A highly radiopaque, highly fluid prepolymer composition that enables deep photopolymerization.

Abstract

The present invention provides a photocurable dental composition that possesses high fluidity and high radiopaqueness, enabling deep light penetration. [Solution] The present invention relates to a highly fluid crosslinkable medical or dental composition, wherein the highly fluid composition comprises a crosslinkable compound, a polymerization initiator, and a solid heterogeneous radioactive opaque agent. i. It has radiopaqueness of at least 3 mmAl / mm according to ISO13116-2014, ii. It remained stable and dispersed for 30 days, iii. It has a fluidity of more than 40 mm according to ISO 6876-2012, and iv. The average particle size of the heterogeneous radioactive opalescent agent is 1 to 500 nm. Also disclosed are crosslinked polymer compositions obtained by crosslinking the aforementioned high-flow crosslinkable medical or dental compositions, and the use of the aforementioned high-flow crosslinkable medical or dental compositions for filling cavities or hollow structures in human or animal subjects.

Description

Background Art

[0001] (Field of the Invention) The present invention relates to a highly fluid crosslinkable medical or dental composition comprising a crosslinkable compound, a polymerization initiator and a non-uniform radiation opacifier. Also disclosed are crosslinked polymer compositions obtained by crosslinking the highly fluid crosslinkable medical or dental composition, and the use of the highly fluid crosslinkable medical or dental composition for filling cavities or hollow structures in human or animal subjects.

[0002] In many biomedical applications, depending on whether to fill a cavity or support surrounding tissues, the use of filler or implant materials is relied upon to achieve the purpose. To visualize these materials after implantation, a certain degree of radiopacity is required so that they can be distinguished from the surrounding tissues by X-ray or CT scans. The level of radiopacity required for the material is determined by the surrounding tissues. That is, when the tissue naturally has a high level of radiopacity, the implanted material must exhibit a higher degree of radiopacity in order to achieve a good level of resolution when visualized.

[0003] For some medical filler materials, due to the high X-ray absorption rate of the surrounding tissues (e.g., bone, dentin, and enamel), a particularly high radiopacity is required. Generally, the radiopacity of the material is increased by adding heavy metal-containing salts or oxides such as BaSO4, ZrO2, YbF3, CaWO4, Ti, TiO2, SrCO3, Bi2O3, BiF3, or other bismuth compounds. [1-5] The use of radiation opacifiers has its drawbacks. For example, due to their high opacity, the transmission of light through these materials is significantly inhibited. Also, because the radiopaque particles are of high density, they tend to separate from the medium in which they are dispersed.

[0004] For example, sufficiently high concentrations of such inorganic fillers are required to achieve the level of radiopaqueness required for dental or endodontic filler applications (>3 mmAl / mm). Adding macro or micro powders of such inorganic fillers to highly fluid aqueous prepolymer solutions significantly reduces fluidity, thus hindering injection through small cannulas and / or effective filling of tubular, hollow structures, voids, or cavities. Furthermore, adding these inorganic powders to highly fluid formulations leads to unstable dispersion, potentially causing the filler particles to separate during injection, solidification, or storage, resulting in the formulation's injectability and uniformity being compromised. In addition, inorganic particles strongly absorb and scatter light, hindering light penetration into deeper layers of the uncured material, thus reducing the curing depth when used in combination with photopolymerizable formulations.

[0005] This is unfortunate, as the use of photopolymerization offers many advantages over other polymerization approaches. Polymerization methods initiated by heat and pressure are limited to biomedical applications because they can harm surrounding tissues, whereas photopolymerization can be achieved using UV or visible light. Another alternative, the two-component redox method, requires mixing immediately before application, making its use more cumbersome and complex. They also impose time constraints, increasing the potential for procedural errors. Photopolymerization, on the other hand, can be selectively initiated when the uncured material has been properly and sufficiently applied.

[0006] WO2018 / 011680 (ECOLE POLYTECHNIQUE FED DE LAUSANNE (EPFL) [CH]) presented a low-viscosity crosslinkable material adapted for delivery to small (diameter range of 10–1000 μM) branched tubular structures. Compositions containing heavy metal-containing radiopaque particles (1–800 μm) obtained high levels of radiopaqueness (up to 68 mmAl / mm). Disadvantages included limited dispersion stability leading to particle separation and aggregation, thus hindering the uniformity and injectability of the composition, and further hindering photopolymerization depth due to light absorption and scattering caused by the particles. These problems were overcome by replacing the particles with water-soluble iodine-containing compounds, but when these iodine-based compounds were used within the polymer network, they diffused. Therefore, it is not possible to visualize the polymerized material after leaching of the radiopaque agent. Examples of commercially available iodine-based contrast agents include Iopamiro, Iopamiron, Iopamidol, Cystografin, DaTscan, Isovue, and Diatrizoate.

[0007] The radiopaque inorganic filler needs to remain within the polymer after curing so that it can always be visualized by X-rays while the material is implanted.

[0008] WO2017 / 149242 (MATHYM[FR]) and WO2018 / 087495 (MATHYM[FR]) present the development and preparation of heavy element-containing fluoride nanoparticles with a diameter of less than 100 nm that form stable suspensions. WO2020 / 109477 (MATHYM[FR]) presents a method for preparing zirconium dioxide nanoparticles that are also stable suspensions.

[0009] EP 1 734 088 A1 (CANON KK [JP]) presents an aqueous ink composition using a water-soluble nonionic photoinitiator containing a poly(ethylene glycol) portion, (poly(ethylene glycol)(2,4,6-trimethylbenzoyl)phenyl phosphinate). This photoinitiator can exhibit high initiation efficiency in aqueous media.

[0010] A photocurable composition is needed that possesses high fluidity and high radiopaqueness, allowing for deep light penetration. In summary, it must satisfy the following characteristics: A highly fluid liquid composition that maintains a stable suspension during storage; Inorganic radiopaque fillers must not interfere with the photopolymerization yield or curing depth, including the level of light transmission by absorption, light scattering, or any other means.

[0011] (Brief description of the present invention) The present invention relates to a highly fluid, crosslinkable medical or dental composition, wherein the highly fluid composition comprises a crosslinkable compound, a polymerization initiator, and a solid, heterogeneous radioactive opaque agent. i. It has radiopaqueness of at least 3 mmAl / mm according to ISO13116-2014, ii. It remained stable and dispersed for 30 days, iii. It has a fluidity of more than 40 mm according to ISO 6876-2012, and iv. The average particle size of the heterogeneous radioactive opalescent agent is 1 to 500 nm.

