Cross-linked hemoglobin preparation method and organ perfusate comprising hemoglobin

Abstract

The invention discloses a cross-linked hemoglobin preparation method, wherein the preparation method comprises the following steps: a, diluting deoxidized hemoglobin, and adding the diluted deoxidizedhemoglobin into an anaerobic reactor; b, arranging an atomizer at the top of the anaerobic reactor, adding a cross-linking agent into the reactor through the atomizer, and carrying out a cross-linking reaction; and c, adding a reducing agent to terminate the cross-linking reaction, and removing the unreacted cross-linking agent and the terminating reducing agent in an ultrafiltration liquid changing manner to obtain the cross-linked hemoglobin. The cross-linked hemoglobin prepared by the preparation method contains low contents of macromolecules (greater than 500 kD) and micromolecules (lessthan 64 kD); by adding the cross-linked hemoglobin into organ perfusate, the phenomena of organ acidosis and lysosomal enzyme activation adverse consequences caused by lack of an oxygen carrying agentin conventional perfusate and cell damage caused by excessive free radicals generated during reperfusion can be solved, and the perfusate is quite simple and convenient to prepare, store, transport and use.

Description

technical field [0001] The invention relates to the technical field of organ preservation in medical technology, in particular to a preparation method of cross-linked hemoglobin, and in particular to an organ perfusate containing the cross-linked hemoglobin. Background technique [0002] Many human diseases come from the necrosis of cells, tissues, and organs, resulting in loss of function, disability, and even death. With the development of modern medicine, organ transplantation technology is becoming more and more mature. From the perspective of surgery: organ transplantation technology is perfect , head replacement surgery is not a big problem. In fact, organ transplantation still faces various difficulties, and the preservation of isolated organs is one of them. Organ transplantation requires the transplantation of living organs. Therefore, from the time when the organ for transplantation is cut off from the donor to the time when its main blood vessels are connected to...

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Problems solved by technology

But glutaraldehyde crosslinking also has its obvious disadvantages. First, the crosslinking reaction is non-specific, because there are about 40 lysine side chain amino groups and four chain terminal amino groups on the surface of hemoglobin that can participate in the reaction, and the reaction is difficult to control. The molecular weight distribution of the product ranges from 32kD to over 1000kD, resulting in a heterogeneous mixture of final products

The control of molecular weight has always been a difficulty for glutaraldehyde cross-linked hemoglobin. Too low molecular weight has poor stability, is easy to dissociate and cause nephrotoxicity, and has low oxygen carrying efficiency; too high molecular weight will increase blood viscosity, which is not conducive to blood flow. and deposits in the inner walls of blood vessels and in the liver or spleen

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