The present inventions relates to bioresorbable sealing powder comprising: (a) water-soluble electrophilic polymer carrying at least 3 reactive electrophilic groups that are capable of reacting with amine groups under the formation of a covalent bond; (b) water-soluble nucleophilic cross-linker carrying at least 2 reactive nucleophilic groups that, in the presence of water, are capable of reacting with the reactive electrophilic groups of the electrophilic polymer under the formation of a covalent bond between the electrophilic polymer and the nucleophilic cross-linker; (c) water-absorbing particles containing at least 50% by weight of said water-absorbing particles of water-insoluble polymer containing reactive nucleophilic groups; (d) water-soluble dispersant that is solid at 20°C, said water-soluble dispersant being selected from monosaccharides, disaccharides, oligosaccharides, sugar alcohols and combinations thereof. wherein the components (a), (b), (c) and (d) may be contained in the same particles or in different particles. The invention also provides a method of preparing the aforementioned bioresorbable sealing powder Further provided are (i) a device for powder application comprising the bioresorbable sealing powder, (ii) a biocompatible, flexible, hemostatic sheet comprising the bioresorbable sealing powder and (iii) a kit of parts for preparing a sealing suspension, said kit comprising the bioresorbable powder, and (iv) a sealing suspension containing the bioresorbable sealing powder.
The present invention relates to a haemostatic powder comprising at least 10 wt. % of particle agglomerates, said particle agglomerates having a diameter in the range of 1-500 μm and comprising:
electrophilic polyoxazoline particles containing electrophilic polyoxazoline carrying at least 3 reactive electrophilic groups that are capable of reacting with amine groups in blood under the formation of a covalent bond; and
nucleophilic polymer particles containing a water-soluble nucleophilic polymer carrying at least 3 reactive nucleophilic groups that, in the presence of water, are capable of reacting with the reactive electrophilic groups of the electrophilic polyoxazoline under the formation of a covalent bond between the electrophilic polyoxazoline and the nucleophilic polymer.
The present invention relates to a haemostatic powder comprising at least 10 wt. % of particle agglomerates, said particle agglomerates having a diameter in the range of 1-500 μm and comprising:
electrophilic polyoxazoline particles containing electrophilic polyoxazoline carrying at least 3 reactive electrophilic groups that are capable of reacting with amine groups in blood under the formation of a covalent bond; and
nucleophilic polymer particles containing a water-soluble nucleophilic polymer carrying at least 3 reactive nucleophilic groups that, in the presence of water, are capable of reacting with the reactive electrophilic groups of the electrophilic polyoxazoline under the formation of a covalent bond between the electrophilic polyoxazoline and the nucleophilic polymer.
When applied to a bleeding site, the haemostatic powder of the present invention turns into a gel while at the same time binding to proteins present in the blood and on the surrounding tissue.
The invention relates to a biocompatible, flexible, haemostatic sheet comprising:
a cohesive fibrous carrier structure comprising a three-dimensional interconnected interstitial space; and
distributed within the interstitial space, a plurality of reactive polymer particles comprising (i) a water-soluble electrophilic polymer carrying at least 3 reactive electrophilic groups that are capable of reacting with amine groups in tissue and blood under the formation of a covalent bond and (ii) a nucleophilic cross-linking agent that contains at least two reactive nucleophilic groups that are capable of reacting with the reactive electrophilic groups of the electrophilic polymer under the formation of a covalent bond, said reactive polymer particles having a diameter in the range of 0.5-100 μm and being present in an amount of at least 3% by weight of the fibrous carrier structure.
The invention relates to a biocompatible, flexible, haemostatic sheet comprising:
a cohesive fibrous carrier structure comprising a three-dimensional interconnected interstitial space; and
distributed within the interstitial space, a plurality of reactive polymer particles comprising (i) a water-soluble electrophilic polymer carrying at least 3 reactive electrophilic groups that are capable of reacting with amine groups in tissue and blood under the formation of a covalent bond and (ii) a nucleophilic cross-linking agent that contains at least two reactive nucleophilic groups that are capable of reacting with the reactive electrophilic groups of the electrophilic polymer under the formation of a covalent bond, said reactive polymer particles having a diameter in the range of 0.5-100 μm and being present in an amount of at least 3% by weight of the fibrous carrier structure.
