Photopolymerizable composition for biological fabric adhesives

Description

FIELD OF INVENTION

[0001] The invention relates to a polymerizable composition intended for use as an adhesive for biological tissues, particularly for non-mineralized biological tissues. The composition of the invention allows, after polymerization, the adhesion of biological tissues to each other, the adhesion of a material, glue, or substance to a biological tissue, the formation of a surgical sealant, or the formation of a skin dressing. STATE OF THE ART

[0002] The adhesives used in conventional dressings, especially skin dressings, are sensitive to moisture, which can cause them to detach. This moisture can come from wound exudate, perspiration, or daily activities.

[0003] Medical adhesives are also useful for replacing or facilitating sutures and for replacing dressings. Medical adhesives are most often applied directly to the tissue, without any surface preparation. Currently available medical adhesives sometimes have insufficient adhesive properties and / or poor long-term stability.

[0004] Furthermore, medical adhesives can be used in a number of surgical techniques. However, the effectiveness of currently available surgical glues is controversial.

[0005] Therefore, there is a need to improve the properties of medical adhesives.

[0006] Medical adhesives can be in the form of polymerizable compositions. Polymerization can occur, for example, through the action of moisture on the tissues to which the composition is applied, or through external chemical or physical initiation, such as under the effect of UV or visible radiation.

[0007] To improve the properties of medical adhesives, compositions containing a light-curing monomer and having low viscosities have been proposed (WO2016 / 185153). These compositions penetrate tissues more easily, resulting in higher-quality bonding thanks to the adhesive anchoring in the tissue after polymerization. In certain indications, these bonds may require the addition of a supplementary adhesive to enhance their properties. Furthermore, these compositions are not readily usable by the general public.

[0008] The present invention aims to provide a new type of medical adhesive to solve these various problems. The compositions according to the invention comprise a polymerizable acrylate monomer, a light-curing resin, and a photoinitiator.

[0009] The compositions according to the invention make it possible to obtain suitable adhesion, both for surgical applications and for general public skin adhesion.

[0010] The concentrations of the constituents of the composition of the invention allow for rapid initiation and polymerization in a few tens of seconds, without causing tissue burns thanks to controlled exothermy.

[0011] Furthermore, the combined presence of a photopolymerizable resin, with the photoinitiator and the polymerizable monomers used, gives the resulting bond flexibility and conformability properties suitable for soft biological tissues, good stability over time under the action of physiological fluids (e.g. blood, exudates, perspiration), prevents the accumulation of perspiration or exudates and provides good water resistance. SUMMARY

[0012] The present invention therefore relates to a polymerizable composition, intended for use as an adhesive for non-mineralized biological tissues, comprising: from 5% to 60% by mass, relative to the total mass of the composition, of a polymerizable monomer comprising an acrylate, methacrylate, acrylamide or methacrylamide function and not comprising a phosphate or phosphonate function; from 0.1% to 5% by mass of a photoinitiator; and a photopolymerizable resin; said composition not comprising a monomer comprising a phosphate or phosphonate function on the one hand and an acrylate, methacrylate, acrylamide or methacrylamide function on the other hand.

[0013] According to one embodiment, the polymerizable monomer is selected from: acrylic acid (AA), tert-butyl acrylate (tBuA), 2-hydroxyethyl methacrylate (HEMA), methacrylic acid (MA), lauryl acrylate (LA), lauryl methacrylate (LMA), 2-ethoxyethyl methacrylate (2EEMA), di(ethylene glycol) ethyl ether acrylate (DEGEA), 2-phenyloxyethyl acrylate (2PEA), 2-ethylhexyl methacrylate (2EHMA), n-butyl acrylate (nBuA), isobornyl acrylate (IBOA), isobornyl methacrylate (IBOMA), cyclic trimethylolpropane formal acrylate (CTFA), 3,3,5-trimethyl cyclohexanol methacrylate, tert-butyl methacrylate (tBuMA), methyl acrylate (MeA), methyl methacrylate (MMA), acrylate 2-ethylhexyl (2EHA), 2-(dimethylamino)ethyl acrylate (DAEA), 3-sulfopropyl acrylate potassium salt (SAPS), 3,3-dimethylacrylic acid (DAA), crotonic acid (CA), triethylene glycol methyl ether methacrylate (TEGMEMA), 2-phenyloxyethyl methacrylate (2PEMA),2-Hydroxyethyl acrylate (HEA), 3-(trimethoxysilyl)propyl methacrylate, ethyl acrylate (EtA), cyclohexyl methacrylate, 3-Hydroxypropyl acrylate, alpha-bromoethyl acrylate, alpha-chloroethyl acrylate, chloromethyl methacrylate, 2-Bromoethyl methacrylate, 2-Naphthyl methacrylate, paratolyl acrylate, parachlorophenyl methacrylate, metabromophenyl acrylate, 2,4,6-Tribromophenyl acrylate, parachlorobenzyl methacrylate, metamethoxybenzyl methacrylate, paraethylbenzyl acrylate, 1,6-Hexanediol dimethacrylate, neopentylglycol diacrylate, thiodiethylene glycol dimethacrylate, bisphenol A ethoxyl diacrylate, bisphenol A ethoxyl dimethacrylate, triacrylate pentaerythritol, glyceryl triacrylate, dipentaerythritol pentaacrylate, trimethylolpropane triacrylate, tris(2-hydroxyethyl) isocyanurate trimethacrylate, polyoxyethylene trimethylolpropane triacrylate, urethane acrylate,Urethane methacrylate, bis(4-methacryloylthiophenyl) sulfide, ethylene glycol acrylate, polyethylene glycol acrylate, ethylene glycol methacrylate, polyethylene glycol methacrylate, ethylene glycol diacrylate, polyethylene glycol diacrylate, ethylene glycol dimethacrylate, polyethylene glycol dimethacrylate, and mixtures thereof.

[0014] According to one embodiment, the polymerizable monomer is selected from: acrylic acid (AA), tert-butyl acrylate (tBuA), 2-hydroxyethyl methacrylate (HEMA), methacrylic acid (MA), lauryl acrylate (LA), lauryl methacrylate (LMA), 2-ethoxyethyl methacrylate (2EEMA), di(ethylene glycol) ethyl ether acrylate (DEGEA), 2-phenyloxyethyl acrylate (2PEA), 2-ethylhexyl methacrylate (2EHMA), n-butyl acrylate (nBuA), isobornyl acrylate (IBOA), isobornyl methacrylate (IBOMA), cyclic trimethylolpropane formal acrylate (CTFA), 3,3,5-trimethyl cyclohexanol methacrylate, tert-butyl methacrylate (tBuMA), methyl acrylate (MeA), methyl methacrylate (MMA), acrylate 2-ethylhexyl (2EHA), 2-(dimethylamino)ethyl acrylate (DAEA), 3-sulfopropyl acrylate potassium salt (SAPS), 3,3-dimethylacrylic acid (DAA), crotonic acid (CA), triethylene glycol methyl ether methacrylate (TEGMEMA), 2-phenyloxyethyl methacrylate (2PEMA),2-Hydroxyethyl acrylate (HEA), 3-(trimethoxysilyl)propyl methacrylate, and mixtures thereof.

[0015] According to one embodiment, the polymerizable monomer is at a concentration ranging from 10% to 40% by mass relative to the total mass of the composition.

