CN114042441A - Method for modifying and immobilizing heparin on surface of hemoperfusion resin microsphere and adsorbent prepared by method - Google Patents
Method for modifying and immobilizing heparin on surface of hemoperfusion resin microsphere and adsorbent prepared by method Download PDFInfo
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- 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
- B01J20/28—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof characterised by their form or physical properties
- B01J20/28014—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 form
- B01J20/28016—Particle form
- B01J20/28021—Hollow particles, e.g. hollow spheres, microspheres or cenospheres
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
- A61K31/726—Glycosaminoglycans, i.e. mucopolysaccharides
- A61K31/727—Heparin; Heparan
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
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- B01D15/00—Separating processes involving the treatment of liquids with solid sorbents; Apparatus therefor
- B01D15/08—Selective adsorption, e.g. chromatography
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- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
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- B01J20/00—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof
- B01J20/22—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof comprising organic material
- B01J20/26—Synthetic macromolecular compounds
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- B—PERFORMING OPERATIONS; TRANSPORTING
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- 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
- B01J20/28—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof characterised by their form or physical properties
- B01J20/28014—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 form
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- 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
Abstract
The scheme belongs to the technical field of blood purification, and discloses a method for modifying and immobilizing heparin on the surface of hemoperfusion resin microspheres and an adsorbent prepared by the method. The method comprises the following steps: soaking the resin microspheres in ammonia water solution containing shellac and heparin salt, heating and evaporating to make shellac adhere to the outer surface of the resin microspheres and the surfaces of the holes thereof, thereby realizing hydrophilic modification and heparin immobilization. The lac used in the scheme is dissolved in an ammonia water solution, the lac is adhered to the surface of a hole of a resin microsphere to realize modification in the process of heating and evaporating the ammonia water, and the hydrophilic end of the lac molecule is exposed on the surface of the hole to improve the blood compatibility of the lac molecule; meanwhile, the immobilized heparin has excellent anticoagulation performance, and can reduce the coagulation phenomenon when blood contacts with the resin microspheres. The preparation method is simple and effective, is suitable for various resin type hemoperfusion products clinically used at present, and improves the safety of clinical application.
Description
Technical Field
The scheme belongs to the technical field of blood purification, and particularly relates to a method for modifying and immobilizing heparin on the surface of hemoperfusion resin microspheres and an adsorbent prepared by the method.
Background
Blood perfusion is a blood purification technique in which the blood of a patient is introduced into an perfusion device filled with an adsorbent, and exogenous or endogenous toxins, drugs or metabolic waste products which cannot be removed by dialysis in the blood are removed through adsorption. The blood perfusion technology is one of the basic treatment modes of blood purification, and is rapidly developed in nearly ten years, and the application range is wider and wider. The resin microspheres are the most common hemoperfusion adsorbent in the market at present, are mainly used for rescuing drugs and toxicosis, and can also be used together with hemodialysis to remove medium-macromolecule toxins in the body of a chronic renal failure maintenance dialysis patient.
The hemoperfusion resin microsphere is generally prepared by polymerizing styrene and divinyl benzene, has rich pore structures, and has adsorption effect on various toxin molecules. Because the benzene ring in the resin microsphere has strong hydrophobicity, blood cells (such as blood platelets) in blood can adhere and aggregate on the surface of the resin microsphere in the clinical use process to cause blood coagulation. Therefore, hydrophilic modification of the pore surface of the resin microspheres is generally required to improve the blood compatibility of the adsorbent. Currently, hemoperfusion resin microspheres used in the market are subjected to pore surface modification by using collodion (nitrocellulose). Dissolving collodion in ethanol, mixing with resin microspheres, stirring, filtering, and air drying to obtain the modified resin microsphere adsorbent. Although collodion improves the blood compatibility of the adsorbent to some extent, the improvement of the anticoagulant capacity of the adsorbent is very limited, and the adsorbent is still prone to produce blood coagulation when in contact with blood. Therefore, in order to perform the blood perfusion, it is generally necessary to inject a certain amount of heparin into the vein of the patient to perform the systemic anticoagulation so as to ensure the smooth performance of the blood perfusion treatment. If the amount of heparin is too large, uncontrolled bleeding may occur in vivo and even multiple organ dysfunction may result. Because the collodion is insoluble in water, heparin cannot be immobilized on the resin microspheres while the surface of the resin holes is modified, and the coagulation phenomenon often occurs during clinical whole blood perfusion. Therefore, a method for carrying heparin on the hydrophilic modification of the surfaces of the holes of the resin microspheres is found, the resin microspheres with the surface anticoagulant capacity are developed, and the method has important significance for reducing the dosage of heparin and improving the treatment safety in the blood perfusion treatment process.