When blood is absorbed by the haemostatic sheet of the present invention, the water-soluble electrophilic polymer in the reactive polymer particles starts dissolving as soon as these particles are ‘wetted’ by the blood, thereby allowing the electrophilic polymer to react with reactive nucleophilic groups in the blood and tissue, as well as with reactive nucleophilic groups of the nucleophilic cross-linking agent, thereby inducing blood coagulation and tissue sealing, both of which contribute to haemostasis.
A61L 15/22 - Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons containing macromolecular materials
simultaneously subjecting the fibrous sheet and the reactive polymer particles to an electric field of 0.1 to 40 kV/mm to impregnate the interconnected interstitial space of the fibrous sheet with the reactive polymer particles.
A61L 24/00 - Surgical adhesives or cementsAdhesives for colostomy devices
D06M 10/00 - Physical treatment of fibres, threads, yarns, fabrics or fibrous goods made from such materials, e.g. ultrasonic, corona discharge, irradiation, electric currents or magnetic fieldsPhysical treatment combined with treatment with chemical compounds or elements
D06M 15/356 - Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds of other unsaturated compounds containing nitrogen, sulfur, silicon or phosphorus atoms
The invention relates to a biocompatible, flexible, bone-adhesive sheet that may suitably be applied in the treatment of bone defects, said bone-adhesive sheet comprising: · a cohesive fibrous carrier structure comprising a three-dimensional interconnected interstitial space; • distributed within the interstitial space, (i) a plurality of polymer particles comprising a water-soluble calcium-binding polymer, said water-soluble calcium-binding polymer carrying at least one calcium binding group or (ii) a plurality of reactive particles comprising an electrophilically activated water-soluble polymer and a plurality of bisphosphonate particles comprising nitrogenous bisphosphonate.
The invention relates to a polyoxazoline (POx) copolymer comprising at least 20 oxazoline units, including at least 4 non-terminal oxazoline units that contain a calcium binding group selected from bisphosphonate, citrate, ethylenediaminetetraacetic acid (EDTA) and combinations thereof. The POx copolymers of the present invention exhibit very high affinity for calcium ions and are capable of forming hydrogels due to reversible cross-linking with Ca2+ ions. The POx copolymers offer the important advantage that they are bioresorbable. Calcium affinity, biodegradability and hydrogel characteristics of the POx copolymer can easily be tuned due to the fact that the POx can easily be derivatised along the entire polymeric backbone and not only at the end-groups. The POx copolymers of the invention may suitably be applied in a variety of biomedical applications, such as barrier membranes, patches, meshes, tapes, bone fixation devices, bone implants, (injectable) hydrogels, bone-setting glue and nanoparticles.
C08G 73/00 - Macromolecular compounds obtained by reactions forming in the main chain of the macromolecule a linkage containing nitrogen, with or without oxygen or carbon, not provided for in groups
The invention relates to a biocompatible, flexible, haemostatic sheet comprising: • a water-resistant cohesive fibrous carrier structure comprising a three-dimensional interconnected interstitial space, said fibrous carrier structure comprising fibres containing a nucleophilic polymer carrying reactive nucleophilic groups; and •distributed within the interstitial space, a plurality of reactive polymer particles comprising a water-soluble electrophilic polymer carrying at least three reactive electrophilic groups that are capable of reacting with amine groups in tissue and blood, as well as with reactive nucleophilic groups of the nucleophilic polymer, under the formation of a covalent bond, said reactive polymer particles having a diameter in the range of 0.5-100 pm and being present in an amount of at least 3% by weight of the fibrous carrier structure. When blood is absorbed by the haemostatic sheet of the present invention, the reactive polymer particles within the sheet start dissolving as soon as they are 'wetted' by the blood, thereby allowing the electrophilic polymer to react with both reactive nucleophilic groups in the blood and tissue and reactive nucleophilic groups in the fibrous carrier structure, thereby inducing blood coagulation and tissue sealing, both of which contribute to haemostasis.
A61L 15/22 - Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons containing macromolecular materials
A61L 15/42 - Use of materials characterised by their function or physical properties
A61L 15/64 - Use of materials characterised by their function or physical properties specially adapted to be resorbable inside the body
A61L 24/04 - Surgical adhesives or cementsAdhesives for colostomy devices containing macromolecular materials
The present invention relates to a haemostatic powder comprising at least 10 wt.% of particle agglomerates, said particle agglomerates having a diameter in the range of 1-500 µm and comprising: electrophilic polyoxazoline particles containing electrophilic polyoxazoline carrying at least 3 reactive electrophilic groups that are capable of reacting with amine groups in blood under the formation of a covalent bond; and nucleophilic polymer particles containing a water-soluble nucleophilic polymer carrying at least 3 reactive nucleophilic groups that, in the presence of water, are capable of reacting with the reactive electrophilic groups of the electrophilic polyoxazoline under the formation of a covalent bond between the electrophilic polyoxazoline and the nucleophilic polymer. When applied to a bleeding site, the haemostatic powder of the present invention turns into a gel while at the same time binding to proteins present in the blood and on the surrounding tissue.
