WO2022247337A1 - 改性大孔吸附树脂及其制备方法和应用 - Google Patents
改性大孔吸附树脂及其制备方法和应用 Download PDFInfo
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- WO2022247337A1 WO2022247337A1 PCT/CN2022/074530 CN2022074530W WO2022247337A1 WO 2022247337 A1 WO2022247337 A1 WO 2022247337A1 CN 2022074530 W CN2022074530 W CN 2022074530W WO 2022247337 A1 WO2022247337 A1 WO 2022247337A1
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- macroporous adsorption
- adsorption resin
- hypochlorite
- peracetic acid
- periodate
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- B01J20/00—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof
- B01J20/28—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof characterised by their form or physical properties
- B01J20/28054—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof characterised by their form or physical properties characterised by their surface properties or porosity
- B01J20/28078—Pore diameter
- B01J20/28085—Pore diameter being more than 50 nm, i.e. macropores
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J20/00—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof
- B01J20/30—Processes for preparing, regenerating, or reactivating
- B01J20/32—Impregnating or coating ; Solid sorbent compositions obtained from processes involving impregnating or coating
- B01J20/3202—Impregnating or coating ; Solid sorbent compositions obtained from processes involving impregnating or coating characterised by the carrier, support or substrate used for impregnation or coating
- B01J20/3206—Organic carriers, supports or substrates
- B01J20/3208—Polymeric carriers, supports or substrates
- B01J20/321—Polymeric carriers, supports or substrates consisting of a polymer obtained by reactions involving only carbon to carbon unsaturated bonds
Definitions
- the invention relates to polymer materials, in particular to a modified macroporous adsorption resin and its preparation method and application.
- macroporous adsorbent resin was used to adsorb barbiturate and glutamine in blood (see patent document US3794584A).
- This kind of resin is generally synthesized by using divinylbenzene with a high content (>50%) as a crosslinking agent, and the specific surface area of the finished product is generally 500-800m 2 /g. Carrying out the Fridel-Crafts reaction to carry out secondary cross-linking can greatly improve the specific surface area, even up to 1000m 2 /g or more (see the literature "Wang Jiaxing et al., Preparation and Application of Biochemical Separation Media, Chemical Industry Press , Beijing, P84").
- the skeleton structure of the macroporous adsorption resin is prepared by free radical suspension polymerization of styrene monomer and divinylbenzene, it is highly non-polar and non-selective, and has poor blood compatibility.
- the traditional technical routes commonly used are: 1) Prepare ultra-high crosslinked high specific surface adsorbent resins by secondary crosslinking, and deposit polymers with good hemocompatibility on the surface Materials (such as heparin, albumin, xanthan gum, hydroxyethyl cellulose, etc.), but this modification method is physical adsorption, and the deposited envelope material may fall off during clinical application; 2) by The para-position of the benzene ring on the polystyrene unit is substituted by chloromethylation, using chloromethyl as an activation group, grafted with polyethylene glycol (PEG), or grafted with a functional spacer arm (such as 2-ethanolamine).
- PEG polyethylene glycol
- a functional spacer arm such as 2-ethanolamine
- Pore structure parameters such as pore volume, porosity and pore size etc.; 5) Utilize m-chloroperoxybenzoic acid, hydrogen peroxide or hydrogen peroxide and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide ( EDC) complex), sodium hypochlorite, sodium bromide and sulfuric acid complex, hydrogen peroxide plus ultraviolet radiation, organic peroxyacids (such as m-chloroperoxybenzoic acid, peracetic acid, peroxybenzoic acid, trifluoroperacetic acid etc.) and other oxidizing substances to oxidize the remaining double bonds on the surface of the macroporous resin to epoxy groups, or further modify it on this basis, but the modification method is relatively complicated to operate, and a large amount of organic substances harmful to the human body are usually used in the reaction.
- EDC 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide
- the solvent is used for swelling, and the by-products produced during the oxidation process of m-chloroperoxybenzoic acid and peroxybenzoic acid, such as m-chlorobenzoic acid and benzoic acid, will also be adsorbed by the resin, which is difficult to clean, and the use of a large number of organic solvents and harmful compounds It will also pollute the environment, resulting in a very complicated post-treatment process. Moreover, during the oxidation process, some epoxy groups may be oxidized, and the density of epoxy groups needs to be closely monitored, and the reaction is difficult to quantitatively control.
- the present invention provides a modified macroporous adsorption resin and its preparation method and application.
- the preparation method of the modified macroporous adsorbent resin can realize the hydrophilic modification of the macroporous adsorbent resin through a one-step reaction, and the operation is simple, no organic solvent is needed, and the reaction by-products are few, and the by-products produced can be eliminated after simple treatment. It is transformed into a completely non-toxic and harmless chemical substance, which will not cause environmental pollution; the adopted hydrophilic modification method does not introduce or produce harmful compounds that are difficult to clean, the post-treatment process is simple, and the clinical application safety is high.
- a kind of preparation method of modified macroporous adsorption resin comprising the following steps:
- the oxidant is a combination of sulfuric acid and peracetic acid, hypochlorite, periodate, a combination of hypochlorous acid and hypochlorite, or a combination of hydrogen peroxide and peracetic acid;
- the hypochlorite is at least one of sodium hypochlorite, potassium hypochlorite and calcium hypochlorite
- the periodate is at least one of sodium periodate and potassium periodate.
- the reaction conditions of the one-step oxidation reaction include: the reaction temperature is 10°C-30°C; and/or,
- the reaction conditions of the one-step oxidation reaction include: the reaction time is 2h-20h.
- the oxidizing agent is a combination of sulfuric acid and peracetic acid, and the one-step oxidation reaction includes the following steps:
- the mass concentration of the sulfuric acid is 1%-5%, and the mass concentration of the peracetic acid is 0.15%-15%.
- the oxidizing agent is hypochlorite
- the one-step oxidation reaction comprises the following steps:
- hypochlorite mixing the hypochlorite and water to prepare an aqueous hypochlorite solution
- the mass concentration of the hypochlorite in the hypochlorite aqueous solution is 0.5%-10%.
- the oxidizing agent is periodate
- the one-step oxidation reaction comprises the following steps:
- the concentration of the periodate in the aqueous solution of the periodate is 0.1M ⁇ 1M.
- the oxidizing agent is a combination of hydrogen peroxide and peracetic acid, and the one-step oxidation reaction includes the following steps:
- the mass concentration of the hydrogen peroxide is 0.1%-10%, and the mass concentration of the peracetic acid is 0.1%-10%.
- Another aspect of the present invention provides the modified macroporous adsorption resin prepared by the preparation method.