[0012] A crosslinkable compound composition containing heavy metal-containing insoluble nanoparticles exhibiting high levels of radiopaqueness (>3 mmAl / mm) was able to maintain a stable suspension without separation or aggregation during storage. Furthermore, the composition exhibited sufficiently high fluidity to be injected through a narrow cannula of approximately 31G with an inner diameter of 0.13 mm and an outer diameter of 0.26 mm. Surprisingly, the use of such nanoparticles reduces light absorption and scattering, resulting in a highly transparent composition with increased light transmittance and consequently a higher curing depth.

[0013] The radiopaque materials used are water-insoluble, highly radiopaque nanoparticles with a diameter of 1 to 500 nm. They may consist of, but are not limited to, metal salts such as barium sulfate, ytterbium halide, bismuth halide, and calcium tungstate; metal oxides such as ytterbium oxide, zirconium oxide, tantalum oxide, cerium dioxide, yttrium oxide, gadolinium oxide, and aluminum oxide; heavy metal-containing silicate glass; and combinations thereof.

[0014] A further object of the present invention is to provide a crosslinked polymer composition obtained by crosslinking the highly fluid crosslinkable medical or dental composition of the present invention, wherein its radiopaqueness of at least 3 mmAl / mm remains unchanged when immersed in an aqueous medium for at least 24 days.

[0015] Another object of the present invention is to provide a process for preparing highly fluid, crosslinkable medical or dental compositions that can be cured to a high depth.

[0016] Once polymerized, the material can permanently maintain its radiopaque properties. Even when the cross-linked material is completely immersed in water, no leaching of the radiopaque material is observed.

[0017] Another object of the present invention is the use of the highly fluid crosslinkable medical or dental composition for filling teeth, dental root canals or dental hiatuses, blood vessels, lymphatic vessels, bronchi and bronchial cavities or hollow structures, or bone cavities in human or animal subjects.

[0018] Other objects and advantages of the present invention will become apparent to those skilled in the art by considering the following detailed description, which proceeds with reference to the accompanying claims. [Modes for carrying out the invention]

[0019] (Detailed description of the invention) Methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present invention, but suitable methods and materials are described below. All publications, patent applications, patents, and other references cited herein are incorporated by reference in their entirety. The publications and applications discussed herein are provided only for their disclosure prior to the filing date of the present application. Nothing in this specification is to be construed as an admission that the present invention is not entitled to antedate such disclosure by virtue of prior invention. Further, the materials, methods, and examples are illustrative only and not intended to be limiting.

[0020] In case of conflict, the present specification, including definitions, will control.

[0021] Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this disclosure belongs. As used herein, the following definitions are provided to facilitate understanding of the present invention.

[0022] As used in the specification and claims, the singular forms "a", "an", and "the" include plural references unless the context clearly dictates otherwise.

[0023] In some cases, the presence of broad words or phrases such as "one or more", "at least", "including but not limited to", or other similar phrases should not be read to imply that a narrower case is intended or required in instances where such broad phrases may not be present.

[0024] The terms "preferred" and "preferably" refer to embodiments of the present disclosure that may provide certain advantages under certain circumstances. However, other embodiments may also be preferred in the same or other circumstances. Further, the description of one or more preferred embodiments is not meant to imply that other embodiments are not useful, nor is it intended to exclude other embodiments from the scope of the present disclosure.

[0025] The term "substantially" with respect to a property or characteristic means that the property or characteristic is shown to a greater extent than its opposite is shown.

[0026] Also, the use of "or" means "and / or" unless otherwise specified.

[0027] Similarly, "comprise", "comprises", "comprising", "include", "includes" and "including" are interchangeable and not intended to be limiting. The term "comprise" is generally used in the sense of including, that is, to allow for the presence of one or more features or components.

[0028] When the description of various embodiments uses the term "comprising", those skilled in the art should further understand that in some specific examples, the embodiments can alternatively be described using the language "consisting essentially of" or "consisting of".

[0029] Also, in this specification, the description of a numerical range by endpoints includes all numerical values included within that range (for example, 1 to 5 includes 1, 1.5, 2, 2.75, 3, 3.80, 4, 5, etc.).

[0030] Unless otherwise indicated, all numerical values ​​used herein and in the embodiments to represent quantities or measurements of materials, properties, etc., are understood in all cases to be modified by the term "approximately." Accordingly, unless otherwise indicated, the numerical parameters described herein and in the appended list of embodiments may vary depending on the desired properties that a person skilled in the art would seek to obtain using the teachings of this disclosure. Not to limit the application of the doctrine of equivalents to the scope of the claimed embodiments, each numerical parameter should be interpreted by applying ordinary rounding techniques, at least in light of the reported number of significant figures.

[0031] Within the scope of this disclosure, the term “composition” is interchangeable with the term “compound.” As used herein, “composition” refers to a mixture of materials or compounds prepared in a certain manner and used for a particular purpose. This concept is also clearly related to methods of combining different compounds to produce a final product.

[0032] The term "prepolymer" refers to a monomer or system of monomers that has reacted to an intermediate molecular weight state. This material can be further polymerized by reactive groups to a fully cured, high molecular weight crosslinked state. Thus, a mixture of a reactive polymer and an unreacted monomer can be called a prepolymer. The terms "prepolymer" and "polymer precursor" are interchangeable. A prepolymer is a stable, usually partially polymerized, chemical intermediate that can later be fully polymerized.

[0033] The term "curing" means the curing or partial curing of a composition by any mechanism, such as heat, light, radiation, electron beam, microwave, chemical reaction, or a combination thereof.

[0034] The terms "precursor," "precursor composition," or "polymer precursor" refer to a substance before a chemical reaction (polymerization). The terms "prepolymer," "polymer precursor," or "polymer intermediate" are interchangeable.

[0035] When it is stated that two or more parts are selected "independently" from a list of atoms or groups, this means that those parts may be the same or different. Therefore, the identity of each part is independent of the identity of one or more other parts.

[0036] In polymer science, the "backbone" chain of a polymer is the longest series of covalently bonded atoms that work together to form a continuous chain of molecules. This science is subdivided into the study of organic polymers, which consist of a carbon backbone, and inorganic polymers, which have backbones containing only major group elements.