A61L 15/22 - Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons containing macromolecular materials
A61L 15/32 - Proteins, polypeptidesDegradation products or derivatives thereof, e.g. albumin, collagen, fibrin, gelatin
A61L 15/42 - Use of materials characterised by their function or physical properties
A61L 15/64 - Use of materials characterised by their function or physical properties specially adapted to be resorbable inside the body
A61L 24/00 - Surgical adhesives or cementsAdhesives for colostomy devices
A61L 24/04 - Surgical adhesives or cementsAdhesives for colostomy devices containing macromolecular materials
The invention relates to a biocompatible, flexible, haemostatic sheet comprising: a cohesive fibrous carrier structure comprising a three-dimensional interconnected interstitial space; and distributed within the interstitial space, a plurality of reactive polymer particles comprising (i) a water-soluble electrophilic polymer carrying at least 3 reactive electrophilic groups that are capable of reacting with amine groups in tissue and blood under the formation of a covalent bond and (ii) a nucleophilic cross-linking agent that contains at least two reactive nucleophilic groups that are capable of reacting with the reactive electrophilic groups of the electrophilic polymer under the formation of a covalent bond, said reactive polymer particles having a diameter in the range of 0.5-100 pm and being present in an amount of at least 3% by weight of the fibrous carrier structure. When blood is absorbed by the haemostatic sheet of the present invention, the water-soluble electrophilic polymer in the reactive polymer particles starts dissolving as soon as these particles are 'wetted' by the blood, thereby allowing the electrophilic polymer to react with reactive nucleophilic groups in the blood and tissue, as well as with reactive nucleophilic groups of the nucleophilic cross-linking agent, thereby inducing blood coagulation and tissue sealing, both of which contribute to haemostasis.
A61L 15/22 - Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons containing macromolecular materials
A61L 15/42 - Use of materials characterised by their function or physical properties
A61L 15/64 - Use of materials characterised by their function or physical properties specially adapted to be resorbable inside the body
The invention relates to a biocompatible, flexible, haemostatic sheet comprising: • a water-resistant cohesive fibrous carrier structure comprising a three-dimensional interconnected interstitial space, said fibrous carrier structure comprising fibres containing a nucleophilic polymer carrying reactive nucleophilic groups; and • distributed within the interstitial space, a plurality of reactive polymer particles comprising a water-soluble electrophilic polymer carrying at least three reactive electrophilic groups that are capable of reacting with amine groups in tissue and blood, as well as with reactive nucleophilic groups of the nucleophilic polymer, under the formation of a covalent bond, said reactive polymer particles having a diameter in the range of 0.5-100 pm and being present in an amount of at least 3% by weight of the fibrous carrier structure. When blood is absorbed by the haemostatic sheet of the present invention, the reactive polymer particles within the sheet start dissolving as soon as they are 'wetted' by the blood, thereby allowing the electrophilic polymer to react with both reactive nucleophilic groups in the blood and tissue and reactive nucleophilic groups in the fibrous carrier structure, thereby inducing blood coagulation and tissue sealing, both of which contribute to haemostasis.
A61L 15/22 - Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons containing macromolecular materials
A61L 15/42 - Use of materials characterised by their function or physical properties
A61L 15/64 - Use of materials characterised by their function or physical properties specially adapted to be resorbable inside the body
A61L 24/00 - Surgical adhesives or cementsAdhesives for colostomy devices
A61L 24/04 - Surgical adhesives or cementsAdhesives for colostomy devices containing macromolecular materials
The present invention relates to a haemostatic powder comprising at least 10 wt.% of particle agglomerates, said particle agglomerates having a diameter in the range of 1-500 μm and comprising: • electrophilic polyoxazoline particles containing electrophilic polyoxazoline carrying at least 3 reactive electrophilic groups that are capable of reacting with amine groups in blood under the formation of a covalent bond; and • nucleophilic polymer particles containing a water-soluble nucleophilic polymer carrying at least 3 reactive nucleophilic groups that, in the presence of water, are capable of reacting with the reactive electrophilic groups of the electrophilic polyoxazoline under the formation of a covalent bond between the electrophilic polyoxazoline and the nucleophilic polymer. When applied to a bleeding site, the haemostatic powder of the present invention turns into a gel while at the same time binding to proteins present in the blood and on the surrounding tissue.
