH units x .of the polyamine considered. nco2 and nAmine are typically measured by NMR spectroscopy 13 C quantitative (NMR 13 Cq), where appropriate supplemented by 2D HMBC or HSQC NMR spectra analyses to assign the different peaks unambiguously. In the NMR spectra 13 C quantitative (NMR 13Cq), the peaks of interest for nAmine measurement are generally between 30 and 60 ppm.

[0108] NNHX is linked to the structure of the starting amine; for example, for lysine, NNHX is equal to 2.

[0109] Step iii) includes for example the precipitation of the CO2-loaded polyamine, its filtration and its possible washing. Alternatively, the CO2-loaded polyamine can be recovered in the form of a solution of said polyamine in the solvent of step i).

[0110] The gas mixture comprising CO2 may consist of CO2.

[0111] The CO2-charged polyamine can be in the form of a powder or a solution.

[0112] Polyelectrophilic monomer

[0113] The electrophilic monomer contains at least one (meth)acrylate function, i.e. at least one function and / or a function representing the covalent bond linking the function to the rest of the molecule.

[0114] The electrophilic monomer is preferably a polymer obtained by polymerization of a polyol with a (meth)acrylate.

[0115] As used herein, a polyol means a hydrocarbon chain comprising at least two hydroxyl -OH functions. The polyol may in particular be selected from the group consisting of ethylene glycol, polyethylene glycol, glycerol, ethoxylated glycerol, poly(ethoxylated glycerol), isopropoxylated glycerol, pentaerythritol, trimethylolpropane (also called 2-Ethyl-2-(hydroxymethyl)-1,3-propanediol), 4-Hydroxy-3-methoxybenzyl alcohol, and mixtures thereof.

[0116] The polyelectrophilic monomer is for example chosen from ethylene glycol diacrylate, poly(ethylene glycol) diacrylate having a number-average molar mass Mn ranging from 250 to 6000 g / mol, poly(ethylene glycol) dimethacrylate having a number-average molar mass Mn ranging from 250 to 6000 g / mol, ethylene glycol dimethacrylate, ethoxylated glycerol triacrylate, poly(ethoxylated glycerol triacrylate), ethoxylated glycerol trimethacrylate, poly(ethoxylated glycerol trimethacrylate), poly(propoxylated glycerol triacrylate), poly(propoxylated glycerol trimethacrylate), isopropoxylated glycerol triacrylate, isopropoxylated glycerol trimethacrylate, pentaerythritol tetraacrylate, pentaerythritol tetramethacrylate, trimethylolpropane triacrylate, trimethylolpropane trimethacrylate, trimethylolpropane, vanillin diacrylate and vanillin dimethacrylate.

[0117] The polyelectrophilic monomer is preferably bio-sourced. For example, glycerol is obtained from triglycerides, animal fats, or vegetable oils. Ethylene glycol can be produced by pyrolysis and subsequent hydrogenation of sugars. Acrylic acid can be obtained from glycerol, malonyl-CoA, or p-alanine.

[0118] The reaction between the CO2-charged polyamine (polynucleophilic species) and the polyelectrophilic monomer leads to the formation of a crosslinked copolymer. This reaction is a copolymerization.

[0119] Advantageously, the reaction between the CO2-charged polyamine and the polyelectrophilic monomer is carried out in water.

[0120] The reaction is preferably carried out at a temperature below 70°C, for example from 25°C to 40°C.

[0121] Preferably, the polyamine is a polynucleophilic species and the monomer with which it reacts during step b) is a polyelectrophilic monomer.

[0122] In a particular embodiment, the CO2-charged polyamine is a CO2-charged lysine and the polyelectrophilic monomer is ethylene glycol diacrylate. Advantageously, at least a portion of the ammonium bicarbonate and carbamate functions of the CO2-charged polyamine, during step b) of the process according to the invention, are converted into gaseous CO2 and into free amine by contact with the polyelectrophilic monomer. The gradual release of gaseous CO2 allows the continuous diffusion of the pore-forming agent, here gaseous CO2. The release of the amine (free amine functions), linked to the gradual release of gaseous CO2, allows controlled polymerization leading to the production of an alternating crosslinked copolymer.