[0016] According to one embodiment, the photoinitiator is selected from 2,4,6-trimethylbenzoyl-phenylphosphinate (TPO-L) oxide, camphorquinone, 4,4'-bis(diethylamino)benzophenone, 4,4'-bis(diethylamino)benzophenone associated with N-phenylglycine (NPG), ethyl-4-(dimethylamino)benzoate (EDB), N-diisopropylethylamine (DIPEAN) or 4-(dimethylamino)benzonitrile (DMABN), biacylphosphine oxide (BAPO), bis(α-5-2,4-cylcopentadien-1-yl)-bis(2,6-difluoro-3-(1H-pyrrol-1-yl)-phenyl) titanium (Irgacure 784), the 1-[4-(2-hydroxyethoxy)-phenyl]-2-hydroxy-2-methyl-1-propane-1-one (Irgacure 2959), 2,4,6-trimethylbenzoyldiphenylphosphine oxide (TPO), 2,2-dimethoxyphenyl-2-acetophenone (DMPA), and mixtures thereof.

[0017] According to one embodiment, the photoinitiator is at a concentration ranging from 0.1% to 2% by mass relative to the total mass of the composition.

[0018] According to one embodiment, the photopolymerizable resin is chosen from: urethane acrylate resins, urethane methacrylate resins, epoxy acrylate resins, and mixtures thereof; preferably the photopolymerizable resin is chosen from urethane acrylate resins, urethane methacrylate resins, difunctional epoxy acrylate resins and mixtures thereof; more preferably the photopolymerizable resin is chosen from: a urethane acrylate resin, a urethane methacrylate resin and mixtures thereof;even more preferentially, the photopolymerizable resin is selected from aliphatic urethane acrylate resins, hydrophobic urethane acrylate resins, aromatic urethane acrylate resins, polyether urethane acrylate resins, aliphatic urethane methacrylate resins, hydrophobic urethane methacrylate resins, aromatic urethane methacrylate resins, polyether urethane methacrylate resins, and mixtures thereof.

[0019] According to one embodiment, the photopolymerizable resin is at a concentration ranging from 10% to 94.9% by mass relative to the total mass of the composition.

[0020] The invention also relates to a composition according to the invention, for its use in the adhesion of non-mineralized biological tissues to each other; for the adhesion of a material to a non-mineralized biological tissue; for the adhesion of an adhesive or substance to the surface of a non-mineralized biological tissue; as a surgical sealant on a non-mineralized biological tissue; for closing or sealing openings created by suture or staple or by tissue resection in a non-mineralized biological tissue; for sealing an opening, incision, or tear in a non-mineralized biological tissue; as a hemostatic agent to stop bleeding on a non-mineralized biological tissue; as a dressing on a non-mineralized biological tissue to cover and protect a wound; for reinforcing a non-mineralized biological tissue; for preventing the formation of lesions on a non-mineralized biological tissue;to fix and stabilize non-mineralized biological tissue; and / or for the treatment of skin lesions.

[0021] According to one embodiment, the composition for its use according to the invention comprises bringing the composition into contact with the non-mineralized biological tissue to be treated, preferably by spreading; and the photopolymerization of said composition.

[0022] The present invention also relates to a method for preparing a polymerizable composition intended for use as an adhesive for non-mineralized biological tissues, comprising a mixing step: of at least one polymerizable monomer comprising an acrylate, methacrylate, acrylamide or methacrylamide function and not comprising a phosphate or phosphonate function; of at least one photoinitiator; and of at least one photopolymerizable resin; said mixture not comprising a monomer comprising a phosphate or phosphonate function on the one hand and an acrylate, methacrylate, acrylamide or methacrylamide function on the other hand.

[0023] According to one embodiment, the mass of the polymerizable monomer varies from 5% to 60% by mass, relative to the total mass of said mixture; and the mass of the photoinitiator varies from 0.1% to 5% by mass, relative to the total mass of said mixture.

[0024] The present invention also relates to a kit comprising the composition of the invention as described above.

[0025] According to one embodiment, the kit further includes a radiation source. DEFINITIONS

[0026] In the present invention, the terms below are defined as follows: " Polymerizable composition "Refers to a composition comprising one or more components that can be polymerized to form a polymer." Polymerizable monomer " refers to a monomer whose polymerization can be initiated by a physical or chemical initiator." Photoinitiator "Refers to a compound which, when added to a monomer, initiates photopolymerization by creating reactive species (e.g., free radicals, cations, anions) under the effect of radiation (UV or visible)." Polymerizable resin " refers to a reactive oligomer of high molecular weight (generally greater than 450 g / mol, preferably greater than 1000 g / mol) that can be polymerized. In the present invention, the polymerizable resin is a photopolymerizable resin, that is to say, one whose polymerization can be initiated under the effect of radiation." Biological tissues"Refers to a group of similar cells of the same origin, grouped into clusters, networks, or bundles (fibers). A biological tissue forms a functional unit, meaning that its cells work together to perform the same function. Biological tissues are assembled to form organs. In the present invention, the term "biological tissue" also encompasses organs in a general sense." Non-mineralized biological tissues " refers to biological tissues excluding bone tissue, bones, and teeth. Non-mineralized biological tissues are generally soft tissues. By " pharmaceutically acceptableWhen referring to a substance or composition, it is understood that the substances or composition are compatible with each other and / or not harmful to the subject, preferably a human being, to whom the substance or composition is administered. In particular, they do not produce an adverse, allergic, or other reaction when administered to the subject. For human administration, compositions must meet the standards of sterility, pyrogenicity, general safety, and purity required by regulatory bodies, such as the Food and Drug Administration (FDA) or the European Medicines Agency (EMA).- " Subject " concerns a warm-blooded animal, preferably a mammal, more preferably a human. Preferably, the subject is a patient, that is to say a subject who is waiting to receive, or who is receiving medical care, or who is / will be the subject of a medical procedure. "From [lower value] to [higher value]"and other similar expressions define a numeric range that includes (i.e., encompasses) both the upper and lower values. Furthermore, any range so defined in this application shall be interpreted as including an explicit disclosure of the corresponding narrower range described by the expression " between [lower value] and [upper value] ", in which both the upper and lower values ​​are excluded from the numeric range (i.e., not encompassed). The term " understand " means that the composition according to the invention includes the elements mentioned. This term also encompasses compositions comprising only the elements mentioned to the exclusion of all others (composition " consisting of (the elements mentioned). DETAILED DESCRIPTION Polymerizable composition

[0027] The present invention therefore relates to a polymerizable composition, intended to be used as an adhesive for biological tissues, in particular for non-mineralized biological tissues, enabling in particular the adhesion of biological tissues to each other, the adhesion of a material to a biological tissue, the formation of a surgical sealing product, or the formation of a skin dressing.

[0028] The invention relates in particular to polymerizable compositions intended for use as adhesives for biological tissues, especially for non-mineralized biological tissues, comprising: at least one polymerizable monomer comprising an acrylate, methacrylate, acrylamide or methacrylamide function and not comprising a phosphate or phosphonate function; at least one polymerization initiator, preferably a photoinitiator; and at least one photopolymerizable resin.

[0029] Polymerization of the composition of the invention makes it possible to form the intended adhesive and to obtain adhesion properties for the resulting system.

[0030] By " adhesive for biological tissues This refers to an adhesive intended for use on biological tissues, particularly for medical use on biological tissues. The components of such an adhesive and the polymerizable composition used to form it must therefore be inherently compatible with biological tissues, especially for medical applications. Specifically, they must not cause any adverse effects (i.e., adverse, allergic, or other reactions) on the biological tissues concerned.