A61L 15/22 - Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons containing macromolecular materials
A61L 15/32 - Proteins, polypeptidesDegradation products or derivatives thereof, e.g. albumin, collagen, fibrin, gelatin
A61L 15/42 - Use of materials characterised by their function or physical properties
A61L 15/64 - Use of materials characterised by their function or physical properties specially adapted to be resorbable inside the body
A61L 24/00 - Surgical adhesives or cementsAdhesives for colostomy devices
A61L 24/04 - Surgical adhesives or cementsAdhesives for colostomy devices containing macromolecular materials
The invention relates to a biocompatible, flexible, haemostatic sheet comprising: • a cohesive fibrous carrier structure comprising a three-dimensional interconnected interstitial space; and • distributed within the interstitial space, a plurality of reactive polymer particles comprising (i) a water-soluble electrophilic polymer carrying at least 3 reactive electrophilic groups that are capable of reacting with amine groups in tissue and blood under the formation of a covalent bond and (ii) a nucleophilic cross-linking agent that contains at least two reactive nucleophilic groups that are capable of reacting with the reactive electrophilic groups of the electrophilic polymer under the formation of a covalent bond, said reactive polymer particles having a diameter in the range of 0.5-100 pm and being present in an amount of at least 3% by weight of the fibrous carrier structure. When blood is absorbed by the haemostatic sheet of the present invention, the water-soluble electrophilic polymer in the reactive polymer particles starts dissolving as soon as these particles are 'wetted' by the blood, thereby allowing the electrophilic polymer to react with reactive nucleophilic groups in the blood and tissue, as well as with reactive nucleophilic groups of the nucleophilic cross-linking agent, thereby inducing blood coagulation and tissue sealing, both of which contribute to haemostasis.
A61L 15/42 - Use of materials characterised by their function or physical properties
A61L 15/64 - Use of materials characterised by their function or physical properties specially adapted to be resorbable inside the body
A61L 15/22 - Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons containing macromolecular materials
The invention provides a method for preparing tissue-adhesive sheets that may suitably be applied as an implantable haemostatic or sealing construct during surgical procedures, said method comprising: • providing a fibrous sheet comprising a three-dimensional interconnected interstitial space; • providing reactive polymer particles comprising a water-soluble electrophilic polymer carrying at least 3 reactive electrophilic groups that are capable of reacting with amine groups in blood under the formation of a covalent bond; • placing the fibrous sheet and the reactive polymer particles between two electrodes; • simultaneously subjecting the fibrous sheet and the reactive polymer particles to an electric field of 0.1 to 40 kV/mm to impregnate the interconnected interstitial space of the fibrous sheet with the reactive polymer particles.
A biocompatible, covalently cross-linked, polymer that is obtained by reacting an electrophilically activated polyoxazoline (EL-POX) with a nucleophilic cross-linking agent is disclosed. The EL-POX comprises m electrophilic groups; and the nucleophilic cross-linking agent comprises n nucleophilic groups, wherein the m electrophilic groups are capable of reacting with the n nucleophilic groups to form covalent bonds; wherein m≥2, n≥2 and m+n≥5; wherein at least one of the m electrophilic groups is a pendant electrophilic group and/or wherein m≥3; and wherein the EL-POX comprises an excess amount of electrophilic groups relative to the amount of nucleophilic groups contained in the nucleophilic cross-linking agent. Biocompatible medical products and kits comprising the cross-linked POX-polymers are also disclosed.
C08J 3/24 - Crosslinking, e.g. vulcanising, of macromolecules
A61K 47/50 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
A process of preparing an adhesive haemostatic product is provided. The process comprises: (a) coating a porous solid substrate with a coating liquid that comprises an electrophilically activated polyoxazoline (EL-POX) and a solvent to produce a coated substrate; and (b) removing the solvent from the coated substrate. The EL-POX comprises at least 2 reactive electrophilic groups. The process enables the application of an EL-POX coating that leaves the pore structure of the substrate largely intact so that the ability of the porous substrate to absorb body fluids, such as blood, remains essentially unaffected. The EL-POX coated haemostatic product obtained by the present process has excellent adhesive properties due to the presence of electrophilic reactive groups that are capable of reacting with e.g. amine groups that are naturally present in tissue, under the formation of covalent bonds.