[0123] However, the ammonium carbamate functions of the CO2-charged polyamine, more thermally stable than the bicarbonate functions, can remain present on the crosslinked copolymer, giving it new physical properties in terms of adhesiveness, hydrophilicity and polarity.

[0124] The process according to the invention makes it possible to manufacture crosslinked copolymers, in particular porous materials made of such crosslinked polymers, without catalysts and without injection of gas or exogenous pore-forming agents during the polymerization process.

[0125] The copolymer obtained, due to its crosslinked appearance, has a homogeneous three-dimensional porous structure with open pores.

[0126] Porous materials

[0127] The invention relates to a porous material consisting of a crosslinked copolymer capable of being obtained or obtained according to the process of the invention.

[0128] Due to the choice of its components, the porous material of the invention is biocompatible and / or biosourced.

[0129] The porous material of the invention typically has:

[0130] - an adhesion force on a surface ranging from 0.5 N to 10 N according to the traction adhesion measurement method. The measurement is carried out with a MARS 60 rheometer, with a Peltier furnace and parallel plane geometries of 8 mm diameter. A displacement speed of 6 mm / min and temperatures between 250C and 40°C are used;

[0131] - an HLB value ranging from 10 to 18 according to the Davies and Griffin method;

[0132] - an apparent density (pa) ranging from 400 to 900 kg / m 3, typically calculated from the equation below where mi is the initial mass of the crosslinked copolymer, r is its radius and h is its height (when the copolymer is in a cylindrical shape). The dimensions of the copolymer are typically measured using a digital caliper,

[0133] [Math 1]

[0134] - a volume swelling index (Q) ranging from 50% to 600%. The volume swelling index is typically measured by cutting the crosslinked copolymer into three pieces at its core. The dimensions of these pieces are typically measured using a digital caliper, then the pieces are placed in enough CH2Q2 to be completely submerged. The medium is then stirred for 24 hours. The swelling index is calculated from the equation below, where Vf is the volume of the copolymer after 24 hours in CH2Q2 and Vi is the initial volume of the crosslinked copolymer;

[0135] [Math 2]

[0136] - an average pore diameter ranging from 50 pm to 1 mm. The average pore diameter is typically determined by X-ray tomography on a GE Phoenix v|tome|xs tomography device with a Varian Paxscan detector. The acquisition is performed with a polychromatic source operating at 280 keV and with a voxel size of 10 pm 3 . Image processing is carried out using Fiji software; and / or

[0137] - a mass degradation temperature at 10% mass (Tdio%) ranging from 150°C to 400°C. The mass degradation temperature at 10% mass is typically measured by thermogravimetric analysis (TGA) on a Mettler Toledo 2 TGA apparatus, with a heating ramp of 10°C / min, from 25°C to 600°C under nitrogen flow. The material of the invention can be depolymerized and is therefore useful as a recyclable material.

[0138] Use of porous materials

[0139] The porous material of the invention, i.e. the crosslinked copolymer capable of being obtained or obtained according to the method of the invention, is in the form of a foam. It is in particular a biocompatible adhesive foam. Biocompatible adhesive foams are particularly useful for reconstructive surgery, for example post-ablation and / or pre-implant reconstructive surgery.

[0140] The porous material of the invention can also be used for the manufacture of orthoses, prostheses and medical devices. In particular, the porous material of the invention can be used for the manufacture of tissue adhesives, pressure-sensitive adhesives (PSAs) for example integrated into transdermal patches (TDD S) or patches.

[0141] The porous material of the invention can also be used as pharmaceutical and cosmetic excipients.

[0142] The porous material of the invention can further be used in fields other than the medical field, for example it can be useful for preparing food packaging, tissue glues and glues for multi-layer materials.

