WO2024245021A1 - Amino-containing polymer, and preparation method therefor and use thereof - Google Patents

Abstract

The present invention relates to the field of blood-contacting medical device coatings, and in particular, to an amino-containing polymer, and a preparation method therefor and the use thereof. The amino-containing polymer is an amino-containing ternary random polymer. The structural formula of the amino-containing polymer is (I), wherein the ratio of m/n/k is 7:1:2; a is 2, 4 or 5, and b is 3, 4 or 5. The weight average molecular weight of the amino-containing polymer is 4000-9000 Da. The polymer has good reaction activity, platelet adhesion resistance, platelet activation resistance and fibrinogen adhesion resistance at the same time, and can be chemically fixed on the surface of a medical device efficiently, to exert an anticoagulant advantage.

Description

A kind of polymer containing amino group and its preparation method and application Technical Field

The invention relates to the field of blood contact medical device coatings, and in particular to an amino group-containing polymer and a preparation method and application thereof.

Background Art

Blood-contact medical devices have been widely used in clinical practice, including intravenous catheters, implantable coronary stents, intracranial blood flow guidance devices, artificial heart valves or ventricular assist devices, hemodialysis and extracorporeal circulation devices, membrane oxygenators and other in vivo and in vitro devices. When using such medical devices, in order to prevent thrombosis and avoid complications that lead to the failure of the above-mentioned medical devices, it is usually necessary to improve the blood compatibility of the materials used to prepare such medical devices. Blood compatibility mainly refers to the phenomenon that when biomaterials come into contact with blood, they will not cause coagulation and platelet adhesion and aggregation, and will not destroy the existing components in the blood. A large number of studies have pointed out that natural cell membranes can effectively resist the adhesion and activation of blood proteins and platelets with their special phospholipid structure, thereby showing excellent anti-thrombotic properties. Therefore, constructing a polymer that mimics the structure of natural cell membranes so that it has both anti-thrombotic properties and reactivity can be widely used in the surface modification of blood-contact medical devices.

The prior art (CN112316218B) discloses a zwitterionic polymer and heparin composite coating, a preparation method and an application thereof. The reactive functional group of the zwitterionic polymer protected by the patent is a carboxyl group. Since the reactivity of the carboxyl group is not high, when the zwitterionic polymer is introduced into the surface of a medical device, it is usually necessary to add an additional catalyst or activator, which increases the modification cost. In addition, the small molecule catalyst or activator is not easy to completely remove and has potential biological toxicity.

The prior art (CN103596996B) discloses a method for preparing a polymer, which prepares an amino-containing phosphorylcholine polymer by reacting an epoxy-containing phosphorylcholine polymer with a small molecule 2-aminoethanethiol (AET). It is worth noting that the epoxy group can not only react with the sulfhydryl group, but also has a relatively high reactivity with the amino group. This preparation method inevitably has side reactions, resulting in the amino content in the polymer not meeting expectations.

Prior art (CN109796616B) discloses a biomimetic polymer and a method and application for making a durable dual biomimetic polymer coating. The ternary polymer structure provided by the patent contains zwitterionic groups, amino reactive groups and quaternary ammonium cationic groups at the same time. However, monomers containing amino reactive groups have high activity and can undergo Michael addition reactions with other monomers containing double bonds. The patent does not protect the amino group, which is likely to lead to a lack of sufficient amino reactive groups in the prepared ternary polymer. At the same time, the patent lacks data for qualitatively characterizing the amino groups in the ternary polymer, which limits its application.

Summary of the invention

Therefore, in order to solve the above problems, the present application provides a novel amino-containing polymer and a preparation method thereof, and applies the polymer to the field of blood-contact medical devices.

In order to solve the above problems, the first aspect of the present invention provides an amino group-containing polymer, wherein the amino group-containing polymer is an amino group-containing ternary random polymer; the amino group-containing polymer has the structural formula:

Wherein, the ratio of m/n/k is 7:1:2; a is 2, 4 or 5, and b is 3, 4 or 5;

The weight average molecular weight of the amino group-containing polymer is 4000-90000 Da.

