Preparation method of adsorbing material for efficiently adsorbing HIV (Human Immunodeficiency Virus) and adsorbing material

Abstract

The invention provides a preparation method of an adsorption material capable of efficiently adsorbing HIV viruses and the adsorption material, and belongs to the technical field of adsorption materials.The preparation method comprises the following steps that CA is added into a solution containing acetone and dimethyl sulfoxide under stirring, stirring continues to enable CA to be completely dissolved, and a CA solution is obtained; adding MIL-125 (Ti) into the CA solution, stirring, and further performing ultrasonic dispersion, so that the MIL-125 (Ti) is uniformly dispersed into the CA solution; water is used as a precipitation bath, the obtained solution is dropwise added into the precipitation bath, and the CA / MIL-125 (Ti) composite microspheres are obtained through phase inversion. The CA / MIL-125 (Ti) composite microspheres prepared by the invention have the advantages of multi-stage adsorption sites, excellent adsorption performance, good blood compatibility and high mechanical strength.

Description

Technical Field

[0001] The invention belongs to the technical field of adsorption materials, and in particular relates to a preparation method of an adsorption material capable of efficiently adsorbing HIV virus and the adsorption material. Background Art

[0002] HIV, as a retrovirus, is not optimistic about its global prevalence. It is extremely harmful, has a high infection rate, and has a great impact on human health. 4+ T cells are the final target of HIV virus, which destroys a large number of immune cells in the human body. After a latent period of several years, even up to ten years or longer, the person develops into an AIDS patient, eventually causing the body to lose its immune function.

[0003] At present, there are two main methods to eliminate HIV virus. One is to use large-pore resin particles as the matrix, and use the electron cloud field force to intervene in the two-dimensional dynamic structure of the HIV receptor group to expose its conservative amino acid sequence. Specific antibodies are designated for this amino acid sequence and terminated on the protein coating on the surface of the resin microspheres. This antibody is used as the target to adsorb HIV virus particles and HIV virus bound to CD4 cells, thereby achieving the purpose of eliminating the virus. The other method is to adsorb HIV virus in plasma by ultrafiltration adsorption.

[0004] However, the method of removing HIV by blood perfusion adsorption using large-pore resin is to remove it by designing antibodies, but due to the high mutation rate of HIV virus, this method may not be suitable for long-term treatment. The ultrafiltration adsorption method is not only not specific enough, it will damage normal cells and beneficial proteins in human blood, and the efficiency of HIV adsorption is also low, and the effect is poor. Summary of the invention

[0005] The problem to be solved by the present invention is to provide a preparation method of an adsorption material capable of efficiently adsorbing HIV virus and the adsorption material.

[0006] In order to solve the above technical problems, the technical solution adopted by the present invention is: a method for preparing an adsorption material for efficiently adsorbing HIV virus, comprising the following steps:

[0007] S1. Add cellulose acetate (CA) to a solution containing acetone and dimethyl sulfoxide under stirring, and continue stirring to completely dissolve CA to obtain a CA solution;

[0008] S2, adding MIL-125(Ti) to the CA solution, stirring, and further ultrasonically dispersing to make the MIL-125(Ti) evenly dispersed in the CA solution;

[0009] S3, using water as a precipitation bath, dripping the solution obtained in step S2 dropwise into the precipitation bath, and obtaining CA / MIL-125 (Ti) composite microspheres through phase inversion.

[0010] Furthermore, the CA / MIL-125(Ti) composite microspheres were immersed in water and then filtered, and were repeatedly washed with deionized water and then dried in a vacuum drying oven. After drying, the mechanical strength of the CA / MIL-125(Ti) composite microspheres was increased.

[0011] Furthermore, the volume ratio of acetone to dimethyl sulfoxide is 1:1.

[0012] Furthermore, the mass ratio of CA to MIL-125(Ti) is 20:1, 10:1, 20:3, 5:1 or 5:2.

[0013] Furthermore, the MIL-125(Ti) is synthesized by a hydrothermal method.

[0014] Furthermore, the synthesis method of MIL-125(Ti) is as follows: tetrabutyl titanate (TBOT) and terephthalic acid (BDC) are added to a mixed solvent of N,N-dimethylformamide (DMF) and methanol, and the mixture is heated continuously to synthesize MIL-125(Ti). The obtained MIL-125(Ti) is a white powder with high crystallinity and porosity.

