In the current aging society, the number of patients with joint diseases including osteoarthritis (hereinafter also referred to as OA) has been steadily increasing. The present inventors provided in the previous application a pharmaceutical composition that comprised a conjugate of hyaluronic acid (hereinafter also referred to as HA) and methotrexate (hereinafter also referred to as MTX) and which was useful as a therapeutic drug for joint diseases (WO05/85294). The conjugate is a remarkable compound in which the characteristic of HA that can be used as a safe intra-articular injection for joint diseases that is a potential substitute for steroid preparations is combined with the characteristic of MTX that is capable of suppressing synovitis.
Subsequent studies, however, have revealed that upon irradiation with light, this compound is prone to gel or experience a drop in molecular weight, i.e., its storage stability is not completely satisfactory. Under the circumstances, it is recommended that pharmaceutical compositions comprising the hyaluronic acid-methotrexate conjugate be stored in a cool dark space until they are taken out of it just before use. Alternatively, aluminum foil or its equivalent may be used to assure complete shielding of light. However, in medical settings such as hospitals, the pharmaceutical compositions, after taken out of the cold dark space or stripped of the light-shielding wrap, may often be left under light for several to ten-odd hours. Thus, the simple means of packaging the container of pharmaceuticals with the light-shielding material is not enough to ensure that the hyaluronic acid-methotrexate conjugate remains stable and an improvement in its photostability has been desired.
USPTO Backgrounds
USPTO Backgrounds