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Hemoglobin-based oxygen carrier and preparation method thereof

A hemoglobin and oxygen-carrying carrier technology, applied in peptide/protein components, blood diseases, pharmaceutical formulations, etc., can solve problems such as instability, increased patient mortality, myocardial infarction, and expensive phospholipids, and achieve stable quality and reduce kidney damage , the effect of good clinical application prospects

Inactive Publication Date: 2013-01-09
WEST CHINA HOSPITAL SICHUAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

There were many problems in the clinical practice of the first two generations of products: HemAssist is a first-generation product, which was abandoned due to a significant increase in the mortality rate of subjects in phase III clinical trials; Polyheme also suffered severe cardiotoxicity in clinical trials The study was terminated; Hemopure (glutaraldehyde-crosslinked polymerized bovine hemoglobin) developed by Biopure in the United States is currently the only product that has been approved for clinical use, and it is limited to marketing in South Africa, but because of the exposure of cardiovascular aspects in phase III clinical studies safety issues, and further research and development were stopped
In 2008, they published a Meta-analysis on HBOC clinical trials in the medical journal "JAMA", pointing out that it increases the mortality of patients and has a potential risk of myocardial infarction. No further clinical trials should be conducted until the mechanism is known
However, such products still have defects, such as packaging materials, especially phospholipids, which are expensive and unstable, and the hemoglobin after physical packaging may be released suddenly, and it is still difficult to avoid the side effects of free / unpolymerized hemoglobin, and there is a potential risk of transfusion

Method used

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  • Hemoglobin-based oxygen carrier and preparation method thereof
  • Hemoglobin-based oxygen carrier and preparation method thereof
  • Hemoglobin-based oxygen carrier and preparation method thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0053] Embodiment 1 Preparation of hemoglobin oxygen-carrying carrier of the present invention

[0054] 1. Preparation method

[0055] (1) Preparation of Mal-PEG-PCL and MPEG-PCL

[0056] 5.0g of caprolactone and 5.0g of monomaleimide polyethylene glycol (Mal-PEG2000) with a molecular weight of 2000 or 5.0g of polyethylene glycol monomethyl ether with a molecular weight of 2000 (MPEG2000) were mixed at a mass ratio of 1:1 Place in a three-necked flask, add the catalyst stannous octoate and an appropriate amount of toluene, and react in an oil bath at 140°C for 4 hours under the conditions of mechanical stirring and nitrogen protection;

[0057] After the temperature of the reaction system drops to room temperature, pour the polymer into cold petroleum ether to precipitate, filter the precipitate, and put the precipitate in a fume hood to volatilize the solvent until the polymer solidifies. The product is vacuum-dried, purified by dialysis, and then frozen Dry to get Mal-PEG-...

Embodiment 2

[0076] Embodiment 2 Preparation of hemoglobin oxygen-carrying carrier of the present invention

[0077] 1. Preparation method

[0078] (1) Preparation of Mal-PEG-PCL

[0079]8.89g of caprolactone and 1.11g of monomaleimide polyethylene glycol (Mal-PEG3500) with a molecular weight of 3500 (Mal-PEG3500) were placed in a three-necked flask at a mass ratio of 8:1, the catalyst stannous octoate and an appropriate amount of toluene were added, and the Under the conditions of mechanical stirring and nitrogen protection, react in an oil bath at 137°C for 6 hours;

[0080] After the temperature of the reaction system drops to room temperature, pour the polymer into cold petroleum ether to precipitate, filter the precipitate, and put the precipitate in a fume hood to volatilize the solvent until the polymer solidifies. The product is vacuum-dried, purified by dialysis, and then frozen Dry to get Mal-PEG-PCL.

[0081] (2) Preparation of PEG-PCL nanoparticles lyophilized powder contain...

Embodiment 3

[0090] Embodiment 3 Preparation of hemoglobin oxygen-carrying carrier of the present invention

[0091] 1. Preparation method

[0092] (1) Preparation of Mal-PEG-PCL and MPEG-PCL

[0093] 8.33g of caprolactone and 1.67g of monomaleimide polyethylene glycol (Mal-PEG5000) with a molecular weight of 5000 or 1.67g of polyethylene glycol monomethyl ether with a molecular weight of 5000 (MPEG5000) were mixed in a mass ratio of 5:1 Place in a three-necked flask, add the catalyst stannous octoate and an appropriate amount of toluene, and react in an oil bath at 137°C for 6 hours under the conditions of mechanical stirring and nitrogen protection;

[0094] After the temperature of the reaction system drops to room temperature, pour the polymer into cold petroleum ether to precipitate, filter the precipitate, and put the precipitate in a fume hood to volatilize the solvent until the polymer solidifies. The product is vacuum-dried, purified by dialysis, and then frozen Dry to get Mal-P...

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Abstract

The invention discloses a hemoglobin-based oxygen carrier, which comprises hemoglobin, haptoglobin and polyethyleneglycol-polyester nanoparticles. Hemoglobin is connected on the surfaces of the polyethyleneglycol-polyester nanoparticles by haptoglobin. The hemoglobin-based oxygen carrier provided by the invention has no obvious toxicity on the cells, the blood plasma does not have obvious free hemoglobin in the blood plasma after the hemoglobin-based oxygen carrier is infused, and no hypertension reaction is produced, so that the defect that the traditional hemoglobin-based oxygen carrier is high in side effects is overcome. The hemoglobin-based oxygen carrier has a good application prospect and a economic benefit.

Description

technical field [0001] The invention relates to a hemoglobin oxygen carrier. Background technique [0002] Blood transfusion has played an important role in modern medicine and is an indispensable medical method for clinical operations, disaster relief and battlefield treatment. However, traditional blood transfusion has many disadvantages. For example, the blood source is single, mainly depends on blood donation, and the human blood type is complex, which requires strict matching before it can be used, which limits its treatment of acute and severe patients and the use of blood in emergency situations. Applications. What's more serious is that blood is easily polluted by viruses such as hepatitis and AIDS, and the problem of old and new blood is becoming more and more concerned, which threatens the safety of blood transfusion. With the development of medical technology, the demand for blood continues to increase, but safe and effective blood sources are becoming increasin...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K38/42A61K47/48A61P7/08
Inventor 李涛杨倩吴畏李茜刘进陈艳芳
Owner WEST CHINA HOSPITAL SICHUAN UNIV
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