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    • 9. 发明申请
    • PHOTOREGULATED REVERSIBLE HYDROGELS FOR DELIVERY AND RELEASING OF DRUGS AND OTHER THERAPEUTICAL REAGENTS
    • 用于递送和释放药物和其他治疗试剂的光敏可逆的水凝胶
    • WO2011022291A3
    • 2011-06-09
    • PCT/US2010045314
    • 2010-08-12
    • UNIV FLORIDATAN WEIHONGKANG HUAIZHI
    • TAN WEIHONGKANG HUAIZHI
    • A61K9/20A61K9/06A61K47/34A61K47/42A61K47/48
    • A61K9/06A61K9/0009A61K41/0028A61K47/34
    • A novel hydrogel delivery systems useful for encapsulating and releasing pharmaceuticals or chemicals is disclosed where water soluble polymers containing crosslinker repeating units that associate or dissociate with complementary crosslinking repeating units or separate linkers to reversibly crosslink the hydrogel. In an exemplary embodiment, a DNA crosslinked hydrogel displays photoreversibility. An exemplary hydrogel delivery system comprises DNA polymer conjugates, wherein complementary DNA sequences are crosslinked with polymer chains and hybridization of the DNA sequences is controlled by photoresponsive moieties. Such hydrogcls can be used to release drug molecules and/or other therapeutic reagents. The exemplary hydrogel employs photosensitive azobenzene moieties that are incorporated into the DNA crosslinker units. The azobenzene moieties respond to different wavelengths of light so that the state of azobenzene isomerization is induced by the proportion of visible and UV light irradiated. The isomer state of the azobenzene dictates whether the complementary DNA sequences hybridize to cross link the DNA polymer conjugates. Thus, irradiation of light (visible or UV) can transform the hydrogel network between a sol and any of multiple gel states to regulate the degree of crosslinking between complementary DNA sequences and, therefore, provide a profile of release of a hydrogel encapsulated pharmaceutical or other chemical.
    • 公开了用于包封和释放药物或化学品的新型水凝胶递送系统,其中包含交联剂重复单元的水溶性聚合物,所述交联剂重复单元与互补交联重复单元或分开的接头缔合或解离以可逆地交联水凝胶。 在一个示例性实施方案中,DNA交联水凝胶显示光可逆性。 示例性水凝胶递送系统包含DNA聚合物缀合物,其中互补DNA序列与聚合物链交联并且DNA序列的杂交由光响应部分控制。 这种水凝胶可用于释放药物分子和/或其他治疗剂。 示例性水凝胶采用掺入DNA交联剂单元的光敏偶氮苯部分。 偶氮苯部分对不同波长的光响应,以致偶氮苯异构化的状态由可见光和UV光照射的比例引起。 偶氮苯的异构体状态指示互补DNA序列是否杂交以交联DNA聚合物缀合物。 因此,光(可见光或UV)的照射可以在溶胶和多种凝胶状态中的任何一种之间转变水凝胶网络,以调节互补DNA序列之间的交联程度,并因此提供水凝胶包封的药物或其他 化学。
    • 10. 发明申请
    • ANCHORED LIGAND AGENTS
    • 安装的配对代理
    • WO2008134069A2
    • 2008-11-06
    • PCT/US2008/005528
    • 2008-04-28
    • UNIVERSITY OF FLORIDA RESEARCH FOUNDATIONTAN, WeihongCAO, ZehuiKIM, Youngmi
    • TAN, WeihongCAO, ZehuiKIM, Youngmi
    • A61K48/00
    • C12N15/115C12N2310/16C12N2310/351C12N2320/50
    • The invention provides novel therapeutic agents comprising ligand molecules such as aptamers linked to a molecular anchor (MA). In the absence of a MA, ligands rapidly diffuse into bulk solution after dissociation from a target molecule. With a MA tightly bound to the target molecule, anchored ligand molecules of the invention remain in close proximity to the active site on the target molecule, even after dissociating from the target, permitting rapid re- binding of ligand to its target. Reversibility of binding to the active site can be effectively and rapidly achieved using antidotes based on the complementary DNA sequences. A preferred embodiment in accordance with the invention is a highly efficient anticoagulant agent that demonstrates binding efficiency to thrombin that is increased many fold relative to a corresponding unanchored aptamer-based ligand.
    • 本发明提供了包含配体分子的新型治疗剂,例如与分子锚(MA)连接的适体。 在不存在MA的情况下,配体在从靶分子解离后迅速扩散到本体溶液中。 使用与目标分子紧密结合的MA,本发明的锚定配体分子即使在与靶分离之后仍保持紧邻目标分子上的活性位点,从而允许配体快速重新结合至其靶。 使用基于互补DNA序列的解毒剂可以有效快速地实现与活性位点结合的可逆性。 根据本发明的优选实施方案是高效抗凝剂,其显示出相对于相应的未锚定的适体基配体增加多倍的凝血酶的结合效率。