[0031] The composition of the invention is specifically intended for use with non-mineralized biological tissues. This implies that, once applied and polymerized, the composition must produce an adhesive with physicochemical properties compatible with non-mineralized biological tissues, i.e., soft tissues. In particular, the following properties must be obtained: good adhesive flexibility, suitable for use on soft biological tissue, to protect the tissue from external factors while ensuring wearing comfort (shock absorption, resistance and resilience to large deformations); good stability over time under the action of physiological fluids (e.g. blood, exudates, perspiration), in particular to maintain adhesion properties in humid environments and to avoid deformation upon contact with physiological fluids, thus maintaining mechanical protection and adhesion to biological tissue; and preventing the accumulation of perspiration or exudates.

[0032] Within the framework of the present invention, when the concentrations of the different components of the composition according to the invention are indicated as a percentage, this refers to the percentage by mass of said component relative to the total mass of said composition. Polymerizable monomers

[0033] The composition of the invention comprises a polymerizable monomer including an acrylate, methacrylate, acrylamide, or methacrylamide functional group and not including a phosphate or phosphonate functional group. In the present invention, this type of monomer may be referred to as " non-phosphate polymerizable monomer "

[0034] According to one embodiment, the non-phosphate polymerizable monomer is selected from the following monomers: acrylic acid (AA), tert-butyl acrylate (tBuA), 2-hydroxyethyl methacrylate (HEMA), methacrylic acid (MA), lauryl acrylate (LA), lauryl methacrylate (LMA), 2-ethoxyethyl methacrylate (2EEMA), di(ethylene glycol) ethyl ether acrylate (DEGEA), 2-phenyloxyethyl acrylate (2PEA), 2-ethylhexyl methacrylate (2EHMA), n-butyl acrylate (nBuA), isobornyl acrylate (IBOA), isobornyl methacrylate (IBOMA), cyclic trimethylolpropane formal acrylate (CTFA), 3,3,5-trimethyl cyclohexanol methacrylate, tert-butyl methacrylate (tBuMA), methyl acrylate (MeA), methyl methacrylate (MMA), 2-ethylhexyl acrylate (2EHA), 2-(dimethylamino)ethyl acrylate (DAEA), potassium salt of 3-sulfopropyl acrylate (SAPS), 3,3-dimethylacrylic acid (DAA), crotonic acid (CA), triethylene glycol methyl ether methacrylate (TEGMEMA),2-Phenyloxyethyl methacrylate (2PEMA), 2-Hydroxyethyl acrylate (HEA), 3-(Trimethoxysilyl)propyl methacrylate, Ethyl acrylate (EtA), Cyclohexyl methacrylate, 3-Hydroxypropyl acrylate, Alpha-Bromoethyl acrylate, Alpha-Chlorethyl acrylate, Chloromethyl methacrylate, 2-Bromoethyl methacrylate, 2-Naphthyl methacrylate, Paratolyl acrylate, Parachlorophenyl methacrylate, Metabromophenyl acrylate, 2,4,6-Tribromophenyl acrylate, Parachlorobenzyl methacrylate, Metamethoxybenzyl methacrylate, Paraethylbenzyl acrylate, 1,6-Hexanediol dimethacrylate, Neopentylglycol diacrylate, Thiodiethylene glycol dimethacrylate, Bisphenol A ethoxyl diacrylate, bisphenol A ethoxyl dimethacrylate, pentaerythritol triacrylate, glyceryl triacrylate, dipentaerythritol pentaacrylate, trimethylolpropane triacrylate, tris(2-hydroxyethyl) isocyanurate trimethacrylate,trimethylolpropane triacrylate, polyethylene, urethane acrylate, urethane methacrylate, bis(4-methacryloylthiophenyl) sulfide, ethylene glycol acrylate, polyethylene glycol acrylate, ethylene glycol methacrylate, polyethylene glycol methacrylate, ethylene glycol diacrylate, polyethylene glycol diacrylate, ethylene glycol dimethacrylate, polyethylene glycol dimethacrylate, and mixtures thereof.

[0035] According to one embodiment, the non-phosphate polymerizable monomer is selected from the following monomers: acrylic acid (AA), acrylate of tert -butyl (tBuA), 2-hydroxyethyl methacrylate (HEMA), methacrylic acid (MA), lauryl acrylate (LA), lauryl methacrylate (LMA), 2-ethoxyethyl methacrylate (2EEMA), di(ethylene glycol) ethyl ether acrylate (DEGEA), 2-phenyloxyethyl acrylate (2PEA), 2-ethylhexyl methacrylate (2EHMA), acrylate n-butyl (nBuA), isobornyl acrylate (IBOA), isobornyl methacrylate (IBOMA), cyclic trimethylolpropane formal acrylate (CTFA), 3,3,5-trimethylcyclohexanol methacrylate (TMCHMA), tert-butyl methacrylate (tBuMA), methyl acrylate (MeA), methyl methacrylate (MMA), 2-ethylhexyl acrylate (2EHA), 2-(dimethylamino)ethyl acrylate (DAEA), 3-sulfopropyl acrylate potassium salt (SAPS), 3,3-dimethylacrylic acid (DAA), crotonic acid (CA), triethylene glycol methyl ether methacrylate (TEGMEMA), 2-phenyloxyethyl methacrylate (2PEMA), 2-hydroxyethyl acrylate (HEA), 3-(trimethoxysilyl)propyl methacrylate, and mixtures thereof.

[0036] According to one embodiment, the non-phosphate polymerizable monomer is selected from the following monomers: acrylate of tert-butyl (tBuA), hydroxyethyl methacrylate (HEMA), acrylic acid (AA), lauryl acrylate (LA), isobornyl acrylate (IBOA), isobornyl methacrylate (IBOMA), 3,3,5-trimethyl cyclohexanol methacrylate (TMCHMA), and mixtures thereof.

[0037] In one embodiment, the non-phosphate polymerizable monomer is a mixture of two or more of the monomers listed above. In particular, the non-phosphate polymerizable monomer is a mixture of acrylic acid and another monomer listed above.

[0038] According to one embodiment, the non-phosphated polymerizable monomer has a molar mass ranging from 50 g.mol-1< to 500 g.mol-1<, preferably from 70 g.mol-1< to 400 g.mol-1<.

[0039] According to one embodiment, the non-phosphate polymerizable monomer is present in the composition of the invention at a concentration ranging from 5% to 60% by mass relative to the total mass of the composition, preferably from 5% to 50% by mass, and more preferably from 5% to 40% by mass. According to another embodiment, the non-phosphate polymerizable monomer is present in the composition of the invention at a concentration ranging from 10% to 40% by mass, preferably from 20% to 40% by mass, and more preferably from 25% to 35% by mass. According to yet another embodiment, the non-phosphate polymerizable monomer is present in the composition of the invention at a concentration ranging from 5% to 30% by mass, and more preferably from 10% to 20% by mass.

[0040] The polymerization of the non-phosphated polymerizable monomer present in the composition of the invention can be initiated by a physical or chemical initiator. According to a preferred embodiment, the polymerization is initiated under the effect of radiation, preferably radiation having a wavelength ranging from 300 nm to 520 nm, and more preferably from 350 nm to 520 nm. The monomers used in the composition of the invention have the advantage of polymerizing rapidly even at low to moderate irradiance ranges, preferably from 5 mW / cm² to 250 mW / cm², preferably from 10 mW / cm² to 100 mW / cm², and more preferably from 10 mW / cm² to 50 mW / cm². These low to moderate irradiance ranges are particularly suitable for use on biological tissues because they do not emit UV C.Moreover, these low to moderate irradiance ranges have the advantage of being accessible with lightweight radiation sources, as opposed to industrial radiation sources which are bulky and have high irradiances (>10 W / cm 2<).