[0037] End groups are an important aspect of polymer synthesis and characterization. In polymer chemistry, end groups are functional groups or structural units located at the ends of polymers or oligomers (IUPACs). In polymer synthesis, such as condensation polymerization and free radical polymerization, end groups are commonly used and can be analyzed, for example, by nuclear magnetic resonance (NMR) to determine the average length of the polymer. Other methods for characterizing polymers in which end groups are used include mass spectrometry and vibrational spectroscopy such as infrared spectroscopy and Raman spectroscopy. These groups are not only important for polymer analysis, but they are also useful for graft polymerization into and from polymer chains to create new copolymers. Finally, they can also be used for crosslinking polymers.

[0038] "(meth)acrylate" is an abbreviation for acrylate, methacrylate, or a combination thereof; "(meth)acrylic" is an abbreviation for acrylic, methacrylic, or a combination thereof; and "(meth)acrylic" is an abbreviation for acrylic, methacrylic, or a combination thereof.

[0039] Here, the terms "highly flowable" or "high flowability" refer to a flow test result of more than 40 mm according to ISO 6876-2012. High flowability is due to low viscosity. ISO 6876-2012 (defined in "Dentistry-Root Canal Sealing Materials" (ISO 6876-2012)) specifies the requirements and test methods for root canal (endodontic) sealing materials that harden with or without the help of moisture and are used for permanent occlusion of root canals with or without the help of point / cone occlusion. It covers only sealers intended for orthograde use, i.e., root fillings placed from the coronal surface of the tooth.

[0040] Flow rate measurements were performed in accordance with ISO 6876-2012. 50 μL of the specified formulation was placed between two glass slides (40 mm × 40 mm × 5 mm; 20 g). A weight (100 g) was placed on top of the slides. After 10 minutes, the minimum and maximum diameters of the spread formulation were measured.

[0041] "Uniform" or "homogeneity" refers to a mixture of solids or liquids where the proportions of their components are the same throughout the given sample.

[0042] "Radiopaqueness" or "radiation density" is the opacity of a material to the radio wave and X-ray portions of the electromagnetic spectrum, measured according to ISO 13116-2014 (as defined in "Dentistry - Test Method for Determining Radio-Opacity of Materials" (ISO 13116-2014)). It means that electromagnetic radiation cannot pass through a particular material.

[0043] A "radioactive opacifier" is a radiopaque material added to a composition to enhance its radiopaque properties.

[0044] "High radiopaqueness" refers to materials that have a radiopaqueness of at least 3 mmAl / mm.

[0045] "Heterogeneity" or "heterogeneity" refers to the state in which components of a mixture are in a different state of matter (e.g., gas, liquid, or solid) compared to the state of the remaining components in the mixture.

[0046] "Total attenuation" refers to the sum of both absorption and scattering of light or other forms of electromagnetic radiation.

[0047] The term "cured" refers to a material or composition that has been solidified or partially solidified by a chemical reaction (e.g., (co)polymerization or crosslinking).

[0048] "Curing depth" refers to the depth to which a certain volume of material can be photopolymerized by exposing it to light from above. The curing depth depends on the activity of the photoinitiation system and the ability of light to penetrate deep into the material. Therefore, highly transparent materials with low absorption of light at the wavelength used for photoinitiation result in a high curing depth. Absorption or total attenuation can be measured with a UV-Vis spectrometer through a 1 cm cuvette.

[0049] A "curved structure" refers to a type of mold that has a conical or cylindrical structure that is curved to a certain depth.

[0050] In polymer chemistry, "crosslinking" typically refers to the process of using crosslinking to facilitate changes in the physical properties of a polymer. The term crosslinking refers to the bonding that links one polymer chain to another. These linkages can take the form of covalent bonds (chemical crosslinking), or they can be due to hydrogen bonding, hydrophobic interactions, or chain entanglement (physical crosslinking). Polymers can be either synthetic or natural polymers. Crosslinking is a general term for the method of forming a relatively short sequence of bonds or chemical bonds to join two polymer chains together. In polymer chemistry, when a synthetic polymer is said to be "crosslinked," it usually means that the entire bulk of the polymer has been subjected to a crosslinking method. The resulting modification of mechanical properties depends heavily on the crosslinking density. Low crosslinking densities result in low fluidity of the polymer molten material. Intermediate crosslinking densities transform rubbery polymers into materials with elastomeric properties and potentially high strength. Very high crosslinking densities can make materials extremely hard or glassy, ​​such as phenol-formaldehyde materials. Crosslinking can be formed by chemical reactions that can be initiated by heat, pressure, pH changes, or irradiation. For example, when an unpolymerized or partially polymerized material is mixed with certain chemicals called crosslinking reagents, a chemical reaction occurs that forms crosslinks. Crosslinking can also be induced in materials that are normally thermoplastic by exposure to radiation sources such as electron beams, gamma rays, or UV light.

[0051] The term "crosslinkable" is used herein to refer to a material that can be crosslinked, also defined as a prepolymer.

[0052] A "polymerization initiator" refers to a compound that initiates the crosslinking of monomer units.

[0053] One object of the present invention is to provide a dispersed, highly fluid, crosslinkable medical or dental composition comprising a crosslinkable compound, a polymerization initiator, and a heterogeneous radioactive opaque agent. i. It has radiopaqueness of at least 3 mmAl / mm according to ISO13116-2014, ii. It remained stable and dispersed for 30 days, iii. It has a fluidity of more than 40 mm according to ISO 6876-2012, and iv. The average particle size of the heterogeneous radioactive opalescent agent is 1 to 500 nm.

[0054] High fluidity is a result of low viscosity. In a preferred embodiment, the composition is 2 × 10 -4 ~1 × 10 3 It has a viscosity of Pa·s, which makes it highly fluid. The viscosity is 1 to 300 s at room temperature (22°C). -1 The shear rate is measured by rheology. The ratio between shear stress and shear rate corresponds to viscosity and remains constant even when the shear rate changes in the case of Newtonian behavior.

[0055] Compositions of crosslinkable compounds and heavy metal-containing insoluble nanoparticles exhibiting high levels of radiopaqueness (>3 mmAl / mm) were able to maintain a stable suspension during storage. Furthermore, the compositions exhibited sufficient fluidity to be injected through small cannulas (30G with inner diameter 0.16 mm and outer diameter 0.31 mm). Surprisingly, due to reduced light absorption and scattering in such nanoparticles, the compositions were extremely transparent (see Example 10) and exhibited high photopenetration, i.e., a high curing depth (>40 mm) could be achieved using a laser (λ=405 nm, p=4 mW) for 20 seconds.