- Yet another aspect of the present invention provides a functional resin, comprising the modified macroporous adsorption resin, and the active groups of the hydroxyl groups grafted on the surface of the modified macroporous adsorption resin.
- the reactive group is an epoxy group
- the functional resin also includes a ligand grafted on the active group.
- Another aspect of the present invention provides the application of the modified macroporous adsorption resin or the functional resin in the adsorption of biological components.
- the biological components refer to biological components contained in blood.
- the present invention has the following beneficial effects:
- the double bonds can be directly oxidized into hydroxyl groups through a one-step oxidation reaction in water to achieve affinity Hydration modification, and the by-products of the reaction are few, and the by-products produced can be converted into completely non-toxic and harmless chemical substances after simple treatment, and will not cause environmental pollution; the hydrophilic modification method adopted does not introduce or Harmful compounds that are difficult to clean are produced.
- the reaction process does not require the use of organic solvents.
- the post-treatment is simple and does not need to consider the intermediate process of the reaction. The steps are simplified, the process is easy to control, and the safety of clinical application is high.
- the invention provides the modified macroporous adsorption resin prepared by the above preparation method. Compared with the macroporous adsorption resin before modification, the pore structure does not change significantly, and has good adsorption performance for biological components.
- the above-mentioned modified macroporous adsorption resin does not use highly toxic organic solvents and organic reagents that are easily adsorbed by the resin and difficult to clean during the modification process. It is environmentally friendly and does not introduce harmful compounds. It is used in the adsorption of biological components. , ensuring the safety of clinical application. At the same time, after hydrophilic modification, the compatibility of the macroporous adsorption resin with blood can also be increased.
- the hydroxyl group on the above-mentioned modified macroporous adsorption resin is activated by connecting the spacer arm, it can further in-situ controllably graft hydrophilic or functional ligands, and then realize the hydrophilic or functional modification of the macroporous adsorption resin.
- Fig. 1 is the contact angle test before modification of the modified macroporous adsorption resin of an embodiment of the present invention
- Fig. 2 is the contact angle test after modification of the modified macroporous adsorption resin of Fig. 1;
- Fig. 3 is the comparison of the hydrophilic effect before and after modification of the modified macroporous adsorption resin of an embodiment of the present invention (A—after modification; B—before modification);
- Fig. 4 is a comparison of blood compatibility effects before and after modification of the modified macroporous adsorption resin according to an embodiment of the present invention (C—before modification; D—after modification).
- modified macroporous adsorption resin of the present invention and its preparation method and application will be further described in detail below in conjunction with specific examples.
- the present invention can be embodied in many different forms and is not limited to the embodiments described herein. On the contrary, the purpose of providing these embodiments is to make the understanding of the disclosure of the present invention more thorough and comprehensive.
- the present invention provides a kind of preparation method of modified macroporous adsorption resin, comprising the following steps:
- the one-step oxidation reaction means that the double bonds contained on the surface of the macroporous adsorption resin can be oxidized into hydroxyl groups through a one-step reaction without other intermediate treatment processes or intermediate products.
- the one-step oxidation reaction refers to the process without going through the epoxy intermediate product.
- the one-step oxidation reaction does not involve other solvents except water. Furthermore, the one-step oxidation reaction does not involve the participation of organic solvents.
- the oxidizing agent is a strong water-soluble oxidizing agent.
- the oxidant is a combination of sulfuric acid and peracetic acid, hypochlorite, periodate, or a combination of hydrogen peroxide and peracetic acid
- the hypochlorite is sodium hypochlorite, potassium hypochlorite, calcium hypochlorite or more At least one of three or any two mixtures
- the periodate is at least one of sodium periodate and potassium periodate.
- the above-mentioned oxidant can fully oxidize the residual double bonds on the surface of the macroporous adsorption resin without producing harmful by-products, or the produced by-products can be converted into completely non-toxic and harmless chemical substances after simple treatment, The post-processing is simplified, no environmental pollution is caused, and the clinical safety of the modified macroporous adsorption resin is guaranteed.
- the oxidizing agent is a combination of peracetic acid and hydrogen peroxide.
- the reaction conditions of the one-step oxidation reaction include: the reaction temperature is 10°C-30°C. Further, the reaction temperature is 15°C to 25°C.
- the reaction conditions of the one-step oxidation reaction include: the reaction time is 2h-20h. Further, the reaction time is 4h-10h.
- the reaction conditions of the one-step oxidation reaction include: stirring during the reaction, and the stirring rate is 150 rpm to 200 rpm.
- washing and/or neutralization of the obtained product is also included. Simple washing and/or neutralization steps are performed on the one-step oxidation reaction product to complete the purification and removal of impurities.
- the oxidizing agent is a combination of sulfuric acid and peracetic acid
- the one-step oxidation reaction includes the following steps:
- a mixed aqueous solution of sulfuric acid and peracetic acid is mixed with the macroporous adsorption resin;
- the mass concentration of sulfuric acid is 1%-5%, and the mass concentration of peracetic acid is 0.15%-15%. Further, in the mixed aqueous solution of sulfuric acid and peracetic acid, the mass concentration of sulfuric acid is 1%-3%, and the mass concentration of peracetic acid is 1%-3%.
- the mixed aqueous solution of sulfuric acid and peracetic acid is used in an amount of 20mL-100mL per 10g of the macroporous adsorption resin. Further, the dosage of the mixed aqueous solution of sulfuric acid and peracetic acid is 30mL-70mL per 10g of macroporous adsorption resin.
- washing refers to washing with absolute ethanol and water respectively
- neutralization refers to washing with alkaline aqueous solution first, and then washing with water to neutrality.
- the oxidizing agent is hypochlorite
- the one-step oxidation reaction includes the following steps:
- hypochlorite mixing hypochlorite and water to prepare an aqueous hypochlorite solution
- the mass concentration of hypochlorite in the hypochlorite aqueous solution is 0.5%-10%. Further, the mass concentration of hypochlorite in the hypochlorite aqueous solution is 0.5%-2%.
- the amount of the hypochlorite aqueous solution is 20mL-100mL per 10g of the macroporous adsorption resin. Further, the dosage of the hypochlorite aqueous solution is 30mL-70mL per 10g of the macroporous adsorption resin.
- washing refers to washing with absolute ethanol and water respectively
- neutralization refers to washing with alkaline aqueous solution first, and then washing with water to neutrality.
- the oxidizing agent is periodate.
- One-step oxidation reaction comprises the following steps:
- the concentration of periodate in the aqueous solution of periodate is 0.1M-1M. Further, the concentration of periodate in the aqueous solution of periodate is 0.1M-0.5M.