[0143] The invention also relates to any article comprising a porous material according to the invention, in particular chosen from a porous hydrogel, a colloidal polymer, a multi-layer food packaging and a transdermal patch.

[0144] FIGURES

[0145] The invention will be described below with reference to the appended figures, given solely as non-limiting examples. Figures 1 to 3 illustrate certain aspects of the invention. Figures 4 to 6 show a porous material in accordance with the invention.

[0146] [Fig. 1 A] schematically represents the four steps of the synthesis of a CO2-loaded lysine powder, namely the dissolution of the lysine leading to obtaining a lysine solution, the bubbling of CO2 into said lysine solution, the precipitation of the CO2-loaded lysine and the filtration of the CO2-loaded lysine. [Fig. lB] schematically represents the two steps of the synthesis of a CO2-loaded lysine solution, namely the dissolution of the lysine leading to obtaining a lysine solution and the bubbling of CO2 into said lysine solution, leading to the CO2-loaded lysine solution.

[0147] [Fig. 2] schematically represents the polymerization between a polyamine charged with CO2, here lysine charged with CO2, which is a dinucleophilic species, and ethylene glycol diacrylate, which is a dielectrophile monomer, leading to the production of an alternating copolymer forming a porous material according to the invention.

[0148] [Fig. 3] is a photograph showing the porogenic effect of CO2 during the formation of the alternating copolymer, i.e. the porous material according to the invention during the polymerization between carbonated lysine and ethylene glycol diacrylate.

[0149] [Fig. 4] is a photograph showing a macroscopic view of the porous material according to the invention obtained from CO2-charged lysine and ethylene glycol diacrylate.

[0150] [Fig. 5] is a photograph showing a microscopic view (1 mm) of the porous material according to the invention obtained from lysine loaded with CO2 and ethylene glycol diacrylate. [Fig. 6] is a photograph showing the compression test applied to the MB iys_co2 copolymer of example 2 (porous material according to the invention obtained from lysine loaded with CO2 and ethylene glycol diacrylate)

[0151] [Fig. 7] represents the cyclic compression / decompression curves at 50% applied to the MB i copolymer ys _co2 from example 2. On the abscissa: deformation (in %). On the ordinate: stress (in kPa).

[0152] [Fig. 8] represents X-ray microtomography images: MA_i ys _o in 2D (A) and in 3D-inverted (B), MA i ys _co2 in 2D (C) and in 3D-inverted (D).

[0153] METHODS

[0154] The maximum stress (o m ax) and the maximum strain (smax) at break

[0155] The maximum stress (o m ax) and the maximum deformation (s m ax) at break are obtained at the break of the material as a result of irreversible compression. They reflect the behavior of the material beyond its elastic range.

[0156] In general, very rigid materials are also very brittle (e.g. glass), they will have very high Young's moduli (in the order of hundreds of GPa) but low maximum stress / maximum strain values. Elastomeric materials (e.g. rubbers) will have a lower Young's modulus (in the order of MPa), with higher maximum stress / maximum strain values, sometimes with deformations of 80% without rupture.

[0157] The measurements are carried out by uniaxial compression of the materials. The samples tested are in the form of cylinders with a diameter of 9-10 mm and a height of 5 mm. The compression is measured using a MARS 60 type Rheometer with a compression cell capable of withstanding up to 50N of resistance. The cell measures force values, in N, related to a compression expressed in mm (corresponding to the compressed length). The stress applied to the material corresponds to the force F exerted (in N) per unit area S of cylindrical samples (in mm 2 ), according to equation (1):

[0158] F

[0159] ° s (1) '

[0160] Gmax is the maximum stress value that the material can withstand before breaking. The strain is expressed in %. It is calculated from the metric data measured by the rheometer (in mm), according to equation (2).

[0161] > 1-10 with £ (2)

[0162] 10 in which

[0163] 1 represents the distance, in mm, of compression at a time t, and lo represents the distance, in mm, at to (ze the height of the cylindrical sample).

