Method for preparing a biodegradable polymer microsphere containing a glucose-regulating peptide

#This application is a 371 of PCT/KR2008/002216 filed on Apr. 18, 2008, which claims the benefit of Korean Patent Application No. 10-2007-0038467 filed on Apr. 19, 2007, the contents of each of which are incorporated herein by reference.

#The present invention relates to a biodegradable polymeric microsphere comprising a biodegradable polymer carrier with a glucose-regulating peptide encapsulated therein, capable of releasing the glucose-regulating peptide in a controlled manner, and a method for the preparation thereof.

#After being administered orally, most protein and peptide drugs lose their active structures in the acidic environment of the stomach or undergo enzymatic degradation. Also, they are adsorbed at very low rates through the gastric or intestinal mucosa. For these reasons, protein or peptide drugs usually take non-oral administration routes, that is, are usually administered by injection. The non-oral administration of protein or peptide drugs must be repeated because most non-orally administered protein or peptide drugs show short half lives and low bioavailability in the body. In addition, their administration may be continued for a long time period, e.g., months, in many cases. In order to avoid these problems, active research into sustained-release dosage formulations has been conducted, resulting in the use of biodegradable polymeric carriers with protein or peptide drugs encapsulated therein, which can release the protein or peptide drugs therefrom as the biodegradation of the polymeric carriers progresses [Heller, J. et al., Controlled release of water-soluble macromolecules from bioerodible hydrogels, Biomaterials, 4, 262-266, 1983; Langer, R., New methods of drug delivery, Science, 249, 1527-1533, 1990; Langer, R., Chem. Eng. Commun., 6, 1-48, 1980; Langer, R. S. and Peppas, N. A., Biomaterials, 2, 201-214, 1981; Heller, J., CRC Crit. Rev. Ther. Drug Carrier Syst., 1(1), 39-90, 1984; Holland, S. J. Tighe, B. J. and Gould, P. L., J. Controlled Release, 155-180, 1986].

#FIG. 1 is a graph showing the in vitro release pattern of the microspheres prepared through a drug dispersion process in Example 1 in accordance with the present invention.

#FIG. 2 is a graph showing the in vitro release patterns of the microspheres prepared in Examples 4 to 8 in accordance with the present invention.

#FIG. 3 is a graph showing the in vitro release patterns of the microspheres prepared in Comparative Examples 1 and 2.

#Below, a detailed description is given of the present invention.

#The present invention pertains to a biodegradable polymeric microsphere for the controlled release of a glucose-regulating peptide, comprising a biodegradable polymer carrier with the glucose-regulating peptide encapsulated therein.

#Examples of the glucose-regulating peptide suitable for use in the present invention include natural, recombinant or synthetic exendin-3, exendin-4 and homologs and agonists thereof, glucagon, glucagon-like peptides (e.g., GLP-1, GLP-2) and homologs and agonists thereof, with preference for synthetic exendin-3, exendin-4 and homologs and agonists thereof. Most preferable is synthetic exendin-4.