- the aqueous solution of periodate is used in an amount of 20mL-100mL per 10g of macroporous adsorption resin. Further, the dosage of the aqueous solution of periodate is 30mL-70mL per 10g of macroporous adsorption resin.
- washing refers to washing with water.
- the oxidizing agent is a combination of hydrogen peroxide and peracetic acid.
- One-step oxidation reaction comprises the following steps:
- the mass concentration of hydrogen peroxide is 0.1%-10%, and the mass concentration of peracetic acid is 0.1%-10%. Further, in the mixed aqueous solution of hydrogen peroxide and peracetic acid, the mass concentration of hydrogen peroxide is 0.5%-2%, and the mass concentration of peracetic acid is 0.5%-2%.
- the amount of the mixed aqueous solution of hydrogen peroxide and peracetic acid is 20mL-100mL per 10g of the macroporous adsorption resin. Further, the dosage of the mixed aqueous solution of hydrogen peroxide and peracetic acid is 30mL-70mL per 10g of macroporous adsorption resin.
- washing refers to washing with water
- neutralization refers to washing with an aqueous alkali solution first, and then washing with water to neutrality.
- the invention provides the modified macroporous adsorption resin prepared by the above preparation method.
- the surface of the modified macroporous adsorption resin has hydroxyl groups, has good hydrophilicity, and has good blood compatibility.
- the invention provides the modified macroporous adsorption resin prepared by the above preparation method. Compared with the macroporous adsorption resin before modification, the pore structure does not change significantly, and has good adsorption performance for biological components.
- the present invention provides a functional resin, comprising the above modified macroporous adsorption resin, and active groups of hydroxyl groups grafted on the surface of the modified macroporous adsorption resin.
- the grafted active groups can be used as linking spacers for further functional modification.
- the active group is an epoxy group.
- the functional resin further includes a ligand grafted to the active group.
- the ligand can be proteins, nucleotides and organic compounds containing amino groups.
- the present invention provides the application of the above modified macroporous adsorption resin or the above functional resin in the adsorption of biological components.
- biological components refer to biological components contained in blood. It can be understood that the above-mentioned application refers to the application of non-disease diagnosis and treatment methods, such as the purification of blood samples separated from the human body.
- This embodiment provides a preparation method of a modified macroporous adsorption resin, using sulfuric acid and peracetic acid as oxidants, the steps are as follows:
- This embodiment provides a method for preparing a modified macroporous adsorption resin, using sodium hypochlorite as an oxidizing agent, and the steps are as follows:
- This embodiment provides a preparation method of a modified macroporous adsorption resin, using sodium periodate as an oxidizing agent, the steps are as follows:
- the obtained macroporous adsorption resin is cleaned with purified water to obtain a modified macroporous adsorption resin.
- This embodiment provides a preparation method of a modified macroporous adsorption resin, using hydrogen peroxide and peracetic acid as oxidants, the steps are as follows:
- epoxy groups are measured on the modified macroporous adsorption resins obtained in Examples 1-4 and Comparative Examples 1-2.
- the epoxy group determination steps are as follows:
- Pyridine hydrochloride solution Dissolve 1.7mL concentrated hydrochloric acid in 98.3mL pyridine, shake well and let stand for 4h before use.
- Detection operation get 0.5g sample (modified macroporous adsorption resin obtained in Examples 1-4, modified macroporous adsorbed resin obtained in step (2) of comparative examples 1-2 and modified macroporous adsorbed resin obtained in step (3) of comparative examples 1-2.
- Macroporous adsorption resin was placed in an Erlenmeyer flask, pipette 25mL pyridine hydrochloride solution into the Erlenmeyer flask, add a suitable size magnet, heated to 138°C with methyl silicone oil, condensed and refluxed for 40min. After the reaction, cool to room temperature, add 3d phenolphthalein indicator, and titrate with 0.1M sodium hydroxide solution standard solution until it is reddish and does not fade within 30s. A blank experiment was performed under the same conditions.
- Epoxy group (V 1 -V 2 ) ⁇ C/M
- V1 the volume (mL) of the sodium hydroxide standard solution consumed by the blank experiment
- epoxy group content after oxidation —the modified macroporous adsorption resin of Examples 1 to 4, the modified macroporous adsorption resin obtained in step (2) of Comparative Examples 1 to 2;
- This example is the contact angle test of the macroporous adsorption resin before and after modification.
- the contact angle decreases from 90.5° to 79.7°, indicating that after the macroporous resin is modified by the hydrogen oxide/peracetic acid mixed solution, its double bond is oxidized and modified to hydroxyl, which increases the macroporous resin. Hydrophilicity of porous resin.
- This example is a test of the hydrophilicity of the macroporous adsorption resin before and after modification.
- This example is the blood compatibility test of the macroporous adsorption resin before and after modification.
- the macroporous resin circulated for half an hour and the flow rate decreased, and the chromatographic column was blocked.
- the chromatographic column was opened, a large amount of sticky matter appeared on the end surface of the chromatographic column.
- the flow rate of the modified macroporous resin was normal during the circulation of bovine whole blood for 2 hours, and no clogging of the chromatographic column occurred. As shown in Figure 4.
- a visible-ultraviolet spectrophotometer to measure pentobarbital sodium at 240nm, creatinine solution at 232nm, and vitamin B12 solution at 361nm
- use ELISA kits to detect IL-6 and TNF- ⁇ concentrations, and calculate the clearance rate before and after modification .
- the scavenging rate is shown in Table 4, and the scavenging rate has no obvious change before and after modification.
