Protein solution preparation and method of stabilizing the same

#This application is a 371 of PCT/JP00/06144, filed Sep. 8, 2000, which claims priority to Japanese application 254896/1999, filed Aug. 9, 1999.

#The present invention relates to protein solution formulations which are easy to handle and stable over long periods. More specifically, the present invention relates to stable protein solution formulations prefilled in a resin container. The present invention also relates to methods for stabilizing protein solution formulations.

#With the development of genetic recombination technology, various protein formulations are supplied in stable amounts. To ensure stability, these formulations are supplied in the dosage form of a lyophilized protein ingredient powder to be dissolved just before use in a water-soluble diluent, either separately packaged, or in the dosage form of a protein solution formulation containing additives which improve stability. When both dosage forms are compared, the solution dosage form is more advantageous in terms of convenience of use, but it is difficult to ensure its stability.

#Suitable resins as container materials for use in the present invention include known medical container materials such as polyethylene (PE), polypropylene (PP), polyethylene terephthalate (PET), polycarbonate, polyethyl methcrylate, preferably resins represented by ring-opened polymers of cycloolefins such as norbornene or tetracyclododecene or derivatives thereof and hydrogenated products thereof; or copolymers having a cyclopentyl residue or substituted cyclopentyl residue inserted into the molecular chain by polymerization of a cycloolefin such as norbornene or tetracyclododecene or a derivative thereof and ethylene or propylene. Cycloolefins here include monocyclic and polycyclic compounds. Preferred are thermoplastic norbornene resines or thermoplastic tetracyclododecene resins. Thermoplastic norbornene resins include ring-opened polymers of norbornene monomers and hydrogenated products thereof, addition polymers of norbornene monomers, and addition polymers of norbornene monomers and olefins. Thermoplastic tetracyclododecene resins include ring-opened polymers of tetracyclododecene monomers and hydrogenated products thereof, addition polymers of tetracyclododecene monomers, and addition polymers of tetracyclododecene monomers and olefins. Thermoplastic norbornene resins are described in, for example, JPA No. 14882/91, JPA No. 122137/91 and JPA No. 63807/92.

#Especially preferred are cycloolefin copolymers (COCs) such as copolymers of norbornene and an olefin such as ethylene, and copolymers of tetracyclododecene and an olefin such as ethylene. Cycloolefin polymers (COPs) obtained by ring-opening polymerization and hydrogenation of norbornene are also preferred. Such COCs and COPs are described in, for example, JPA No. 300939/93 or JPA No. 317411/93. Preferred structures of such COCs and COPs are shown below.

#(1) Examples of COC (copolymers of tetracyclododecene and ethylene)