Furthermore, the amino-containing polymer is obtained by random copolymerization of 2-methacryloyloxyethyl phosphorylcholine, an acrylate monomer of amino hydrochloride and an acrylamide monomer of amino hydrochloride; wherein the acrylate monomer of amino hydrochloride is at least one of 2-aminoethyl methacrylate hydrochloride, 2-aminobutyl methacrylate hydrochloride, and 2-aminopentyl methacrylate hydrochloride; and the acrylamide monomer of amino hydrochloride is at least one of N-(3-aminopropyl)methacrylamide hydrochloride, N-(4-aminobutyl)methacrylamide hydrochloride, and N-(5-aminopentyl)methacrylamide hydrochloride.

In the present application, the anticoagulant performance of the product is effectively improved by selecting the above three monomers for mixing. The specific ratio of 2-aminoethyl methacrylate hydrochloride and N-(3-aminopropyl) methacrylamide hydrochloride reflects more reactive groups, improves the reaction efficiency of the polymer and increases the probability of free radical reaction.

In addition, 2-methacryloyloxyethyl phosphorylcholine has good anticoagulant properties (platelet adhesion and fibrinogen adsorption). On the one hand, the surface containing phosphorylcholine (PC) end groups is inert to blood cells and does not It can adsorb and activate platelets, and will not cause hemolysis of red blood cells; on the other hand, because the PC end groups carry equal amounts of positive and negative charges, they can form very strong hydration with water molecules, weakening the interaction with proteins. The adsorption of proteins is basically reversible, so the adsorbed proteins can maintain their natural conformation. In this application, the substrate grafted with amino-containing PC polymers has a significantly better anticoagulant effect. There is no necessary and significant correlation between platelet adhesion rate and protein adsorption rate and polymer molecular weight and amino content. Its anti-adhesion effect is mainly determined by the enrichment and uniformity of PC end groups successfully grafted to the surface of the substrate.

The second aspect of the present invention provides a method for preparing the above-mentioned amino-containing polymer, comprising the following steps: (1) dissolving 2-methacryloyloxyethyl phosphorylcholine, an acrylate monomer of amino hydrochloride, and an acrylamide monomer of amino hydrochloride in a reaction solvent to obtain a monomer mixture; (2) mixing an initiator into the reaction solvent in proportion to obtain an initiator solution; (3) mixing the monomer mixture obtained in step (1) and the initiator solution obtained in step (2) in proportion, adjusting the pH value of the solution to 1 to 6 with an acid solution, then removing water and oxygen, controlling the temperature under inert gas protection for a reaction of 6 to 72 hours, and purifying to obtain the amino-containing polymer;

The acrylate monomer of the amino hydrochloride is at least one of 2-aminoethyl methacrylate hydrochloride, 2-aminobutyl methacrylate hydrochloride, and 2-aminopentyl methacrylate hydrochloride; the acrylamide monomer of the amino hydrochloride is at least one of N-(3-aminopropyl) methacrylamide hydrochloride, N-(4-aminobutyl) methacrylamide hydrochloride, and N-(5-aminopentyl) methacrylamide hydrochloride;

In the step (1), the molar ratio of 2-methacryloyloxyethyl phosphorylcholine, the acrylate monomer of amino hydrochloride and the acrylamide monomer of amino hydrochloride is 7:1:2.

As a preferred solution, the reaction temperature in step (3) is 30°C to 100°C.

As a further preferred embodiment, the reaction temperature in step (3) is 45°C to 60°C.