- This example is the functional modification of modified macroporous adsorption resin (containing amino ligand). The steps are as follows
- Ligand material Bilirubin adsorption Ethylenediamine 0.5 ⁇ mol/mL 3,3'-Diaminodipropylamine 0.8 ⁇ mol/mL
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Abstract
本发明涉及一种改性大孔吸附树脂及其制备方法和应用。所述改性大孔吸附树脂的制备方法，包括如下步骤：获取大孔吸附树脂；所述大孔吸附树脂的表面包含双键；混合水、氧化剂以及所述大孔吸附树脂进行一步氧化反应，将所述双键氧化成羟基；其中，所述氧化剂为硫酸和过氧乙酸的组合、次氯酸盐、高碘酸盐、或者过氧化氢和过氧乙酸的组合。所述次氯酸盐为次氯酸钠、次氯酸钾、次氯酸钙中的至少一种，所述高碘酸盐为高碘酸钠、高碘酸钾中的至少一种。该改性大孔吸附树脂的制备方法，能够通过一步反应实现大孔吸附树脂的亲水性改性，且无需采用有机溶剂、对环境友好、反应副产物少且易清洗，对人体安全性高。
Description
本发明涉及高分子材料，特别是涉及一种改性大孔吸附树脂及其制备方法和应用。
早在1974年，大孔吸附树脂即被用于吸附血液中的巴比妥酸盐和谷氨酰胺(参见专利文献US3794584A)。这类树脂一般采用高含量(>50％)的二乙烯基苯为交联剂进行合成，成品的比表面积一般在500～800m
2/g，在此基础上，进一步通过采用氯甲醚类试剂进行付-克(Fridel-Crafts)反应进行二次交联，可使比表面大幅提高，甚至可高达1000m
2/g以上(参见文献“王佳兴等，生化分离介质的制备与应用，化学工业出版社，北京，P84”)。然而，由于大孔吸附树脂的骨架结构是苯乙烯单体和二乙烯基苯经自由基悬浮聚合制备而成，本身是高度非极性和非选择性的，血液相容性也较差。
为了改善大孔吸附树脂的血液相容性，通常采用的传统技术路线有：1)通过二次交联制备超高交联的高比表面吸附树脂，通过表面沉积血液相容性好的高分子材料(如肝素、白蛋白，黄原胶，羟乙基纤维素等)，但这种修饰方式为物理吸附，所沉积的包膜物质在临床应用过程中，存在脱落的风险；2)通过在聚苯乙烯单元上苯环对位进行氯甲基化取代，利用氯甲基作为活化基团，接枝聚乙二醇(PEG)，或接枝功能性间隔臂(如2-乙醇胺)后进一步接枝肝素、胆碱或丝氨酸，或进一步羧基化，但这种方法需要使用一类致癌物质氯甲醚，后续净化处理工艺复杂且会产生大量危废，生产成本高；3)与亲水性单体(如甲基丙烯酸羟乙酯(HEMA))进行共聚，制备含有亲水基团的大孔吸附树脂，但由于树脂生产行业为高污染行业，大型吸附树脂制备厂家工艺成熟，基本不会针对血液吸附领域开发专门的产线，因此，尚无相关产品获得应用；4)利用大孔树脂表面残留的双键接枝亲水性单体(如HEMA，N-烷基丙烯酰胺，丙烯酸酯类)，但该方法涉及在树脂表面进行自由基聚合二次引发，反应过程难以控制，接枝聚合物的链长和接枝层的厚度不可控，较大可能会影响基体大孔吸附树脂的孔结构参数，如孔体积、孔隙率和孔径大小等；5)利用间氯过氧苯甲酸，双氧水或双氧水与1-(3-二甲氨基丙基)-3-乙基碳二亚胺(EDC)复合物)，次氯酸钠、溴化钠和硫酸的复合物，双氧水加紫外辐照、有机过氧酸(如间氯过氧苯甲酸、过氧乙酸、过氧苯甲酸、三氟过氧乙酸等)等氧化性物质将大孔树脂表面残留的双键氧化为环氧基，或在此基础上进一步改性，但该改性方法操作较为繁复，且反应中通常使用大量对人体有害的有机溶剂进行溶胀，间氯过氧苯甲酸、过氧苯甲酸在氧化过程中产生的副产物，如间氯苯甲酸、苯甲酸还会被树脂吸附，难以清洗干净，大量有机溶剂和有害化合物的使用也会污染环境，导致后处理工艺非常复杂。且在氧化过程中，会存在环氧基部分被氧化的情况，需要密切监测环氧基密度，反应难以定量控制。
发明内容
基于此，本发明提供一种改性大孔吸附树脂及其制备方法和应用。该改性大孔吸 附树脂的制备方法，能够通过一步反应实现大孔吸附树脂的亲水性改性，且操作简单，无需采用有机溶剂、反应副产物少，所产生的副产物经过简单处理可以转化为完全无毒无害的化学物质，不会带来环境污染；所采用的亲水改性方法不引入或产生难以清洗的有害化合物，后处理工艺简单，临床应用安全性高。
本发明的一方面，提供一种改性大孔吸附树脂的制备方法，包括如下步骤：
获取大孔吸附树脂，所述大孔吸附树脂的表面包含双键；
混合水、氧化剂以及所述大孔吸附树脂进行一步氧化反应，将所述双键氧化成羟基；
其中，所述氧化剂为硫酸与过氧乙酸的组合、次氯酸盐、高碘酸盐、次氯酸与次氯酸盐的组合、或者过氧化氢与过氧乙酸的组合；
所述次氯酸盐为次氯酸钠、次氯酸钾和次氯酸钙中的至少一种，所述高碘酸盐为高碘酸钠和高碘酸钾中的至少一种。
在其中一个实施例中，所述一步氧化反应的反应条件包括：反应温度为10℃～30℃；及/或，
所述一步氧化反应的反应条件包括：反应时间为2h～20h。
在其中一个实施例中，所述氧化剂为硫酸与过氧乙酸的组合，所述一步氧化反应包括如下步骤：
混合所述硫酸、过氧乙酸和水，制备硫酸和过氧乙酸的混合水溶液；
将所述硫酸和过氧乙酸的混合水溶液与所述大孔吸附树脂混合；
其中，所述硫酸和过氧乙酸的混合水溶液中，所述硫酸的质量浓度为1％～5％，所述过氧乙酸的质量浓度为0.15％～15％。
在其中一个实施例中，所述氧化剂为次氯酸盐，所述一步氧化反应包括如下步骤：
混合所述次氯酸盐和水，制备次氯酸盐水溶液；
将所述次氯酸盐水溶液与所述大孔吸附树脂混合；