Disclosure of Invention
In view of this, the present disclosure is to overcome at least one of the deficiencies in the prior art, provide a new, simple and effective method for surface modification and heparin immobilization on hemoperfusion resin microspheres, and solve the technical problems of insufficient improvement of blood compatibility and short blood coagulation time in the prior art.
In order to solve the technical problem, the following technical scheme is adopted:
in a first aspect, the present disclosure provides a method for modifying and immobilizing heparin on the surface of a hemoperfusion resin microsphere, comprising: soaking the resin microspheres in ammonia water solution containing shellac and heparin salt, heating and evaporating to make shellac self-assemble on the outer surface of the resin microspheres and the surfaces of the holes thereof, thereby realizing hydrophilic modification and heparin immobilization.
The technical scheme includes that firstly, after the shellac is dissolved in an ammonia water solution, a proper amount of heparin salt is added to be mixed and dissolved, then the resin microspheres are added and stirred at normal temperature, the shellac and the heparin salt are made to penetrate into holes of the resin microspheres, then ammonia water is evaporated by heating, the shellac is made to be self-assembled and attached to the outer surfaces of the resin microspheres and the surfaces of the holes of the resin microspheres, and heparin molecules are immobilized on the surfaces of the resin microspheres. In the scheme, the lac is adhered to the surfaces of the resin microspheres (including the outer surfaces and the hole surfaces thereof) in a self-assembly manner, the lac is adhered to the surfaces of the resin microspheres through hydrophobic interaction, and hydrophilic groups of the lac are exposed outside, so that the blood compatibility of the obtained adsorbent can be improved; the immobilized heparin salt has excellent anticoagulation performance, and can reduce the coagulation phenomenon when blood contacts with the resin microspheres, thereby improving the anticoagulation performance. The scheme is simple and effective, is suitable for various resin hemoperfusion products clinically used at present, and improves the safety of clinical application.
In a second aspect, the present disclosure provides a blood perfusion adsorbent prepared by the method provided in the first aspect of the present disclosure.
This scheme compares with prior art has following beneficial effect:
the lac used in this scheme dissolves in aqueous ammonia solution, and the adhesion is on resin microsphere surface and hole surface in the heating evaporation aqueous ammonia in-process, and hydrophilic end can expose on resin microsphere surface and improve its blood compatibility, and the heparin of immobilization has good anticoagulation performance simultaneously, can reduce the blood coagulation phenomenon that appears when blood and resin microsphere contact. The preparation method is simple and effective, is suitable for various resin type hemoperfusion products clinically used at present, and improves the safety of clinical application.
The implementation of the scheme shows that the clinical treatment effect and safety are improved in blood perfusion. Adsorption data and anticoagulation experiments show that after the resin microspheres are treated by the preparation method, the adsorption quantity to creatinine, sodium pentobarbital and VB12 is slightly reduced, the blood coagulation time is prolonged from 20 minutes to 40-120 minutes, and the requirement of clinical perfusion for avoiding blood coagulation is met.
Drawings
FIG. 1 is a chemical structural formula of shellac.
FIG. 2 is a graph of the variable relationship between toxin clearance and shellac concentration.
FIG. 3 is a graph of the variable relationship between clotting time and added heparin concentration.
Detailed Description
The scheme provides a method for modifying and immobilizing heparin on the surface of the hemoperfusion resin microsphere, which is simple and effective, is suitable for producing various resin hemoperfusion products clinically used at present, and improves the safety of clinical application.
The method for modifying and immobilizing heparin on the surface of the hemoperfusion resin microsphere comprises the following steps: soaking the resin microspheres in ammonia water solution containing shellac and heparin salt, heating and evaporating to make shellac self-assemble on the outer surface of the resin microspheres and the surfaces of the holes thereof, thereby realizing hydrophilic modification and heparin immobilization.