Among them, by designing the molar ratio of the three monomers in the polymer reaction process, and by regulating the reaction temperature and pH value, it is possible to further control the molecular weight of the polymer within a suitable range, while further ensuring that the reaction has a higher polymer yield and significantly reducing the generation of side reactions. The applicant found in the actual reaction research process that in the ternary random copolymerization reaction, the ratio of the three monomers, the regulation of the pH value and the setting of the reaction temperature can effectively control the overall reaction process. If the ratio of the three monomers, the pH value and the reaction temperature are not suitable, it is easy to cause the polymerization reaction to fail or the resulting polymer to have a poor anticoagulant effect. Therefore, the ratio of the three monomers, the pH value and the reaction temperature play an important role in achieving the expected anticoagulant effect for the polymer of the present application. For the ternary random copolymerization reaction, the ratio of the monomers, the pH value and the reaction temperature are also important reaction conditions, thereby obtaining a preferred anticoagulant material.

As a preferred solution, the acrylic acid ester monomer of the amino hydrochloride is 2-aminoethyl methacrylate hydrochloride.

As a preferred solution, the acrylamide monomer of the amino hydrochloride is N-(3-aminopropyl)methacrylamide Amine hydrochloride.

As a preferred solution, the reaction solvent is at least one of water, methanol, ethanol, isopropanol, dimethyl sulfoxide, ethyl acetate, N,N-dimethylformamide, and tetrahydrofuran.

As a preferred solution, the reaction solvent is at least one of water, methanol, ethanol and isopropanol.

As a preferred solution, the initiator is peroxide and/or azo.

As a preferred embodiment, the initiator is at least one of azobisisobutyronitrile, azobiscyanovaleric acid, azobisisoheptylnitrile, azoisobutylcyanoformamide, azobisisobutylamidine hydrochloride, dimethyl azobisisobutyrate, benzoyl peroxide, ammonium persulfate, potassium persulfate, tert-butyl benzoyl peroxide and 2-methyl ethyl peroxide.

As a preferred solution, the acid solution is at least one of phosphoric acid, sulfuric acid, carbonic acid, hydrochloric acid, lactic acid, citric acid, and benzoic acid solutions of the corresponding reaction solvents.

As a preferred solution, the mass ratio of the initiator to the acrylic acid ester monomer of amino hydrochloride is 0.05-10:90-99.5.

As a preferred solution, the mass ratio of the initiator to the acrylic acid ester monomer of amino hydrochloride is 1:99.

As a preferred solution, the mass ratio of the monomer mixture to the initiator solution is 65-99:1-35.

As a preferred solution, the mass ratio of the monomer mixture to the initiator solution is 70:30.

As a preferred solution, the mass ratio of the total amount of monomers to the reaction solvent is 10:60.

In the present application, the change in molecular weight is determined by the selection and addition amount of the reaction monomer and initiator, and the range of molecular weight change is also within the controllable range of free radical polymerization of compounds such as 2-methacryloyloxyethyl phosphorylcholine. In the exploration of the technical solution, the applicant found that when the 2-methacryloyloxyethyl phosphorylcholine monomer is polymerized with the amino-containing acrylate monomer, the 2-methacryloyloxyethyl phosphorylcholine also uses its own active group (double bond) to synthesize a homopolymer, such as poly-2-methacryloyloxyethyl phosphorylcholine, so in some embodiments, the increase in polymer molecular weight does not result in a significant increase in amino content. The purpose of designing amino groups in the compound is actually to promote the grafting rate of PC and the substrate and improve the grafting effect. Although it is generally believed that the higher the amino content, the easier it is for PC to be grafted onto the substrate, relevant experiments have shown that PC will reach "grafting saturation" after a certain amount of grafting on the substrate, and simply increasing the amino group content of the polymer is not enough to increase its grafting rate. Therefore, in some embodiments, even if the molecular weight is not very high (4000-7000Da), the amino-containing polymer can be uniformly grafted to the substrate surface and have a good anticoagulant effect; but if the substrate surface cannot be grafted with more amino-containing polymers, a certain space occupancy effect will occur, and the surface grafting and anticoagulation will also have poor results. The technical solution of the present application can achieve a wider range of molecular weight selection, and to a greater extent meet the use requirements of characteristic polymers in the medical field.

