Preserving a hemoglobin blood substitute with a transparent overwrap

Abstract

The invention relates to a method for preserving the stability of a hemoglobin blood substitute comprising maintaining the hemoglobin blood substitute in an atmosphere substantially free of oxygen. The invention also involves a method for producing a stable polymerized hemoglobin blood-substitute from blood. The method of this invention includes mixing blood with an anticoagulent to form a blood solution, washing the red blood cells in the blood solution and then separating the washed red blood cells from the white blood cells. This method also includes disrupting the red blood cells to release hemoglobin and form a hemoglobin solution, which is then treated by high performance liquid chromatography to form a hemoglobin eluate. The hemoglobin eluate is then deoxygenated, contacted with a first sulfhydryl compound to form an oxidation-stabilized deoxygenated hemoglobin solution, and mixed with a cross-linking agent to form a polymerization reaction mixture, which is then polymerized. The polymerized hemoglobin solution is then diafiltered with a physiologic solution and with a sulfhydryl compound, whereby the polymerized hemoglobin solution is made physiologically acceptable, and whereby the sulfhydryl compound scavenges oxygen, to form a stable polymerized hemoglobin blood-substitute, which is then packaged and stored in an atmosphere substantially free of oxygen.

Description

RELATED APPLICATIONS[0001] This application is a continuation of U.S. Ser. No. 09 / 348,881, filed on Jul. 7, 1999, which is a continuation-in-part of U.S. Ser. No. 09 / 173,189, filed on Oct. 14, 1998, which is a continuation-in-part of U.S. Ser. No. 08 / 974,658, filed on Nov. 19, 1997, now abandoned, which is a continuation of U.S. Ser. No. 08 / 471,583, filed on Jun. 7, 1995, now issued U.S. Pat. No. 5,691,452, which is a continuation-in-part of U.S. Ser. No. 08 / 458,916, filed on Jun. 2, 1995, now issued U.S. Pat. No. 5,840,582, which is a continuation of U.S. Ser. No. 08 / 409,337, filed on Mar. 23, 1995, now issued U.S. Pat. No. 5,854,209. The entire teachings of the above applications are incorporated herein by reference.BACKGROUND OF THE INVENTION[0002] There exists a need for a blood-substitute to treat or prevent hypoxia resulting from blood loss (e.g, from acute hemorrhage or during surgical operations), resulting from anemia (e.g., pernicious anemia or sickle cell anemia), or resu...

AI Technical Summary

Benefits of technology

[0013] The advantages of this invention are numerous. One advantage is that the hemoglobin stored according to the methods of this invention has a greater degree of purity and longer shelf-life. High barrier overwraps provide an addition level of product quality even when high barrier primary packaging is employed. In addition, the transparent high barrier overwraps of the present invention provide extremely high oxygen and water vapor barrier properties but have no saran (polyvinylidene chloride, PVDC) layer. PVDC poses a medical waste problem because chlorinated products such as polycyclic aromatic hydrocarbons and hydrochloric acid are generated during incineration. Clear overwraps allow the label of the primary package to be seen. Therefore, a second label typically is not required on the overwrap. In addition, product quality inspection and primary package integrity can also be evaluated. Furthermore, as demonstrated for the first time herein, automation equipment can be used with the clear oxygen barrier laminates, allowing production of very large numbers of packages in a short period of time with very little human labor and without the loss of barrier properties. The blood-substitute remains stable at room temperature for periods of two years or more, a significant improvement over previous methods.

Problems solved by technology

PVDC poses a medical waste problem because chlorinated products such as polycyclic aromatic hydrocarbons and hydrochloric acid are generated during incineration.

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