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Hemoglobin type oxygen-carrying nano gel and preparation method and application thereof

The technology of hemoglobin and nanogel is applied in the field of hemoglobin oxygen-carrying nanogel and its preparation, which can solve the problems of high price of phospholipids, complicated process, instability, etc., achieve good application prospects and economic benefits, overcome side effects, and The effect of improving safety

Active Publication Date: 2016-07-13
WEST CHINA HOSPITAL SICHUAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, this type of product still has defects, such as packaging materials, especially phospholipids, which are expensive and unstable, and the process is relatively complicated. The hemoglobin after physical packaging cannot avoid the phenomenon of sudden release of hemoglobin, and there is a potential risk of transfusion
[0007] The patent application with publication number 102861322 discloses a hemoglobin oxygen-carrying carrier, which contains hemoglobin, haptoglobin and polyethylene glycol-polyester nanoparticles. On the granule surface, it can form a stable complex with haptoglobin through hemoglobin, which reduces the toxicity of hemoglobin to a certain extent, but still has certain toxicity and needs further improvement

Method used

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  • Hemoglobin type oxygen-carrying nano gel and preparation method and application thereof
  • Hemoglobin type oxygen-carrying nano gel and preparation method and application thereof
  • Hemoglobin type oxygen-carrying nano gel and preparation method and application thereof

Examples

Experimental program
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Effect test

Embodiment 1

[0074] Embodiment one: the preparation of raw material of the present invention

[0075] 1. Synthesis method of mPEG-PEI 1

[0076] Weigh polyethylene glycol monomethyl ether mPEG (Mw=2000-10000) in a three-neck flask, dissolve it in anhydrous toluene, weigh 10 times the molar amount of isophorone diisocyanate (IPDI) and dissolve it in the toluene solution , add a catalytic amount of stannous octoate, mix the above two solutions, and reflux at 80°C for 8 to 10 hours. The obtained product was precipitated with ice petroleum ether (petroleum ether frozen at -20°C for more than 4 hours), repeated several times, and dried in vacuum at 40°C for 48 hours to obtain mPEG-IPDI for use;

[0077] Then accurately weigh 1.1 times the molar amount of branched PEI (polyethyleneimine) (Mw=600-10000) and dissolve it in anhydrous toluene, and magnetically stir to help dissolve;

[0078] Then the MPEG-IPDI obtained in the previous step reaction was dissolved in toluene solution and transferred...

Embodiment 2

[0092] Example 2 Preparation of hemoglobin / haptoglobin nanogel (hemoglobin oxygen-carrying nanogel) of the present invention

[0093] 1. Preparation of copolymer material mPEG-PEI-g-SH

[0094] Polyethylene glycol monomethyl ether (mPEG-COOH): Mn=2000g / mol

[0095] Branched PEI (AlfaAsea): Mn=600g / mol

[0096] Isophorone diisocyanate (IPDI): Mn=222.28g / mol

[0097] Mercapto polyethylene glycol NHS ester (SH-PEG-NHS): Mn=200g / mol

[0098] The mPEG-PEI-g-SH copolymer material of the present invention was prepared using mPEG-COOH with Mn=2000 and PEI with Mn=1200. See Example 1 for specific reaction conditions. The specific steps are: 1. Synthesize mPEG-PEI according to mPEG-PEI synthesis method 1 in Example 1; 2. Synthesize according to mPEG-PEI-g-SH synthesis method 2 in Example 1 to obtain the nanocarrier material mPEG-PEI-g- sh. The NMR image of the product is as image 3 As shown in a, it shows that it has been successfully synthesized. According to elemental analysis...

Embodiment 3

[0115] Example 3 Preparation of hemoglobin / haptoglobin nanogel (hemoglobin oxygen-carrying nanogel) of the present invention

[0116] 1. Preparation of nanogel mPEG-PEI-g-SH

[0117] Monofunctional polyethylene glycol (mPEG-COOH): Mn=5000g / mol

[0118] Branched PEI (AlfaAsea): Mn=1800g / mol

[0119] 2-iminothiolane (Traut's reagent)

[0120] 1-(3-Dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC·HCl):

[0121] N-Hydroxysuccinimide (NHS):

[0122] The mPEG-PEI-G-SH copolymer material of the present invention was prepared using mPEG-COOH with Mn=5000 and PEI with Mn=1800. See Example 1 for specific reaction conditions. The specific steps are: 1. Synthesize mPEG-PEI according to the mPEG-PEI synthesis method 2 in Example 1; 2. Synthesize according to the mPEG-PEI-g-SH synthesis method 1 in Example 1 to obtain the nanocarrier material mPEG-PEI-g- sh. The NMR image of the product is as image 3 As shown in b, it shows that it has been successfully synthesized. Acco...

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Abstract

The invention discloses hemoglobin type oxygen-carrying nano gel.The hemoglobin type oxygen-carrying nano gel is nano hydrogel formed by polyethylene glycol-polyethyleneimine segmented copolymer and the covalent binding product of hemoglobin through crosslinking, haptoglobin is connected to the hemoglobin, and the polyethyleneimine segment of the polyethylene glycol-polyethyleneimine segmented copolymer contains a grafting group.The invention further discloses a preparation method and application of the hemoglobin type oxygen-carrying nano gel.The hemoglobin type oxygen-carrying nano gel has the advantages that the nano gel is low in toxicity to vascular endothelial cells, promising in application prospect and good in economic benefits, and the defect that an existing hemoglobin type oxygen-carrying carrier is high in side effect is overcome.

Description

technical field [0001] The invention relates to a hemoglobin oxygen-carrying nano gel and its preparation method and application. 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 still has many disadvantages. For example, its blood source is single, mainly relying on blood donation, and due to the complexity of human blood types, it needs to be used after strict matching, which limits its application in the treatment of acute and severe patients and in emergencies. 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 effectiv...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K38/42A61K9/06A61K47/48A61P7/08
CPCA61K38/42
Inventor 李涛杨倩彭锦荣刘进钱志勇
Owner WEST CHINA HOSPITAL SICHUAN UNIV