其中，所述次氯酸盐水溶液中所述次氯酸盐的质量浓度为0.5％～10％。
在其中一个实施例中，所述氧化剂为高碘酸盐，所述一步氧化反应包括如下步骤：
混合所述高碘酸盐和水，制备高碘酸盐的水溶液；
将所述高碘酸盐的水溶液与所述大孔吸附树脂混合；
其中，所述高碘酸盐的水溶液中所述高碘酸盐的浓度为0.1M～1M。
在其中一个实施例中，所述氧化剂为过氧化氢和过氧乙酸的组合，所述一步氧化反应包括如下步骤：
混合所述过氧化氢、过氧乙酸和水，制备过氧化氢和过氧乙酸的混合水溶液；
将所述过氧化氢和过氧乙酸的混合水溶液与所述大孔吸附树脂混合；
所述过氧化氢和过氧乙酸的混合水溶液中，所述过氧化氢的质量浓度为0.1％～10％，所述过氧乙酸的质量浓度为0.1％～10％。
本发明的又一方面，提供所述的制备方法制备得到的改性大孔吸附树脂。
本发明的又一方面，提供一种功能树脂，包括所述改性大孔吸附树脂，以及接枝于所述改性大孔吸附树脂表面的所述羟基的活性基团。
在其中一个实施例中，所述活性基团为环氧基；及/或，
所述功能树脂还包括接枝于所述活性基团的配基。
本发明的又一方面，提供所述的改性大孔吸附树脂或者所述的功能树脂在生物组分吸附中的应用。
在其中一个实施例中，所述生物组分是指包含在血液中的生物组分。
与传统技术相比较，本发明具有如下有益效果：
本发明提供的改性大孔吸附树脂的制备方法，通过采用特定的氧化剂对大孔吸附树脂表面的残留双键进行氧化处理，能够在水中经一步氧化反应直接将双键氧化成羟基，实现亲水化改性，且反应的副产物少，所产生的副产物经过简单处理可以转化为完全无毒无害的化学物质，不会带来环境污染；所采用的亲水改性方法不引入或产生难以清洗的有害化合物，反应的过程无需采用有机溶剂，后处理简单，不需要考虑反应中间过程，简化步骤，工艺易于控制，临床应用安全性高。
本发明提供如上制备方法制备得到的改性大孔吸附树脂，与改性前的大孔吸附树脂相比，孔道结构不会发生明显变化，对生物组分具有良好的吸附性能。
上述改性大孔吸附树脂，在改性过程中不使用毒性较大的有机溶剂和易被树脂吸附而难以清洗的有机试剂，对环境友好，不会引入有害化合物，在应用于生物组分吸附时，保证了临床应用的安全性。同时，亲水化改性后，还能够增加大孔吸附树脂与血液的相容性。
另外，上述改性大孔吸附树脂上的羟基通过连接间隔臂活化后，可以进一步原位可控接枝亲水性或功能性配基，进而实现大孔吸附树脂亲水或功能化修饰。
图1为本发明一实施例的改性大孔吸附树脂改性前接触角测试；
图2为图1的改性大孔吸附树脂改性后接触角测试；
图3为本发明一实施例的改性大孔吸附树脂改性前后的亲水性效果对比(A——改性后；B——改性前)；
图4为本发明一实施例的改性大孔吸附树脂改性前后的血液相容性效果对比(C——改性前；D——改性后)。
以下结合具体实施例对本发明的改性大孔吸附树脂及其制备方法和应用作进一步详细的说明。本发明可以以许多不同的形式来实现，并不限于本文所描述的实施方式。相反地，提供这些实施方式的目的是使对本发明公开内容理解更加透彻全面。
除非另有定义，本文所使用的所有的技术和科学术语与属于本发明的技术领域的技术人员通常理解的含义相同。本文中在本发明的说明书中所使用的术语只是为了描述具体的实施例的目的，不是旨在于限制本发明。
本发明提供一种改性大孔吸附树脂的制备方法，包括如下步骤：
获取大孔吸附树脂，大孔吸附树脂的表面包含双键；
混合(溶剂)水、氧化剂以及大孔吸附树脂进行一步氧化反应，将双键氧化成羟基。
可以理解地，一步氧化反应是指通过一步反应即可将大孔吸附树脂表面包含的双 键氧化成羟基，中间无其他中间处理过程或中间产物。与传统方法相对应地，一步氧化反应是指无需经过环氧基中间产物的过程。
在其中一个具体的示例中，一步氧化反应无除了水以外的其他溶剂参与。进一步，一步氧化反应无有机溶剂参与。
在其中一个具体的示例中，氧化剂为水溶性强氧化剂。进一步地，氧化剂为硫酸和过氧乙酸的组合、次氯酸盐、高碘酸盐、或者过氧化氢和过氧乙酸的组合，次氯酸盐为次氯酸钠、次氯酸钾、次氯酸钙或以上三种或任意两种的混合物中的至少一种，高碘酸盐为高碘酸钠、高碘酸钾中的至少一种。上述氧化剂能够在对在大孔吸附树脂的表面残留双键进行充分氧化的同时，不会产生有害的副产物，或所产生的副产物经过简单处理可以转化为完全无毒无害的化学物质，简化了后处理，不会带来环境污染，保证了改性大孔吸附树脂的临床安全性。作为优选地，氧化剂为过氧乙酸和过氧化氢的组合。
在其中一个具体的示例中，一步氧化反应的反应条件包括：反应温度为10℃～30℃。进一步地，反应温度为15℃～25℃。
在其中一个具体的示例中，一步氧化反应的反应条件包括：反应时间为2h～20h。进一步地，反应时间为4h～10h。
在其中一个具体的示例中，一步氧化反应的反应条件包括：反应的过程中进行搅拌，搅拌的速率为150rpm～200rpm。
在其中一个具体的示例中，一步氧化反应结束后，还包括对所得产物进行洗涤和/或中和。对一步氧化反应产物进行简单的洗涤和/中和的步骤，即可完成产物的纯化除杂。
具体地，在其中一个具体的示例中，氧化剂为硫酸与过氧乙酸的组合，所述一步氧化反应包括如下步骤：
混合所述硫酸、过氧乙酸和水，制备硫酸和过氧乙酸的混合水溶液；
将硫酸和过氧乙酸的混合水溶液与所述大孔吸附树脂混合；
其中，硫酸和过氧乙酸的混合水溶液中，硫酸的质量浓度为1％～5％，过氧乙酸的质量浓度为0.15％～15％。进一步地，硫酸和过氧乙酸的混合水溶液中，硫酸的质量浓度为1％～3％，过氧乙酸的质量浓度为1％～3％。
在其中一个具体的示例中，硫酸和过氧乙酸的混合水溶液的用量为每10g大孔吸附树脂加入20mL～100mL。进一步地，硫酸和过氧乙酸的混合水溶液的用量为每10g大孔吸附树脂加入30mL～70mL。