Shellac (Shellac) is a natural substance obtained from the secretion of Sclerotinia scleotiorum, the main components are lactone and lactide formed by esterification polymerization of eleostearic acid and chitosanoic acid, the average molecular weight is about 1000, and C can be used60H90O5The chemical structure is shown in figure 1, and the surface of the material contains abundant hydroxyl and carboxyl. Shellac is completely non-toxic and was originally used as a food additive, and purified and bleached shellac was called white shellac. Since the white shellac is soluble in ethanol and an alkaline aqueous solution and has coating formability after drying, it is commonly used as an edible coating material derived from natural products and having high safety for coating tablets such as confectionary and pharmaceutical products, but its use for hydrophilic modification of resin microspheres has not been reported.
The technical scheme includes that firstly, after the shellac is dissolved in an ammonia water solution, a proper amount of heparin salt is added to be mixed and dissolved, then, the resin microspheres are added and stirred at normal temperature, the shellac and the heparin salt are made to penetrate into holes of the resin microspheres, then, ammonia water is evaporated by heating, the shellac is made to adhere to the surfaces of the holes of the resin microspheres in a self-assembly manner, and heparin molecules are immobilized on the surfaces of adsorbents. According to the scheme, the lac realizes hydrophilic modification on the surfaces of the holes of the resin microspheres, and the hydrophilic groups of the lac are exposed outside, so that the blood compatibility of the adsorbent can be improved; the immobilized heparin salt has excellent anticoagulation performance, and can reduce the coagulation phenomenon when blood contacts with the resin microspheres, thereby improving the anticoagulation performance.
Since the shellac can be dissolved in the alkaline aqueous solution, by controlling the conditions, the hydrophobic alkyl group of the shellac can be attached to the surface of the pores of the resin microsphere while exposing the hydrophilic carboxyl group part, enhancing the biocompatibility of the resin microsphere. Meanwhile, heparin salt can also be dissolved in an alkaline aqueous solution, and the resin microspheres can be immobilized on the outer surfaces and the hole surfaces of the resin microspheres while the resin microspheres are subjected to surface modification by the lac, so that the anticoagulant property of the resin microspheres is improved. In the scheme, the surface modification of the holes of the resin microspheres and the immobilization of heparin are carried out simultaneously, a novel method which is simple to prepare is provided, and the problem that the hemoperfusion resin microspheres are coagulated in the clinical use process is solved.
Specifically, the method for modifying and immobilizing heparin on the surface of the hemoperfusion resin microsphere comprises the following steps:
s1, infiltration: soaking the resin microspheres in an ammonia water solution containing shellac and heparin salt, and stirring at room temperature for 0.5-2 hours to allow shellac and heparin salt to permeate into the holes of the resin microspheres;
s2, surface modification: heating and evaporating ammonia water to enable the lac to be self-assembled on the outer surface of the resin microsphere and the surfaces of the holes of the resin microsphere, so that hydrophilic modification is realized and heparin is immobilized;
s3, washing: washed with purified water.
Preferably, in the permeation step, the concentration of the ammonia water solution is 0.05-0.5 mol/L. The concentration of the lac in the ammonia water solution is 0.05-1% (g/mL); the concentration of the heparin salt in the ammonia water solution is 0.1-1 g/L, the heparin salt is selected from heparin sodium, heparin calcium or heparin lithium, and the heparin sodium is more preferable.
Preferably, in the surface modification step, the heating temperature is 50-80 ℃.
Further, the method for modifying and immobilizing heparin on the surface of the hemoperfusion resin microsphere comprises the following steps:
s1, infiltration: soaking the resin microspheres in an ammonia water solution containing 0.05-1% (g/mL) of shellac and 0.1-1 g/L of heparin sodium, wherein the concentration of the ammonia water is 0.05-0.5 mol/L, and stirring at room temperature for 0.5-2 hours to enable the shellac and the heparin sodium to penetrate into the holes of the resin microspheres;
s2, surface modification: heating at 50-80 ℃ to evaporate ammonia water, so that the lac is self-assembled on the outer surface of the resin microsphere and the surface of the hole of the resin microsphere, hydrophilic modification is realized, and heparin is immobilized;
s3, washing: washed with purified water.
Therefore, the scheme also provides the blood perfusion adsorbent prepared by the method.
In order to allow those skilled in the art to better understand the present invention, the following description is provided with reference to specific embodiments. The process methods used in the examples are all conventional methods unless otherwise specified; the materials used, unless otherwise specified, are commercially available.
Wherein the macroporous adsorption resin is purchased from Tianjin Kaishi resin science and technology Limited company, and has the model of: YKDH-19; shellac was purchased from south kyoto biotechnology limited.
Example 1
1.5g of shellac was added to 150mL of an aqueous ammonia solution of 0.5mol/L concentration and dissolved by stirring. 150mg of heparin sodium was further added to prepare 150mL of an aqueous ammonia solution containing 1.0% (g/mL) of shellac and 1g/L of heparin sodium. 100mL of hemoperfusion resin microspheres are added into the solution for soaking, and are slowly stirred for 2 hours, so that the purple gel and the heparin sodium can be favorably diffused into pores of the adsorbent. And then heating to 80 ℃ in a fume hood until the ammonia water solution is completely evaporated to obtain the adsorbent with the surface modified by the lac and the immobilized heparin. And finally, filtering and collecting the adsorbent, washing with purified water, and drying to obtain the finished adsorbent.
Example 2
0.75g of shellac was added to 150mL of an aqueous ammonia solution of 0.2mol/L concentration and dissolved by stirring. 75mg of heparin sodium was further added thereto to prepare 150mL of an aqueous ammonia solution containing 0.5% (g/mL) of shellac and 0.5g/L of heparin sodium. 100mL of hemoperfusion resin microspheres are added into the solution for soaking, and are slowly stirred for 1 hour, so that the purple gel and heparin sodium can be favorably diffused into pores of the adsorbent. And then heating to 80 ℃ in a fume hood until the ammonia water solution is completely evaporated to obtain the adsorbent with the surface modified by the lac and the immobilized heparin. And finally, filtering and collecting the adsorbent, washing with purified water, and drying to obtain the finished adsorbent.
Example 3
0.30g of shellac was added to 150mL of an aqueous ammonia solution of 0.2mol/L concentration and dissolved by stirring. 75mg of heparin sodium is added continuously to prepare 150mL of an ammonia solution containing 0.2% (g/mL) of shellac and 0.5g/L of heparin sodium. 100mL of hemoperfusion resin microspheres are added into the solution for soaking, and are slowly stirred for 1 hour, so that the purple gel and heparin sodium can be favorably diffused into pores of the adsorbent. And then heating to 70 ℃ in a fume hood until the ammonia water solution is completely evaporated to obtain the adsorbent with the surface modified by the lac and the immobilized heparin. And finally, filtering and collecting the adsorbent, washing with purified water, and drying to obtain the finished adsorbent.
Example 4
0.15g of shellac was added to 150mL of an aqueous ammonia solution of 0.2mol/L concentration and dissolved by stirring. 30mg of heparin sodium was further added to prepare 150mL of an aqueous ammonia solution containing 0.1% (g/mL) of shellac and 0.2g/L of heparin sodium. 100mL of hemoperfusion resin microspheres are added into the solution for soaking, and are slowly stirred for 1 hour, so that the purple gel and heparin sodium can be favorably diffused into pores of the adsorbent. And then heating to 70 ℃ in a fume hood until the ammonia water solution is completely evaporated to obtain the adsorbent with the surface modified by the lac and the immobilized heparin. And finally, filtering and collecting the adsorbent, washing with purified water, and drying to obtain the finished adsorbent.
Example 5
0.15g of shellac was added to 150mL of an aqueous ammonia solution of 0.1mol/L concentration and dissolved by stirring. Further, 15mg of heparin sodium was added thereto to prepare 150mL of an aqueous ammonia solution containing 0.1% (g/mL) of shellac and 0.1g/L of heparin sodium. 100mL of hemoperfusion resin microspheres are added into the solution for soaking, and slowly stirred for 0.5h, which is beneficial to the dispersion of the purple gel and the heparin sodium into pores of the adsorbent. And then heating to 80 ℃ in a fume hood until the ammonia water solution is completely evaporated to obtain the adsorbent with the surface modified by the lac and the immobilized heparin. And finally, filtering and collecting the adsorbent, washing with purified water, and drying to obtain the finished adsorbent.
