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Adsorbent used for blood or plasma perfusion to remove endotoxin and preparation method thereof

A plasma perfusion and adsorbent technology, applied in the field of biomedicine, can solve the problems of practical application obstacles, small amount of ligand coupling, increased risk, etc., achieve high mechanical strength and physical and chemical stability, improve adsorption capacity, and excellent adsorption effect of ability

Active Publication Date: 2017-01-18
NANKAI UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, there is no clinical application of such products in my country so far.
[0006] Domestic scholars or the industry have also made a lot of efforts, and applied for many patents, such as 200810028948.2, ZL03144383.4, 200510046452.4, etc., respectively using cellulose, chitosan, and agarose gel as carriers, and endotoxin affinity molecules as ligands. Although the adsorbent has achieved good in vitro adsorption effect, it has brought obstacles to practical application due to problems such as poor carrier strength and small amount of ligand coupling.
In order to improve the strength of the adsorbent, patents 200180040297.9, 201310161110.1, etc. use styrene-divinylbenzene as the skeleton to covalently modify small molecular ligands to prepare endotoxin adsorbents, but because the average pore size of such adsorbents is generally small (5-10nm ), while the molecular weight of LPS is generally above 100,000 Daltons, and the molecular size is too large to fully and effectively enter the inner pores of the adsorbent. At the same time, due to the strong hydrophobic effect of this type of carrier, it lacks the adsorption selectivity for beneficial proteins in blood.
The 201110113987.4 patent uses agarose carrier to graft molecular clusters, and then grafts lysine or betaine to make endotoxin adsorbents. As a macromolecule, due to steric hindrance, the molecular cluster has a limited immobilization capacity on the carrier. And the production process is complicated and expensive
Adsorbents using polymyxin B as the endotoxin affinity ligand have also been studied a lot, but the potential nephrotoxicity and neurotoxicity of polymyxin B increase many risks in clinical application. The application of the product has issued a warning

Method used

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  • Adsorbent used for blood or plasma perfusion to remove endotoxin and preparation method thereof

Examples

Experimental program
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Effect test

Embodiment 1

[0030] (1) Preparation of carrier microspheres

[0031] Add 15g of vinyl acetate, 30g of triallyl ethyl cyanurate, 15ml of ethyl acetate and 30ml of n-heptane into 2000ml of Sankouping, heat up to 30°C, stir well and add 0.9g of azobisisobutyl Cyanide, add 1500ml aqueous solution (containing 0.5% polyvinyl alcohol and 10% sodium chloride) after dissolving, adjust the stirring speed to make the droplets reach a suitable size and disperse evenly, heat up to 65°C, keep warm for 2 hours, and then heat up to 85°C ℃ for 2 hours, and filtered to obtain a white spherical polymer. The white spherical polymer was thoroughly washed with water and ethanol in turn, and dried in the air. Add the above dried white spherical polymer into 2% NaOH methanol solution, and carry out alcoholysis reaction at 40°C for 12 hours. After the reaction, suction filter, fully wash with methanol, and dry to obtain the desired carrier microspheres. The carrier microspheres have a particle size of 150-450um,...

Embodiment 2

[0037] (1) Preparation of carrier microspheres

[0038] Add 20g of vinyl acetate, 5g of triallyl ethyl cyanurate, 20ml of ethyl acetate and 20ml of n-heptane into 1500ml of Sankouping, heat up to 45°C, stir well and add 0.5g of azobisisobutyl Cyanide, after dissolving, add 1000ml aqueous solution (containing 1.0% polyvinyl alcohol and 5% sodium chloride), adjust the stirring speed to make the droplets reach a suitable size and disperse evenly, heat up to 75°C, keep warm for 4 hours, and then heat up to 90°C °C for 3 hours, filter the white spherical polymer. The white spherical polymer was thoroughly washed with water and ethanol in turn, and dried in the air. Add the above dried white spherical shape into 2% NaOH methanol solution, and carry out alcoholysis reaction at 45°C for 24 hours. After the reaction is completed, suction filter, fully wash with methanol, and dry to obtain the desired carrier microspheres. The particle size of the carrier microsphere is 200-400um, the...

Embodiment 3

[0044] (1) Preparation of carrier microspheres

[0045] Add 15g of vinyl acetate, 15g of triallyl ethyl cyanurate, 25ml of ethyl acetate and 10ml of n-heptane into 1500ml of Sankouping, heat up to 40°C, stir well and add 0.3g of azobisisobutyl Cyanide, add 1000ml of aqueous solution (containing 1.5% polyvinyl alcohol and 3% sodium chloride) after dissolving, adjust the stirring speed to make the droplets reach a suitable size and disperse evenly, heat up to 65°C, heat-preserve and polymerize for 6 hours, then heat up to 95°C °C for 4 hours, filter the white spherical polymer. The white spherical polymer was thoroughly washed with water and ethanol in turn, and dried in the air. Add the dried white spheres into 2% methanol solution of NaOH, and carry out alcoholysis reaction at 40°C for 6 hours. After the reaction, filter with suction, fully wash with methanol, and dry in the air to obtain the desired carrier microspheres. The carrier microspheres have a particle size of 250-...

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Abstract

The invention relates to an adsorbent used for blood or plasma perfusion to remove endotoxin (lipopolysaccharide) and a preparation method thereof. The adsorbent is a nano-composite structure adsorbent. Large-aperture polyvinyl alcohol serves as a carrier, amino (ammonio) carbon nanotubes (single-walled or multi-walled) serve as a ligand, epichlorohydrin or glutaraldehyde, etc. serves as a crosslinking agent, and the ligand and the carrier microspheres undergo covalent coupling to obtain the adsorbent. The adsorbent is simple to prepare, and an endotoxin adsorption property is good. The adsorbent is suitable for blood or plasma perfusion to remove excessive endotoxin in the body of a patient.

Description

[0001] Technical field: [0002] The invention belongs to the technical field of biomedicine. The invention relates to an adsorbent used for hemoperfusion to remove endotoxin in blood and a preparation method thereof. [0003] technical background: [0004] Endotoxin (ET) is a highly toxic pyrogenic substance, which is generally lipopolysaccharide (LPS) released from the cell wall of Gram-negative bacteria after death. After lipopolysaccharide enters the blood, endotoxemia is formed. Endotoxemia is one of the common clinical fatal diseases, with a mortality rate as high as 40%-90%. Nearly 4 million people in the United States, Europe and Japan suffer from endotoxemia every year. Due to the overuse of antibiotics in my country, millions of people suffer from endotoxemia every year, and there is currently no effective treatment. [0005] Hemoperfusion technology can effectively remove the total toxins and pathogenic substances in the blood, and has been widely used in the treat...

Claims

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Application Information

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IPC IPC(8): B01J20/26B01J20/30A61K33/44A61K47/69A61K47/58A61P31/04A61K31/765
CPCA61K31/765A61K33/44B01J20/20B01J20/267A61K2300/00
Inventor 欧来良宗文辉俞耀庭
Owner NANKAI UNIV
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