在其中一个具体的示例中，一步氧化反应结束后，还包括对所得产物进行洗涤和中和的步骤。进一步地，洗涤是指分别用无水乙醇和水进行清洗；中和是指先采用碱水溶液进行清洗，然后再采用水洗至中性。
具体地，在其中一个具体的示例中，氧化剂为次氯酸盐，一步氧化反应包括如下步骤：
混合次氯酸盐和水，制备次氯酸盐水溶液；
将次氯酸盐水溶液与大孔吸附树脂混合；
其中，次氯酸盐水溶液中次氯酸盐的质量浓度为0.5％～10％。进一步地，次氯酸盐水溶液中次氯酸盐的质量浓度为0.5％～2％。
在其中一个具体的示例中，次氯酸盐水溶液的用量为每10g大孔吸附树脂加入 20mL～100mL。进一步地，次氯酸盐水溶液的用量为每10g大孔吸附树脂加入30mL～70mL。
在其中一个具体的示例中，一步氧化反应结束后，还包括对所得产物进行洗涤和中和的步骤。进一步地，洗涤是指分别用无水乙醇和水进行清洗；中和是指先采用碱水溶液进行清洗，然后再采用水洗至中性。
具体地，在其中一个具体的示例中，氧化剂为高碘酸盐。一步氧化反应包括如下步骤：
混合高碘酸盐和水，制备高碘酸盐的水溶液；
将高碘酸盐的水溶液与大孔吸附树脂混合；
其中，高碘酸盐的水溶液中高碘酸盐的浓度为0.1M～1M。进一步地，高碘酸盐的水溶液中高碘酸盐的浓度为0.1M～0.5M。
在其中一个具体的示例中，高碘酸盐的水溶液的用量为每10g大孔吸附树脂加入20mL～100mL。进一步地，高碘酸盐的水溶液的用量为每10g大孔吸附树脂加入30mL～70mL。
在其中一个具体的示例中，一步氧化反应结束后，还包括对所得产物进行洗涤的步骤。进一步地，洗涤是指用水进行清洗。
具体地，在其中一个具体的示例中，氧化剂为过氧化氢和过氧乙酸的组合。一步氧化反应包括如下步骤：
混合所述过氧化氢、过氧乙酸和水，制备过氧化氢和过氧乙酸的混合水溶液；
将所述过氧化氢和过氧乙酸的混合水溶液与所述大孔吸附树脂混合；
过氧化氢和过氧乙酸的混合水溶液中，过氧化氢的质量浓度为0.1％～10％，过氧乙酸的质量浓度为0.1％～10％。进一步地，过氧化氢和过氧乙酸的混合水溶液中，过氧化氢的质量浓度为0.5％～2％，过氧乙酸的质量浓度为0.5％～2％。
在其中一个具体的示例中，过氧化氢和过氧乙酸的混合水溶液的用量为每10g大孔吸附树脂加入20mL～100mL。进一步地，过氧化氢和过氧乙酸的混合水溶液的用量为每10g大孔吸附树脂加入30mL～70mL。
在其中一个具体的示例中，一步氧化反应结束后，还包括对所得产物进行洗涤和中和的步骤。进一步地，洗涤是指用水进行清洗；中和是指先采用碱水溶液进行清洗，然后再采用水洗至中性。
本发明提供如上制备方法制备得到的改性大孔吸附树脂。该改性大孔吸附树脂表面为羟基，具备良好的亲水性，且血液相容性好。
本发明提供如上制备方法制备得到的改性大孔吸附树脂，与改性前的大孔吸附树脂相比，孔道结构不会发生明显变化，对生物组分具有良好的吸附性能。
进一步地，可在上述改性大孔吸附树脂基础上经过进一步活化或反应进行接枝功能化基团，拓展其用途。
本发明提供一种功能树脂，包括如上改性大孔吸附树脂，以及接枝于改性大孔吸附树脂表面的羟基的活性基团。
接枝的活性基团可以作为连接间隔臂进一步进行功能化修饰。在其中一个具体的示例中，活性基团为环氧基。
在其中一个具体的示例中，功能树脂还包括接枝于活性基团的配基。具体地，该配基可以为蛋白、核苷酸以及含有氨基的有机化合物。
本发明提供如上改性大孔吸附树脂或者如上功能树脂在生物组分吸附中的应用。进一步地，生物组分是指包含在血液中的生物组分。可以理解地，上述应用是指非疾病的诊断和治疗方法的应用，如对脱离人体的血液样本进行净化。
以下为具体的实施例。
实施例1
本实施例提供一种改性大孔吸附树脂的制备方法，采用硫酸和过氧乙酸作为氧化剂，步骤如下：
(1)取10g大孔吸附树脂，加入50mL含2％硫酸、2％过氧乙酸的水溶液中，所得反应液在20℃温度，180rpm搅拌转速条件下，反应6小时；
(2)反应完成后，所得大孔吸附树脂用无水乙醇和纯化水清洗干净；
(3)清洗后的大孔吸附树脂中加入其体积5倍体积的1M氢氧化钠水溶液清洗，再用用纯化水清洗至中性，得到改性大孔吸附树脂。
实施例2
本实施例提供一种改性大孔吸附树脂的制备方法，采用次氯酸钠作为氧化剂，步骤如下：
(1)取10g大孔吸附树脂，加入50mL 1％次氯酸钠水溶液，所得反应液在20℃温度，180rpm搅拌转速条件下，反应6小时；
(2)反应完成后，所得大孔吸附树脂用无水乙醇和纯化水清洗干净；
(3)清洗后的大孔吸附树脂中加入其体积5倍体积的1M氢氧化钠水溶液清洗，再用用纯化水清洗至中性，得到改性大孔吸附树脂。
实施例3
本实施例提供一种改性大孔吸附树脂的制备方法，采用高碘酸钠作为氧化剂，步骤如下：
(1)取10g大孔吸附树脂，加入50mL浓度0.3M高碘酸钠水溶液，所得反应液在20℃温度，180rpm搅拌转速条件下，反应6小时；
(2)反应完成后，所得大孔吸附树脂用纯化水清洗干净，得到改性大孔吸附树脂。
实施例4
本实施例提供一种改性大孔吸附树脂的制备方法，采用过氧化氢和过氧乙酸作为氧化剂，步骤如下：
(1)取10g大孔吸附树脂，加入50mL含1％过氧化氢和1％过氧乙酸的水溶液，所得反应液在20℃温度，180rpm搅拌转速条件下，反应6小时；
(2)反应完成后，所得大孔吸附树脂用纯化水清洗干净；
(3)清洗后的大孔吸附树脂中加入其体积5倍体积的1M氢氧化钠水溶液清洗，再用用纯化水清洗至中性，得到改性大孔吸附树脂。
对比例1
本对比例采用传统的方法进行大孔吸附树脂的改性，采用的氧化剂为间氯过氧苯甲酸。步骤如下：
(1)取10g大孔吸附树脂，加入50mL二氯甲烷浸泡24小时，更换等体积新二氯甲烷，在冰水浴下(控温0～4℃)缓慢加入1.0g过氧间氯苯甲酸，待完全溶解后，所得反应液在20 ℃温度，180rpm搅拌转速条件下，反应0.5～4小时；
