Process for the production of crosslinked hemoglobin in the presence of sodium tripolyphosphate

• US 5,128,452 A
• Filed: 04/19/1989
• Issued: 07/07/1992
• Est. Priority Date: 04/19/1989
• Status: Expired due to Fees

• Current Assignee: Baxter International Inc.
• Original Assignee: Baxter International Inc.
• Inventors: Nelson, Deanna J., Hai, Ton T., Srnak, Ana
• Primary Examiner(s): Wax, Robert A.
• Assistant Examiner(s): Ekstrom, Richard C.
• Application Number:
  US07/340,609
• Time in Patent Office: 1,175 Days
• Field of Search: 514/6, 530/385
• US Class Current: 530/385
• CPC Class Codes: A61K 38/00 Medicinal preparations containing peptides peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00
• CPC Class Codes: C07K 14/805 Haemoglobins; Myoglobins

Abstract

A process for the production of crosslinked hemoglobin comprises crosslinking hemoglobin in the presence of sodium tripolyphosphate.

Claims

1. A process for making crosslinked hemoglobin comprising:

adding sodium tripolyphosphate to a hemoglobin solution and reacting the hemoglobin with a crosslinking agent.

3. The process of claim 1 wherein the crosslinking agent is a member selected from the group consisting of glutaraldehyde, glyoxylate, polyether glycols, bis(3,5-dibromosalicyl) diesters and bis(3,5-dibromosalicyl) fumarate.

5. The process of claim 1 wherein the molar ratio of hemoglobin to sodium tripolyphosphate is from about 1:

1 to about 1.30.

7. The process of claim 3 wherein the molar ratio of hemoglobin to crosslinking agent is from about 1:

1 to about 1;

50.

8. The process of claim 3 wherein the crosslinking reaction is conducted to a temperature of about 5°

C. to about 40°

C.

2. A process for making crosslinked hemoglobin comprising:

lysing red blood cells to produce a hemoglobin containing lysate, adding sodium tripolyphosphate to the lysate, deoxygenating the hemoglobin in the lysate, and reacting the hemoglobin with a crosslinking agent.

4. The process of claim 2 wherein the crosslinking agent is a member selected from the group consisting of glutaraldehyde, glyoxylate, polyether glycols, bis(3,5-dibromosalicyl) diesters and bis(3,5-dibromosalicyl) fumarate.

6. The process of claim 2 wherein the molar ratio of hemoglobin to sodium tripolyphosphate is from about 1:

1 to about 1.30.

9. The process of claim 2 wherein the pH of the hemoglobin and sodium tripolyphosphate solution is within the range of 6.5 to about 10.0 prior to deoxygenating the hemoglobin.