Peptidic physiologically active substances, such as hormones, cytokines, hematopoietic factors, growth factors, enzymes, soluble or solubilized receptors, antibodies, peptidic antigens, blood coagulation factors, or adhesion factors, are mainly administered in the form of, for example, an injection by a parenteral administration method in view of the ease of being digested with in vivo digestive enzymes, hydrophilicity, instability, etc. The administration by injection accompanies pain upon administration. Therefore, from the viewpoint of improving QOL (quality of life) and increasing compliance, making physiological active substances as mentioned above or the like into sustained release formulations has been desired to extend administration intervals and avoid frequent administration (Non-patent Literature (NPL) 1 and 2).
As a means for technically solving this problem, numerous studies have been reported on sustained release microcapsule formulations containing a protein having a physiologically active effect and/or a pharmacologically active effect. For example, Patent Literature (PTL) 1 discloses a microcapsule comprising an amorphous water-soluble physiologically active substance and a high-molecular-weight polymer. PTL 1 discloses in the Examples that an amorphous antiplatelet drug (S)-4-[(4-amidinobenzoyl)glycyl]-3-methoxycarbonylmethyl-2-oxopiperazine-1-acetic acid is dispersed in a dichloromethane solution of a lactic acid-glycolic acid copolymer in which L-arginine has been dissolved, and the dispersion is finely divided into particles with a polytron and then formed into an S/O/W emulsion in an aqueous sodium chloride solution.
PTL 2 further discloses a sustained release formulation comprising a physiologically active substance-containing matrix and a cationic substance and/or a polyol, the formulation being capable of suppressing the initial release of the physiologically active substance. PTL 2 discloses that a powder (a Solid phase) obtained by freeze-drying a physiologically active substance solution is dispersed in a solution of a biologically active polymer in an organic solvent (an Oil phase), and the resulting S/O dispersion is added to an aqueous solvent (a Water phase) to produce an S/O/W emulsion.
In addition to the above, there are many reports on sustained release microcapsule formulations comprising a protein having a physiologically active effect and/or a pharmacologically active effect (PTL 3, PTL 4, NPL 3, and NPL 4).
USPTO Backgrounds
USPTO Backgrounds