(2)反应完成后，所得大孔吸附树脂用无水乙醇和纯化水清洗干净；
(3)清洗后的大孔吸附树脂中加入其体积5倍体积的1M氢氧化钠水溶液清洗，在20℃温度，180rpm搅拌转速条件下，反应24小时，将环氧基转化为羟基基团，再用纯化水清洗至中性，得到改性大孔吸附树脂。
对比例2
本对比例采用传统的方法进行大孔吸附树脂的改性，采用的氧化剂为过氧化氢和硫酸。步骤如下：
(1)取10g大孔吸附树脂，加入50mL纯化水，加入反应溶剂总体积的3％(体积分数)的硫酸，再加入10mL浓度为30％双氧水，所得反应液在20℃温度，180rpm搅拌转速条件下，反应48小时；
(2)反应完成后，所得大孔吸附树脂用无水乙醇和纯化水清洗干净；
(3)清洗后的大孔吸附树脂中加入其体积5倍体积的1M氢氧化钠水溶液清洗，在20℃温度，180rpm搅拌转速条件下，反应24小时，将环氧基转化为羟基基团，再用用纯化水清洗至中性，得到改性大孔吸附树脂。
实施例1～4和对比例1～2反应特点对比如表1所示：
表1
实施例5
本实施例对实施例1～4以及对比例1～2所得的改性大孔吸附树脂进行环氧基测定。
环氧基测定步骤如下：
盐酸吡啶溶液：1.7mL浓盐酸溶于98.3mL吡啶中，摇匀放置4h后使用。
检测操作：取0.5g样品(实施例1～4的改性大孔吸附树脂、对比例1～2步骤(2)所得改性大孔吸附树脂以及对比例1～2步骤(3)所得改性大孔吸附树脂)置于锥形瓶中，用移液枪移取25mL盐酸吡啶溶液至锥形瓶中，加入合适大小的磁子，用甲基硅油加热至138℃冷凝回流40min。反应结束后，冷却到室温，加入3d酚酞指示剂，用0.1M氢氧化钠溶标准液滴定至微红色并30s内不退色。相同条件下做空白实验。
环氧基＝(V
1-V
2)·C/M
V1＝空白实验所消耗的氢氧化钠标准溶液的体积(mL)
V2＝样品实验所消耗的氢氧化钠标准溶液的体积(mL)
C＝氢氧化钠标准溶液的浓度(mol/L)
M＝样品称取的量(g)
环氧基测定结果如下表2所示：
表2
| 氧化后环氧基含量 | 水解后环氧基含量 | |
| 对比例1 | 0.2mmol/g | 未检出 |
| 对比例2 | 0.05mmol/g | 未检出 |
| 实施例1 | 未检出 | 无须水解 |
| 实施例2 | 未检出 | 无须水解 |
| 实施例3 | 未检出 | 无须水解 |
| 实施例4 | 未检出 | 无须水解 |
注：氧化后环氧基含量——实施例1～4的改性大孔吸附树脂、对比例1～2步骤(2)所得改性大孔吸附树脂；
水解后环氧基含量对比例1～2步骤(3)所得改性大孔吸附树脂。
实施例6
本实施例为改性前后大孔吸附树脂的接触角测试。
采用实施例4中改性前后的大孔吸附树脂，经研磨后，用油压压片机制备成直径13mm、厚1mm的片状样品，然后进行接触角测试，结果如图1～2和表3所示：
表3
| 样品 | 接触角 |
| 改性前大孔树脂 | 90.5° |
| 改性后大孔树脂 | 79.7° |
可知，大孔树脂经改性后，接触角从90.5°下降至79.7°，说明大孔树脂经过氧化氢/过氧乙酸混合溶液改性后，将其双键氧化改性为羟基，增加了大孔树脂的亲水性。
实施例7
本实施例为改性前后大孔吸附树脂的亲水性测试。
采用实施例4中改性前后的大孔吸附树脂，经105℃下干燥4小时除去大孔树脂中水分，分别加入纯化水中，观察改性前后大孔树脂的亲水效果，结果如图3所示。可知，改性前大孔树脂全部漂浮于水面上，改性后大孔树脂由于增加了亲水性而全部沉入水底。
实施例8
本实施例为改性前后大孔吸附树脂的血液相容性测试。
分别称取实施例4中改性前后大孔树脂5.0g(湿重)装于不同层析柱中，使用50mL抗凝牛全血自下而上以10mL/min的流速循环2小时，观察层析柱流速变化、是否产生堵塞现象，循环2小时后打开层析柱，观察层析柱端面状态。
改性前大孔树脂循环半小时后出现流速降低，层析柱堵塞现象，打开层析柱，发现层析柱端面出现大量粘稠物。改性后大孔树脂在2小时牛全血循环过程中流速正常，未出现层析柱堵塞现象，打开层析柱，层析柱端面未有粘稠物出现。如图4所示。
由以上结果可知，大孔树脂经过氧化氢/过氧乙酸混合溶液改性后，显著提高了大孔树脂的血液相容性。
实施例9
本实施例为改性前后大孔吸附树脂的吸附试验方法：
分别称取实施例4中改性前后大孔树脂2.94g(湿重)，置于50mL锥形瓶中，加入25ml的100mg/L浓度的戊巴比妥钠溶液，25ml的35mg/L的肌酐溶液，25ml的25mg/L的维生素B
12溶液，25ml IL-6浓度为600pg/mL的PBS溶液，25ml的500pg/ml的TNF-α溶液，置于37℃、60rpm的摇床下振荡2h。用可见-紫外分光光度计分别在240nm测量戊巴比妥钠、232nm测量肌酐溶液、361nm测量维生素B
12溶液，使用ELISA试剂盒检测IL-6和TNF-α浓度，计算改性前后的清除率。清除率如表4所示，改性前后清除率没有明显变化。
表4
| 物质 | 戊巴比妥钠 | 肌酐 | 维生素B 12 | IL-6 | TNF-α |
| 改性前的清除率 | 96.12％， | 19.22％ | 94.58％ | 95.6％ | 93.2 |
| 改性后的清除率 | 95.46％ | 18.17％ | 94.44％ | 96.2 | 91.3 |
实施例10
本实施例为改性大孔吸附树脂的功能化修饰(硫酸多粘菌素B配基)。步骤如下：
(1)称取实施例4中改性大孔吸附树脂10g，加入10mL浓度1M的氢氧化钠溶液、3mL环氧溴丙烷和7mL、1，4-丁二醇二缩水甘油醚和0.02g硼氢化钠，搅拌，30℃下反应1.5h，反应结束后用大量的注射用水冲洗干净，得到环氧活化的大孔树脂；
