RASMUSSEN, Grethe,KINDERMANN, Susanne,RAU, Harald,WEGGE, Thomas
申请号：
ES10790843
公开号：
ES2667025T3
申请日:
2010.12.15
申请国别(地区):
ES
年份:
2018
代理人:
摘要：
Method of manufacturing a dry composition comprising a therapeutically effective amount of a rhGH polymer prodrug and one or more lyoprotectants, wherein the growth hormone is transiently bound to a polymer carrier, the rhGH polymer prodrug having the chemical structure shown in (A), in which HN-rhGH represents the rhGH residue attached to the transient linker； R1, R2, R3, R4 and R5 are independently selected from hydrogen, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tertiary butyl； PEG is a water soluble polyethylene glycol polymer containing at least 50% by weight of ethylene oxide units attached to the transient linker； n>； = 1 or 2； and X is selected from C1 to C8 alkyl or C1 to C12 heteroalkyl； The method comprising the steps of (i) mixing the rhGH polymer prodrug with trehalose dihydrate and succinic acid to produce a composition comprising rhGH polymer prodrug 10-300 mg / ml succinic acid 5-50 mM trehalose dihydrate 25-850 mg / ml, (ii) adjust the pH of the composition of step (i) to a pH ranging from pH 4.5 to pH 5.5 with tris, (iii) transfer amounts of the mixture from step (i ) equivalent to the desired number of dosages to suitable chambers of a container, (iv) drying the mixture and (v) sealing the container； the order of stages (ii) and (iii) can be changed.Método de fabricación de una composición seca que comprende una cantidad terapéuticamente eficaz de un profármaco de polímero de rhGH y uno o más lioprotectores, en el que la hormona de crecimiento está unida transitoriamente a un portador de polímero, teniendo el profármaco de polímero de rhGH la estructura química mostrada en (A), en la que HN-rhGH representa el residuo de rhGH unido al enlazador transitorio； R1, R2, R3, R4 y R5 se seleccionan independientemente de hidrógeno, metilo, etilo, propilo, isopropilo, butilo, isobutilo, butilo terciario； PEG es un polímero de polietilenglicol soluble en agua que contiene al menos 50 % en peso de unidades de óxido de etileno unidas al enlazador tr