A process of preparing an adhesive haemostatic product is provided. The process comprises: (a) coating a porous solid substrate with a coating liquid that comprises an electrophilically activated polyoxazoline (EL-POX) and a solvent to produce a coated substrate; and (b) removing the solvent from the coated substrate. The EL-POX comprises at least 2 reactive electrophilic groups. The process enables the application of an EL-POX coating that leaves the pore structure of the substrate largely intact so that the ability of the porous substrate to absorb body fluids, such as blood, remains essentially unaffected. The EL-POX coated haemostatic product obtained by the present process has excellent adhesive properties due to the presence of electrophilic reactive groups that are capable of reacting with e.g. amine groups that are naturally present in tissue, under the formation of covalent bonds.
A biocompatible, covalently cross-linked, polymer that is obtained by reacting an electrophilically activated polyoxazoline (EL-PDX) with a nucleophilic cross-linking agent is disclosed. The EL-PDX comprises m electrophilic groups; and the nucleophilic cross-linking agent comprises n nucleophilic groups, wherein the m electrophilic groups are capable of reacting with the n nucleophilic groups to form covalent bonds; wherein m≥2, n≥2 and m+n≥5; wherein at least one of the m electrophilic groups is a pendant electrophilic group and/or wherein m≥3; and wherein the EL-PDX comprises an excess amount of electrophilic groups relative to the amount of nucleophilic groups contained in the nucleophilic cross-linking agent. Biocompatible medical products and kits comprising the cross-linked PDX-polymers are also disclosed.
A61L 24/04 - Surgical adhesives or cementsAdhesives for colostomy devices containing macromolecular materials
A61L 27/18 - Macromolecular materials obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
A61L 31/06 - Macromolecular materials obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
A61L 24/06 - Surgical adhesives or cementsAdhesives for colostomy devices containing macromolecular materials obtained by reactions only involving carbon-to-carbon unsaturated bonds
A61K 47/34 - Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers
C08J 3/24 - Crosslinking, e.g. vulcanising, of macromolecules
A61K 47/50 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
19.
Cross-linked polymers and medical products derived from nucleophilically activated polyoxazoline
One aspect of the invention relates to a biocompatible medical product comprising at least 1% by weight of dry matter of a covalently cross-linked polymer that is obtained by reacting a nucleophilically activated polyoxazoline (NU-PDX) with an electrophilic cross-linking agent other than an electrophilically activated polyoxazoline, said NU-PDX comprising m nucleophilic groups; and said electrophilic cross-linking agent comprising n electrophilic groups, wherein the m nucleophilic groups are capable of reaction with the n electrophilic groups to form covalent bonds; wherein m≧2, n≧2 and m+n≧5; and wherein the NU-PDX comprises at least 30 oxazoline units in case the electrophilic cross-linking agent is an isocyanate.
Also provided is a kit for producing the aforementioned biocompatible cross-linked polymer.
The biocompatible cross-linked polymers according to the invention have excellent implant and/or sealing characteristics.
The invention provides a process of preparing an adhesive haemostatic product, said process comprising the steps of: providing a porous solid substrate; coating the substrate with a coating liquid that comprises an electrophilically activated polyoxazoline (EL-POX) and a solvent to produce a coated substrate, said EL-POX containing at least 2 reactive electrophilic groups; removing the solvent from the coated substrate. The present process enables the application of an EL-POX coating that leaves the pore structure of the substrate largely intact so that the ability of the porous substrate to absorb body fluids, such as blood, remains essentially unaffected. The EL-POX coated haemostatic product obtained by the present process has excellent adhesive properties due to the presence of electrophilic reactive groups that are capable of reacting with e.g. amine groups that are naturally present in tissue, under the formation of covalent bonds. The present invention also provides a tissue-adhesive haemostatic product selected from a coated mesh, a coated foam and a coated powder, said haemostatic product comprising: a porous solid substrate having a porosity of at least 5vol.%.% and comprising an outer surface that comprises a nucleophilic polymer containing reactive nucleophilic groups; an adhesive coating that covers at least a part of the solid substrate, said coating comprising an electrophilically activated polyoxazoline (EL-POX), said EL-POX containing on average at least 1 reactive electrophilic group.
