For the N-terminus of the Silodosin Rapaflo rhaFGF. Effect of PEGylation on the structural and thermal stability t of thermal resistance is one of the most important factors rhaFGF to keep intact, because the drug proteases are most active at h Higher temperatures. The mitogenic activity of t was rhaFGF of native and pegylated rhaFGF need during the incubation of a Transient Reduced ngigen way. After 96 h of incubation maintained native rhaFGF anf only 23.7% of Nglichen mitogenic activity of t, w While the pegylated rhaFGF receive 61.3% of anf Nglichen activity of t, indicating increased Hten thermal tolerance of pegylated rhaFGF. Then, the m Chtige resistance of pegylated rhaFGF to proteolysis by incubation of two forms of rhaFGF with trypsin was examined in 2 mM for various times, then visualized by their integrity T SDS-PAGE. 3B shows that protect after 20 minutes, 31.3% of pegylated rhaFGF best w During almost all of the non-pegylated had been digested rhaFGF. These results show that increased Hte PEGylation fa Is significant resistance to proteolysis of rhaFGF. The gr Stability was ere t of Change due rhaFGF PEGylation also experience Verg Proven llungsmittel induced unfolding equi librium. As shown in Figure 3C, it is clear that the PEGylation ht the fraction of native protein at a concentration of 2.0 M urea and above are obtained. Concentrations of urea, giving the native protein content of 0.5, 4.2 M and 5.4 M for unmodified and pegylated rhaFGF respectively. These data show that PEGylation reduces the Ausma RhaFGF of it and thus the stability of t of the protein structure. The pharmacokinetics of pegylated rhaFGF Based on the pharmacokinetic curves of the four eliminated, the lifetime of the plasma half-life of unmodified rhaFGF about 23.89 minutes, w While that of the 109,469 minutes rhaFGF pegylated, reflecting an increase of 4.6 times the half-life in vivo compared with pegylated rhaFGF rhaFGF mother tongue. Functional assessment of pegylated rhaFGF in diabetic wound healing properties previously described biochemical and physiological clearly demonstrate that pegylated rhaFGF clearly increased Ht their resistance to a long incubation time and trypsin treatment in vitro and engaged Ngern the time half-life in vivo.
These properties have encouraged us to determine whether these improvements can be a better therapeutic effect than the native form, as given in vivo. Therefore, a hyperglycemia Mix animal model with a single dose of STZ induced 60 mg / kg in SD rats, the hyperglycemia Chemistry until the end of experimental causes. STZ-induced diabetic rats showed a slow weight gain may need during the experimental period, consistent with our previous studies in rats and diabetic mouse models.22, 23 to 2 months after the hyperglycemia Chemistry, a br Lure was formed skin and br the mechanical removal of the skin Lee was taken to make a deep trauma. Aboriginal and pegylated RhaFGF rats were treated with and without diabetes to wound healing. We observed the size E of the unhealed wound at various times after treatment. In non-diabetic state, although not able to significantly reduce the wound healed rhaFGF from day 3 to day 14 after treatment, three groups of injuries were completely healed within 18 days after treatment. Diabetic rats.