Medical macromolecular microsphere adsorbent for a blood perfusion apparatus and a preparation method thereof

Patent metadata

Field	Value
Publication number	US-10758889-B2
Application number	US-201816001941-A
Country	US
Kind code	B2
Filing date	Jun 7, 2018
Priority date	Apr 8, 2016
Publication date	Sep 1, 2020
Grant date	Sep 1, 2020

Abstract

A medical macromolecular microsphere adsorbent for a blood perfusion apparatus and a preparation method thereof are provided. The polystyrene-divinylbenzene microspheres are graded by different pore sizes and specific surface areas, medically purified, and grafted by a bioactivity-controlled grafting technology. In the microsphere adsorbent, the volume ratio of microspheres with pore sizes of 1-10 μm, 10-100 μm and 100 μm is 1:(1-10):(1-20), the content of residual monomers in the microsphere has O.D190-400 nm≤0.03. The microsphere adsorbent not only can adsorb harmful micromolecules in blood but also can effectively adsorb harmful medium-molecules and macromolecules in blood, thereby meeting clinical application demands.

First claim

We claim:

1. A medical macromolecular microsphere adsorbent for a blood perfusion apparatus, wherein the microsphere adsorbent consists of three polystyrene-divinylbenzene microspheres having diameters being 1-10 μm, 10-100 μm and 100-500 μm respectively in a volume ratio of 1:(1-10):(1-20); the surface of the microsphere adsorbent is grafted with vinyl pyrrolidone and/or 2-methylacryloxy ethyl phosphorylcholline; the content of residual monomers in the microsphere adsorbent has O.D190-400 nm≤0.03.

2. The medical macromolecular microsphere adsorbent for a blood perfusion apparatus according to claim 1 , wherein the surface area of the microsphere adsorbent is 400 m 2 /g-1800 m 2 /g.

3. The medical macromolecular microsphere adsorbent for a blood perfusion apparatus according to claim 1 , wherein a raw material of the polystyrene-divinylbenzene macromolecular microsphere meets regulations of FDA, the mass content of divinylbenzene is larger than 79%, and the polystyrene-divinylbenzene macromolecular microsphere can bear a heavy load of 300-450 g and has a suspension double-bond content of 2.2-3.1 mmol/g.

4. A method for preparing for a medical macromolecular microsphere adsorbent for a blood perfusion apparatus according to claim 1 , characterized by comprising the following steps:
1) grading of a pore size and a specific surface area of a microsphere adsorbent: separating polystyrene-divinylbenzene macromolecular microspheres according to diameters being 1-10 μm, 10-100 μm and 100-500 μm respectively; and mixing the microspheres within three size ranges in a volume ratio of 1:(1-10):(1-20);
2) medical purification of the microsphere adsorbent: washing the microsphere adsorbent obtained in step 1) utilizing hydrochloric acid, ammonium hydroxide and ethanol water in turn, and then carrying out rinsing combined treatment and gradient elution on the microsphere adsorbent;
3) grafting a bioactive aglucon on the surface of the microsphere adsorbent utilizing a bioactivity-controlled grafting technology: immersing the microsphere adsorbent purified in step 2) into a bioactive aglucon solution for 1-24 h, the bioactive aglucon being polyvinylpyrrolidone and/or 2-methylacryloxy ethyl phosphorylcholine; and then grafting the microsphere under ultraviolet light after being taken out, wherein, the intensity of light is 50 uw/cm2-150 uw/cm2, and grafting time is 1-4 h; and
4) posttreatment of the microsphere adsorbent: immersing the grafted microsphere for 1-3 h utilizing buffer solution after being taken out, and washing with deionized water; carrying out freeze drying to obtain the medical macromolecular microsphere adsorbent for the blood perfusion apparatus.

5. The method for preparing for a medical macromolecular microsphere adsorbent for a blood perfusion apparatus according to claim 4 , wherein the mass concentration of hydrochloric acid is 1%-5%; the mass concentration of ammonium hydroxide is 5%-10%; the mass concentration of ethanol water is 10-20%.

6. The method for preparing for a medical macromolecular microsphere adsorbent for a blood perfusion apparatus according to claim 4 , wherein the mass concentration of the bioactive aglucon solution is 1%-10%.

7. The method for preparing for a medical macromolecular microsphere adsorbent for a blood perfusion apparatus according to claim 4 , wherein the ultraviolet light is distanced from the to-be-treated solution by 1 m.

8. The method for preparing for a medical macromolecular microsphere adsorbent for a blood perfusion apparatus according to claim 4 , wherein the freeze drying is carried out in a freeze drying machine, and the freeze drying time is 12-24 h.

9. The method for preparing for a medical macromolecular microsphere adsorbent for a blood perfusion apparatus according to claim 4 , wherein the buffer solution is phosphate buffer saline (PBS).

10. The method for preparing for a medical macromolecular microsphere adsorbent for a blood perfusion apparatus according to claim 4 , wherein the number of times of washing with deionized water is 3-10 times.

Assignees

• Univ South China Tech

Inventors

• Ren Li
• Wang Yingjun
• Liu Sa
• Wang Lin
• Zheng Jian

Classifications

• B01J20/28004 Primary

  Sorbent size or size distribution, e.g. particle size · CPC title

• B01J20/28019

  Spherical, ellipsoidal or cylindrical · CPC title

• B01J20/267

  Cross-linked polymers · CPC title

• B01J20/28057

  Surface area, e.g. B.E.T specific surface area · CPC title

• B01J20/28064

  being in the range 500-1000 m2/g · CPC title