The third aspect of the present invention provides an application of the above-mentioned amino group-containing polymer, which is application of the amino group-containing polymer in surface coatings for blood-contact medical devices.

Beneficial effects:

1. The present application provides an amino-containing polymer, which can realize the selective design of the molecular weight of the polymer, and effectively improves the application effect of the polymer in the field of blood-contact medical devices. The ternary random polymer obtained by copolymerizing 2-methacryloyloxyethyl phosphorylcholine, acrylate monomer of amino hydrochloride and acrylamide monomer of amino hydrochloride with appropriate proportions can form a good branched structure, and its advantages are reflected in two aspects: on the one hand, the ternary random polymer can adjust the number of reactive groups to ensure good reaction sites and corresponding branching spaces; on the other hand, since the ternary random polymer contains sufficient reactive sites, in addition to being fixed on the surface of medical devices, it can also be further grafted with anticoagulant drugs, endothelial cell-targeting peptides and fluorescent dyes, thereby obtaining a variety of biological activities.

2. The present application provides a method for preparing an amino-containing ternary random polymer, which is obtained by copolymerizing 2-methacryloyloxyethyl phosphorylcholine, an acrylate monomer of amino hydrochloride, and an acrylamide monomer of amino hydrochloride; this structure has both good chemical reactivity and anticoagulant properties, and can be chemically fixed on the surface of medical devices to increase their anticoagulant properties; the preparation method can effectively improve the plasticity and anticoagulant properties of the polymer by regulating the process during the polymer preparation process.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a graph showing the NMR data of the polymer prepared in Example 1 of the present application.

FIG. 2 is a data graph showing the molecular weight test results of the polymer prepared in Example 1 of the present application.

FIG. 3 is a data graph showing the molecular weight test results of the polymer prepared in Comparative Example 1 of the present application.

FIG. 4 is a data graph showing the molecular weight test results of the polymer prepared in Comparative Example 2 of the present application.

FIG. 5 is a data graph showing the molecular weight test results of the polymer prepared in Comparative Example 3 of the present application.

FIG6 is a data graph showing the results of quantitative fluorescence testing of the amino group of the polymer prepared in Example 1 of the present application.

FIG. 7 is a graph showing the test results of the anti-platelet adhesion of the polymer prepared in Example 1 of the present application.

FIG8 is a graph showing the NMR data of the polymer prepared in Comparative Example 4 of the present application.

DETAILED DESCRIPTION

Example 1

The first aspect of the present embodiment provides a method for preparing the above-mentioned amino-containing polymer, comprising the following steps: (1) dissolving three monomers, namely 2-methacryloyloxyethyl phosphorylcholine, 2-aminoethyl methacrylate hydrochloride (acrylic ester monomer of amino hydrochloride) and N-(3-aminopropyl) methacrylamide hydrochloride (acrylamide monomer of amino hydrochloride) in a reaction solvent to obtain a monomer mixture; (2) mixing an initiator into the reaction solvent in proportion to obtain an initiator solution; (3) mixing the monomer mixture obtained in step (1) and the initiator solution obtained in step (2) in proportion, adjusting the pH value of the solution to 3.5 with an acid solution, then removing water and oxygen, controlling the temperature under the protection of an inert gas for a reaction for 24 hours, and purifying the obtained product.

The reaction temperature in step (3) is 55°C.

The reaction solvent is methanol; the initiator is dimethyl azobisisobutyrate; and the acid solution is a methanol solution of phosphoric acid.

In step (1), the molar ratio of 2-methacryloyloxyethyl phosphorylcholine, 2-aminoethyl methacrylate hydrochloride and N-(3-aminopropyl)methacrylamide hydrochloride is 7:1:2.

The mass ratio of the total amount of monomers to the reaction solvent in step (1) is 10:60.

In step (3), the mass ratio of the initiator to the amino hydrochloride acrylate monomer is 1:99.

