Crosslinked gels comprising polyalkyleneimines, and their uses as medical devices
申请人:HyperBranch Medical Technology, Inc.
公开号:US11027043B1
公开(公告)日:2021-06-08
One aspect of the present invention generally relates to methods of sealing a wound or tissue plane or filling a void splace. In a preferred embodiment, the wound is an ophthalmic, pleural or dural wound. In certain instances, the compositions used to seal the wound or tissue plane comprises a polyalkyleneimine. In a preferred embodiment, the polyalkyleneimine is polyethyleneimine. Treatment of the polyethyleneimine with a cross-linking reagent causes the polyethyleneimine polymers to polymerize forming a seal. In certain instances, the cross-linking reagent is a polyethylene glycol having reactive terminal groups. In certain instances, the reactive terminal groups are activated esters, such as N-hydroxy succinimide ester. In certain instances, the reactive terminal groups are isocyanates. In certain instances, the polyethyleneimine has a lysine, cysteine, isocysteine or other nucleophilic group attached to the periphery of the polymer. In certain instances, the polyethyleneimine is mixed with a second polymer, such as a polyethylene glycol containing nucleophilic groups. In certain instances, the compositions used to seal the wound or tissue plane are formed by reacting a polyalkyleneimine bearing electrophilic groups with a cross-linking reagent containing nucleophilic groups. In certain instances, the electrophilic groups on the polyalkyleneimine are activated esters, such as N-hydroxy succinimide ester. In certain instances, the compositions used to seal the wound or tissue plane are formed by reacting a polyalkyleneimine bearing photopolymerizable groups with ultraviolet or visibile light. Compositions used to seal the wound which contain PEI or a derivative of PEI are found to adhere tightly to the tissue. Other aspects of the present invention relate to methods of filling a void of a patient or adhering tissue. In certain instances, the methods use a polyalkyleneimine. In a preferred embodiment, the polyalkyleneimine is polyethyleneimine. Another aspect of the present invention relates to a polymeric composition formed by exposing a polyalkyleneimine to an activated polyalkylene glycol. In certain instances, the composition is attached to mammalian tissue.
本发明的一个方面一般涉及密封伤口或组织平面或填充空隙的方法。在一个优选的实施方案中,伤口是眼科、胸膜或硬脑膜伤口。在某些情况下,用于密封伤口或组织平面的组合物包括聚亚烷基亚胺。在一个优选的实施方案中,聚烯亚胺是聚乙烯亚胺。用交联试剂处理聚乙烯亚胺可使聚乙烯亚胺聚合物聚合形成密封。在某些情况下,交联试剂是具有活性末端基团的聚乙二醇。在某些情况下,活性末端基团是活化酯,如 N-羟基琥珀酰亚胺酯。在某些情况下,活性末端基团是异氰酸酯。在某些情况下,聚乙烯亚胺的聚合物外围附有赖氨酸、半胱氨酸、异半胱氨酸或其他亲核基团。在某些情况下,聚乙烯亚胺与第二种聚合物混合,例如含有亲核基团的聚乙二醇。在某些情况下,用于密封伤口或组织平面的组合物是由含亲电基团的聚亚烷基亚胺与含亲核基团的交联试剂反应形成的。在某些情况下,聚亚烷基亚胺上的亲电基团是活化酯,如 N-羟基琥珀酰亚胺酯。在某些情况下,用于密封伤口或组织平面的组合物是通过使带有可光聚合基团的聚亚烷基亚胺与紫外线或可见光反应而形成的。用于密封伤口的组合物含有 PEI 或 PEI 的衍生物,可与组织紧密粘合。本发明的其他方面涉及填补患者或粘附组织空隙的方法。在某些情况下,这些方法使用聚烯亚胺。在一个优选的实施方案中,聚烯亚胺是聚乙烯亚胺。本发明的另一方面涉及一种聚合组合物,该组合物通过将聚亚烷基亚胺暴露于活化的聚亚烷基二醇而形成。在某些情况下,该组合物附着在哺乳动物组织上。