(2)将10mL 50mg/mL的硫酸多粘菌素B(PMB)溶液(用0.2mol/L的磷酸盐缓冲液配制)加入上述环氧活化的大孔树脂中，控制体系pH值为7.4，在37℃恒温体系里反应20h，停止反应，用大约20倍体积的注射用水冲洗树脂，冲洗干净后，加入20mL浓度0.2M的乙醇胺溶液封闭未反应的环氧基，20℃反应10h，反应结束后，用大量注射用水冲洗干净，制备PMB修饰的大孔树脂。
实施例11
本实施例为功能化修饰后大孔吸附树脂的吸附试验方法：
取0.2g实施例10制得的PMB修饰的大孔树脂，加入到10mL的无热源锥形瓶中，再分别加入含内毒素1EU/mL、含IL-6浓度600pg/mL和含TNF-α浓度100ng/ml的血浆6mL，震荡吸附2h(温度37℃，震荡速率180rpm)，然后用动态浊毒法测定吸附后的内毒素浓度，使用ELISA试剂盒检测IL-6和TNF-α浓度，并计算吸附材料的吸附量和清除率。结果表5所示。
表5
| 物质 | 内毒素 | IL-6 | TNF-α |
| 清除率 | 35％ | 63.1％ | 45.1％ |
实施例12
本实施例为改性大孔吸附树脂的功能化修饰(含氨基配基).步骤如下
(1)称取实施例4中改性大孔吸附树脂10g，加入10mL浓度1M的氢氧化钠溶液、3mL环氧溴丙烷和7mL、1，4-丁二醇二缩水甘油醚和0.02g硼氢化钠，搅拌，30℃下反应1.5h，反应结束后用大量的注射用水冲洗干净，得到环氧活化的大孔树脂；
(2)分别加入10mL 0.1g/mL的乙二胺溶液、10mL 0.1g/mL3，3′-二氨基二丙胺到上述环氧活化的大孔树脂中，在37℃反应20h，停止反应，用大约20倍体积的注射用水冲洗树脂，反应结束后，用大量注射用水冲洗干净，制备含氨基配基的大孔树脂。
实施例13
本实施例为功能化修饰后大孔吸附树脂的吸附试验方法：
取1mL实施例12制得的含氨基配基的大孔树脂，加入到10mL胆红素血浆10mL，震荡吸附2h(温度37℃，震荡速率90rpm)，取出室温下静置，分别测定吸附前后血浆中的胆红素含量，并计算吸附材料的吸附量。结果表6所示。
表6
| 配基材料 | 胆红素吸附量 |
| 乙二胺 | 0.5μmol/mL |
| 3，3′-二氨基二丙胺 | 0.8μmol/mL |
以上所述实施例的各技术特征可以进行任意的组合，为使描述简洁，未对上述实施例中的各个技术特征所有可能的组合都进行描述，然而，只要这些技术特征的组合不存在矛盾，都应当认为是本说明书记载的范围。
以上所述实施例仅表达了本发明的几种实施方式，其描述较为具体和详细，但并不能因此而理解为对发明专利范围的限制。应当指出的是，对于本领域的普通技术人员来说，在不脱离本发明构思的前提下，还可以做出若干变形和改进，这些都属于本发明的保护范围。因此，本发明专利的保护范围应以所附权利要求为准。
Claims (10)
- 一种改性大孔吸附树脂的制备方法，其特征在于，包括如下步骤：获取大孔吸附树脂，所述大孔吸附树脂的表面包含双键；混合水、氧化剂以及所述大孔吸附树脂进行一步氧化反应，将所述双键氧化成羟基；其中，所述氧化剂为硫酸与过氧乙酸的组合、次氯酸盐、高碘酸盐、次氯酸与次氯酸盐的组合、或者过氧化氢与过氧乙酸的组合；所述次氯酸盐为次氯酸钠、次氯酸钾和次氯酸钙中的至少一种，所述高碘酸盐为高碘酸钠和高碘酸钾中的至少一种。
- 根据权利要求1所述的改性大孔吸附树脂的制备方法，其特征在于，所述一步氧化反应的反应条件包括：反应温度为10℃～30℃；及/或，所述一步氧化反应的反应条件包括：反应时间为2h～20h。
- 根据权利要求1或2所述的改性大孔吸附树脂的制备方法，其特征在于，所述氧化剂为硫酸与过氧乙酸的组合，所述一步氧化反应包括如下步骤：混合所述硫酸、过氧乙酸和水，制备硫酸和过氧乙酸的混合水溶液；将所述硫酸和过氧乙酸的混合水溶液与所述大孔吸附树脂混合；其中，所述硫酸和过氧乙酸的混合水溶液中，所述硫酸的质量浓度为1％～5％，所述过氧乙酸的质量浓度为0.15％～15％。
- 根据权利要求1或2所述的改性大孔吸附树脂的制备方法，其特征在于，所述氧化剂为次氯酸盐，所述一步氧化反应包括如下步骤：混合所述次氯酸盐和水，制备次氯酸盐水溶液；将所述次氯酸盐水溶液与所述大孔吸附树脂混合；其中，所述次氯酸盐水溶液中所述次氯酸盐的质量浓度为0.5％～10％。
- 根据权利要求1或2所述的改性大孔吸附树脂的制备方法，其特征在于，所述氧化剂为高碘酸盐，所述一步氧化反应包括如下步骤：混合所述高碘酸盐和水，制备高碘酸盐的水溶液；将所述高碘酸盐的水溶液与所述大孔吸附树脂混合；其中，所述高碘酸盐的水溶液中所述高碘酸盐的浓度为0.1M～1M。
- 根据权利要求1或2所述的改性大孔吸附树脂的制备方法，其特征在于，所述氧化剂为过氧化氢和过氧乙酸的组合，所述一步氧化反应包括如下步骤：混合所述过氧化氢、过氧乙酸和水，制备过氧化氢和过氧乙酸的混合水溶液；将所述过氧化氢和过氧乙酸的混合水溶液与所述大孔吸附树脂混合；所述过氧化氢和过氧乙酸的混合水溶液中，所述过氧化氢的质量浓度为0.1％～10％，所述过氧乙酸的质量浓度为0.1％～10％。
- 权利要求1～6任一项所述的制备方法制备得到的改性大孔吸附树脂。
- 一种功能树脂，其特征在于，包括权利要求7所述改性大孔吸附树脂，以及接枝于所述改性大孔吸附树脂表面的所述羟基的活性基团。
- 根据权利要求8所述的功能树脂，其特征在于，所述活性基团为环氧基；及/或，所述功能树脂还包括接枝于所述活性基团的配基。
- 权利要求7所述的改性大孔吸附树脂或者根据权利要求8～9任一项所述的功能树脂在生物组分吸附中的应用。
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