In step (3), the mass ratio of the monomer mixture to the initiator solution is 70:30.

The reaction yield was 89%.

The second aspect of this embodiment provides a method for preparing an amino-containing terpolymer, and the obtained polymer has the structural formula:

Among them, the ratio of m/n/k is 7:1:2.

The peak molecular weight Mp of the polymer is 82615 Da, and the weight average molecular weight Mw is 78561 Da.

Example 2

The polymer prepared in Example 1 was coated on the surface of blood-contact medical devices, and the anti-protein and anti-platelet adhesion experiments were performed to evaluate the results. The results showed that the polymer could improve the anti-protein adhesion and anti-platelet adhesion of the surface of blood-contact medical devices and improve blood compatibility.

Comparative Example 1

The specific implementation of Comparative Example 1 is the same as that of Example 1, except that the three monomers are 2-methacryloyl Oxyethyl phosphorylcholine, 2-aminoethyl methacrylate hydrochloride (acrylic ester monomer of amino hydrochloride) and N-(4-aminobutyl) methacrylamide hydrochloride (acrylamide monomer of amino hydrochloride), the molar ratio of the three monomers is 8:3:3, the reaction temperature in step (3) is 45°C, the pH value is adjusted to 5 with acid solution, the reaction solvent is water, the initiator is azobiscyanovaleric acid, the acid solution is an aqueous solution of carbonic acid, and the reaction yield is 76%.

The structural formula of the obtained polymer is:

Among them, the ratio of m/n/k is 8:3:3.

The peak molecular weight Mp of the obtained polymer was 9370 Da, and the weight average molecular weight Mw was 11259 Da.

Comparative Example 2

The specific implementation of Comparative Example 2 is the same as that of Example 1, except that: the three monomers are 2-methacryloyloxyethyl phosphorylcholine, 2-aminoethyl methacrylate hydrochloride (acrylic ester monomer of amino hydrochloride) and N-(5-aminopentyl) methacrylamide hydrochloride (acrylamide monomer of amino hydrochloride), and the molar ratio thereof is 8:1:1. The reaction temperature in step (3) is 60°C, the pH value is adjusted to 6 with acid solution, the reaction solvent is isopropanol, the initiator is azobisisobutyronitrile, and the reaction yield is 65%.

The structural formula of the obtained polymer is:

Among them, the ratio of m/n/k is 8:1:1.

The peak molecular weight Mp of the obtained polymer was 4302 Da, and the weight average molecular weight Mw was 5442 Da.

Comparative Example 3

The specific implementation of Comparative Example 3 is the same as that of Example 1, except that: the three monomers are 2-methacryloyloxyethyl phosphorylcholine, 2-aminoethyl methacrylate hydrochloride (acrylic ester monomer of amino hydrochloride) and N-(4-aminobutyl) methacrylamide hydrochloride (acrylamide monomer of amino hydrochloride), and the molar ratio thereof is 4:3:3. The reaction temperature in step (3) is 50° C., the pH value is adjusted to 4.5 with acid solution, the reaction solvent is water, the initiator is azobisisobutyramidine hydrochloride, and the reaction yield is 43%.

Among them, the ratio of m/n/k is 4:3:3.

The peak molecular weight Mp of the obtained polymer was 7073 Da, and the weight average molecular weight Mw was 7808 Da.

Comparative Example 4

Comparative Example 4 The first aspect provides a method for preparing the above-mentioned amino-containing polymer, comprising the following steps: (1) dissolving 2-methacryloyloxyethyl phosphorylcholine and 2-aminoethyl methacrylate hydrochloride monomer (acrylic ester monomer of amino hydrochloride) in a reaction solvent to obtain a monomer mixture; (2) mixing an initiator into the reaction solvent in proportion to obtain an initiator solution; (3) mixing the monomer mixture and the initiator solution in proportion, adjusting the pH to 3.5 with acid solution, then removing water and oxygen, controlling the temperature under inert gas protection for 24 hours, and purifying to obtain the obtained product.