The invention provides a process of preparing an adhesive haemostatic product, said process comprising the steps of: providing a porous solid substrate; coating the substrate with a coating liquid that comprises an electrophilically activated polyoxazoline (EL-POX) and a solvent to produce a coated substrate, said EL-POX containing at least 2 reactive electrophilic groups; removing the solvent from the coated substrate. The present process enables the application of an EL-POX coating that leaves the pore structure of the substrate largely intact so that the ability of the porous substrate to absorb body fluids, such as blood, remains essentially unaffected. The EL-POX coated haemostatic product obtained by the present process has excellent adhesive properties due to the presence of electrophilic reactive groups that are capable of reacting with e.g. amine groups that are naturally present in tissue, under the formation of covalent bonds. The present invention also provides a tissue-adhesive haemostatic product selected from a coated mesh, a coated foam and a coated powder, said haemostatic product comprising: a porous solid substrate having a porosity of at least 5vol.%.% and comprising an outer surface that comprises a nucleophilic polymer containing reactive nucleophilic groups; an adhesive coating that covers at least a part of the solid substrate, said coating comprising an electrophilically activated polyoxazoline (EL-POX), said EL-POX containing on average at least 1 reactive electrophilic group.
One aspect of the invention relates to a biocompatible medical product comprising at least 1% by weight of dry matter of a covalently cross-linked polymer that is obtained by reacting a nucleophilically activated polyoxazoline (NU-POX) with an electrophilic cross-linking agent other than an electrophilically activated polyoxazoline, said NU-POX comprising m nucleophilic groups; and said electrophilic cross-linking agent comprising n electrophilic groups, wherein the m nucleophilic groups are capable of reaction with the n electrophilic groups to form covalent bonds; wherein m≧2, n≧2 and m+n≧5; and wherein the NU-POX comprises at least 30 oxazoline units in case the electrophilic cross-linking agent is an isocyanate. Also provided is a kit for producing the aforementioned biocompatible cross-linked polymer. The biocompatible cross-linked polymers according to the invention have excellent implant and/or sealing characteristics.
One aspect of the invention relates to a biocompatible, covalently cross-linked, polymer that is obtained by reacting an electrophilically activated polyoxazoline (EL-POX) with a nucleophilic cross-linking agent, said electrophilically activated POX comprising m electrophilic groups; and said nucleophilic cross-linking agent comprising n nucleophilic groups, wherein the m electrophilic groups are capable of reaction with the n nucleophilic groups to form covalent bonds; wherein m≧2, n≧2 and m+n≧5; wherein at least one of the m electrophilic groups is a pendant electrophilic group and/or wherein m≧3; and wherein the EL-POX comprises an excess amount of electrophilic groups relative to the amount of nucleophilic groups contained in the nucleophilic cross-linking agent. The invention further relates to biocompatible medical products comprising such a cross-linked POX-polymer. Also provided is a kit for producing a biocompatible, cross-linked POX-polymer. The invention further provides a tissue adhesive medical product comprising at least 1% by weight of dry matter of EL-POX, said EL-POX comprising at least 2 electrophilic groups, including at least one pendant electrophilic group. The polymers according to the invention have excellent implant and/or sealing characteristics.
A61L 24/04 - Surgical adhesives or cementsAdhesives for colostomy devices containing macromolecular materials
A61K 47/34 - Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers
A61L 27/18 - Macromolecular materials obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
A61L 31/06 - Macromolecular materials obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
One aspect of the invention relates to a biocompatible, covalently cross-linked, polymer that is obtained by reacting an electrophilically activated polyoxazoline (EL-POX) with a nucleophilic cross-linking agent, said electrophilically activated POX comprising m electrophilic groups; and said nucleophilic cross-linking agent comprising n nucleophilic groups, wherein the m electrophilic groups are capable of reaction with the n nucleophilic groups to form covalent bonds; wherein m=2, n=2 and m+n =5; wherein at least one of the m electrophilic groups is a pendant electrophilic group and/or wherein m=3; and wherein the EL-POX comprises an excess amount of electrophilic groups relative to the amount of nucleophilic groups contained in the nucleophilic cross-linking agent. The invention further relates to biocompatible medical products comprising such a cross-linked POX-polymer. Also provided is a kit for producing a biocompatible, cross-linked POX-polymer. The invention further provides a tissue adhesive medical product comprising at least 1% by weight of dry matter of EL-POX, said EL-POX comprising at least 2 electrophilic groups, including at least one pendant electrophilic group. The polymers according to the invention have excellent implant and/or sealing characteristics.