[0164] Smax is the maximum strain value that the material can withstand before breaking.

[0165] Measurement of Young's modulus (E)

[0166] Young's modulus represents the stiffness of the material with respect to small deformations, it is expressed in units of pressure. It is measured in the elastic domain of the material when it undergoes the first stresses applied to the material, typically between 5% and 10% of deformation when it presents a linear profile of Stress (kPa) curve as a function of the deformation (%). Young's modulus is calculated as the ratio between the stress o_ and the deformation s, according to equation (3):

[0167] TT

[0168] E - - (3)

[0169] E where stress G and strain s are measured as described above, with strain between 5% and 10%.

[0170] Tack test of adhesion

[0171] The sample consists of a strip 1 mm high, 1 cm wide and 3 cm long. The test includes 3 phases:

[0172] 1) driving a punch to a distance of 0.2 mm to ensure full contact and maximum adhesion between the punch and the sample,

[0173] 2) return to punch balance, and

[0174] 3) raising the punch from this equilibrium position at constant speed.

[0175] The measured force is then a function of the force holding the punch on the sample, therefore the adhesion force. Two parameters can reflect this adhesion, the maximum detachment stress (in kPa), or the necessary detachment energy (in Jm 2 ).

[0176] Compression / decompression stress test at x% deformation

[0177] Stress tests are used to assess the robustness of the material following repeated stress. It consists of cycles, generally 5, of compression / decompression over a significant deformation (usually 50%). The protocol is the same as that of a compression test.

[0178] EXAMPLES

[0179] The following examples are given for illustrative purposes only and should not be construed as limiting the invention in any way.

[0180] EXAMPLE 1: Synthesis of a crosslinked copolymer according to the invention

[0181] First step: synthesis of a lysine powder loaded with CO2

[0182] This synthesis is inspired by the synthesis described by J. Bru, (Bru, Jean. L-Lysine Carbamate. DE2951132A1, July 10, 1980)) and is based on the carbamatation (I) and / or carbonation (II) reactions of lysine below.

[0183] The synthesis of CO2-loaded lysine powder comprises the following steps: dissolution of lysine in an aqueous KOH solution leading to obtaining a K-Lysine solution (lysine potassium salt) and the addition of methanol leading to the precipitation of the KC1 formed which is removed by filtration (1), bubbling of CO2 into said K-Lysine solution, precipitation of the CO2-loaded lysine and filtration of the CO2-loaded lysine (2) according to the reaction scheme below and Figure 1 A:

[0184] [Chem 7]

[0185] [Chem 8] in which X is a carbamate function, a bicarbonate ion (HCO3) or a carboxylate ion, Y is a primary, secondary or tertiary ammonium or possibly a metal ion (Li + , N / A + , K + , Mg 2+ , That 2+ ).

[0186] Synthesis of CO2-charged lysine in solid form

[0187] 10g of lysine. HCl (lysine hydrochloride) was solubilized in 10 mL of H2O and 6.17 g of KOH. Then, 50 mL of methanol was added to the previously obtained lysine solution, resulting in the precipitation of the formed KC1 which was removed by filtration. Then, CO2 was bubbled into the solution using a strainer at a flow rate of 0.100 m 3 / min. After 10 min, a precipitate formed and bubbling was maintained for at least 1 h. The precipitate was then filtered and washed with a few milliliters of cold methanol, and the solid was then dried under vacuum to evaporate the residual methanol.

[0188] A fine beige powder was obtained. The analysis of this fine powder was carried out by NMR spectroscopy 13 Cq; this analysis confirmed the presence of CO2 in the medium in the form of hydrogen carbonate or ammonium carbamate for an OCN loading rate = 0.6.

[0189] The CO2-charged lysine powder obtained according to the reaction presented above comprises, preferably consists of, a mixture of lysine having ammonium carbamate functions and ammonium bicarbonate functions.