The reaction temperature in step (3) is 55°C.

The reaction solvent is methanol; the initiator is dimethyl azobisisobutyrate; and the acid solution is a methanol solution of phosphoric acid.

In step (1), the molar ratio of 2-methacryloyloxyethyl phosphorylcholine to 2-aminoethyl methacrylate hydrochloride is 8:2.

The mass ratio of the total amount of monomers to the reaction solvent in step (1) is 10:60.

In step (3), the mass ratio of the initiator to the amino hydrochloride acrylate monomer is 1:99.

The mass ratio of the monomer mixture to the initiator solution in step (3) is 50:1.

The reaction yield was 81%.

The second aspect of this comparative example provides a method for preparing an amino-containing binary polymer, and the structural formula of the obtained polymer is:

Among them, the ratio of m/n is 8:2.

The weight average molecular weight Mw of the obtained polymer was 5042 Da.

Comparative Example 5

The specific implementation of Comparative Example 5 is the same as that of Comparative Example 4, except that the reaction temperature in step (3) is 80° C., and the pH is adjusted to 6 with acid solution.

The weight average molecular weight Mw of the obtained polymer was 5017 Da.

Comparative Example 6

The specific implementation of Comparative Example 6 is the same as that of Comparative Example 4, except that the molar ratio of 2-methacryloyloxyethyl phosphorylcholine to 2-aminoethyl methacrylate hydrochloride is 1:1.

The general structural formula of the obtained polymer is the same as that of Comparative Example 4, wherein the ratio of m/n is 1:1.

The weight average molecular weight Mw of the obtained polymer was 9563 Da.

Comparative Example 7

The specific implementation of Comparative Example 7 is the same as that of Comparative Example 4, except that the mass ratio of the initiator to the amino hydrochloride acrylate monomer is 5:95.

The weight average molecular weight Mw of the obtained polymer was 40000 Da.

Performance Testing

1. The results of NMR, molecular weight, amino qualitative and anti-platelet adhesion tests on the polymer prepared in Example 1 and NMR test on the polymer prepared in Comparative Example 4 are recorded in Figures 1, 2, 6, 7 and 8, respectively. NMR test: Bruker 400M H-NMR was used.

2. The molecular weights of Comparative Example 1, Comparative Example 2 and Comparative Example 3 were measured and the results are recorded in Figures 3 to 5 respectively; the molecular weight test was conducted by GPC gel permeation chromatography.

3.Amino content, platelet adhesion, platelet activation, and fibrinogen adsorption rate tests:

Amino qualitative test: First, prepare a 3 mg/mL fluorescent amine acetone solution and refrigerate it in the dark for later use. Then, accurately weigh the polymer of Example 1 and dissolve it in phosphate buffer solution (PBS) to prepare a 1.mg/mL polymer solution. Accurately pipette 1 mL of this polymer solution, add 3 mL of fluorescent amine acetone solution, mix and shake well, react at room temperature in the dark for 10 minutes, and finally observe whether fluorescence is generated under the excitation of excitation light with a wavelength of 380 nm.

Amino group quantitative test: First, prepare a 3 mg/mL fluorescent amine acetone solution, and keep it away from light and refrigerate for use. Subsequently, accurately weigh glycine and dissolve it in phosphate buffered saline (PBS) to prepare a 1 mg/mL glycine solution. Accurately pipette 1 mL of glycine solution, add it to 3 mL of fluorescent amine acetone solution, mix and shake well as the fluorescent amine-glycine reaction derivative mother solution. Subsequently, dilute the mother solution with PBS into a series of solutions with a concentration range of 0.1-3 nmol/mL, and then measure the fluorescence intensity of the series of solutions at an excitation wavelength of 380 nm to obtain a standard curve of amino group concentration and fluorescence intensity in glycine. Test the amino content of different embodiments and comparative examples according to the standard curve.

