PHARMACEUTICAL COMPOSITION AND METHOD OF TREATMENT OF HUMAN DISEASES ASSOCIATED WITH HUMAN GROWTH

摘要

1. A pharmaceutical composition comprising in vivo a clinically effective amount of a pegylated prodrug of recombinant human growth hormone (rhGH) conjugate, wherein the PEG is coupled to rhGH via a self-hydrolyzable (self-cleavable) time linker; wherein said prodrug conjugate is characterized in that: (1): the conjugate has a GH activity of less than 5% with respect to native growth hormone without PEG; and (2): the linker self-hydrolysis rate is such that the in vivo half-life is from 10 hours to 600 hours, as well as suitable pharmaceutical excipients. 2. The pharmaceutical composition according to claim 1, wherein the self-hydrolysis rate is such that the in vivo half-life is up to 5 times shorter than the in-vitro half-life of the corresponding PEGylated prodrug hGH conjugate. 3. The pharmaceutical composition according to claim 2, wherein the in vivo half-life is up to 3 times shorter than the in vitro half-life of the corresponding PEGylated prodrug hGH conjugate. 4. The pharmaceutical composition according to claim 2 or 3, wherein the in vivo half-life is up to 2 times shorter or almost identical to the in vitro half-life of the corresponding pegylated pro-drug hGH conjugate. 5. The pharmaceutical composition according to PP. 1 and 2, where the composition is a composition for subcutaneous administration, intramuscular injection or intravenous administration. The pharmaceutical composition according to PP. 1 and 2, where the PEGylated prodrug has a total PEG load on the growth hormone molecule, which is at least 25 kDa. 7. The pharmaceutical composition according to PP. 1 and 2, where the prodrug conjugate has the chemical structure (A): where ΗΝ-rhGH is an rhGH residue attached to a temporary linker; R1, R2, R3, R4 and R5