Bionic immune adsorbent using PAMAM (polyamidoamine) as spacer arm as well as preparation method and application thereof

A biomimetic immunization, spacer arm technology, applied in chemical instruments and methods, other chemical processes, alkali metal oxides/hydroxides, etc., can solve the heavy economic burden on patients, difficult protein sterilization process, protein immunosorbents High price and other problems, to achieve good chemical stability and mechanical strength, good hydrophilicity and blood compatibility, and improve the effect of ligand immobilization efficiency

Active Publication Date: 2015-04-08
JAFRON BIOMEDICAL
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, protein-based ligands have some defects that cannot be ignored: proteins are difficult to withstand the harsh sterilization process and are easy to fall off from the carrier. A heavy economic burden; protein ligands are difficult to modify chemical functional groups, so they cannot be coupled to the carrier at the most suitable angle
However, after trying a variety of optimization methods for epoxy activation, it was found that the epoxy value of the activated carrier was difficult to significantly increase, and the immobilization capacity of the ligand was also difficult to further increase.

Method used

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  • Bionic immune adsorbent using PAMAM (polyamidoamine) as spacer arm as well as preparation method and application thereof
  • Bionic immune adsorbent using PAMAM (polyamidoamine) as spacer arm as well as preparation method and application thereof
  • Bionic immune adsorbent using PAMAM (polyamidoamine) as spacer arm as well as preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0057] Preparation of Alkynylated Sepharose

[0058] Dissolve 0.05g of 18-crown-6 in 15ml of water in a 100mL Erlenmeyer flask, then add 4.0g of agarose, after the agarose is uniformly dispersed, add 0.3mL of propargyl bromide, and stir at 20°C for 60h. After the reaction is completed, wash and drain to obtain the alkynylated agarose gel:

[0059]

[0060] Gel is agarose in this example.

[0061] Synthesis of G3.0PAMAM Dendrimer

[0062] In a 250ml round bottom flask, first add 70ml of methanol, then add methyl acrylate (23.42g, 272mmol), place it in an ice-water bath for a period of time, so that the temperature of the system is about 0°C, and then continuously dropwise add the 30ml of methanol solution of 3-azidopropylamine (2.7g, 27.2mmol) was added dropwise and continued to react at 0°C for 1.5h, then heated to 35°C for 36h. After completion of the reaction, the product was distilled under reduced pressure to obtain G 0.5PAMAM; in a 250ml round-bottomed flask, first ...

Embodiment 2

[0078] Preparation of alkynylated cellulose gel

[0079] Dissolve 0.26g of 18-crown-6 in 20ml of water in a 100ml Erlenmeyer flask, then add 4.0g of cellulose gel balls, add 1.2ml of propargyl bromide after the cellulose is uniformly dispersed, and react at 40°C for 30h. After the reaction was completed, the alkynylated cellulose gel was obtained by washing and drying.

[0080] Synthesis of G2.0PAMAM Dendrimer

[0081] In a 250ml round bottom flask, first add 70ml of methanol, then add methyl acrylate (23.42g, 272mmol), place it in an ice-water bath for a period of time, so that the temperature of the system is about 10°C, and then continuously dropwise add the 30ml of methanol solution of 3-azidopropylamine (5.4g, 54.4mmol) was added dropwise and continued to react at 10°C for 0.5h, then heated to 20°C for 12h. After completion of the reaction, the product was distilled under reduced pressure to obtain G0.5PAMAM; in a 250ml round-bottomed flask, first add 100ml of methanol,...

Embodiment 3

[0090] Preparation of Alkynylated PVA Gel

[0091] Dissolve 0.13g of 18-crown-6 in 18mL of water in a 100mL Erlenmeyer flask, then add 4.0g of polyvinyl alcohol (PVA) gel balls, after the PVA is uniformly dispersed, add 0.6mL of propargyl bromide, and react at 60°C for 6h . After completion of the reaction, wash and dry to obtain alkynylated PVA gel.

[0092] G 4.0 Synthesis of PAMAM Dendrimer

[0093] In a 250ml round bottom flask, first add 70ml of methanol, then add 300mmol of methyl acrylate, place it in an ice-water bath for a period of time, so that the temperature of the system is about -10°C, and then continuously dropwise add 20.0mmol of 3- The methanol solution of azidopropylamine was 30ml, after the dropwise addition was completed, the reaction was continued at -10°C for 1.5h, and then the temperature was raised to 50°C for 50h. After the reaction is completed, the product is distilled under reduced pressure to obtain G0.5PAMAM; in a 250ml round bottom flask, fir...

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Abstract

The invention provides a bionic immune adsorbent using PAMAM (polyamidoamine) as a spacer arm. The bionic immune adsorbent has the following chemical structure of Gel-PAMAM-AA as shown in the specification, wherein Gel represents a hydroxy-containing hydrophilic carrier; AA represents amino acid; n is 0, 1, 2 or 3; and PAMAM is polyamidoamine dendrimer, the hydrophilic carrier is agarose, cellulose or polyvinyl alcohol, and the amino acid is L-histidine, phenylalanine or tryptophan. The invention also provides a preparation method of the bionic immune adsorbent. By using the dendric macromolecular PAMAM as a spacer arm, the outer surface of the carrier has more active sites for coupling more ligands; by adjusting the position and direction of a triazole ring, the triazole ring is farther from the dendric PAMAM, so that adsorption of target substances is facilitated, and the adsorbent has specific adsorption; and the cost is low, the process is simple, and the reaction condition is mild.

Description

technical field [0001] The invention belongs to biomedical equipment, and provides a preparation method of a bionic immunosorbent for blood purification, in particular an immunosorbent that can be used for blood perfusion and a preparation method thereof. Background technique [0002] Immunoadsorption therapy is a new technology developed in the past two decades, which is used to treat some diseases that are difficult to be effective by traditional methods. At present, the clinical application of immunoadsorption can treat a variety of autoimmune diseases by specifically eliminating autoantibodies. For example, protein immunosorbents with protein A, G, etc. as ligands have good biospecific affinity to immunoglobulin (IgG), and immunosorbents containing such biospecific ligands have been proven to remove autoantibodies And treat various autoimmune diseases, so it has been widely used in biological purification and clinical practice. However, protein-based ligands have some ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): B01J20/26B01J20/28B01J20/30G01N33/544
CPCB01J20/26B01J20/28042B01J20/3085B01J2220/445G01N33/544
Inventor 董凡胡小艳
Owner JAFRON BIOMEDICAL
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