For administration of a therapeutic agent, oral administration is generally employed. Oral administration of a physiologically active peptide or protein, however, causes hydrolysis of the peptide or protein by a digestive enzyme to decrease disadvantageously the absorbability from the digestive tract. Accordingly, such physiologically active peptide or protein is usually administered by repetition of intramuscular or subcutaneous injections or by intravenous drip infusion. These methods, however, are not preferable in a chronic administration, although they are acceptable in a case where the repetition of the injection is extremely limited. By way of illustrating, for the therapy of viral hepatitis type C, interferon-.alpha. is continuously administered daily throughout 4 weeks or more (see "Journal of Clinical and Experimental Medicine (IGAKU NO AYUMI)", 161, 5, 359-363 (1992)). In such chronic or frequent administration, however, the patient is obliged to be restrained to a great extent. Therefore, development of an effective and economic administration system for such physiologically active peptide or protein has been demanded.
Japanese Patent Application Laid-open No. 2930/1988 (JP-A-63-2930) discloses a system where a polypeptide is dispersed in a polylactide. Japanese Patent Publication No. 502117/1988 (JP-B-63-502117) and Japanese Patent Application Laid-open No. 234820/1992 (JP-A-4-234820) disclose pharmaceutical preparations using a liposome, and Japanese Patent Publication No. 502574/1991 (JP-B-3-502574) proposes a pharmaceutical preparation where a liposome containing a physiologically active polypeptide is dispersed in a gel.
When these pharmaceutical preparations are administered, however, the drugs are unexpectedly released to a large extent in the initial stage of administration. Thus the drug concentration in blood is increased and the releasing rate of the drug can not be maintained in a certain range. Furthermore, since an organic solvent is used in the manufacture of the preparation, the polypeptide is denaturated to decrease the physiological activity.
Japanese Patent Application Laid-open No. 2930/1988 (JP-A-63-2930) discloses a sustained releasable system for a physiologically active polypeptide, which comprises an atherocollagen-matrix and the physiologically active polypeptide dispersed in the matrix. The atherocollagen used as a base is, however, derived from a foreign or different animal from human being, and it may probably show antigenicity.
Japanese Patent Application Laid-open No. 22012/1988 (JP-A-63-22012) discloses a system prepared by dispersing a physiologically active polypeptide in a water-insoluble matrix and compression-molding the dispersion, as a sustained releasable pharmaceutical preparation for parenteral administration of the polypeptide. The pharmaceutical preparation controls the release of the physiologically active polypeptide by utilizing erosion of the matrix in vivo. Therefore, the polypeptide may be enzymatically degraded or decomposed so as to lower the biological availability.
Japanese Patent Application Laid-open No. 85328/1986 (JP-A-61-85328) discloses a pharmaceutical preparation which comprises a composition of a physiologically active polypeptide and a polyglycerol fatty acid ester, wherein the polyglycerol fatty acid ester is dispersed in water. The pharmaceutical preparation is, however, restricted with regard to a dosage form since it is a solution. Furthermore, since the polyglycerol fatty acid ester is utilized to promote the percutaneous absorption of the physiologically active polypeptide, and the drug can hardly be released for a longer period of time, e.g. for 24 hours or more.