The present inventors et al. succeeded in forming a diblock polymer from a cyclic nitroxide radical compound, which encompasses 4-hydroxy-2,2,6,6-tetramethylpiperidin-1-oxyl or the like functioning as a radical scavenger for reactive oxygen species or the like, without adversely affecting the function of the compound, and filed a patent application for inventions relating to this diblock polymer per se and use of the diblock polymer in a certain technical field (see Patent Document 1). Furthermore, the present inventors et al. produced a so-called A-B-A type triblock copolymer in which two blocks (A) each having a cationically chargeable cyclic nitroxide radical as a pendant group are covalently bonded to both terminals of a poly(ethylene glycol) (PEG) chain (B). It has been confirmed and reported that such triblock copolymers form so-called flower micelles by using the formation of an ion complex with a polyanionic polymer in an aqueous medium as the driving force, that micelles formed in this way undergo gelation in response to biological environments, and that the thus formed gel exhibits high retainability in a local site and exhibits a high anti-inflammatory effect in inflammation models (for example, see Non-Patent Document 1, Non-Patent Document 2, Non-Patent Document 3 and Non-Patent Document 4, which are lecture proceedings for these reports).
Meanwhile, peptides and polypeptides, which encompass enzymes, proteins, and the like, have come to be used as drugs, and especially medical drugs, that utilize the specific reactivity, functionality or activity of such peptides and polypeptides. However, such peptides and polypeptides are decomposed by enzymes such as proteases in living bodies, which causes a variety of problems such as bioavailability of the peptides and polypeptides becoming extremely low and the occurrence of resistance and toxicity. In recent years, these problems have been solved by modification of poly(ethylene glycol), so called PEGylation of such substances, but many problems exist, such as a lowering of activity and reaction complexity. Attempts have been made to stabilize such substances by utilizing enzyme charging and complexing using polymers having the opposite charge (Non-Patent Document 5 and Non-Patent Document 6), but putting such methods to practical use have been impaired due to such complexes readily breaking down as a result of high ionic strength in living bodies. Furthermore, because polymers and the like are used in matrixes per se, the matrix is per se can cause inflammation, which is a problem.
USPTO Backgrounds
USPTO Backgrounds