[0041] According to one embodiment, the composition according to the invention does not comprise a monomer comprising, on the one hand, a phosphate or phosphonate function and, on the other hand, a methacrylate, acrylate, acrylamide, or methacrylamide function. In the present invention, this type of monomer may be designated by the expression " phosphate polymerizable monomerAccording to one embodiment, the composition according to the invention does not comprise a polymerizable monomer selected from glycerol dimethacrylate phosphate, ethylene glycol methacrylate phosphate, polyethylene glycol methacrylate phosphate, methacryloyloxy decyl hydrogen phosphate, methacryloyloxy ethyloxy hydrogen phosphate, glycerol monomethacrylate phosphate, triethylene glycol monomethacrylate phosphate, methacryloyloxy propyl phosphate, methacryloyloxy hexyl phosphate, phosphonic aminoethyl methacrylated, bis(glyceryl dimethacrylate) phosphate and mixtures thereof.According to one embodiment, the composition according to the invention does not comprise a polymerizable phosphate monomer selected from CAS [14206-25-8], [14235-57-5], [86242-61-7], [932019-41-6], [1980781-17-6], [60161-88-8], [87243-97-8], [1980048-95-0], [918802-80-9], [63411-25-6], [1980064-07-0], [22432-83-3], [1980781-08-5], [252210-28-9], [1114567-37-1], [80730-17-2], [518991-74-7], [87243-96-7], [1980062-84-7], [518991-75-8], [252210-30-3], [22432-84-4], [727415-30-7], [727415-31-8], [784139-89-5] or [1194231-98-5] and their mixtures. According to one embodiment, the composition according to the invention does not comprise a polymerizable phosphate monomer of formula I as described in WO2020 / 169681, in particular 10-MDP (C 14 H 27 O 6 P, CAS number [85590-00-7]) or MEP (C 12 H 19 O 8 P, CAS number [32435-46-4]).

[0042] According to one embodiment, the composition according to the invention does not comprise a monomer whose polymerization can be initiated solely by contact with water, the moisture of biological tissues, and / or ambient humidity. According to another embodiment, the composition according to the invention does not comprise a monomer from the cyanoacrylate family. Photopolymerizable resins

[0043] The composition of the invention comprises a photopolymerizable resin. Advantageously, the presence of a photopolymerizable resin in the composition of the invention gives the adhesive obtained after polymerization optimal flexibility properties for the intended applications, particularly for the adhesion of non-mineralized biological tissues, while limiting the exothermicity of the polymerization reaction of the composition to an acceptable level. An acceptable exothermicity corresponds to a temperature during the polymerization of the composition that does not cause burning of the tissues on which the composition is polymerized, nor any sensation of burning. Preferably, the exothermicity is controlled to ensure a polymerization temperature below 60°C.

[0044] Furthermore, the presence of the photopolymerizable resin in the composition of the invention contributes to giving the adhesive obtained after polymerization good stability over time under the action of physiological fluids and good water resistance, and to preventing the accumulation of perspiration or exudates.

[0045] According to one embodiment, the photopolymerizable resin used in the composition of the invention is a resin which forms a flexible material after polymerization.

[0046] According to one embodiment, the photopolymerizable resin is chosen from urethane acrylate resins, urethane methacrylate resins, epoxy acrylate resins, and their mixtures.

[0047] In one embodiment, the photopolymerizable resin is a urethane acrylate resin or a urethane methacrylate resin. In a particular embodiment, the photopolymerizable resin is a urethane acrylate resin.

[0048] In one embodiment, the urethane resin is selected from aliphatic acrylate urethane resins, hydrophobic acrylate urethane resins, aromatic acrylate urethane resins, polyether urethane acrylate resins, aliphatic methacrylate urethane resins, hydrophobic methacrylate urethane resins, aromatic methacrylate urethane resins, polyether urethane methacrylate resins, and mixtures thereof.

[0049] In one embodiment, the aliphatic urethane acrylate resin is selected from Allnex Ebecryl 9907®, Allnex Ebecryl 230®, Allnex Ebecryl 250®, Allnex Ebecryl 8315® (tetraacrylate), Allnex Ebecryl 4491®, Allnex Ebecryl 1271®, and mixtures thereof. In one embodiment, the aromatic urethane acrylate resin is Allnex Ebecryl 210®. In one embodiment, the hydrophobic urethane acrylate resin is Dymax Bomar BRC-843S®. In one embodiment, the polyether urethane acrylate resin is Dymax Bomar BR-3641AJ®.

[0050] According to one embodiment, the photopolymerizable resin is selected from Allnex Ebecryl 9907 ®< , Allnex Ebecryl 230 ®< , Allnex Ebecryl 250 ®< , Allnex Ebecryl 8315 ®< (tetraacrylate), Allnex Ebecryl 4491 ®< , Allnex Ebecryl 1271 ®< , Allnex Ebecryl 210 ®< , Dymax Bomar BRC-843S ®< , Dymax Bomar BR-3641AJ ®< , and their mixtures.

[0051] According to a particular embodiment, the photopolymerizable resin is Allnex Ebecryl 9907 ®< .

[0052] According to one embodiment, the photopolymerizable resin is an epoxy acrylate resin; preferably a difunctional epoxy acrylate resin; more preferably the difunctional epoxy acrylate resin is chosen from: bisphenol A epoxy diacrylate resins, such as for example Allnex Ebecryl 3708 ®< , epoxy soybean oil acrylate resins, such as for example Rahn Genomer 2312 ®< , and mixtures thereof.

[0053] According to another embodiment, the photopolymerizable resin is a difunctional epoxy acrylate resin, in particular a bisphenol A epoxy diacrylate resin, such as for example Allnex Ebecryl 3708 ®< .

[0054] According to one embodiment, the composition of the invention comprises at least 10% by mass, relative to the total mass of the composition, of photopolymerizable resin. According to another embodiment, the composition of the invention comprises from 10% to 94.9% by mass of photopolymerizable resin, preferably from 50% to 94.9%. According to another embodiment, the composition of the invention comprises from 65% to 94.75% by mass of photopolymerizable resin. According to yet another embodiment, the composition of the invention comprises 65%, 68%, 69%, 79%, 89%, and 94.75% by mass of photopolymerizable resin.

[0055] The polymerization of the photopolymerizable resin can be initiated under the effect of radiation. Preferably, said radiation has a wavelength ranging from 300 nm to 520 nm, preferably from 350 nm to 520 nm. Preferably said UV radiation has an irradiance power ranging from 5 mW / cm² to 250 mW / cm², preferably from 10 mW / cm² to 100 mW / cm², preferably from 10 mW / cm² to 50 mW / cm². Photoinitiators

[0056] The composition of the invention includes a polymerization initiator, preferably a photoinitiator.

[0057] According to one embodiment, the photoinitiator is capable of inducing polymerization under the effect of radiation having a wavelength ranging from 300 nm to 520 nm, preferably from 350 nm to 520 nm.

