PARATHYROID HORMONE ANALOGUES FOR THE TREATMENT OF OSTEOPOROSIS

摘要

This invention describes human parathyroid hormone analogues that have increased bone regeneration activity and increased bio-availability. The described peptides are hPTH-(1-31) formations that are cyclic, for instance, in formation of lactams or between Glu<22> and Lys<26> or between Lys<26> and Asp<30>. In addition, the natural Lys<27> can be substituted by Leu or other hydrophobic remnants, like Ile, norleucin, Met, Val, Ala, Trp or Phe. Usually these analogues have increased ability to stimulate adenylyl cyclase in rat osteosarcoma cells and have an increased ability to restore bone mass in female rats with their ovaries removed. These analogues have increased activity and bio-availability, which is evident in their hypotensic effect on rats. There is also a description of an experiment in which hypotensic activity is correlated with osteogenic activity.