[0190] Synthesis of CO2-charged lysine in solution

[0191] Alternatively, the synthesis of the CO2-loaded lysine solution comprises two steps, namely the dissolution of lysine leading to the production of a lysine solution and the bubbling of CO2 into said lysine solution, as illustrated in Figure 1B.

[0192] 10g of lysine. HCl were solubilized in 10 mL of H2O and 6.17 g of KOH. The resulting solution was poured dropwise into 4 volumes of cold absolute ethanol, resulting in the precipitation of the KC1 formed, which was then removed by filtration. Then, CO2 was bubbled into the solution using a strainer at a flow rate of 0.100 m 3 / min. The reaction is monitored by pH measurement. When the pH is stable, bubbling is stopped and the lysine solution loaded with CO2 is obtained.

[0193] The analysis of this solution was carried out by NMR spectroscopy 13 C; this analysis confirmed the presence of CO2 in the medium in the form of hydrogen carbonate or ammonium carbamate for an OCN loading rate = 0.6.

[0194] The CO2-charged lysine solution obtained according to the reaction presented above comprises a mixture of CO2-charged lysines randomly presenting ammonium carbamate functions and / or ammonium bicarbonate functions.

[0195] Second step: Production of the porous material

[0196] The manufacture of porous materials is based on the polymerization reaction of glycol diacrylate with lysine (Lys) loaded with CO2 according to the reaction scheme below.

[0197] [Chem 9]

[0198] Lysine solutions with a concentration defined between [0.5-2] mol / L as well as lysine solutions with a loading rate defined between OCN = 0 and OCN = 0.8 and a concentration between [1-5] mol / L were prepared.

[0199] An example of a formulation comprises an amount of K-Lysine of concentration 2 mol / L, equal to 2.2 mmol (1.1 mL), 2.2 mmol (0.4 mL) of K-Lysine loaded with CO2 of concentration 5 mol / L comprising an initial loading rate at OCN = 0.4 as well as 5 g of poly(ethylene glycol) diacryalte (575 g / mol).

[0200] The resulting formulation was then vortexed for 10 seconds and a polyelectrophilic / polyamine emulsion was produced. The emulsion was heated to 37°C in an oven without stirring. Gelation of the medium could be observed within 10 min, and then a porous hydrogel / foam was produced and crosslinked within 3 to 4 hours.

[0201] EXAMPLE 2: Synthesis of crosslinked copolymers according to the invention obtained with various polyamines

[0202] The polyamines used in this example are: 1) K-Lysine (lysine potassium salt), 2) Spermidine, 3) Cadaverine, 4) tris(2-aminoethyl)amine (TREN). The electrophilic monomer used in this example is poly(ethylene glycol) dimethacrylate with a number-average molar mass Mn equal to 575 g / mol (PEGDA575).

[0203] First step: synthesis of a polyamine solution loaded with CO2

[0204] Following the protocol of the first step of example 1 (to obtain a lysine solution loaded with CO2), the CO2 loading is carried out by injecting a flow rate of 0.lmL / s of gaseous CO2 into a 2M solution of totally deprotonated polyamine, initially at a pH of 12. The final saturated solution is buffered to a pH of approximately 8.5. Analyses by NMR spectroscopy 13 C showed that at pH 8.50, polyamines exhibit the CO2 loading rates aN indicated in Table 1.

[0205] Table 1:

[0206] Second step: Production of the porous material

[0207] The protocol of the second step of Example 1 was followed, with the following modifications: Series A: the reaction medium was heated to 40°C for 3 hours.

[0208] Series B: the reaction medium was heated at 50°C for 6 hours.

[0209] Table 2 below summarizes the tests performed.

[0210] Table 2: (Temp. = Temperature) Characterization of the crosslinked copolymers obtained

[0211] For each copolymer obtained, the Young's modulus, the maximum stress o were measured ma x and the maximum deformation s m ax (see table 3).

[0212] The Young's Modulus E (expressed in kPa) is used to assess the stiffness of the copolymer at low deformations. The maximum strain at break (expressed in %) and the maximum stress at break (expressed in kPa) are measured for large deformations and quantify the elasticity of the material by defining the limit between the elastic domain (reversible deformation) and the plastic domain (irreversible deformation).

