drug carrier cell penetration molecule, methods for facilitating incorporation of a biologically active compound (bac) into a cell, for improving the bioavailability of a drug or bac, for introducing a drug or bac at a site, and for altering expression of an endogenous or exogenous gene, and, composition.
ADAM JAMES REGINALD GADD,KEITH FOSTER,WOUTER EILERS
申请号：
BR112018012641
公开号：
BR112018012641A2
申请日:
2016.12.21
申请国别(地区):
BR
年份:
2018
代理人:
摘要：
The invention relates to improvements in drug delivery and more particularly to the use of cell penetrating agents (cpas) or cell penetrating peptides (cpps) which have been stabilized by, for example: i) stapling two amino acids to forming stapled cpps or (ii) stitching three or more amino acids to form stitched cpps. These stabilized cpps are conjugated to a biologically active drug or compound (bac) directly or via a bifunctional ligand (bfl) so that the bac can be carried across a cell membrane by the cpp. the resulting molecules are referred to as drug carrier cell penetration molecules (dccpms). The preferred bac is an electrically low charge oligonucleotide such as a morpholino phosphorodiamidate (pmo) oligonucleotide. The invention also relates to a method for facilitating the incorporation of a bac into a cell, the use of a dccpm in the treatment of a disease requiring alteration of an endogenous or exogenous gene, a method for improving the bioavailability of a drug or bac , a method of introducing a drug or bac at a site that is refractory to the drug or bac in its native state, a method of treating an individual comprising administering the dccpms of the invention and a pharmaceutical composition comprising dccpm and one or more pharmaceutically acceptable excipients.a invenção se refere a melhorias na entrega de fármacos e, mais particularmente, ao uso de agentes de penetração de célula (cpas) ou peptídeos de penetração de célula (cpps) que foram estabilizados por, por exemplo: i) grampeamento de dois aminoácidos para formar cpps grampeados (staps) ou ii) costura de três ou mais aminoácidos para formar cpps costurados (stips). esses cpps estabilizados são conjugados a um fármaco ou composto biologicamente ativo (bac) diretamente ou através de um ligante bifuncional (bfl) de modo que o bac possa ser portado através de uma membrana celular pelo cpp. as moléculas resultantes são referidas como moléculas de penetração de células portadoras de fármacos (dccp
