Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Peptide containing doai
Patent
1996-08-02
1999-09-21
Russell, Jeffrey E.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Peptide containing doai
514 12, 530317, 530324, A61K 3829, C07K 14635
Patent
active
059554258
ABSTRACT:
This invention describes analogs of human parathyroid hormone which have increased activities in bone restoration, and increased bioavailabilities. The peptides described are derivatives of hPTH-(1-31) which have lactams formed for example, between either Glu.sup.22 and Lys.sup.26 or Lys.sup.26 and Asp.sup.30. In addition, the natural Lys.sup.27 may be substituted by either a Leu or other hydrophobic residues, such as Ile, norleucine, Met, Val, Ala, Trp, or Phe. Typically, these analogs have enhanced abilities to stimulate adenylyl cyclase in rat osteosarcoma cells, and show increased activities in bone restoration, using the ovariectomized rat model. The analogs also show enhanced activities and bioavailabilities, as demonstrated by their hypotensive effects in the rat.
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Barbier Jean-Rene
Morley Paul
Neugebauer Witold
Ross Virginia J. S.
Whitfield James F.
National Research Council of Canada
Russell Jeffrey E.
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