公开(公告)号：US09089539B2

公开(公告)日：2015-07-28

申请号：US14182706

申请日：2014-02-18

Applicant: Indiana University Research and Technology Corporation

Inventor： Richard D. DiMarchi ,  Arnab De

IPC: A61K38/00 ,  C07K14/62 ,  A61K38/28 ,  A61K9/00 ,  A61K38/26 ,  A61K47/48 ,  A61K39/395

CPC classification number: A61K38/28 ,  A61K9/0019 ,  A61K38/26 ,  A61K39/395 ,  A61K47/48215 ,  A61K47/48246 ,  A61K47/60 ,  A61K47/64

Abstract: Prodrug formulations of bioactive polypeptides are provided wherein the bioactive polypeptide has been modified by the linkage of a dipeptide to the bioactive polypeptide through an ester linkage. The prodrugs disclosed herein in some embodiments have extended half lives of at least 1.5 hours (e.g., at least 10 hours), and more typically greater than 20 hours and less than 70 hours, and are converted to the active form at physiological conditions through a non-enzymatic reaction driven by chemical instability.

Abstract translation: 提供生物活性多肽的前药制剂，其中生物活性多肽已经通过二酯与生物活性多肽的连接通过酯键进行了修饰。 在一些实施方案中本文公开的前体药物具有至少1.5小时（例如，至少10小时），更通常大于20小时和小于70小时的半衰期延长，并且在生理条件下通过 由化学不稳定驱动的非酶反应。