[0015] Another object of the present invention is to provide a CA / MIL-125 (Ti) composite microsphere adsorption material obtained by the above preparation method.

[0016] Due to the adoption of the above technical solution, the present invention has the following beneficial effects:

[0017] The invention combines CA with MIL-125 (Ti) to prepare a CA / MIL-125 (Ti) composite microsphere adsorption material with multi-level adsorption sites, excellent adsorption performance and good blood compatibility.

[0018] Specifically, the multi-level adsorption sites utilize the characteristics of CA being soluble in organic solvents but insoluble in water. Using dimethyl sulfoxide and acetone as the organic phase can not only fully dissolve cellulose acetate, but also the organic solvent can exchange with water during the phase inversion process, acting as a porogen for the microspheres, thereby ensuring that the microspheres have both CA macroporous structure and MIL-125 (Ti) micropores and mesopores multi-level adsorption sites. The excellent adsorption performance is attributed to the following three points: (1) MIL-125 (Ti) has a high specific surface area (S BET =1157m 2 g -1) and good pore structure, and CA / MIL-125(Ti) composite microspheres have a multi-level pore structure, which is conducive to the virus entering the pore structure of the adsorption material; (2) the Ti metal center of MIL-125(Ti) can coordinate with the virus surface protein, and the metal ions can also induce the inactivation and degradation of the virus protein; (3) the ligand of the adsorption material contains a large number of carboxyl groups and π-π hydrophobic domains, which can adsorb viruses through hydrophobic forces and hydrogen bonds. Good blood compatibility is achieved through low hemolysis rate and no cytotoxicity.

[0019] It can be seen that the CA / MIL-125 (Ti) composite microspheres of the present invention have good specificity, will not have much impact on human blood components, and the adsorption rate of albumin, a beneficial protein for the human body, is close to 0. Moreover, the composite microspheres with only 40% MIL-125 (Ti) loading can effectively eliminate HIV virus, and the adsorption rate in plasma is as high as 97.37%, which is 90 times that of pure cellulose acetate microspheres, and can achieve efficient elimination of HIV virus from the source. BRIEF DESCRIPTION OF THE DRAWINGS

[0020] The present invention will be described in detail below with reference to the accompanying drawings and in combination with examples, and the advantages and implementation methods of the present invention will become more obvious. The contents shown in the accompanying drawings are only used to explain the present invention and do not constitute any limitation to the present invention in any sense. In the accompanying drawings:

[0021] Figure 1 The figure is a bar graph showing the adsorption rate of HIV lentivirus statically adsorbed by CA / MIL-125(Ti) composite microspheres with different MIL-125(Ti) contents in PBS solution.

[0022] Figure 2 The figure is a bar graph showing the static adsorption titer of HIV lentivirus by CA / MIL-125(Ti) composite microspheres with different MIL-125(Ti) contents in PBS solution.

[0023] Figure 3 The figure is a bar graph showing the adsorption rate of the CA / MIL-125(Ti) composite microspheres with different MIL-125(Ti) contents in the present invention for static adsorption of HIV lentivirus in plasma.

[0024] Figure 4 The figure is a bar graph showing the titer of static adsorption of HIV lentivirus in plasma by CA / MIL-125(Ti) composite microspheres with different MIL-125(Ti) contents in the present invention. DETAILED DESCRIPTION

[0025] The present invention provides a method for preparing an adsorption material for efficiently adsorbing HIV virus, comprising the following steps:

[0026] S1. Under magnetic stirring, add 1.8 g of cellulose acetate (CA) to 20 mL of a solution containing acetone and dimethyl sulfoxide, and continue stirring for 30 min to completely dissolve CA to obtain a CA solution.

[0027] Wherein, the volume ratio of acetone to dimethyl sulfoxide is 1:1.

[0028] S2. Add a certain amount of MIL-125(Ti) to the CA solution, stir magnetically for 1 hour, and then disperse ultrasonically for 1 hour to evenly disperse the MIL-125(Ti) in the CA solution.

[0029] Among them, the mass ratio of CA to MIL-125(Ti) is 20:1, 10:1, 20:3, 5:1 or 5:2.

[0030] MIL-125(Ti) is a metal-organic framework material with a Ti(IV) metal center, terephthalic acid ligands and a large specific surface area.

[0031] MIL-125(Ti) was synthesized by hydrothermal method. Tetrabutyl titanate (TBOT) and terephthalic acid (BDC) were added to a mixed solvent of N,N-dimethylformamide (DMF) and methanol, and heated continuously at 150°C for 48 hours to synthesize MIL-125(Ti). The obtained MIL-125(Ti) was a white powder with high crystallinity and porosity.

