Adsorbent capable of being used for removing endotoxin and inflammatory factors in blood of sepsis patient and preparation method of adsorbent

Abstract

The invention discloses an adsorbent capable of being used for removing endotoxin and inflammatory factors in the blood of a sepsis patient and a preparation method of the adsorbent. The adsorbent is prepared on the basis of a carrier which is prepared on the basis of a carrier through surface activation and grafting of ligands such as polyamino amino acid or polypeptide and the like, wherein the carrier is prepared by taking nanometer calcium carbonate-styrene-divinylbenzene as a basic framework, a mixture of methylbenzene, gasoline (or liquid wax), multi-carbon alcohol and the like as a pore-foaming agent and benzoyl peroxide as an initiator. The adsorbent has a developed mesoporous structure and a high specific surface area, the synergistic effect of a nanometer material and active ligands greatly improves the removal efficiency of the adsorbent on pathogenic factors in the blood or the plasma, and animal test results show that the survival rate of a sepsis mouse can be effectively improved. The adsorbent is simple to prepare, has an efficient removal effect on endotoxin, TNF-alpha, IL-1beta, IL-6, IL-8 and other pathogenic factors, and is suitable for removing excessive endotoxin and pathogenic inflammatory factors in the body of a patient through blood or plasma perfusion.

Description

technical field [0001] The invention belongs to the technical field of biomedicine. The invention relates to an adsorbent used for hemoperfusion to remove endotoxin and inflammatory factors in blood and a preparation method thereof. Background technique [0002] Sepsis is a severe inflammatory reaction caused by various infections (bacteria or virus, etc.), often due to the lack of effective inflammatory response control methods, leading to the occurrence of sepsis, and the number of patients worldwide is about 18 million every year Humans, even with the highly developed medical treatment today, the fatality rate is still as high as 30% to 50%. The novel coronavirus pneumonia (CoronaVirus Disease 2019, COVID-19), which has continued in 2019, has caused the death of a large number of critically ill patients because of the outbreak of the inflammatory waterfall. Effectively remove endotoxins and cytokines that induce inflammatory factor storms, such as tumor necrosis factor-...

AI Technical Summary

Problems solved by technology

However, oXiris is expensive, and the adsorption effect on the pro-inflammatory factor TNF-α is not good, and it is difficult to avoid the chain reaction caused by TNF-α

The CytosorbTM adsorbent, which was launched in Europe in 2011, is a polystyrene divinylbenzene porous microsphere covered with polyvinylpyrrolidone. A small molecular weight inflammatory factor such as IL-6, IL-10, etc., but the adsorption of TNF-α with a large molecular weight (trimer molecular weight 51kD) is only 20%~30%, and almost no endotoxin is adsorbed. Clinical trial for sepsis treatment proves to be a failure

[0005]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, agarose The gel is used as the carrier, and the endotoxin-affinity molecule is used as the ligand to make the adsorbent. Although a good in vitro adsorption effect has been achieved, the problems of poor carrier strength and small coupling amount of the ligand have brought obstacles to practical application.

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. about), while the molecular weight of lipopolysaccharide (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. Adsorption selectivity of beneficial proteins

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

In terms of the removal of inflammatory factors, although my country has patents in this area (such as 201310593832.4, etc.), there is still a gap in the adsorption performance compared with foreign countries, and there is no such product in China.

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