Example 6
0.075g of shellac was added to 150mL of an aqueous ammonia solution of 0.05mol/L and dissolved by stirring. Further, 15mg of heparin sodium was added thereto to prepare 150mL of an aqueous ammonia solution containing 0.05% (g/mL) of shellac and 0.1g/L of heparin sodium. 100mL of hemoperfusion resin microspheres are added into the solution for soaking, and slowly stirred for 0.5h, which is beneficial to the dispersion of the purple gel and the heparin sodium into pores of the adsorbent. And then heating to 50 ℃ in a fume hood until the ammonia water solution is completely evaporated to obtain the adsorbent with the surface modified lac and the immobilized heparin. And finally, filtering and collecting the adsorbent, washing with purified water, and drying to obtain the finished adsorbent.
Comparative example 1
Resin microspheres without any treatment.
Comparative example 2
Resin microspheres (pearl sea Jian Sai products) which are subjected to surface modification treatment by collodion are on the market.
Comparative example 3
Resin microspheres (porch ailer products) are available on the market, which are surface-modified with collodion.
Comparative example 4
Except that the ammonia solution is replaced by Na2CO3The procedure of example 1 was repeated except that the aqueous solution was used.
Example 5
The same procedure as in example 1 was repeated, except that the aqueous ammonia solution was replaced with an aqueous NaOH solution.
The above examples and comparative examples were tested as follows:
1. and (3) testing the adsorption performance: testing the adsorption performance of the resin microsphere sample on sodium pentobarbital, creatinine and VB12 according to an adsorption performance testing method of a standard YY0464-2009 disposable hemoperfusion apparatus;
2. total coagulation test: 1mL of a sample to be tested was added to a glass test tube, rinsed 3 times with physiological saline, and then 2mL of fresh rabbit blood was added along the tube wall. After 5min, the tube was tilted every 1min until the blood in the tube did not flow, and the time at this time was recorded as the clotting time.
The results of the finished performance tests for each example and comparative example are shown in the following table:
| sample (I) | Pentobarbital sodium (%) | Creatinine (%) | VB12(％) | Blood coagulation time (min) |
| Example 1 | 62.1 | 62.5 | 53.2 | 86 |
| Example 2 | 65.2 | 65.4 | 58.2 | 82 |
| Example 3 | 72.8 | 73.2 | 63.2 | 76 |
| Example 4 | 78.9 | 78.4 | 68.6 | 65 |
| Example 5 | 82.1 | 81.4 | 72.2 | 55 |
| Example 6 | 83.4 | 82.2 | 75.1 | 51 |
| Comparative example 1 | 93.8 | 91.2 | 81.4 | 26 |
| Comparative example 2 | 80.1 | 79.6 | 70.2 | 52 |
| Comparative example 3 | 78.2 | 80.1 | 67.5 | 46 |
| Comparative example 4 | 87.1 | 85.5 | 78.6 | 31 |
| Comparative example 5 | 86.8 | 85.8 | 78.5 | 32 |
The data in the above table show that: after the surface modification of the lac, the blood coagulation time is obviously prolonged (compared with the comparative example 1 in each embodiment and comparative examples 2 and 3), and the surface modification of the lac has very important influence on the improvement of the blood compatibility of the resin microspheres. Secondly, compared with the collodion treatment (comparing each example with comparative examples 2 and 3), the method for surface modification of lac and heparin immobilization in the scheme can obviously prolong the blood coagulation time, and the blood coagulation time is prolonged in sequence along with the increase of the content of immobilized heparin. Compared with the collodion treatment (comparing each example with comparative examples 2 and 3), the method for modifying the surface of the lac and immobilizing the heparin in the scheme has the advantages that the clearance rates of sodium pentobarbital, creatinine and VB12 are reduced in sequence with the increase of the content of the lac, but the clearance rates are reduced slightly. Compared with the collodion treatment (comparing examples 5 and 6 with comparative examples 2 and 3), the method for modifying the surface of the lac and immobilizing the heparin in the scheme has the advantages that the clearance rate of sodium pentobarbital, creatinine and VB12 and the blood coagulation time are improved when the content of the lac is lower than that of the comparative example. Compared with the collodion treatment (comparing example 4 with comparative examples 2 and 3), the method for modifying the surface of the lac and immobilizing the heparin in the scheme has the advantages that when the content of the lac is 0.1 percent (g/mL), the clearance rates of sodium pentobarbital, creatinine and VB12 in the examples are equivalent to those of the comparative examples, but the blood coagulation time is greatly improved. Compared with ammonia water (comparative examples 4 and 5 and various examples), the blood coagulation time is obviously reduced and is not obviously improved compared with the original resin microsphere (comparative example 1) by adopting other alkali, which indicates that lac is not modified on the surface of the hole and heparin is not immobilized on the resin microsphere.
