Biodegradable cross-linkers having a polyacid connected to reactive groups for cross-linking polymer filaments
申请人:Access Pharmaceuticals, Inc.
公开号:US06521431B1
公开(公告)日:2003-02-18
Biodegradable cross-linkers are provided having a polyacid core with at least two acidic groups covalently connected to reactive groups usable to cross-link polymer filaments. Between at least one reactive group and an acidic group of the polyacid is a biodegradable region which preferably consists of a hydroxyalkyl acid ester sequence having 1, 2, 3, 4, 5 or 6 hydroxyalkyl acid ester groups. The polyacid may be attached to a water soluble region that is attached to the biodegradable region having attached reactive groups. The hydroxyalkyl acid ester group is preferably a lactate or glycolate. Polyacids include diacids, triacids, tetraacids and pentaacids, and the reactive group may contain a carbon-carbon double bond. A network of cross-linked polymer filaments having adefined biodegradation rate can be formed using the cross-linkers. The network may contain biologically active molecules, and can be in the form of a microparticle or nanoparticle, or hydrogel. The polymer filaments may be preformed polymer filaments of polynucleic acids, polypeptides, proteins or carbohydrates. The cross-linkers may be copolymerized with charged monomers such as acrylic monomers containing charged groups. Applications of the cross-linkers and network include controlled release of drugs and cosmetics, tissue engineering, wound healing, hazardous waste remediation, metal chelation, swellable devices for absorbing liquids and prevention of surgical adhesions.
提供具有至少两个酸性基团的聚酸核心的可生物降解的交联剂,该核心与可用于交联聚合物纤维的反应性基团共价连接。在至少一个反应性基团和聚酸的酸性基团之间存在一个可生物降解的区域,该区域最好由具有1、2、3、4、5或6个羟烷酸酯基团的羟烷酸酯序列组成。聚酸可以连接到与附有反应性基团的可生物降解区域连接的水溶性区域。羟烷酸酯基团最好是乳酸或乙二醇酸酯。聚酸包括二酸、三酸、四酸和五酸,反应性基团可能含有碳-碳双键。可以使用这些交联剂形成具有定义的生物降解速率的交联聚合物纤维网络。该网络可以包含生物活性分子,并且可以采用微粒或纳米粒子,或者是水凝胶的形式。聚合物纤维可能是聚核酸、多肽、蛋白质或碳水化合物的预制聚合物纤维。这些交联剂可以与含带电基团的丙烯酸单体共聚合。交联剂和网络的应用包括药物和化妆品的控释、组织工程、伤口愈合、危险废物处理、金属螯合、吸收液体的膨胀设备以及预防手术粘连。