[0058] According to one embodiment, the photoinitiator is selected from: 2,4,6-trimethylbenzoyl-phenylphosphinate (TPO-L) oxide, camphorquinone, 4,4'-bis(diethylamino)benzophenone, 4,4'-bis(diethylamino)benzophenone combined with N-phenylglycine (NPG), ethyl-4-(dimethylamino)benzoate (EDB), N-diisopropylethylamine (DIPEAN) or 4-(dimethylamino)benzonitrile (DMABN), biacylphosphine oxide (BAPO), bis(α-5-2,4-cylcopentadien-1-yl)-bis(2,6-difluoro-3-(1H-pyrrol-1-yl)-phenyl) titanium (Irgacure 784), the 1-[4-(2-hydroxyethoxy)-phenyl]-2-hydroxy-2-methyl-1-propane-1-one (Irgacure 2959), 2,4,6-trimethylbenzoyldiphenylphosphine oxide (TPO), 2,2-dimethoxyphenyl-2-acetophenone (DMPA), and mixtures thereof.

[0059] According to a particular embodiment, the photoinitiator is TPO-L.

[0060] According to one embodiment, the photoinitiator is present in the composition of the invention at a concentration ranging from 0.1% to 5% by mass, relative to the total mass of the composition, preferably from 0.1% to 2% by mass, preferably from 0.25% to 2% by mass, more preferably from 0.5% to 2% by mass.

[0061] Unexpectedly, the photoinitiator plays a role in the adhesion properties after polymerization, which can be varied depending on the quantity and type of photoinitiator used.

[0062] The use of a thermal or redox polymerization initiator is not excluded from the scope of the present invention. Among the usable redox initiators, the dibenzoyl peroxide / amine (trimethylaniline) pair may be mentioned in particular. Special compositions

[0063] According to a particular embodiment, the composition of the invention comprises: from 5% to 30% by mass, relative to the total mass of the composition, of a non-phosphated polymerizable monomer; from 0.25% to 5% by mass of a photoinitiator; and from 65% to 94.75% by mass of a photopolymerizable resin.

[0064] According to a particular embodiment, the composition of the invention comprises: from 10% to 30% by mass, relative to the total mass of the composition, of a polymerizable non-phosphate monomer selected from tert-butyl acrylate (tBuA), hydroxyethyl methacrylate (HEMA), acrylic acid (AA), lauryl acrylate (LA), isobornyl acrylate (IBOA), isobornyl methacrylate (IBOMA), and 3,3,5-trimethyl cyclohexanol methacrylate (TMCHMA); from 0.25% to 5% by mass of TPO-L; and from 65% to 94.75% by mass of aliphatic acrylate urethane resin such as Allnex Ebecryl 9907 ®< .

[0065] According to a particular embodiment, the composition of the invention comprises: from 10% to 30% by mass, relative to the total mass of the composition, of a non-phosphated polymerizable monomer selected from acrylate tert -butyl (tBuA), hydroxyethyl methacrylate (HEMA), acrylic acid (AA), lauryl acrylate (LA), isobornyl acrylate (IBOA), isobornyl methacrylate (IBOMA), and 3,3,5-trimethyl cyclohexanol methacrylate (TMCHMA); 0.25% to 5% by mass of TPO-L; and 65% to 94.75%, preferably 65% ​​to 89.75%, by mass of a light-curing resin selected from aliphatic urethane acrylate resins such as Allnex Ebecryl 9907 ®; difunctional epoxy acrylate resins such as Allnex Ebecryl 3708 ®< epoxy acrylate resin (corresponding to a modified bisphenol A epoxy diacrylate resin) or Rahn Genomer 2312 ®< epoxy acrylate resin (corresponding to an epoxyd soybean oil acrylate resin), and their mixtures.

[0066] According to one embodiment, the composition of the invention further comprises a pharmaceutically acceptable vehicle. According to another embodiment, the composition of the invention is solvent-free. Properties of the compositions

[0067] According to one embodiment, the composition of the invention is in liquid form.

[0068] According to one embodiment, the composition of the invention has a viscosity of less than 120 Pa.s at 20°C, preferably less than 107 Pa.s at 20°C, and preferably less than 55 Pa.s at 20°C. The viscosity of the composition can be measured in particular by a rotary viscometer, a cone / plate viscometer, a falling ball viscometer, a glass capillary viscometer, a flow-section viscometer, or by pressure extrusion, preferably in accordance with standard NF EN 12092.

[0069] Adjusting the viscosity of the composition allows control over the thickness of the layer deposited on the biological tissue before polymerization, depending on the intended use of the adhesive formed after polymerization. For example, a thin layer, 0.5 mm or less thick, is preferred for bonding a material to biological tissue or for bonding an adhesive or substance to the surface of biological tissue. A thicker layer, 1 mm or more thick, is preferred for forming a dressing on biological tissue to cover and protect a wound.

[0070] According to one embodiment, the composition according to the invention is not a hydrogel. Kit

[0071] The present invention also relates to a kit, or set of parts, comprising a composition according to the invention and a radiation source.

[0072] Preferably the radiation source of the assembly of parts can emit radiation suitable for polymerizing and / or assisting polymerization and / or accelerating the polymerization of the constituents of the composition.

[0073] In the context of the present invention, the term " source of radiation " refers to any artificial means capable of producing radiation with wavelengths ranging from 300 nm to 520 nm, preferably from 350 nm to 520 nm. Preferably, said UV radiation has an irradiance power ranging from 5 mW / cm² to 250 mW / cm², preferably from 10 mW / cm² to 100 mW / cm², and preferably from 10 mW / cm² to 50 mW / cm². Advantageously, these irradiance ranges can be obtained from lightweight radiation sources suitable for consumer use, as opposed to bulky industrial radiation sources with high irradiances (>10 W / cm²). In one embodiment, the radiation source is a UV LED source." Method for preparing a polymerizable composition

[0074] The invention also relates to a method for preparing a polymerizable composition according to the invention. In particular, the invention relates to a method for preparing a polymerizable composition intended for use as an adhesive for non-mineralized biological tissues, said method comprising or consisting of a mixing step: of at least one polymerizable monomer comprising an acrylate, methacrylate, acrylamide or methacrylamide function, and not comprising a phosphate or phosphonate function as described above; of at least one photoinitiator as described above; and of at least one photopolymerizable resin as described above;

[0075] said mixture not comprising a monomer comprising a phosphate or phosphonate function on the one hand and an acrylate, methacrylate, acrylamide or methacrylamide function on the other hand.

[0076] According to one embodiment, the mass of the polymerizable monomer in the mixture represents from 5% to 60% of the total mass of said mixture.

[0077] According to one embodiment, the mass of the photoinitiator in the mixture represents from 0.1% to 5% of the total mass of said mixture. Use of polymerizable compositions

[0078] The invention also relates to the use of the polymerizable compositions of the invention as an adhesive for biological tissues, in particular for non-mineralized biological tissues.

[0079] In particular, the polymerizable compositions of the invention can be used on biological tissues, especially on non-mineralized biological tissues, as a surgical adhesive, surgical sealing product, or skin dressing.

[0080] More particularly, the present invention relates to the use of the polymerizable compositions of the invention on biological tissues, in particular non-mineralized biological tissues: for the adhesion of biological tissues to each other, for the adhesion of a material to a biological tissue, for the adhesion of an adhesive or substance to the surface of a biological tissue, as a surgical sealant, for plugging or sealing openings created by suture or staple or tissue resection (e.g., hemostasis, aerostasis, lymphostasis), for plugging an opening, incision or tear in a biological tissue, as a hemostatic to stop bleeding, alone or in addition to conventional hemostasis techniques such as suturing, compression or electrocoagulation, as a dressing on a biological tissue to cover and protect a wound, to reinforce a biological tissue, to fix and stabilize a biological tissue, for the treatment of skin lesions.