[0213] Table 3: (normalized values)

[0214] *: absence of material breakage

[0215] It is observed that the structure of polyamines plays an important role in the mechanical properties of the materials studied.

[0216] Indeed, for many NH patterns X equivalent, the crosslinked copolymers MA i ys_co2 (Lysine) and MA_ead_co2 (cadaverine) have drastically different mechanical properties. The presence of the carboxylate group in alpha of K-Lysine thus affects the reactivity of the latter, and the crosslinking of the system.

[0217] This results in a significant impact on mechanical properties. For example, TREN, which is an amine with a number of NEL units of 3 and allows the establishment of 6 bonds via Aza-Michael type reactions (reactions involved in polymerization), has the highest stiffness here (3.6 MPa).

[0218] In the case of lysine, analysis of the solid-state NMR spectra showed that free acrylate functions were still present. Therefore, crosslinking is not complete, which may explain the significantly lower values ​​obtained for the MA i copolymer. ys_co2. It is also likely that the average distance between crosslinking sites has an impact on stiffness.

[0219] Overall, the stiffer the crosslinked copolymers, the earlier their stress failure. Crosslinked copolymers incorporating an amine other than lysine withstand a higher maximum stress and a lower maximum strain.

[0220] Additional characterization of the MB I copolymer VS co2

[0221] MB i copolymer ys _co2 has particularly strong adhesive properties. Adhesion measurements in the tack-free test revealed an adhesion energy of 3.4±0.95 Jm 2 and a peeling stress of 12.9±3.7 kPa.

[0222] It is further noted that the Young's modulus of the MB i copolymer ys_co2 is relatively low, allowing maximum deformation at very high stress (75% compression) without rupture (see Figure 6).

[0223] MB i copolymer ys _co2 was thus subjected to stress tests with a maximum deformation of 50% over 5 cycles (see Figure 7). It can be seen that even after 5 compression / decompression cycles at 50%, the cycles overlap. This reflects the robustness of the copolymer, which retains the same energy after a compression / decompression cycle. Thus, the material deforms reversibly, without altering its internal structure.

[0224] In conclusion, the crosslinked copolymers of the invention have a behavior typical of flexible materials, with relatively low Young's moduli (of the order of kPa), and with relatively reliable maximum stress / maximum strain values ​​as well.

[0225] One hypothesis is that CO2 capture generates positive and negative charges on the polymer, a higher charge rate and therefore a higher charge density that can generate adhesiveness through electrostatic interactions (for a correlation between charge density and adhesiveness, see: Derjaguin, BV, Aleinikova, IN & Toporov, YP “On the role of electrostatic forces in the adhesion of polymer particles to solid surfaces.” Prog. Surf. Sci. 1994, 45 f , 119-123. https: / / doi.org / 10.1016 / 0079-6816(94)90042-6).

[0226] EXAMPLE 3: Synthesis of comparative crosslinked copolymers obtained with various polyamines

[0227] Preparation of crosslinked copolymers

[0228] The polyamines used in this example are: 1) K-Lysine (lysine potassium salt), 2) Spermidine, 3) tris(2-aminoethyl)amine (TR), at 2M.

[0229] The electrophilic monomer used in this example is poly(ethylene glycol) dimethacrylate with a number-average molar mass Mn equal to 575 g / mol (PEGDA575). For this comparative example, materials derived from polyamines either not charged with CO2, or for which the CO2 was substituted by another acid (HCO2H) were prepared similarly to Example 2. More precisely, for the series ending with "0" (no acid), the polyamines were not charged with CO2, and were polymerized directly with PEGDA575. For the example prepared with formic acid, the polyamine was also not charged with CO2: the formic acid salt was formed prior to the crosslinking reaction.

[0230] The different reaction conditions are summarized in Table 4 below.