[0056] The radiopaque material used is water-insoluble, highly radiopaque (>3 mmAl / mm) nanoparticles with a diameter of 1 to 1000 nm. In a preferred embodiment, the nanoparticles have a diameter of 1 to 100 nm. In a more preferred embodiment, the nanoparticles have a diameter of 1 to 20 nm. In the most preferred embodiment, the nanoparticles have a diameter of 1 to 5 nm.

[0057] According to embodiments of the present invention, a highly fluid, crosslinkable medical or dental composition is photopolymerized to a curing depth of at least 1 mm. More preferably, it is photopolymerized to a curing depth of at least 10 mm. Most preferably, it is photopolymerized to a curing depth of at least 20 mm.

[0058] According to another embodiment, the heterogeneous radioactive opaler is in the form of a powder or suspension and is selected from the group consisting of water-insoluble metals, or metal oxides, metal salts, or metal complexes. Preferably, the heterogeneous radioactive opaler is selected from the group consisting of or including metal salts such as barium sulfate, ytterbium halide, bismuth halide, calcium tungstate, or metal oxides such as ytterbium oxide, zirconium oxide, tantalum oxide, cerium dioxide, yttrium oxide, gadolinium oxide, aluminum oxide; heavy metal-containing silicate glass; and / or combinations thereof.

[0059] According to a preferred embodiment, the highly fluid crosslinkable medical or dental composition of the present invention further comprises a suitable solvent, the suitable solvent comprising or consisting of water, acetone, DMSO, or alcohol, or a mixture thereof.

[0060] The term "suitable solvent" as used herein refers to a non-reactive solvent that does not (co)polymerize with a highly fluid, crosslinkable medical or dental composition, also known herein as a curable composition, and that uniformly dissolves the components of the composition at the required concentration without inhibiting the polymerization reaction.

[0061] According to a preferred embodiment, a suitable solvent essentially consists of water (including deionized or ionic or buffering agents), acetone, DMSO, alcohols, or mixtures thereof. In another embodiment of the present invention, a suitable solvent may include other reagents or compounds. In yet another embodiment, these reagents or compounds are NaOCl, EDTA, HEDP, chlorhexidine, NaOH, Ca(OH)2, or other reagents commonly used for irrigating, disinfecting, or irrigating dental root canals.

[0062] In particular, the highly fluid crosslinkable medical or dental composition of the present invention, also called a photocurable highly radiopaque prepolymer composition, contains 5 to 90% by weight of a crosslinkable compound, 5 to 90% by weight of a heterogeneous radioactive opacifier, 5 to 90% by weight of a suitable solvent, and 0.001 to 10% by weight of a polymerization initiator. Preferably, the highly fluid composition of the present invention contains 20 to 70% by weight of a crosslinkable material, 20 to 60% by weight of a heterogeneous radioactive opacifier, 5 to 60% by weight of a suitable solvent, and 0.001 to 2% by weight of a polymerization initiator.

[0063] Embodiments of the highly fluid crosslinkable medical or dental compositions of the present invention preferably contain about 36 to 90% by weight of heterogeneous radiocaprate, particularly 36 to 60% by weight of heterogeneous radiocaprate, or particularly 36 to 40% by weight of heterogeneous radiocaprate. Such a content of heterogeneous radiocaprate is advantageous in that it allows for the achievement of a desired level of radiopaqueness.

[0064] The heterogeneous radioactive opaler may preferably have an average particle size of 5 to 20 nm as measured by a transmission electron microscope.

[0065] Embodiments of the composition of the present invention may preferably contain about 20 to 90% by weight of a suitable solvent, particularly 30 to 60% by weight of a suitable solvent, or particularly 30% by weight of a suitable solvent.

[0066] According to one embodiment of the present invention, the polymerization initiator is a UV or visible light photoinitiator. A quasi-stoichiometric amount of photoinitiator is required to initiate the polymerization reaction. This photoinitiator is activated by a UV or visible light photoinitiator and is selected from the group including, but not limited to, quinones, α-hydroxyketones, acylgermanium derivatives, bis(acyl)phosphine oxide derivatives, mono(acyl)phosphine oxide derivatives, or mixtures thereof.

[0067] According to further embodiments of the present invention, the crosslinkable compound is water-soluble. Preferably, the water-soluble crosslinkable compound comprises or consists of a polymer functionalized with polymerizable terminal groups.

[0068] In particular, crosslinkable compounds contain terminal groups that have the ability to polymerize when initiated by a polymerization initiator via chemical, thermal, or light energy.

[0069] According to a preferred embodiment, the crosslinkable compound comprises terminal groups having the ability to polymerize when initiated by a polymerization initiator; and is also water-soluble. In a more preferred embodiment of the present invention, the water-soluble crosslinkable prepolymer has formula I: JPEG2026053612000001.jpg140164R1 and R2 are such that R1 is either the same as or different from the terminal group of R2, where R1 and R2 are selected from the group consisting of methoxy; acrylate; methacrylate; acrylamide; methacrylamide; and vinyl sulfone; except that when R1 is methoxy, R2 is not methoxy.

[0070] A further object of the present invention is to provide a process for preparing a highly fluid, crosslinkable, and highly radiopaque composition that can be cured to a high depth, the process comprising the following steps: a) Dissolve the crosslinkable compound in a suitable solvent (as defined above); b) Add a stable suspension of insoluble, radiopaque nanoparticles; c) Add the radical photopolymerization initiator as a solution in a suitable solvent or as a fine powder.

[0071] As shown in Example 10, the uniformity and fluidity of different radioactive opacities in crosslinkable compound formulations or dispersions were investigated. Radioactive opacities with a diameter greater than 1 μm separated into the formulation over a period of 30 days or less. On the other hand, formulations containing nanoparticle-sized radioactive opacities remained suspended throughout a 30-day period between 5 and 37°C. Formulations without radioactive opacities or those containing radioactive opacities with a diameter of 5 to 20 nm passed easily through a 30G cannula and did not separate in the syringe after 1 hour. Other radiopaque powders tested were difficult or impossible to pass through the cannula and mostly separated in the syringe. Flow measurements according to ISO 6876-2012 showed that formulations without radioactive opacities or radiopaque nanoparticles spread beyond the limits of the apparatus (over 40 mm).