[0081] The invention therefore relates to a polymerizable composition according to the invention for its use on biological tissues, in particular on non-mineralized biological tissues, as a surgical adhesive, surgical sealing product, or skin dressing.

[0082] The present invention also relates to a polymerizable composition according to the invention for use as a surgical adhesive for bonding biological tissues to each other, for bonding a material to a biological tissue, for bonding an adhesive or substance to the surface of a biological tissue, as a surgical sealant, for closing or sealing openings created by sutures or staples or by tissue resection, for sealing an opening, incision, or tear in a biological tissue, as a hemostatic agent to stop bleeding, as a dressing on a biological tissue to cover and protect a wound, for reinforcing a biological tissue, for fixing and stabilizing a biological tissue, and for the treatment of skin lesions. The biological tissues are preferably non-mineralized.

[0083] The present invention also relates to a composition according to the invention for its use as a surgical adhesive for the adhesion of non-mineralized biological tissues to each other, for example to make a suture, in particular a skin wound suture.

[0084] The present invention also relates to a composition according to the invention for its use as a surgical adhesive for the adhesion of a material to a non-mineralized biological tissue, for example to make a dressing or an operating field adhere to the skin.

[0085] The present invention also relates to a composition according to the invention for use as a surgical adhesive for the adhesion of a glue or substance to the surface of a non-mineralized biological tissue, for example to enhance the properties of a surgical glue.

[0086] The present invention also relates to a composition according to the invention for its use as a surgical sealant, in particular for plugging or sealing orifices created by a suture with thread or staple or by tissue resection, in non-mineralized biological tissue.

[0087] The present invention also relates to a composition according to the invention for its use as a surgical sealant for plugging an orifice, an incision or a tear in non-mineralized biological tissue.

[0088] The present invention also relates to a composition according to the invention for its use as a hemostatic agent to stop bleeding.

[0089] The present invention also relates to a composition according to the invention for its use in forming a dressing on a non-mineralized biological tissue to cover and protect a wound.

[0090] The present invention also relates to a composition according to the invention for its use as a surgical adhesive to reinforce non-mineralized biological tissue.

[0091] The present invention also relates to a composition according to the invention for its use as a surgical adhesive to prevent the formation of lesions on a tissue, in particular a skin tissue; for example to prevent the formation of blisters.

[0092] The present invention also relates to a composition according to the invention for its use as a surgical adhesive for fixing and stabilizing non-mineralized biological tissue.

[0093] The present invention also relates to a composition according to the invention for its use in the treatment of skin lesions.

[0094] It has been demonstrated that the compositions according to the invention exhibit superior adhesive properties and safety compared to prior art compositions. These compositions are therefore particularly suitable for topical use as dressings for wounds and / or for the treatment of all skin lesions. Method for implementing the compositions of the invention

[0095] The present invention also relates to a method for implementing the polymerizable composition of the invention, comprising the following steps: (i) bringing the biological tissue to be treated into contact with a composition according to the invention; (ii) optionally allowing the composition to penetrate said tissue; and (iii) inducing the polymerization of said composition.

[0096] In one embodiment, in step (i), the biological tissue to be treated is brought into contact with the composition by spreading, spraying, or by contacting it using a pre-coated material such as a pre-coated patch. In one embodiment, contact is achieved by spreading.

[0097] According to one embodiment, step (i) aims to coat totally or partially the biological tissue to be treated.

[0098] According to one embodiment, step (ii) is optional. The penetration time of the composition into the tissue before its polymerization can range from 0 to 5 minutes.

[0099] In a preferred embodiment, step (iii) is carried out using UV or visible light radiation. The characteristics of the radiation used, in particular its power and wavelength, are adapted to the constituents of the composition, especially the nature of the polymerizable monomer and the nature of the polymerization initiator. In one embodiment, the radiation used to induce polymerization has a wavelength ranging from 300 nm to 520 nm, preferably from 350 nm to 520 nm. In another embodiment, the radiation used to induce polymerization has an irradiance power ranging from 5 mW / cm² to 250 mW / cm², preferably from 10 mW / cm² to 100 mW / cm², preferably from 10 mW / cm² to 50 mW / cm².

[0100] According to one embodiment, the composition of the invention gives, after polymerization, a biocompatible system.

[0101] The compositions according to the invention make it possible to obtain, after polymerization, excellent adhesion, both for surgical applications and for a level of skin adhesion suitable for application by the general public.

[0102] The concentrations of the constituents of the composition of the invention allow for rapid initiation and polymerization in a few tens of seconds, preferably a polymerization of less than 1 minute, without causing burning of the tissues.

[0103] Furthermore, the combined presence of a photopolymerizable resin, with the polymerizable monomers used and the photoinitiator, gives the resulting bond flexible properties and good stability over time under the action of physiological fluids ( e.g. blood, exudates, perspiration), prevents the accumulation of perspiration or exudates and provides good water resistance.

[0104] The method according to the invention is preferably non-invasive. The term "non-invasive" means that the method according to the invention does not involve any surgical steps to access the tissue to be treated. Thus, the method according to the invention is performed on biological tissue that is directly accessible (e.g., skin) or previously made accessible by other methods.

[0105] The method according to the invention is preferably a non-invasive method for covering and protecting a skin lesion. The method according to the invention is preferably a non-invasive method for bringing the edges of a skin wound together. "Cutaneous" refers to a location on the skin, lips, or oral mucosa.

[0106] Alternatively, the method according to the invention is a method for the adhesion of a material to a biological tissue, for the adhesion of biological tissues to each other, for the adhesion of an adhesive or substance to the surface of a biological tissue, surgical sealing, for plugging or sealing orifices created by a suture with thread or staple or by tissue resection (e.g., hemostasis, aerostasis, lymphostasis), for plugging an orifice, an incision or a tear in a biological tissue, for stopping bleeding, for covering and protecting a wound, for strengthening a biological tissue, for preventing the formation of lesions on a biological tissue, or for fixing and stabilizing a biological tissue. EXAMPLES

[0107] The present invention will be better understood by reading the following examples which illustrate the invention in a non-limiting way. Example 1: Evaluation of compositions according to the invention

[0108] Aim :Various polymerizable compositions according to the invention have been prepared and evaluated for use as an adhesive for biological tissues. Compositions :

[0109] Compositions according to the invention have been prepared with the following commercially available compounds: Photoinitiator: TPO-L (ethyl phenyl(2,4,6-trimethylbenzoyl)phosphinate); light-curing resin: Allnex Ebecryl 9907 aliphatic urethane acrylate resin; Allnex Ebecryl 3708 epoxy acrylate resin (corresponding to a bisphenol A epoxy diacrylate resin); Genomer 2312 epoxy acrylate resin (corresponding to an epoxy soybean oil acrylate resin) from RAHN; non-phosphate polymerizable monomers: acrylate of tert-butyl (tBuA), hydroxyethyl methacrylate (HEMA), acrylic acid (AA), lauryl acrylate (LA), isobornyl acrylate (IBOA), isobornyl methacrylate (IBOMA), 3,3,5-trimethyl cyclohexanol methacrylate (TMCHMA).

[0110] The compositions listed in Table 1 were prepared by mixing the different components. In Table 1, the proportions of the different components are given as percentages by mass relative to the total mass of the composition.

