| 摘要 |
<p>The present invention relates to a method for enhancing the stability of hemoglobin products comprising deoxygenating hemoglobin by gas exchange through a permeable membrane. It is based, in part, on the observation that hemoglobin was rendered significantly more stable upon deoxygenation; methemoglobin formation from hemoglobin process by the methods of the invention was surprisingly low. In particular embodiments of the invention, the stable hemoglobin-based products are deoxygenated prior to storage, so as to prolong shelf-life. In alternative embodiments of the invention, hemoglobin may be deoxygenated prior to chemical treatment, including but not limited to conjugation to polyalkylene oxide. The present invention offers the advantages of decreasing the rate of conversion of hemoglobin to methemoglobin in solution, and diminishes the need for chemical reducing agents or stabilizing agents, such as sugars. Because the presence of chemical reducing agents or sugars may be clinically problematic, the present invention provides for hemoglobin pharmaceutical preparations of superior purity.</p> |
