Preparation method of bipolymerized hemoglobin

A technology of hemoglobin and deoxyhemoglobin, which is applied in the field of preparation of blood substitutes, can solve the problems of complex operation, high cost, and inconspicuous effect, and achieve the effect of simple operation

Active Publication Date: 2018-06-12
BLOOD TRASFUSION INST CHINESE ACAD OF MEDICAL SCI
View PDF5 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] In order to prepare HBOCs products with smaller molecular weight, uniform molecular weight distribution, higher polymerization rate, and lower dimer content, those skilled in the art have made a lot of efforts and attempts, but the effect is not obvious, or better effect Requires high cost and complex operations to obtain

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Examples

Experimental program
Comparison scheme
Effect test

preparation example Construction

[0024] A method for preparing double polymerized hemoglobin, comprising the following steps:

[0025] 1), under the condition of inert gas and stirring, the bis(2-hydroxyethyl)iminotris(hydroxymethyl)methane solution of diaspirin is slowly added dropwise into the matrix-free human deoxyhemoglobin aqueous liquid for intramolecular exchange joint reaction to obtain a first polymer product.

[0026] Specifically, under inert gas and stirring conditions, a solution of bis(2-hydroxyethyl)iminotris(hydroxymethyl)methane (Bis-Tris) of double aspirin (DBBF) was slowly added dropwise to the substrate-free human In the aqueous liquid of deoxygenated hemoglobin (that is, T-state hemoglobin), the intramolecular cross-linking reaction is carried out at 20° C. to 37° C. to obtain the first polymer product.

[0027] The inert gas is nitrogen or argon.

[0028] DBBF belongs to the intramolecular cross-linking agent of hemoglobin, and there are two identical aldehyde groups in its structure,...

example 1

[0051] The preparation process of this example double polymerized hemoglobin is as follows:

[0052] 1) Under inert gas nitrogen and stirring conditions, the bis(2-hydroxyethyl)iminotris(hydroxymethyl)methane solution of bis(2-hydroxyethyl)imino tri(hydroxymethyl)methane that the pH is 9.0 is slowly added dropwise until the hemoglobin content is 6.0% (weight) The intramolecular cross-linking reaction is carried out in the matrix-free human placental hemoglobin aqueous liquid to prepare the first polymer product. Wherein, the stirring speed is 700 rpm, the molar ratio of double aspirin to human placental hemoglobin is 4:1, the temperature of the intramolecular crosslinking reaction is 30° C., and the time is 100 min.

[0053] 2) Under the condition of inert gas nitrogen, send glutaraldehyde into the first polymer product prepared in the above step 1) through a titanium rod filter element (the molar ratio of glutaraldehyde to the first polymer product is 6:1), and stir The spee...

example 2

[0056] The preparation process of this example double polymerized hemoglobin is as follows:

[0057] 1) Under inert gas nitrogen and stirring conditions, the bis(2-hydroxyethyl)iminotris(hydroxymethyl)methane solution of bis(2-hydroxyethyl)imino tri(hydroxymethyl)methane with a pH of 9.5 is slowly added dropwise until the hemoglobin content is 10% (by weight) The intramolecular cross-linking reaction is carried out in the matrix-free human placental hemoglobin aqueous liquid to prepare the first polymer product. Wherein, the stirring speed is 900 rpm, the molar ratio of double aspirin to human placental hemoglobin is 5:1, the temperature of intramolecular cross-linking reaction is 28° C., and the time is 110 min.

[0058] 2) Under the condition of inert gas nitrogen, send glutaraldehyde into the first polymer product prepared in the above step 1) through a titanium rod filter element (the molar ratio of glutaraldehyde to the first polymer product is 8:1), and stir The speed i...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

PUM

No PUM Login to view more

Abstract

The invention provides a preparation method of bipolymerized hemoglobin and belongs to the technical field of blood substitutes. The preparation method includes: 1), in inert gas and stirring conditions, slowly dropwise adding bis(2-hydroxyethyl) imido tri(hydroxymethyl) methane solution of biaspirin into matrix-less human deoxyhemoglobin waterborne liquid for intramolecular crosslinking reactionto obtain a first polymerization product; 2), feeding an aldehyde group type difunctional crosslinking agent into the firs polymerization product obtained in the step 1), and performing intermolecularcrosslinking reaction while stirring to obtain bipolymerized hemoglobin. By the preparation method, a polymerized hemoglobin product of 130-250kD in average molecular weight can be prepared, effective conversion rate can reach 90.0%, and dipolymer content is lower than 9%. The preparation method is simple to operate and is an effective way to solve the problem that a polymerization product when glutaraldehyde is used to prepare low-average-molecular-weight polymerized hemoglobin is too high in dipolymer content.

Description

technical field [0001] The invention belongs to the technical field of preparation of blood substitutes, in particular to a method for preparing double polymerized hemoglobin. In particular, it is a method for preparing double polymerized hemoglobin with lower average molecular weight, narrower molecular weight distribution range, higher effective conversion rate and less dimer content. Background technique [0002] Because unmodified hemoglobin loses the regulation of 2,3-bisphosphoglycerate in red blood cells, the oxygen affinity of hemoglobin increases, which affects the release of oxygen and cannot effectively supply oxygen to tissues; at the same time, unmodified hemoglobin colloids in plasma High osmotic pressure; and unmodified hemoglobin due to the coating of no cell membrane, the half-life of the tetramer in the body is only 2 to 4 hours, and it is rapidly decomposed into dimers and monomers and filtered from the kidneys to form Hemoglobinuria can cause nephrotoxic...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

Application Information

Patent Timeline
no application Login to view more
Patent Type & Authority Applications(China)
IPC IPC(8): C07K14/805C07K1/113
CPCC07K14/805
Inventor 周文涛李燊杨成民王红刘嘉馨
Owner BLOOD TRASFUSION INST CHINESE ACAD OF MEDICAL SCI
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Try Eureka
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap