A kind of material and the preparation method and application thereof for adsorbing uric acid
Technical field
The invention belongs to blood purification treatment field, it is related to a kind of material for adsorbing uric acid and preparation method thereof and answers
With.
Background technique
Uric acid is the final product of purine nucleotides catabolic process in human body, and production quantity is more stable in normal human.
And nephrotic has a large amount of toxicants including uric acid including and accumulates because of poor kidney or kidney failure in blood.It is excessive
Uric acid can not only cause uremic multiple complications, but also renal failure can be further speeded up.
Haemodialysis is clinically to reduce the main method of nephrotic's toxic material in blood, but high payment for medical care is
What most of patients were difficult to bear;Oral adsorbent agent there is a problem of biocompatibility and adsorptive selectivity difference, clinic makes
With the effect is unsatisfactory;Blood perfusion technique is that the blood of excessive endogenous metabolism toxicant in another removing human body is net
Change technology, it can rely on its unique mechanism of action, be removed the intracorporal toxin of patient using efficient adsorbent, for
Nephrosis is treated to save the life of patient and be of great significance.Designing and prepare a kind of pair of uric acid has high-adsorption-capacity and biology
The good adsorbent material of compatibility is the key point of blood perfusion technique.
Polyethyleneimine (PEI) is a kind of water soluble polymer, and N atom abundant has very strong on strand
Protophilia, therefore can be generated strongly with the hydroxyl (proton donor) in 2,6, the 8- trihydroxypurine of tautomer of uric acid
Interaction of hydrogen bond.There is scholar to be based on this principle PEI is grafted on Silica Surface being used to adsorb removing uric acid, but blood compatibility
Property is undesirable.
It interpenetrates and develops as modern life science, medicine, material science etc. are multi-disciplinary, there is biocompatibility
High molecular material play increasingly important role.In order to further increase or improve performance, most of high molecular materials
It is modified to need to carry out surface, the various physical and chemical performances of high molecular material and biology performance are assigned or improve, such as hydrophily, parent
With adsorptivity, biocompatibility and cell adhesion etc..Modified material can be used for biosensor, large biological molecule and
The separation of DNA, the identification of cell and label and the controlled release of drug etc..
Polymethylacrylic acid beta-hydroxy ethyl ester (PHEMA) is a kind of widely used bio-medical material, has good life
Object compatibility has the higher hydroxyl of reactivity on macromolecular chain, is easy to be chemically modified.Use PHEMA as biology
Biocompatible carrier material has been applied to many research fields.Based on this, present invention design is prepared for polymethylacrylic acid β-
Hydroxyl ethyl ester is that the absorption uric acid material of matrix is applied to blood perfusion technique.
Summary of the invention
In order to solve the problems, such as that current uric acid adsorbent material absorption property is not high and poor biocompatibility, the present invention provide one
Material and the preparation method and application thereof of the kind for adsorbing uric acid, it is micro- to be grafted to epoxidised PHEMA for polyethyleneimine (PEI)
The material PEI-PHEMA microballoon having to uric acid compared with high adsorption capacity has been made in ball surface.
The purpose of the present invention can be achieved through the following technical solutions:
It is a kind of for adsorbing the material of uric acid, which is made by following step:
(1) it prepares PHEMA microballoon: dispersing agent Span-60 is dissolved in composition continuous phase oil phase in atoleine;By methyl-prop
Olefin(e) acid beta-hydroxy ethyl ester and the miscible composition dispersed phase water phase of secondary distilled water are added ammonium persulfate and carry out cross-linking polymerization;
(2) epoxidation of PHEMA microballoon: NaOH solution and epoxychloropropane are added in PHEMA microballoon, by epoxy group base
Group is introduced into microsphere surface;
(3) PEI is grafted in epoxidation PHEMA microsphere surface: PEI and 1 being added in the microballoon that surface there are cycloalkyl groups,
4- dioxane carries out graft reaction, the PEI-PHEMA micro-sphere material that surface grafting has PEI is obtained, for adsorbing uric acid.
The present invention also provides a kind of for adsorbing the preparation method of the material of uric acid, which includes following step
It is rapid:
(1) it prepares PHEMA microballoon: dispersing agent Span-60 is dissolved in composition continuous phase oil phase in atoleine;By methyl-prop
Olefin(e) acid beta-hydroxy ethyl ester and the miscible composition dispersed phase water phase of secondary distilled water are added ammonium persulfate and carry out cross-linking polymerization;
(2) epoxidation of PHEMA microballoon: NaOH solution and epoxychloropropane are added in PHEMA microballoon, by epoxy group base
Group is introduced into microsphere surface;
(3) PEI is grafted in epoxidation PHEMA microsphere surface: PEI and 1 being added in the microballoon that surface there are cycloalkyl groups,
4- dioxane carries out graft reaction, obtains the PEI-PHEMA microballoon that surface grafting has PEI.
In step (1), the PHEMA microballoon preparation manipulation are as follows: 0.40-0.60g dispersing agent Span-60 is dissolved in 30-
In 40ml atoleine, continuous phase oil phase is constituted;7ml β-hydroxyethyl methacry-late and 2ml secondary distilled water is miscible, it is added
Crosslinking agent N, N '-methylene-bisacrylamide of 0.45g constitutes dispersed phase water phase;Water phase is added to formation reverse phase in oily phase to hang
Floating polymerization-filling, is passed through N2, 400rpm stirs 30min, raises the temperature to 55-70 DEG C, initiator ammonium persulfate is added, in N2
It protects lower polymerization reaction 8 hours, filters out microballoon, respectively with petroleum ether, acetone washing, be dried in vacuo, obtain flat at 50 DEG C
Equal partial size is 140-170 μm of transparent PHEMA microballoon.
In step (2), the epoxidation of the PHEMA microballoon is operated are as follows: PHEMA microballoon 1g is added, 10% NaOH is added
Solution 15ml impregnates swelling 3h;Epoxychloropropane 3-6ml is added, is stirred, reacts 10h at 30 DEG C;By microballoon dehydrated alcohol
With distillation water washing, it is dried in vacuo to get the PHEMA microballoon of cycloalkyl groups is had to surface.
In step (3), the epoxidation PHEMA microsphere surface grafting PEI operation are as follows: 4-6ml PEI is dissolved in Isosorbide-5-Nitrae-
In the mixed solution of dioxane and water, epoxidised PHEMA microballoon is added in the solution and is swollen 2h, it is anti-at 50-70 DEG C
7-10h is answered, is filtered out microballoon by grafting polyethylene imine in microsphere surface by the ring-opening reaction between amido and epoxy bond
It is washed to neutrality with distillation, vacuum drying is at 50 DEG C to get the PEI-PHEMA microballoon for having PEI to surface grafting.
Application of the material in absorption uric acid that the present invention also provides a kind of for adsorbing uric acid, the material of the absorption uric acid
Expect that the adsorbance of uric acid be 81.60mg/g.
Beneficial effects of the present invention: the present invention has good biology using polymethylacrylic acid beta-hydroxy ethyl ester (PHEMA)
Compatibility uses PHEMA as biological compatibility carrier material, is grafted upper PEI again after epoxidation processing is carried out to it, just obtains
Both there is biocompatibility, there is the adsorbent material of the amido largely to uric acid molecule with strong suction-operated on surface again, in blood
The value that the uric acid molecule in blood has potential application is removed in purification treatment field with this material;
The adsorbent material of the method for the invention preparation has very high absorption property, at low cost, material use to uric acid
Rate is high, is able to satisfy the requirement of industrialized production;
The PEI-PHEMA microballoon that the material of absorption uric acid produced by the present invention, i.e. surface grafting have PEI, at 25 DEG C, pH
When being 7.0,81.60mg/g is reached to the adsorbance of uric acid.
Detailed description of the invention
In order to facilitate the understanding of those skilled in the art, the present invention will be further described below with reference to the drawings.
Fig. 1 is the electron scanning micrograph of PHEMA microballoon;
Fig. 2 is that effect proves one PEI-PHEMA microballoon of experiment to the absorption isotherm of uric acid;
Fig. 3 is that effect proves two PEI-PHEMA microballoons of experiment to the absorption isotherm of uric acid.
Specific embodiment
Following will be combined with the drawings in the embodiments of the present invention, and technical solution in the embodiment of the present invention carries out clear, complete
Site preparation description, it is clear that described embodiments are only a part of the embodiments of the present invention, instead of all the embodiments.It is based on
Embodiment in the present invention, it is obtained by those of ordinary skill in the art without making creative efforts all other
Embodiment shall fall within the protection scope of the present invention.
It is a kind of for adsorbing the preparation method of the material of uric acid, this method utilizes polymethylacrylic acid beta-hydroxy ethyl ester
(PHEMA) chemical modification, using polymethylacrylic acid beta-hydroxy ethyl ester polymer microballoon as biological compatibility carrier material,
Cycloalkyl groups grafting polyethylene imine (PEI) again is first introduced on its surface, is prepared for the PEI-PHEMA that surface grafting has PEI
Microballoon;
Embodiment 1
(1) preparation of PHEMA microballoon: 0.40-0.60g dispersing agent Span-60 is dissolved in 30-40ml atoleine, structure
At continuous phase oil phase;
7ml β-hydroxyethyl methacry-late and 2ml secondary distilled water is miscible, crosslinking agent N, N '-methylene of 0.45g is added
Base bisacrylamide constitutes dispersed phase water phase;
Water phase is added in oily phase and forms inverse suspension system, is passed through N2, 400rpm stir 30min, temperature is increased
To 55-70 DEG C, initiator ammonium persulfate is added, in N2It protects lower polymerization reaction 8 hours, microballoon is filtered out, respectively with petroleum ether, third
Ketone washing, is dried in vacuo at 50 DEG C, and obtaining average grain diameter is 140-170 μm of transparent PHEMA microballoon;
(2) epoxidation of PHEMA microballoon: being added PHEMA microballoon 1g, and the NaOH solution 15ml for being added 10% impregnates swelling
3h;Epoxychloropropane 3-6ml is added, is stirred, reacts 10h at 30 DEG C;By microballoon dehydrated alcohol and distillation water washing, vacuum
The dry PHEMA microballoon to get to surface with cycloalkyl groups;
(3) PEI is grafted in epoxidation PHEMA microsphere surface: 4-6ml PEI is dissolved in the mixed of 1,4- dioxane and water
It closes in solution, epoxidised PHEMA microballoon is added in the solution and is swollen 2h, 7-10h is reacted at 50-70 DEG C, passes through amido
Microballoon is filtered out by grafting polyethylene imine in microsphere surface and is washed to neutrality with distillation by the ring-opening reaction between epoxy bond,
Vacuum drying is at 50 DEG C to get the PEI-PHEMA microballoon for having PEI to surface grafting.
Embodiment 2
(1) preparation of PHEMA microballoon: 0.50g dispersing agent Span-60 is dissolved in 35ml atoleine, constitutes continuous phase
Oily phase;
7ml β-hydroxyethyl methacry-late and 2ml secondary distilled water is miscible, crosslinking agent N, N '-methylene of 0.45g is added
Base bisacrylamide constitutes dispersed phase water phase;
Water phase is added in oily phase and forms inverse suspension system, is passed through N2, 400rpm stir 30min, temperature is increased
To 65 DEG C, initiator ammonium persulfate is added, in N2It protects lower polymerization reaction 8 hours, microballoon is filtered out, respectively with petroleum ether, acetone
Washing, is dried in vacuo at 50 DEG C, obtains the transparent PHEMA microballoon that average grain diameter is 160 μm or so;
(2) epoxidation of PHEMA microballoon: being added PHEMA microballoon 1g, and the NaOH solution 15ml for being added 10% impregnates swelling
3h;Epoxychloropropane 5ml is added, is stirred, reacts 10h at 30 DEG C;By microballoon dehydrated alcohol and distillation water washing, vacuum is dry
The dry PHEMA microballoon to get to surface with cycloalkyl groups;
(3) PEI is grafted in epoxidation PHEMA microsphere surface: 4-6ml PEI is dissolved in the mixed of 1,4- dioxane and water
It closes in solution, epoxidised PHEMA microballoon is added in the solution and is swollen 2h, 7-10h is reacted at 50-70 DEG C, passes through amido
Microballoon is filtered out by grafting polyethylene imine in microsphere surface and is washed to neutrality with distillation by the ring-opening reaction between epoxy bond,
Vacuum drying is at 50 DEG C to get the PEI-PHEMA microballoon for having PEI to surface grafting.