[0231] Table 4, nt: not tested; ns: not stable (liquid)

[0232] Characterization of the crosslinked copolymers obtained

[0233] For each copolymer obtained, the Young's modulus (Table 5), the maximum stress (Table 6) and the maximum strain (Table 7) were measured. The results are compared with the values ​​obtained for the corresponding crosslinked copolymers of Example 2 to facilitate comparison.

[0234] Table 5: Young's modulus (E) expressed in kPa (normalized values) nm not measured

[0235] Table 6: Maximum stress o ma x expressed in kPa (standardized values)

[0236] Table 7: Maximum deformation (s ma x) expressed in % (normalized values)

[0237] Crosslinked copolymers MA_i ys _o and MA_i ys_F exhibit fracture properties typical of flexible materials: they are very low in rigidity, so the measured Young's modulus values ​​are much lower than those obtained for the MA iy copolymer S _co2. Their structure, close to liquid, does not allow them to break, hence the absence of data on their maximum deformation (MA_i ys _o and MB_i ys _o) or significant but unreliable maximum deformations (MAJJ-S).

[0238] Except in the case of lysine, the use of a polyamine loaded with CO2 leads to a loss of rigidity (hence lower Young's moduli) of the copolymers, which is beneficial in the context of biomedical applications in which materials that are too rigid (and therefore not or very little degradable) would not be suitable.

[0239] In the case of lysine, this allows for optimal rigidity to be achieved, allowing deformation more suitable for biomedical applications. Furthermore, the use of a CO2-loaded polyamine has a beneficial effect improving both the maximum stress and the maximum strain at break. An interpretative hypothesis would be that the release of CO2 during crosslinking allows the appearance of pores, and that the porosity thus formed provides flexibility resulting in superior resistance to mechanical stresses, and in particular compression.

[0240] Finally, an analysis in X-ray micro-computed tomography (u-CT) allowed to compare MA_i ys _o (figure 8). The MA_i control material ys_o has a structure made up of areas of very dense material (white area) connected by areas of less dense material. We note the very sparse presence of cavities. The measured density is 0.98 with very few pores. For MA i ys _co2, the material has a much more porous internal structure than MA i ys _o. A density measurement could be carried out on a set of 300 layers using microtomography. For the MA i material ys _co2, a density of 0.87 was measured. The inverted 3D images of the porous structures of each material show a clear difference in internal structure.

Claims

CLAIMS 1. Process for manufacturing a crosslinked copolymer comprising the following steps: a) Supply - a polyelectrophilic monomer comprising at least one (meth)acrylate function, and - a polyamine loaded with CO2 obtained by reaction between a gaseous mixture comprising CO2 and a polyamine of formula (I): in which R 2 independently represents a hydrogen atom, a C1-C6 alkyl, or a C1-C6 alkyl substituted in the terminal position by an NR group 5 R 6 R 1 , R 3 , R 4 , R 5 and R 6 are independently a hydrogen atom or a C1-C6 alkyl, R is a hydrogen atom or a carboxylic acid function, m is 1, 2, 3, 4, 5, 6, 7 or 8, and each n is independently 0, 1, 2, 3, 4 or 5, this reaction involving at least one amine function of the polyamine of formula (I) reacting with a CO2 molecule and transforming into an ammonium bicarbonate function or a carbamate function, it being understood that only the primary and secondary amine functions can transform into a carbamate function, b) Reaction between the CO2-charged polyamine and the polyelectrophilic monomer provided in step a), preferably at a temperature below 70°C, preferably in an aqueous medium, leading to the formation of the crosslinked copolymer.

2. A method of manufacturing a crosslinked copolymer according to claim 1, wherein the electrophilic monomer is a polymer obtained by polymerization of a polyol with a (meth)acrylate, the polyol preferably being selected from the group consisting of ethylene glycol, polyethylene glycol, glycerol, ethoxylated glycerol, poly(ethoxylated glycerol), isopropoxylated glycerol, pentaerythritol, trimethylolpropane (also called 2-Ethyl-2-(hydroxymethyl)-1,3-propanediol), 4-Hydroxy-3- methoxybenzyl, and mixtures thereof.

