Abstract: The present inventions relates to bioresorbable sealing powder comprising: 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; 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; water-absorbing particles containing at least 50% by weight of said water-absorbing particles of water-insoluble polymer containing reactive nucleophilic groups; water-soluble dispersant that is solid at 20° C., said water-soluble dispersant being selected from monosaccharides, disaccharides, oligosaccharides, sugar alcohols and combinations thereof.

Abstract: 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.

Abstract: 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.

Abstract: 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.

Abstract: 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 ?m 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.

Abstract: 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 ?m and being present in an amount of at least 3% by weight of the fibrous carrier structure.

Abstract: 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 ?m and being present in an amount of at least 3% by weight of the fibrous carrier structure.

Abstract: 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.

Abstract: 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.

Abstract: 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 to 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.

Abstract: 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.

Abstract: 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.

Abstract: 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.

Abstract: 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.

Abstract: 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.

Abstract: 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.

Abstract: 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.

Abstract: 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.

Abstract: 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.

Abstract: One aspect of the invention relates to a pharmaceutical dosage unit for sublingual, buccal, pulmonary or oral administration, said dosage unit having a weight of 20-500 mg and comprising 1-80 wt. % of a microgranulate that is distributed throughout a solid hydrophilic matrix; said microgranulate being characterized in that it: has a volume weighted average diameter of 5-100 m; contains at least 0.01 wt. %, preferably at least 0.1 wt. % of one or more water-insoluble pharmaceutically active substances; contains at least 10 wt. %, preferably at least 20 wt. % of an emulsifier component; and is capable of forming a micro-emulsion upon contact with saliva or water. The dosage units of the present invention achieve the inherent benefits of oral delivery while at the same time realizing a high transmucosal absorption rate of the cannabinoids contained therein.