[0072] Furthermore, all radioactive opaque agents with a diameter greater than 1 μm were separated in the formulation over a period of 30 days.

[0073] The polymerization yield of the radiopaque formulation was evaluated in polystyrene cuvettes, as in Example 6. The results showed that nano-radioactive opacifiers did not inhibit polymerization, but the larger radioactive opacifier particles tested dramatically inhibited polymerization or separated within the material formulation and polymerized effectively (see Examples 10 and 11).

[0074] When polymerization was carried out in a conical shape to evaluate the polymerization depth in linear and curved structures, radiopaque nanoparticles showed minimal inhibition of curing depth compared to formulations without radioactive opacifiers (see Example 12).

[0075] The required amount of radiopaqueness (>3 mmAl / mm) was evaluated by analyzing the varying concentrations of nanoparticles in the formulation, as shown in Example 13. It was determined that more than 36% w / w of nanoparticles were necessary to achieve the desired level of high radiopaqueness.

[0076] A further object of the present invention is to provide a crosslinked polymer composition obtained by crosslinking the highly fluid crosslinkable medical or dental composition of the present invention, wherein its radiopaqueness of at least 3 mmAl / mm according to ISO 13116-2014 remains unchanged even when immersed in an aqueous medium for at least 24 days.

[0077] Once polymerized, the crosslinked polymer composition can maintain its radiopaqueness for the lifetime of the implanted material, which can be up to 50 years. When the crosslinked polymer composition was completely immersed in water and PBS buffer for 24 days, no loss of radiopaqueness was observed, as can be seen in Example 9.

[0078] Another object of the present invention is the use of highly fluid, crosslinkable medical or dental compositions for filling teeth, root canals or dental hiatuses, blood vessels, lymphatic vessels, bronchi and bronchial cavities or hollow structures, or bone cavities in human or animal subjects.

[0079] Advantageously, the highly fluid crosslinkable medical or dental composition can be injected through a small 31G cannula with an inner diameter of 0.13 mm and an outer diameter of 0.26 mm, and the highly fluid composition can be photopolymerized to a curing depth of at least 1 mm in a curved tubular structure.

[0080] Those skilled in the art will understand that the inventions described herein are susceptible to variations and modifications other than those specifically described. It is understood that the inventions include all such variations and modifications without departing from their spirit or essential characteristics. Furthermore, the inventions include, individually or collectively, all steps, features, compositions and compounds mentioned or indicated herein, as well as any and all combinations or two or more of the aforementioned steps or features. Therefore, this disclosure is considered non-limiting in all exemplary embodiments, and the scope of the inventions is indicated by the appended claims, intended to encompass all modifications that fall within the meaning and equivalence thereof.

[0081] Various sources are cited throughout this specification, each of which is incorporated in its entirety by reference.

[0082] The above description will be better understood by referring to the following embodiments. However, these embodiments are illustrative of ways of carrying out the present invention and are not intended to limit the scope of the invention. [Examples]

[0083] material Unless otherwise noted, all synthetic reagents, crosslinking reagents, and radioactive opacifiers were obtained from general chemical laboratories. Heavy metal-containing glass powders were obtained from SCHOTT AG - BU Electronic Packaging, Landshut, Germany. Nanoparticle suspensions of radioactive opacifiers were obtained from MATHYM SAS, Champagne Au Mont d'Or, France.

[0084] Example 1: Synthesis Poly(ethylene glycol) 6k (1 equivalent) and triethylamine (1.5 equivalents) were added to dry DCM (0.17 M) in a round-bottom flask equipped with a magnetic star bar. Next, methacryloyl chloride (freshly distilled, 1.3 equivalents) was added at 0°C, and the reaction was stirred and left overnight in the dark at 25°C. Once completed, the mixture was passed through a basic alumina column using DCM as the eluent. The filtrate was concentrated to approximately 5% volume under reduced pressure. The resulting crude oil was added to diethyl ether, which was rapidly stirred at room temperature, and stirred for 30 minutes. The mixture was then cooled to 0°C and stirred for a further 30 minutes. The precipitate was collected by vacuum filtration over frit, washed with diethyl ether, and dried under high vacuum to obtain the product poly(ethylene glycol) dimethacrylate 6k (PEG-DMA 6k) as a white solid. 1H NMR (d6-DMSO, 300 MHz) δ (ppm): 6.03 (t, J = 1.2 Hz, 2H, vinyl), 5.69 (t, J = 1.6 Hz, 2H, vinyl), 4.22 - 4.19 (m, 4H, CH2), 3.67 - 3.63 (m, 4H, CH2), 3.51 (s, skeleton), 1.88 (t, J = 1.1 Hz, 3H, CH3).

[0085] Example 2: Synthesis Pluronic® 10R5 (1 equivalent) was packed into a round-bottom flask coupled with a magnetic stirring rod and dissolved in dry DCM (0.1 M). Dry triethylamine (2 equivalents) was added to the solution. Next, methacryloyl chloride (freshly distilled, 1.75 equivalents) was added at 0°C, and the reaction was stirred and left overnight in the dark at 25°C. After completion, the reaction was quenched with water and extracted with DCM. The combined organic extract was passed through a basic alumina plug and eluted with DCM. Next, the solvent was removed under reduced pressure to obtain a viscous oil. The crude oily residue was dissolved in water and dialyzed against water for 24 hours using a Spectra / Por 6 membrane tube. The dialyzed solution was then freeze-dried until dry to obtain product 10R5-DMA as a viscous colorless oil. ¹H NMR (CDCl3, 300 MHz) δ (ppm): 6.08 (dd, J = 1.0, 1.8 Hz, 2H, vinyl), 5.53-5.52 (m, 2H, vinyl), 5.09-5.02 (m, 1H, CH), 3.63-3.36 (m, PEG and PPG CH framework), 3.41 (t, J = 6.5 Hz, 4H, CH2), 1.92 (m, 6H, CH3), 1.26-1.23 (m, 6H, CH3), 1.13-1.11 (m, PPG CH3 framework).

