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公开(公告)号：US20230310698A1
公开(公告)日：2023-10-05
申请号：US18000872
申请日：2021-07-27
发明人： Sander Cornelis Gerardus LEEUWENBURGH , Jan Cornelis Maria VAN HEST , Maria Jose SANCHEZ-FERNANDEZ , Rosa Pilar Felix LANAO , Joost OPSTEEN , Johannes Caspar Mathias Elizabeth BENDER
CPC分类号： A61L24/0094 , A61L15/58 , A61L24/0036 , A61L2430/02
摘要： 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.-
公开(公告)号：US20240042094A1
公开(公告)日：2024-02-08
申请号：US18258256
申请日：2022-01-22
IPC分类号： A61L24/00
CPC分类号： A61L24/0042 , A61L24/0094 , A61L2400/04
摘要： 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.
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.-
公开(公告)号：US20220153930A1
公开(公告)日：2022-05-19
申请号：US17586428
申请日：2022-01-27
发明人： Sander Cornelis Gerardus LEEUWENBURGH , Jan Cornelis Maria VAN HEST , María José SÁNCHEZ-FERNÁNDEZ , Rosa Pilar FELIX LANAO , Joost OPSTEEN , Johannes Caspar Mathias Elizabeth BENDER
IPC分类号： C08G73/02
摘要： 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.-
公开(公告)号：US20220133949A1
公开(公告)日：2022-05-05
申请号：US17573564
申请日：2022-01-11
发明人： Abraham Reinier KEEREWEER , Rosa Pilar FÉLIX LANAO , Joost OPSTEEN , Johannes Caspar Mathias Elizabeth BENDER
摘要： 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.
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公开(公告)号：US20190125922A1
公开(公告)日：2019-05-02
申请号：US16226374
申请日：2018-12-19
摘要： 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.
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公开(公告)号：US20220133948A1
公开(公告)日：2022-05-05
申请号：US17573541
申请日：2022-01-11
发明人： Hubert Clemens PELLIKAAN , Abraham Reinier KEEREWEER , Johannes Caspar Mathias Elizabeth BENDER
摘要： 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.
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公开(公告)号：US20180221531A1
公开(公告)日：2018-08-09
申请号：US15516467
申请日：2015-10-05
CPC分类号： A61L15/26 , A61L15/325 , A61L15/425 , A61L15/58 , A61L2400/04
摘要： 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.
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公开(公告)号：US20220133947A1
公开(公告)日：2022-05-05
申请号：US17573537
申请日：2022-01-11
发明人： Abraham Reinier KEEREWEER , Rosa Pilar FÉLIX LANAO , Joost OPSTEEN , Johannes Caspar Mathias Elizabeth BENDER
摘要： 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 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 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.
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公开(公告)号：US20220133943A1
公开(公告)日：2022-05-05
申请号：US17573574
申请日：2022-01-11
发明人： Abraham Reinier KEEREWEER , Rosa Pilar FÉLIX LANAO , Joost OPSTEEN , Johannes Caspar Mathias Elizabeth BENDER , Gerard LLANOS
IPC分类号： A61L15/22
摘要： 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.
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10.发明申请公开(公告)号：US20190231923A1
公开(公告)日：2019-08-01
申请号：US16378245
申请日：2019-04-08
CPC分类号： A61L24/046 , A61K47/50 , A61L24/06 , A61L27/18 , A61L31/06 , C08G73/0233 , C08J3/246 , C08J2300/10 , C08J2379/02 , C08L79/02
摘要： 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.
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