It is as follows that above steps corresponds to reaction equation:
(1) preparation of PHEMA microballoon:
(2) epoxidation of PHEMA microballoon:
(3) PEI is grafted in epoxidation PHEMA microsphere surface:
Effect proves experiment one:
The epoxidised PHEMA microballoon of 1g is added in four-hole boiling flask, 6ml PEI is added and is dissolved in Isosorbide-5-Nitrae-dioxane and water
Mixed solution, be swollen 2h, graft reaction 8h carried out under 70 DEG C of constant temperatures, microballoon is filtered out, be washed to neutrality with distillation, 50
It is dried in vacuo at DEG C to get the PEI-PHEMA microballoon for being 8.73g/100g to grafting degree.Using the grafting microballoon to uric acid solution
Static Adsorption is carried out, the absorption property to uric acid is investigated: the PEI-PHEMA microballoon of 0.1g being added to initial concentration difference respectively
In the uric acid solution (100ml, pH=7.0) of (0.1-1.0mg/mL), 3h is vibrated in gas bath constant temperature oscillation case at 25 DEG C, is drawn
Supernatant liquor measures equilibrium concentration, utilizes formula calculated equilibrium adsorbance Qe at ultraviolet spectrophotometry (680nm) after dilution
(mg/g).Draw PEI-PHEMA microballoon to the adsorption isothermal curve of uric acid, as shown in Figure 2.
C in formula0, Ce (mg/L) be respectively before adsorbing and absorption up to after balance in solution uric acid concentration, m (g) is PEI-
The quality of PHEMA microballoon, V (mL) are adsorption liquid volume.
Figure it is seen that when pH value of solution is 7.0, PEI-PHEMA microballoon is preferable to the absorption property of uric acid at 25 DEG C,
Adsorbance reaches 81.60mg/g.
Effect proves experiment two:
The epoxidised PHEMA microballoon of 1g is added in four-hole boiling flask, 5ml is added, 4ml PEI is dissolved in Isosorbide-5-Nitrae-dioxane
With the mixed solution of water, it is swollen 2h, graft reaction 10h is carried out under 70 DEG C of constant temperatures, microballoon is filtered out, is washed to distillation
Property, it is dried in vacuo at 50 DEG C, respectively obtains the PEI-PHEMA microballoon that PEI grafting degree is 7.28g/100g and 6.44g/100g.Make
Static Adsorption is carried out to uric acid solution with both microballoons, investigates the absorption property to uric acid.Method proves experiment referring to effect
One, and Contrast on effect is carried out with it, as a result as shown in Figure 3.
From figure 3, it can be seen that when pH value of solution is 7.0, the PEI-PHEMA microballoon of different grafting degrees is to uric acid at 25 DEG C
There is a degree of absorption, and as the increase adsorbance of grafting degree is also in increased rule, when maximum grafting degree, absorption
Amount reaches 81.60mg/g.
Present invention disclosed above preferred embodiment is only intended to help to illustrate the present invention.There is no detailed for preferred embodiment
All details are described, are not limited the invention to the specific embodiments described.Obviously, according to the content of this specification,
It can make many modifications and variations.These embodiments are chosen and specifically described to this specification, is in order to better explain the present invention
Principle and practical application, so that skilled artisan be enable to better understand and utilize the present invention.The present invention is only
It is limited by claims and its full scope and equivalent.