[0086] Example 3: Synthesis Poly(ethylene glycol) (1 equivalent) was packed into a round-bottom flask coupled with a magnetic stirring rod. Dichloromethane (DCM, 0.17 M) and triethylamine (1.6 equivalents) were added, and the solution was cooled to 0°C. Next, methanesulfonyl chloride (1.25 equivalents) was slowly added, and the reaction was stirred at 0°C for 45 minutes, then warmed to room temperature overnight. After completion, the reaction was quenched with water and extracted with DCM. The aqueous phase was washed with DCM. The combined organic layers were dried on magnesium sulfate. The mixture was filtered, and the filtrate was concentrated to approximately 5% volume under reduced pressure. The resulting crude oil was added to diethyl ether rapidly stirred at room temperature, and stirred for 30 minutes. The mixture was then cooled to 0°C and stirred for another 30 minutes. The precipitate was collected by vacuum filtration on frit, washed with diethyl ether, and dried under high vacuum to obtain poly(ethylene glycol) dimethylate (PEG DOM) as a white solid. 1H NMR (DMSO-d6, 300 MHz) δ (ppm): 4.34-4.27 (m, 4H, MsOCH2), 3.72-3.63 (m, 4H, CH2), 3.51 (br s, backbone), 3.17 (s, 6H, CH3).

[0087] Poly(ethylene glycol) dimethylate was transferred to a round-bottom flask coupled with a magnetic stirring rod. 25% aqueous ammonia solution (approximately 5 mL / mmol or until viscosity decreased) was added to the flask, and it was sealed with a stopper and metal clamp. The reaction was vigorously stirred for approximately 3 days. After confirming complete conversion by 1H NMR, the aqueous layer was extracted 3 / 4 times with dichloromethane, and the combined organic extract was dried over magnesium sulfate and concentrated under reduced pressure, but only a viscous oil was obtained. The remaining residue was vigorously stirred, and then diethyl ether was added until a substantial precipitate was observed. The solution was further cooled in an ice bath to maximize the precipitate yield. The precipitate was collected by vacuum filtration over frit, washed with diethyl ether, and further dried under high vacuum to obtain poly(ethylene glycol)diamine 2k as a white solid. 1H NMR (DMSO-d6, 300 MHz) δ (ppm): 3.51 (br s, backbone), 3.36 (t, J = 5.8 Hz, 4H, CH2), 2.66 (t, J = 5.7 Hz, 4H, CH2).

[0088] Poly(ethylene glycol)diamine (1 equivalent) was packed into a round-bottom flask fitted with a magnetic stirring rod and dissolved in dichloromethane (0.18 M). Acryloyl chloride (distilled, 1.65 equivalents) was added, followed by sodium hydroxide solution (1 M, 1.6 equivalents). The two-phase solution was vigorously stirred at 25°C for 1.5 hours (up to 5 hours). After the reaction was complete (evaluated by 1H NMR), sodium hydroxide solution (1 M, 1.6 equivalents) was added, and the mixture was stirred for 5 minutes. The mixture was transferred to a separatory funnel, and the aqueous layer was extracted by DCM. The organic phase was passed through a basic alumina plug. This plug was washed with DCM as the eluent. Next, the solvent was removed under reduced pressure, but only a viscous oil remained. The remaining residue was vigorously stirred. Then, diethyl ether was added until a more pronounced precipitate was observed. The solution was further cooled in an ice bath to maximize the precipitate yield. The precipitate was collected by vacuum filtration on frit and washed with diethyl ether. This white powder was dried under high vacuum to remove the ether, and then freeze-dried to obtain poly(ethylene glycol)diacrylamide 2K. 1H NMR (CDCl3, 300 MHz) δ (ppm): 6.54 (br s, 2H, NH), 6.28 (dd, J = 1.5, 17.0 Hz, 2H, vinyl), 6.14 (dd, J = 10.0, 17.0 Hz, 2H, vinyl), 5.61 (d, J = 10.0 Hz, 2H, vinyl), 3.63 (br s, backbone), 3.52 (dd, J = 5.0, 10.1 Hz, 4H, CH2);13C NMR (CDCl3, 75 MHz) δ (ppm): 165.7, 131.2, 126.2, 70.7, 70.4, 69.9, 39.4.

[0089] Example 4: Synthesis Poly(ethylene glycol) (1 equivalent) was packed into a round-bottom flask coupled with a magnetic stirring rod. Dichloromethane (DCM, 0.17 M) and triethylamine (1.6 equivalents) were added, and the solution was cooled to 0°C. Next, methanesulfonyl chloride (1.25 equivalents) was slowly added, and the reaction was stirred at 0°C for 45 minutes, then warmed to room temperature overnight. After completion, the reaction was quenched with water and extracted with DCM. The aqueous phase was washed with DCM. The combined organic layers were dried on magnesium sulfate. The mixture was filtered, and the filtrate was concentrated to approximately 5% by volume under reduced pressure. The resulting crude oil was added to diethyl ether, which was rapidly stirred at room temperature, and stirred for 30 minutes. The mixture was then cooled to 0°C and stirred for a further 30 minutes. The precipitate was collected by vacuum filtration on frit, washed with diethyl ether, and dried under high vacuum to obtain poly(ethylene glycol) dimethylate as a white solid. 1H NMR (DMSO-d6, 300 MHz) δ (ppm): 4.34-4.27 (m, 4H, MsOCH2), 3.72-3.63 (m, 4H, CH2), 3.51 (br s, backbone), 3.17 (s, 6H, CH3).

[0090] A round-bottom flask, fitted with a magnetic stirring rod, was packed with dry THF (0.15 M) and sodium hydride (2 equivalents, 60% dispersion in mineral oil) under an argon atmosphere. The solution was cooled in an ice bath, and 1,3-propanediol (2.5 equivalents) was slowly added. The mixture was allowed to stand for 6 hours, stirring while being warmed to room temperature. Next, polyethylene glycol dimethylate (1 equivalent) was slowly added to the mixture. A reflux condenser was then connected, and the reaction mixture was heated under reflux overnight. When complete conversion was achieved, the reaction mixture was cooled to room temperature. After cooling, water and dichloromethane were added. The aqueous phase was further extracted with dichloromethane (2 / 3 times). The combined organic extract was dried on magnesium sulfate and concentrated under reduced pressure to approximately 5% volume. The remaining residue was vigorously stirred, and then diethyl ether was added until a substantial precipitate was observed. The solution was further cooled in an ice bath to maximize the precipitate yield. The precipitate was collected by vacuum filtration on frit, washed with diethyl ether, and dried under high vacuum to obtain poly(ethylene glycol)di(propane-3-ol) 2k as a white solid. ¹H NMR (DMSO-d6, 300 MHz) δ (ppm): 4.34 (t, J = 5.2 Hz, 2H, OH), 3.51 (br s, skeleton), 1.63 (p, J = 6.5 Hz, 4H, CH2).

