Parenteral pharmaceutical composition containing humanized monoclonal antibody fragment and stabilizing method thereof
This invention relates to a parenteral pharmaceutical composition which comprises a humanized monoclonal antibody fragment, a nonionic surface active agent and saccharides, wherein its pH is weakly acidic. The invention also relates to a method for the stabilization of a humanized antibody fragment, which comprises formulating a nonionic surface active agent and saccharides and adjusting the pH to a weakly acidic level. According to the invention, a stable parenteral pharmaceutical composition or parenteral pharmaceutical preparation can be provided, which comprises a humanized monoclonal antibody fragment and has no using limitations such as cold place preservation avoiding freezing, transfer and handling avoiding shaking, particle removing operation by a filter when used and the like.
1 - 16 . (canceled)
17 . A method for storage-stabilizing a humanized monoclonal antibody fragment in a liquid or freeze-dried composition, comprising:
(a) formulating a pharmaceutical composition comprising a humanized monoclonal antibody fragment, a nonionic surface active agent, and saccharides, wherein the pH is weakly acidic, and
(b) storing said composition in a liquid or freeze-dried state.
18 . The method of claim 17 , wherein said composition is stored at a temperature above 0° C.
19 . The method of claim 18 , wherein said composition is stored at a temperature from above 0° C. to about 60° C.
20 . The method of claim 19 , wherein said composition is stored at about room temperature.
21 . The method of claim 17 , wherein the concentration of said humanized monoclonal antibody fragment is from about 0.01 mg/ml to about 10 mg/ml.
22 . The method of claim 17 , wherein said composition includes a buffering substance that acts to adjust the pH value to approximately 4 to 6.
23 . The method of claim 21 , wherein said buffering substance is sodium phosphate and/or sodium citrate.
24 . The method of claim 21 , wherein said buffering substance is at a concentration of from about 1 mM to about 500 mM.
25 . The method of claim 17 , wherein said nonionic surface active agent is polysorbate 80.
26 . The method of claim 17 , wherein the concentration of said nonionic surface active agent is from about 1×10 −5 % by weight to about 1% by weight.
27 . The method of claim 17 , wherein said saccharides are purified sucrose and/or mannitol.
28 . The method of claim 17 , wherein the concentration of said saccharides is from about 0.01% by weight to about 50% by weight.
29 . The method of claim 17 , wherein said composition is stored in an oxygen-reduced atmosphere.
30 . The method of claim 17 , wherein said humanized monoclonal antibody fragment is a humanized monoclonal antibody Fab fragment.
31 . The method of claim 30 , wherein said humanized monoclonal antibody Fab fragment is a Fab fragment of a humanized monoclonal antibody for a fibrinogen receptor of a human platelet membrane glycoprotein GPIIb/IIIa.
32 . The method of claim 31 , wherein said humanized monoclonal antibody Fab fragment is a humanized C4G1 Fab antibody.