Quantitative test of platelet adhesion rate: First, the amino-containing polymer prepared in this application is fixed on the surface of the titanium sheet, and then the platelet-rich plasma (PRP) solution is added. After incubation at 37°C for 2 hours, the PRP is removed. Antibodies and developer for activating platelets are added according to the requirements of the kit (lactate dehydrogenase (LDH) activity detection kit, Solarbio/Solaibao), and the absorbance value at a wavelength of 450nm is measured using an ELISA instrument. The platelet adhesion rates of different embodiments and comparative examples are tested and calculated according to the standard curve.

Quantitative test of platelet activation rate: First, the amino-containing polymer prepared in this application is fixed on the surface of the titanium sheet, and then a platelet-rich plasma (PRP) solution is added. After incubation at 37°C for 2 hours, the PRP is removed, and the platelet-activating antibody and developer are added according to the requirements of the kit (β-TG ELISA kit, mlbio/enzyme-linked biology), and the absorbance value at the wavelength given by the kit is measured using an enzyme marker. The platelet activation rates of different embodiments and comparative examples are tested and calculated according to the standard curve.

Fibrinogen (Fg) adsorption quantitative test: First, the amino-containing polymer prepared in this application is fixed on the surface of the titanium sheet, and then the Fg solution is added. After incubation at 37°C for 2 hours, the Fg is removed. According to the requirements of the kit (BCA protein quantitative kit, Cwbio/Kangwei Century), the Fg antibody and developer are added, and the absorbance value at a wavelength of 562nm is measured using an ELISA instrument. The fibrinogen adsorption rate of different embodiments and comparative examples is tested and calculated according to the standard curve.

The “/” in Table 1 indicates that no relevant tests were conducted. In Table 1, the platelet adhesion rate (%) data is preferentially compared. The amino content is a routine test item for the product and does not directly indicate the final application performance of the product.

Table 1

Through the examples, comparative examples and Table 1, it can be seen that the amino-containing ternary random polymer prepared by the preparation method provided by the present invention, the structural polymer prepared in Example 1 has good reactivity, anti-platelet adhesion, anti-platelet activation and anti-fibrinogen adhesion capabilities. It is conducive to stable and efficient chemical fixation on the surface of medical devices, and exerts anticoagulant advantages. At the same time, due to its unique group structure, it can effectively graft anticoagulant drugs, target endothelial cell polypeptides and fluorescent dyes, thereby obtaining a variety of biological activities, and is suitable for promotion in the field of medical devices.

Claims (11)