[0032] S3. Using 40 mL of water as a precipitation bath, the solution obtained in step S2 was dripped into the precipitation bath dropwise, and the CA / MIL-125 (Ti) composite microspheres were obtained by phase inversion.

[0033] The dripping rate is controlled to obtain microspheres of appropriate size.

[0034] In order to further increase the mechanical strength of CA / MIL-125(Ti) composite microspheres, the CA / MIL-125(Ti) composite microspheres were immersed in water for 24 h, filtered, repeatedly washed with deionized water, and dried in a 40°C vacuum drying oven for 12 h to obtain the final CA / MIL-125(Ti) composite microspheres with a specific surface area of ​​200-250 m 2 g -1 The average pore volume is 4.12-4.68 cm 3 g -1 The average pore size is 620-680nm, the adsorption rate is 30-99%, the hemolysis rate is 2%-4%, and the cytotoxicity level is 0 or 1.

[0035] like Figures 1 to 4As shown, the static adsorption of HIV lentivirus by CA / MIL-125(Ti) composite microspheres with different MIL-125(Ti) contents in PBS solution and plasma shows that when the content of MIL-125(Ti) in CA / MIL-125(Ti) is 5%, 10%, 15%, 20% or 40%. As the content of MIL-125(Ti) increases, the adsorption capacity of CA / MIL-125(Ti) for viruses gradually increases. When the content of MIL-125(Ti) is 40%, its adsorption rate can reach 97.37%, and the virus titer can be reduced by at least two orders of magnitude.

[0036] It can be seen that the CA / MIL-125(Ti) composite microspheres of the present invention can effectively eliminate HIV virus with a MIL-125(Ti) loading of only 40%, and the adsorption rate in plasma is as high as 97.37%, which is 90 times that of CA microspheres, and can achieve efficient elimination of HIV virus from the source.

[0037] Another object of the present invention is to provide a CA / MIL-125 (Ti) composite microsphere adsorption material obtained by the above preparation method.

[0038] The embodiments of the present invention are described in detail above, but the contents are only preferred embodiments of the present invention and cannot be considered to limit the scope of implementation of the present invention. All equivalent changes and improvements made within the scope of the present invention should still fall within the scope of the present invention.

Claims

1. A method for preparing an adsorbent material for efficiently adsorbing HIV virus, characterized in that: The following steps are involved: S1. Under stirring, CA is added to a solution containing acetone and dimethyl sulfoxide, and stirring is continued to completely dissolve CA to obtain a CA solution; S2, adding MIL-125(Ti) to the CA solution, stirring, and further ultrasonically dispersing to make the MIL-125(Ti) evenly dispersed in the CA solution; S3, using water as a precipitation bath, dripping the solution obtained in step S2 dropwise into the precipitation bath, and obtaining CA / MIL-125 (Ti) composite microspheres through phase inversion.

2. The method for preparing an adsorbent material for efficiently adsorbing HIV virus according to claim 1, characterized in that: The CA / MIL-125(Ti) composite microspheres were immersed in water and then filtered, and were repeatedly washed with deionized water and then dried in a vacuum drying oven.

3. The method for preparing an adsorbent material for efficiently adsorbing HIV virus according to claim 1, characterized in that: In step S1, the volume ratio of acetone to dimethyl sulfoxide is 1:

1.

4. The method for preparing an adsorbent material for efficiently adsorbing HIV virus according to claim 1, characterized in that: In step S2, the mass ratio of CA to MIL-125(Ti) is 20:1, 10:1, 20:3, 5:1 or 5:

2.

5. The method for preparing an adsorbent material for efficiently adsorbing HIV virus according to claim 1, characterized in that: In step S2, the MIL-125(Ti) is synthesized by a hydrothermal method.

6. The method for preparing an adsorbent material for efficiently adsorbing HIV virus according to claim 5, characterized in that: The synthesis method of MIL-125 (Ti) is as follows: TBOT and BDC are added into a mixed solvent of DMF and methanol, and the mixture is heated continuously to synthesize MIL-125 (Ti).

7. A CA / MIL-125 (Ti) composite microsphere adsorption material obtained by the preparation method of an adsorption material for high-efficiency adsorption of HIV virus according to any one of claims 1 to 6.

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