[0111] Composition 15 (without photopolymerizable resin) is not part of the invention and is presented in Table 1 as a reference composition. The emission spectrum of the UV LED source used to polymerize the formulations is centered on 395 nm and used at an irradiance of 20 mW / cm². Criteria evaluated:

[0112] Polymerization time: rapid photopolymerization is targeted, preferably lasting less than 1 minute, in order to control bonding and facilitate use, while being carried out at low to moderate irradiance ranges (preferably from 5 mW / cm² to 250 mW / cm²) which are suitable for use on biological tissues (i.e.no UV C emission) and accessible with light radiation sources, as opposed to industrial radiation sources; the conversion rate: a high final conversion rate is targeted, preferably a conversion rate greater than 90%, for optimized polymerization and to avoid the presence of too high a proportion of unpolymerized compounds in the final adhesive which could be toxic; exothermicity: the exothermicity of the polymerization reaction must be limited for the comfort of the subject and must not cause tissue burns; tissue adhesion and bond strength over time (in particular the strength. in vivoAdhesion and durability must be sufficiently good to support the tissue healing process and limit the number of dressing changes, which can cause irritation or damage to the surrounding tissue. Water resistance: good resistance to water (and biological fluids) is required to maintain adhesion properties in moist environments, prevent deformation upon contact with water / physiological fluids to maintain mechanical protection and adhesion to biological tissue, and provide lasting protection to the skin in case of contact or immersion in an aqueous environment (daily household activities, hand washing, showering, water sports, etc.).) while avoiding maceration of the fabric under the bonding; the flexibility of the formed network: the formed network must have a flexibility adapted to use on soft biological tissue in order to protect the fabric from the outside and ensure wearing comfort (shock absorption, resistant and resilient to large deformations); the mechanical resistance of the formed network, including resistance to crumbling and tearing. Methodology :

[0113] Qualitative assessment of membership in vivo is performed by a qualitative skin assessment on the hand of volunteer testers (N = 1 to 5 tests). A qualitative adhesion scale was developed (Table 2) taking into account the following criteria for evaluating adhesion and hold: - adhesion at t = 0; - anchoring in the superficial layer of the skin; - hold over time; and - resistance to stress. [Table 2] 0 no adherence at t = 0, no anchoring 1 Adhesion at t = 0, very weak anchorage, detachment within minutes, no resistance to stress 2 adhesion at t = 0, weak anchorage, holding power < 1h, no resistance to stress 3 adhesion at t = 0, weak anchoring, hold for 2 to 4 hours, low resistance to stress 4 Adhesion at t = 0, weak anchorage, hold for 4 to 8 hours, low resistance to stress 5 adhesion at t = 0, average anchoring, hold time 4h to 8h, average resistance to stress 6 adhesion at t = 0, average anchorage, hold time 8h to 12h, average resistance to stress 7 Adhesion at t = 0, average anchorage, 12-24 hour hold, good to average resistance to stress 8 Adhesion at t = 0, good anchoring, 24-36 hour hold, good resistance to stress 9 Adhesion at t = 0, good anchoring, 36-48 hour hold, very good resistance to stress 10 Adhesion at t = 0, excellent anchoring, hold > 48h, excellent resistance to stress

[0114] The polymerization time and final conversion rate are evaluated by kinetic monitoring of photopolymerization in ATR-IR. The disappearance of the IR absorption bands characteristic of acrylates is quantified under UV LED radiation 395nm at an irradiance of 17 mW / cm².

[0115] The exothermic reaction of photopolymerization is evaluated qualitatively. in vivo through a qualitative skin assessment on the hands of volunteer testers. The sensation scale is described as follows: No heat felt; + slight exothermic reaction felt; ++ moderate exothermic reaction felt; +++ high exothermic reaction felt; x pain on polymerization.

[0116] Flexibility is qualitatively assessed in two ways. First, the bending resistance of polymer films obtained by polymerization under 395 nm UV LED radiation for 1 min at an irradiance of 17 mW / cm² is qualitatively assessed. Second, flexibility is qualitatively assessed in vivo via an assessment of wearing comfort on the hand of volunteer testers. The following flexibility scale is used: 0. Brittle, vitreous film, uncomfortable, can cause irritation on the edges of the bonding; +Deformable but rigid film, uncomfortable; ++Flexible film, comfortable; +++Very flexible film, comfortable, perfectly follows the movements of biological tissue.

[0117] Mechanical strength is qualitatively assessed in two ways. First, polymer films obtained by polymerization under 395 nm UV LED radiation for 1 min at an irradiance of 17 mW / cm² are subjected to manual tearing. Second, brittleness is qualitatively assessed by manual shearing of the surface and edges of the plate. The following mechanical strength scale is used: Hydrogel texture, crumbles and tears easily under stress; +fragile and sensitive to tearing; ++medium sensitivity to tearing; +++tear resistant; ++++very tear resistant.

[0118] Water sensitivity is assessed qualitatively in two ways. First, polymer films obtained by polymerization under 395 nm UV LED radiation for 1 min at an irradiance of 17 mW / cm² are immersed in water at 40°C for 24 to 72 hours, and macroscopic observations (bleaching, deformation, softening, embrittlement) are recorded. Second, water sensitivity is assessed qualitatively by a handwashing test administered to volunteer testers. The following water sensitivity scale is used: No change; slight to moderate swelling; significant bleaching / swelling; significant bleaching / swelling / deformation / loss of mechanical strength; total physical deterioration (destruction of the sample). Results

[0119] The results obtained for the different compositions tested are reported in Table 3.

[0120] The conversion rates obtained for all compositions of the invention tested above are greater than 90%.

[0121] The compositions of the invention exhibit the desired properties of adhesion to biological tissue, as well as the desired properties of flexibility and conformability adapted to non-mineralized biological tissues. Furthermore, the compositions of the invention allow for the formation of bonds with good long-term stability.

[0122] However, the results show that a composition lacking a photopolymerizable resin does not provide both good adhesion and flexibility. Furthermore, the polymer film produced by this composition is highly sensitive to water. Indeed, the polymer film from composition 15 was severely degraded, and its immersion in water at 40°C for 24 to 72 hours led to its destruction.

Claims

1. A polymerizable composition, intended for use as an adhesive for non-mineralized biological tissues, comprising: - from 5% to 60% by mass, relative to the total mass of the composition, of a polymerizable monomer comprising an acrylate, methacrylate, acrylamide, or methacrylamide function and not comprising a phosphate or phosphonate function; - from 0.1% to 5% by mass of a photoinitiator; and - a photopolymerizable resin; said composition not comprising a monomer comprising a phosphate or phosphonate function on the one hand and an acrylate, methacrylate, acrylamide, or methacrylamide function on the other hand.