An amino group-containing polymer, characterized in that: the amino group-containing polymer is an amino group-containing ternary random polymer; The structural formula of the amino-containing polymer is:
Wherein, the ratio of m/n/k is 7:1:2; a is 2, 4 or 5, and b is 3, 4 or 5; The weight average molecular weight of the amino group-containing polymer is 4000-90000 Da. The amino-containing polymer according to claim 1, characterized in that: the amino-containing polymer is obtained by random copolymerization of 2-methacryloyloxyethyl phosphorylcholine, an acrylate monomer of amino hydrochloride and an acrylamide monomer of amino hydrochloride; wherein the acrylate monomer of amino hydrochloride is at least one of 2-aminoethyl methacrylate hydrochloride, 2-aminobutyl methacrylate hydrochloride, and 2-aminopentyl methacrylate hydrochloride; and the acrylamide monomer of amino hydrochloride is at least one of N-(3-aminopropyl) methacrylamide hydrochloride, N-(4-aminobutyl) methacrylamide hydrochloride, and N-(5-aminopentyl) methacrylamide hydrochloride. A method for preparing an amino group-containing polymer, characterized in that it comprises the following steps: (1) dissolving 2-methacryloyloxyethyl phosphorylcholine, an acrylate monomer of amino hydrochloride, and an acrylamide monomer of amino hydrochloride in a reaction solvent to obtain a monomer mixture; (2) mixing an initiator into the reaction solvent in proportion to obtain an initiator solution; (3) mixing the monomer mixture obtained in step (1) and the initiator solution obtained in step (2) in proportion, adjusting the pH value of the solution to 1-6 with an acid solution, then removing water and oxygen, controlling the temperature under inert gas protection for a reaction of 6-72 hours, and purifying to obtain an amino group-containing polymer; The acrylate monomer of the amino hydrochloride is at least one of 2-aminoethyl methacrylate hydrochloride, 2-aminobutyl methacrylate hydrochloride, and 2-aminopentyl methacrylate hydrochloride; the acrylamide monomer of the amino hydrochloride is at least one of N-(3-aminopropyl) methacrylamide hydrochloride, N-(4-aminobutyl) methacrylamide hydrochloride, and N-(5-aminopentyl) methacrylamide hydrochloride; In the step (1), the molar ratio of 2-methacryloyloxyethyl phosphorylcholine, the acrylate monomer of amino hydrochloride and the acrylamide monomer of amino hydrochloride is 7:1:2. The method for preparing an amino-containing polymer according to claim 3, characterized in that the reaction temperature in step (3) is 30 to 100°C. The method for preparing an amino-containing polymer according to claim 3, characterized in that the mass ratio of the initiator to the amino hydrochloride acrylate monomer in step (3) is 0.05-10:90-99.5. The method for preparing an amino-containing polymer according to claim 3, characterized in that the mass ratio of the monomer mixture to the initiator solution in step (3) is 65-99:1-35. The method for preparing an amino-containing polymer according to claim 3, characterized in that the reaction solvent in step (1) and the reaction solvent in step (2) are each independently selected from at least one of water, methanol, ethanol, isopropanol, dimethyl sulfoxide, ethyl acetate, N,N-dimethylformamide, and tetrahydrofuran. The method for preparing an amino-containing polymer according to claim 3, wherein the initiator is a peroxide and/or an azo initiator. The method for preparing an amino-containing polymer according to claim 3, characterized in that the acid solution is at least one of phosphoric acid, sulfuric acid, carbonic acid, hydrochloric acid, lactic acid, citric acid, and benzoic acid solutions of the corresponding reaction solvents. A method for preparing an amino group-containing polymer, characterized in that it comprises the following steps: (1) dissolving 2-methacryloyloxyethyl phosphorylcholine, an acrylate monomer of amino hydrochloride, and an acrylamide monomer of amino hydrochloride in a reaction solvent to obtain a monomer mixture; (2) mixing an initiator into the reaction solvent in proportion to obtain an initiator solution; (3) mixing the monomer mixture obtained in step (1) and the initiator solution obtained in step (2) in proportion, adjusting the pH value of the solution to 1-6 with an acid solution, then removing water and oxygen, controlling the temperature under inert gas protection for a reaction of 6-72 hours, and purifying to obtain an amino group-containing polymer; The reaction temperature in step (3) is 30-100°C; In the step (1), the mass ratio of the total amount of monomers to the reaction solvent is 10:60; In the step (3), the mass ratio of the initiator to the acrylic acid ester monomer of amino hydrochloride is 0.05-10:90-99.5; In the step (3), the mass ratio of the monomer mixture to the initiator solution is 65-99:1-35; The acrylic acid ester monomer of the amino hydrochloride is at least one of 2-aminoethyl methacrylate hydrochloride, 2-aminobutyl methacrylate hydrochloride, and 2-aminopentyl methacrylate hydrochloride; The amine monomer is at least one of N-(3-aminopropyl)methacrylamide hydrochloride, N-(4-aminobutyl)methacrylamide hydrochloride, and N-(5-aminopentyl)methacrylamide hydrochloride; In the step (1), the molar ratio of 2-methacryloyloxyethyl phosphorylcholine, the acrylate monomer of amino hydrochloride and the acrylamide monomer of amino hydrochloride is 7:1:2. An application of the amino-containing polymer according to claim 1 or 2, characterized in that the amino-containing polymer is used in surface coatings for blood-contact medical devices.