Aim To study the most stable pH value of endomorphin-1 solution and toestimate the shelf-life of EM-1 solution. Methods The content of EM-1 in its solution was determinedby HPLC, and stability was studied by accelerat...Aim To study the most stable pH value of endomorphin-1 solution and toestimate the shelf-life of EM-1 solution. Methods The content of EM-1 in its solution was determinedby HPLC, and stability was studied by accelerated tests. Results The most stable pH value of EM-1solution was observed. By the accelerated tests we obtained the Arrhe-nius relationship and thepharmacokinetic parameters. Conclusion The most stable pH value of EM-1 solution is 4.5 -4.8. Thet_(1/2)(25℃) is 45 d.展开更多
Endomorphin-1 is an endogenous opioid peptide that mediates pain relief through interaction with the μ-opioid receptor in the central nervous system. To enhance the metabolic stability of this tetrapeptide, cyclisati...Endomorphin-1 is an endogenous opioid peptide that mediates pain relief through interaction with the μ-opioid receptor in the central nervous system. To enhance the metabolic stability of this tetrapeptide, cyclisation through the formation of a disulfide bridge between the side chains of cysteine residues added to the sequence was explored. A further increase in stability was achieved through N-terminal modification with lipoamino acid and lactose succinamic acid, and the inclusion of D-amino acids. The latter also provided an alternative spatial arrangement of the aromatic side chains. The lipidated cyclic derivatives were insoluble in aqueous buffer, however, the cyclic peptides and glycopeptides showed greatly improved stability towards enzymatic degradation in human plasma.展开更多
文摘Aim To study the most stable pH value of endomorphin-1 solution and toestimate the shelf-life of EM-1 solution. Methods The content of EM-1 in its solution was determinedby HPLC, and stability was studied by accelerated tests. Results The most stable pH value of EM-1solution was observed. By the accelerated tests we obtained the Arrhe-nius relationship and thepharmacokinetic parameters. Conclusion The most stable pH value of EM-1 solution is 4.5 -4.8. Thet_(1/2)(25℃) is 45 d.
文摘Endomorphin-1 is an endogenous opioid peptide that mediates pain relief through interaction with the μ-opioid receptor in the central nervous system. To enhance the metabolic stability of this tetrapeptide, cyclisation through the formation of a disulfide bridge between the side chains of cysteine residues added to the sequence was explored. A further increase in stability was achieved through N-terminal modification with lipoamino acid and lactose succinamic acid, and the inclusion of D-amino acids. The latter also provided an alternative spatial arrangement of the aromatic side chains. The lipidated cyclic derivatives were insoluble in aqueous buffer, however, the cyclic peptides and glycopeptides showed greatly improved stability towards enzymatic degradation in human plasma.