[0091] Poly(ethylene glycol)di(propane-3-ol) (1 equivalent) was packed into a round-bottom flask coupled with a magnetic stirring rod and dissolved in dry DCM (0.17 M). Triethylamine (1.5 equivalents) was added to the solution. Next, methacryloyl chloride (freshly distilled, 1.3 equivalents) was added at 0°C, and the reaction was stirred and left overnight in the dark at 25°C. Once completed, the mixture was passed through a basic alumina column using DCM as the eluent. The filtrate was concentrated to approximately 5% volume under reduced pressure. The resulting crude oil was added to diethyl ether rapidly stirred at room temperature and stirred for 30 minutes. The mixture was then cooled to 0°C and stirred for another 30 minutes. The precipitate was collected by vacuum filtration on frit, washed with diethyl ether, and dried under high vacuum to obtain poly(ethylene glycol)di(propane-3-methacrylate) 2k as a white solid. 1H NMR (CDCl3, 300 MHz) δ (ppm): 6.01 (dd, J = 0.8, 1.7 Hz, 2H, vinyl), 5.47 (t, J = 1.7 Hz, 2H, vinyl), 4.16 (t, J = 6.4 Hz, 4H, CO2CH2), 3.57 (br s, 13C NMR (CDCl3, 75 MHz) δ (ppm): 167.3, 136.3, 125.2, 70.6, 70.5, 70.2, 67.7, 61.8, 28.9, 18.2.

[0092] Example 5: Synthesis Ethyl (2,4,6-trimethylbenzoyl)phenyl phosphinate (TPO-L, 1 equivalent) was added to 2-butanone (0.6 M) being stirred at room temperature. Then, anhydrous lithium iodide (1.1 equivalents) was added. After 10 minutes, a pale orange solution was obtained. This solution was heated to 60°C in an oil bath and stirred at this temperature for 24 hours. The suspension was cooled to room temperature, filtered, and the filtrate was washed with cold 2-butanone, and then with diethyl ether. The solid material was dried under vacuum. Lithium phenyl-2,4,6-trimethylbenzoyl phosphinate (LAP) was obtained as a white solid.

[0093] One equivalent of the LAP product was dissolved in 0.5 M distilled water and vigorously stirred at room temperature. Dilute aqueous sulfuric acid was then added until a precipitate formed. Ethyl acetate was added to the resulting suspension and vigorously stirred, after which the phases were separated. The aqueous layer was further extracted with ethyl acetate. The combined organic layers were washed with distilled water and dried on anhydrous sodium sulfate. After evaporating the solvent under reduced pressure, a pale yellow solid was obtained. This yellow compound was dissolved in 0.4 M dichloromethane. Then, 2 equivalents of oxalyl chloride were added in fractions at room temperature. After 20 hours, the mixture was evaporated under reduced pressure. Dry toluene was added to the residual oil and evaporated again to dryness to obtain a yellow oil, which was used in the next step without further purification.

[0094] Dichloromethane (0.1 M) was added to yellow oil (1.75 equivalents), followed by the addition of poly(ethylene glycol) methyl ether (950 g / mol; 1 equivalent) and triethylamine (2 equivalents). The reaction mixture was stirred overnight at room temperature. The solution was then concentrated under vacuum to obtain yellow oil, which was vigorously stirred, and diethyl ether was added until a substantial precipitate was observed. The flask was further cooled to maximize the precipitate yield. The precipitate was collected by vacuum filtration, washed with diethyl ether, and dried under high vacuum to obtain poly(ethylene glycol) methyl ether (2,4,6-trimethylbenzoyl)phenyl phosphinate (LAP-PEG) as a white solid. 1H NMR (300 MHz, deuterium oxide) δ 7.88 - 7.74 (m, 3H), 7.62 (td, J = 7.6, 3.9 Hz, 2H), 6.95 (s, 2H), 4.30 - 4.23 (m, 2H), 3.71 (s, PEG backbone), 3.57 (s, 5H), 3.40 (s, 3H), 2.27 (s, 3H), 2.08 (s, 6H);31P NMR (121 MHz, deuterium oxide) δ 19.5;13C NMR (75 MHz, deuterium oxide) δ 216.9, 215.4, 141.4, 135.7, 135.1, 134.7, 134.7, 134.4, 132.8, 132.6, 129.5, 129.3, 128.7, 123.6, 71.0, 69.6, 66.2, 66.1, 58.1, 30.2, 20.4.

[0095] Example 6: Measurement Method The photopolymerization yield was determined by gravimetric analysis of the cured polymer mass. A solution containing PEG DMA 6k (15% w / w), poly(ethylene glycol) methyl ether (2,4,6-trimethylbenzoyl)phenyl phosphinate (0.1% w / w), and heterogeneous radioactive opacifier (30% m / m), prepared according to Example 1, was prepared in deionized water. 1000 mg of the premixed solution was loaded into a 2 mL polystyrene cuvette. The cuvette was placed in a blue light source (Atlas Photonics Sarl, LUMOS 43) at a wavelength λ=405 nm and an output density of 200 mW / cm². -2 The sample was irradiated for 2 minutes. The solid hydrogel was removed, the residual liquid was wiped off, and its weight was measured. The ratio of solid cured material to liquid uncured material was calculated and used as the measurement of the photopolymerization yield.

[0096] Example 7: Measurement Method The photopolymerization depth was investigated by irradiating a sample of the material in a white plastic tube. A solution containing PEG DMA 6k (30% w / w), poly(ethylene glycol) methyl ether (2,4,6-trimethylbenzoyl)phenyl phosphinate (0.1% w / w), and different radioactive opacifiers (40% m / m) prepared according to Example 1 was prepared in deionized water. This premixed solution was then placed in a white plastic tube ( The sample (JPEG2026053612000002.jpg88 = 500 μm, length = 4 cm) was injected and irradiated from above for 20 seconds with a dental curing lamp (Dentlight Inc, FUSION 5). After curing, the length of the solid hydrogel was measured and used as a measure of the depth of photopolymerization. To investigate curved structures, the following mold was used:

[0097] There is a cylindrical opening at the top with a diameter of 2 mm and a depth of 4 mm. At the bottom of the cylindrical cavity is a conical opening with a diameter of 1 mm, and there is a taper where the opening decreases in diameter by minus 6% for every 1 mm of depth. After 8 mm there is a 130° bend, which terminates at a diameter of 0.28 mm. The vertical depth of the entire mold was 16 mm.