In conclusion, the method for modifying the hole surface of the resin microsphere and immobilizing the heparin can obviously prolong the blood coagulation time and improve the anticoagulation performance of the adsorbent, thereby increasing the safety of clinical blood perfusion. Adsorption data and anticoagulation experiments show that after the resin microspheres are treated by the preparation method, the adsorption quantity to creatinine, sodium pentobarbital and VB12 is slightly reduced, the blood coagulation time is prolonged from 20 minutes to 40-120 minutes, and the requirement of clinical perfusion for avoiding blood coagulation is met.
In addition, the heparin salt can be selected from calcium heparin or lithium heparin, in addition to the raw materials used in the above examples.
It should be understood that the above-mentioned embodiments of the present invention are only examples for clearly illustrating the present invention, and are not intended to limit the embodiments of the present invention. Other variations and modifications will be apparent to persons skilled in the art in light of the above description. And are neither required nor exhaustive of all embodiments. Any modification, equivalent replacement, and improvement made within the spirit and principle of the present invention should be included in the protection scope of the claims of the present invention.
Claims (9)
1. A method for modifying and immobilizing heparin on the surface of a hemoperfusion resin microsphere is characterized in that the resin microsphere is soaked in an ammonia water solution containing shellac and heparin salt, and heated and evaporated to enable the shellac to be self-assembled on the outer surface of the resin microsphere and the surface of a hole of the resin microsphere, so that hydrophilic modification and heparin immobilization are realized.
2. The method for modifying and immobilizing heparin on the surface of hemoperfusion resin microspheres according to claim 1, comprising the following steps:
and (3) infiltration: soaking the resin microspheres in an ammonia water solution containing shellac and heparin salt, and stirring at room temperature for 0.5-2 hours to allow shellac and heparin salt to permeate into the holes of the resin microspheres;
surface modification: heating and evaporating ammonia water to enable the lac to be self-assembled on the outer surface of the resin microsphere and the surfaces of the holes of the resin microsphere, so that hydrophilic modification is realized and heparin is immobilized;
washing: washed with purified water.
3. The method for modifying and immobilizing heparin on the surface of hemoperfusion resin microspheres according to claim 1, wherein the concentration of the ammonia water solution in the permeation step is 0.05-0.5 mol/L.
4. The method for modifying and immobilizing heparin on the surface of hemoperfusion resin microspheres according to claim 1, wherein the concentration of the lac in the ammonia water solution in the permeation step is 0.05-1% (g/mL).
5. The method for modifying and immobilizing heparin on the surface of hemoperfusion resin microspheres according to claim 1, wherein the concentration of the heparin salt in the ammonia water solution in the permeation step is 0.1-1 g/L.
6. The method according to claim 1, wherein the heparin salt is heparin sodium, heparin calcium or heparin lithium in the step of infiltration.
7. The method for surface modification and heparin immobilization on hemoperfusion resin microspheres according to claim 6, wherein in the step of infiltration, the heparin salt is heparin sodium.
8. The method for surface modification and heparin immobilization on hemoperfusion resin microspheres according to claim 1, wherein the heating temperature in the surface modification step is 50-80 ℃.
9. A hemoperfusion sorbent prepared by the method of any one of claims 1 to 8.
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