2. The composition according to claim 1, wherein the polymerizable monomer is selected from: acrylic acid (AA), tert-butyl acrylate (tBuA), 2-hydroxyethyl methacrylate (HEMA), methacrylic acid (MA), lauryl acrylate (LA), lauryl methacrylate (LMA), 2-ethoxyethyl methacrylate (2EEMA), di(ethylene glycol) ethyl ether acrylate (DEGEA), 2-phenyloxyethyl acrylate (2PEA), 2-ethylhexyl methacrylate (2EHMA), n-butyl acrylate (nBuA), isobornyl acrylate (IBOA), isobornyl methacrylate (IBOMA), cyclic trimethylolpropane formal acrylate (CTFA), 3,3,5 trimethyl cyclohexanol methacrylate, tert-butyl methacrylate (tBuMA), methyl acrylate (MeA), methyl methacrylate (MMA), 2-ethylhexyl acrylate (2EHA), 2-(dimethylamino)ethyl acrylate (DAEA), 3-sulfopropyl acrylate potassium salt (SAPS), 3,3-dimethylacrylic acid (DAA), crotonic acid (CA), triethylene glycol methyl ether methacrylate (TEGMEMA), 2-phenyloxyethyl methacrylate (2PEMA), 2-hydroxyethyl acrylate (HEA), 3-(trimethoxysilyl)propyl methacrylate, ethyl acrylate (EtA), cyclohexyl methacrylate, 3-hydroxypropyl acrylate, alpha-bromoethyl acrylate, alphachloroethyl acrylate, chloromethyl methacrylate, 2-bromoethyl methacrylate, 2-naphthyl methacrylate, paratolyl acrylate, parachlorophenyl methacrylate, metabromophenyl acrylate, 2,4,6-tribromophenyl acrylate, parachlorobenzyl methacrylate, metamethoxybenzyl methacrylate, paraethylbenzyl acrylate, 1,6-hexanediol dimethacrylate, neopentyl glycol diacrylate, thiodiethylene glycol dimethacrylate, bisphenol A ethoxylate diacrylate, bisphenol A ethoxylate dimethacrylate, pentaerythritol triacrylate, glyceryl triacrylate, dipentaerythritol pentaacrylate, trimethylolpropane triacrylate, tris(2-hydroxyethyl) isocyanurate trimethacrylate, trimethylolpropane polyoxyethylene triacrylate, urethane acrylate, urethane methacrylate, bis(4-methacryloylthiophenyl) sulfide, ethylene glycol acrylate, polyethylene glycol acrylate, ethylene glycol methacrylate, polyethylene glycol methacrylate, ethylene glycol diacrylate, polyethylene glycol diacrylate, ethylene glycol dimethacrylate, polyethylene glycol dimethacrylate, and mixtures thereof.

3. The composition according to claim 1 or 2, wherein the polymerizable monomer is selected from: acrylic acid (AA), tert-butyl acrylate (tBuA), 2-hydroxyethyl methacrylate (HEMA), methacrylic acid (MA), lauryl acrylate (LA), lauryl methacrylate (LMA), 2-ethoxyethyl methacrylate (2EEMA), di(ethylene glycol) ethyl ether acrylate (DEGEA), 2-phenyloxyethyl acrylate (2PEA), 2-ethylhexyl methacrylate (2EHMA), n-butyl acrylate (nBuA), isobornyl acrylate (IBOA), isobornyl methacrylate (IBOMA), cyclic trimethylolpropane formal acrylate (CTFA), 3,3,5 trimethyl cyclohexanol methacrylate, tert-butyl methacrylate (tBuMA), methyl acrylate (MeA), methyl methacrylate (MMA), 2-ethylhexyl acrylate (2EHA), 2-(dimethylamino)ethyl acrylate (DAEA), potassium salt of 3-sulfopropyl acrylate (SAPS), 3,3-dimethylacrylic acid (DAA), crotonic acid (CA), triethylene glycol methyl ether methacrylate (TEGMEMA), 2-phenyloxyethyl methacrylate (2PEMA), 2-hydroxyethyl acrylate (HEA), 3-(trimethoxysilyl)propyl methacrylate, and mixtures thereof.

4. The composition according to any one of claims 1 to 3, wherein the polymerizable monomer is at a concentration ranging from 10% to 40% by mass relative to the total mass of the composition.

5. The composition according to any one of claims 1 to 4, wherein the photoinitiator is selected from 2,4,6-trimethylbenzoyl-phenylphosphinic oxide (TPO-L), camphorquinone, 4,4'-bis(diethylamino)benzophenone, 4,4'-bis(diethylamino)benzophenone associated with N-phenylglycine (NPG), ethyl-4-(dimethylamino)benzoate (EDB), N-diisopropylethylamine (DIPEAN) or 4-(dimethylamino)benzonitrile (DMABN), biacylphosphine oxide (BAPO), bis(.eta.5-2,4-cyclopentadien-1-yl)-bis(2,6-difluoro-3-(1H-pyrrol-1-yl)-phenyl) titanium (Irgacure 784), 1-[4-(2-hydroxyethoxy)-phenyl]-2-hydroxy-2-methyl-1-propane-1-one (Irgacure 2959), 2,4,6-trimethylbenzoyldiphenylphosphine oxide (TPO), 2,2-dimethoxyphenyl-2-acetophenone (DMPA), and mixtures thereof.

6. The composition according to any one of claims 1 to 5, wherein the photoinitiator is at a concentration ranging from 0.1% to 2% by mass relative to the total mass of the composition.

7. The composition according to any one of claims 1 to 6, wherein the photopolymerizable resin is selected from: urethane acrylate resins, urethane methacrylate resins, epoxy acrylate resins, and mixtures thereof; preferably the photopolymerizable resin is selected from urethane acrylate resins, urethane methacrylate resins, difunctional epoxy acrylate resins and mixtures thereof; more preferably the photopolymerizable resin is selected from: a urethane acrylate resin, a urethane methacrylate resin and mixtures thereof; even more preferably the photopolymerizable resin is selected from aliphatic urethane acrylate resins, hydrophobic urethane acrylate resins, aromatic urethane acrylate resins, polyether urethane acrylate resins, aliphatic urethane methacrylate resins, hydrophobic urethane methacrylate resins, aromatic urethane methacrylate resins, polyether urethane methacrylate resins and mixtures thereof.

8. The composition according to any one of claims 1 to 7 wherein the photopolymerizable resin is at a concentration ranging from 10% to 94.9% by mass relative to the total mass of the composition.

9. The composition according to any one of claims 1 to 8 for use in adhering non-mineralized biological tissues together; for adhering a material to a non-mineralized biological tissue; for adhering a glue or substance to the surface of a non-mineralized biological tissue; as a surgical sealant on a non-mineralized biological tissue; for sealing or plugging orifices created by suturing with thread or with staples or by tissue resection in a non-mineralized biological tissue; for sealing an orifice, an incision or a tear in a non-mineralized biological tissue; as a hemostatic agent to stop bleeding on a non-mineralized biological tissue; as a dressing on a non-mineralized biological tissue to cover and protect a wound; for reinforcing a non-mineralized biological tissue; for preventing the formation of lesions on a non-mineralized biological tissue; for fixing and stabilizing a non-mineralized biological tissue; and / or for treating skin lesions.

10. The composition for use according to claim 9 comprising contacting the composition with the non-mineralized biological tissue to be treated preferably by spreading; and photopolymerizing said composition.

11. A method for preparing a polymerizable composition intended for use as an adhesive for non-mineralized biological tissues comprising a step of mixing: - at least one polymerizable monomer comprising an acrylate, methacrylate, acrylamide or methacrylamide function and not comprising a phosphate or phosphonate function; - at least one photoinitiator; and - at least one photopolymerizable resin; said mixture not comprising a monomer comprising a phosphate or phosphonate function on the one hand and an acrylate, methacrylate, acrylamide or methacrylamide function on the other hand.

12. The method according to claim 11 wherein the mass of the polymerizable monomer ranges from 5% to 60% by mass relative to the total mass of said mixture; and the mass of the photoinitiator ranges from 0.1% to 5% by mass relative to the total mass of said mixture.

13. A kit comprising a device containing the polymerizable composition according to any one of claims 1 to 8.

14. The kit according to claim 13 further comprising a radiation source.