3. A method of manufacturing a crosslinked copolymer according to claim 1 or 2, wherein the polyelectrophilic monomer is ethylene glycol diacrylate, poly(ethylene glycol) diacrylate having a number-average molar mass Mn ranging from 250 to 6000 g / mol, poly(ethylene glycol) dimethacrylate having a number-average molar mass Mn ranging from 250 to 6000 g / mol, ethylene glycol dimethacrylate, ethoxylated glycerol triacrylate, poly(ethoxylated glycerol triacrylate), ethoxylated glycerol trimethacrylate, poly(ethoxylated glycerol trimethacrylate), propoxylated poly(glycerol triacrylate), poly(propoxylated glycerol trimethacrylate), isopropoxylated glycerol triacrylate, isopropoxylated glycerol trimethacrylate, pentaerythritol tetraacrylate, tetramethacrylate pentaerythritol, trimethylolpropane triacrylate, trimethylolpropane trimethacrylate, vanillin diacrylate or vanillin dimethacrylate.

4. Process for manufacturing a crosslinked copolymer according to any one of claims 1 to 3, in which the polyamine loaded with CO2 is of formula (II): in which X represents an NR group 2a or an ammonium group NHR 2a+ , Y represents an NR group 3a or an ammonium group NHR 3a+ , R 2a independently represents a hydrogen atom, a C1-C6 alkyl, or a C1-C6 alkyl substituted in the terminal position by an NR group 5a R 6a , R 1 and R 4 are independently a hydrogen atom or a C1-C6 alkyl, R 3a , R 5a and R 6a are independently a hydrogen atom, a C1-C6 alkyl or a carboxylic acid function, R is a hydrogen atom or a carboxylic acid function, m is 1, 2, 3, 4, 5, 6, 7 or 8, and each n is independently 0, 1, 2, 3, 4 or 5.

5. Process for manufacturing a crosslinked copolymer according to any one of the Claims 1 to 4, wherein the polyamine of formula (I) is selected from the following polyamines: M being an alkali metal preferably chosen from lithium (Li), sodium (Na), magnesium (Mg), calcium (Ca) and potassium (K).

6. Process for manufacturing a crosslinked copolymer according to any one of claims 1 to 5, in which the CO2-charged polyamine of formula (II) corresponds to one or more of the following formulas: in which n is as defined in claim 1, M is an alkali metal preferably chosen from lithium (Li), sodium (Na), magnesium (Mg), calcium (Ca) and potassium (K), x is equal to 2 or 3, y is equal to x-2.

7. A method of manufacturing a crosslinked copolymer according to claim 6 in which the CO2-charged polyamine is a CO2-charged lysine corresponding to one or more of the following formulas: in which A is an NH2 or NH3 group, M is an alkali metal preferably chosen from lithium (Li), sodium (Na) and potassium (K).

8. Porous material comprising a crosslinked copolymer having a homogeneous three-dimensional porous structure with open pores capable of being obtained or obtained by the process according to any one of claims 1 to 7.

9. Porous material according to claim 8, characterized in that it has an average pore diameter ranging from 50 μm to 1 mm, determined by X-ray tomography.

10. Porous material according to claim 8 or 9, characterized in that it has an apparent density (pa) ranging from 400 to 900 kg / m 3 , calculated from the following equation [Math 1] where mi is the initial mass of the crosslinked copolymer, r is its radius and h is its height when the copolymer is in a cylindrical shape, the dimensions of the copolymer being measured using a digital caliper.

11. Use of a porous material according to any one of claims 8 to 10, as tissue adhesive, pressure-sensitive adhesives (PSA) for example integrated into transdermal patches (TDDS) or patches, as pharmaceutical and cosmetic excipients or glues for multi-layer materials.

12. An article comprising a porous material as defined in any one of claims 8 to 10.

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