[0098] Example 8: Sample Preparation The hydrogel sample was prepared using a prepolymer (30% w / w) composition prepared according to Examples 1-4, different radioactive opacifiers (30-40% w / w), poly(ethylene glycol) methyl ether (2,4,6-trimethylbenzoyl)phenyl phosphinate (0.25% w / w), and deionized water in a cylindrical sample form (V = approximately 250 μL). The mixture was pipetteed into a container (8mm = 8mm, height = 5mm) and photopolymerized using a blue light source with a wavelength of 400-460nm. When a radioactive opaque agent was added as an aqueous suspension, the amount of water was reduced as appropriate.

[0099] Example 9: Comparative Example PEG DMA 6k and nano-YbF3 (40% w / w, d) prepared according to Example 1 mean,TEM A 2 mm thick hydrogel sample containing (=20 nm) was prepared according to Example 8. The sample was then immersed in 5 mL of water or phosphate-buffered saline on a shaking plate. The sample was collected after 3, 8, and 24 days. The radiopaqueness of the sample was measured according to ISO 13116-2014. The radiopaqueness per 1 mm of the immersed sample was compared to that of a fresh, unimmersed sample, and no significant difference was found during the immersion period. [Table 1]

[0100] Example 10: Comparative Example Compositions containing different radioactive opacifiers were prepared according to Example 7, and their uniformity, injectability (by ability to pass through a 30G cannula using a PacDent Luer-Lock Endo Irrigation Syringe (1.2 mL; black)), fluidity (according to ISO 6876-2012), and total attenuation through a 1 cm cuvette at 405 nm were compared after storage at 37°C for 30 days. The tests were performed sequentially, and if a sample did not meet the required criteria, it was not subjected to subsequent tests. "-" indicates that the radioactive opacifier was not tested. [Table 2]

[0101] Example 11: Comparative Example The photopolymerization yields of compositions containing different radioactive opacifiers were compared according to Example 6. [Table 3]

[0102] Example 12: Comparative Example According to Examples 7 and 8, the photopolymerization depth in linear and curved structures of compositions containing different radioactive opacifiers was compared. [Table 4]

[0103] Example 13: Comparative Example PEG DMA 6k prepared according to Example 1 and different amounts of nano-YbF3(d mean,TEM A hydrogel sample containing (=20 nm) was prepared according to Example 8. The radiopaqueness per 1 mm of sample was determined in accordance with ISO 13116-2014. [Table 5]

[0104] Example 14: Comparative Example A composition containing PEG DMA 6k prepared according to Example 1 and a different radioactive opaque agent was prepared according to Example 8. The total decay was measured through a 1 cm cuvette at 405 nm before and after storage at 37°C for 30 days. [Table 6]

[0105] References [1] Y. Aoyagi, H. Takahashi, N. Iwasaki, E. Honda, T. Kurabayashi, Dental Materials Journal 2005, 24, 315-320. [2]FM Collares, FA Ogliari, GS Lima, VRC Fontanella, E. Piva, SMW Samuel, International Endodontic Journal 2010, 43, 792-797. [3] H. Kamohara, T. Takeshita, Root Canal Filling Material, nd, US2002051952(A1). [4] W. Jia, B. Alpert, Root Canal Filling Material, nd, US2003113686(A1). [5]JE Klee, Dental Filling Composition and Method, nd, US5624976(A).

Claims

1. A highly fluid crosslinkable composition for medical or dental use, wherein the composition comprises a crosslinkable compound, a polymerization initiator, and a heterogeneous solid radiation opaque agent. i. It has radiopaqueness of at least 3 mmAl / mm according to ISO 13116-2014, ii. It remains stably dispersed at 5-37°C for 30 days, where stably means that the heterogeneous solid that precipitates is less than 1%. iii. It has a fluidity of over 40 mm according to ISO 6876-2012, measured at room temperature (22°C). iv. The heterogeneous radioactive opaler has an average particle size between 1 and 500 nm, as measured by a transmission electron microscope according to ISO 21363-2020. v. The heterogeneous radioactive opaque agent is in the form of a powder or suspension and is selected from the group consisting of water-insoluble metals, metal oxides, metal salts, or metal complexes. vi. The composition contains 36 to 90% by weight of the heterogeneous radioactive opaler, The composition further comprises water as a solvent, 5 to 70% by weight of the crosslinkable compound, 5 to 60% by weight of the solvent, and 0.001 to 2% by weight of the polymerization initiator. A composition characterized by the following features.

2. Furthermore, a white plastic tube ( The composition according to claim 1, characterized in that when a sample (within 500 μm and length = 4 cm) is irradiated from above with a standard dental hardening lamp for 20 seconds, it photopolymerizes to a hardening depth of at least 1 mm.

3. The composition according to claim 1 or 2, characterized in that it photopolymerizes to a curing depth of at least 10 mm.

4. The heterogeneous radioactive opaler is selected from the group consisting of metal salts such as barium sulfate, ytterbium halide, bismuth halide, and calcium tungstate, or metal oxides such as ytterbium oxide, zirconium oxide, tantalum oxide, cerium dioxide, yttrium oxide, gadolinium oxide, and aluminum oxide; heavy metal-containing silicate glass; and combinations thereof, according to any one of claims 1 to 3.

5. The composition according to any one of claims 1 to 4, further comprising a suitable solvent, wherein the suitable solvent consists of acetone, DMSO, or an alcohol or a mixture thereof.

6. The composition according to any one of claims 1 to 5, wherein the polymerization initiator is a UV or visible light photoinitiator.

7. The composition according to claim 6, wherein the UV or visible light photoinitiator is selected from quinone, α-hydroxyketone, acylgermanium derivative, bis(acyl)phosphine oxide derivative, mono(acyl)phosphine oxide derivative, or a mixture thereof.

8. The composition according to any one of claims 1 to 7, wherein the crosslinkable compound is water-soluble.

9. The composition according to claim 8, wherein the water-soluble crosslinkable compound comprises a polymer functionalized with polymerizable terminal groups.

10. A crosslinked polymer composition obtained by crosslinking the composition according to any one of claims 1 to 9, characterized in that its radiopaqueness of at least 3 mmAl / mm remains unchanged when immersed in an aqueous medium for at least 24 days.

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