Amino-containing polymer, and preparation method therefor and use thereof

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

[0001] The present invention relates to the field of blood-contact medical device coatings, and in particular to an amino-containing polymer and a preparation method and application thereof. Background Art

[0002] Blood-contacting medical devices are widely used clinically, including intravenous catheters, implantable coronary stents, intracranial blood flow redirecting devices, artificial heart valves or ventricular assist devices, hemodialysis and extracorporeal circulation devices, membrane oxygenators, and other in vitro and in vivo devices. To prevent thrombosis and complications that could lead to device failure, the hemocompatibility of the materials used to make these devices is often improved. Hemocompatibility primarily refers to the ability of a biomaterial to resist coagulation and platelet adhesion and aggregation upon contact with blood, thereby destroying existing blood components. Numerous studies have shown that natural cell membranes, due to their unique phospholipid structure, effectively resist the adhesion and activation of blood proteins and platelets, thereby exhibiting excellent antithrombotic properties. Therefore, the construction of a polymer that mimics the structure of natural cell membranes, imparting both antithrombotic properties and reactivity, could be widely used in the surface modification of blood-contacting medical devices.

[0003] Prior art (CN112316218B) discloses a zwitterionic polymer and heparin composite coating, a preparation method, and its application. The reactive functional group of the zwitterionic polymer protected by this patent is a carboxyl group. Due to the low reactivity of the carboxyl group, when introducing the zwitterionic polymer onto 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.

[0004] Prior art (CN103596996B) discloses a method for preparing a polymer. This patent describes a method for preparing an amino-containing phosphorylcholine polymer by reacting an epoxy-containing phosphorylcholine polymer with the small molecule 2-aminoethanethiol (AET). It is noteworthy that epoxy groups not only react with sulfhydryl groups but also have a high reactivity with amino groups. This preparation method inevitably involves side reactions, resulting in the amino group content in the polymer not meeting expectations.

[0005] Prior art (CN109796616B) discloses a biomimetic polymer and a method and application for producing a durable dual-bionic polymer coating. The patent provides a ternary polymer structure that simultaneously contains zwitterionic groups, amino-reactive groups, and quaternary ammonium cationic groups. However, monomers containing amino-reactive groups are highly reactive and can undergo Michael addition reactions with other monomers containing double bonds. However, the patent does not protect the amino groups, which may result in a lack of sufficient amino-reactive groups in the prepared ternary polymer. Furthermore, the patent lacks data to qualitatively characterize the amino groups in the ternary polymer, limiting its application.

[0006] Summary of the Invention

[0007] 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.

[0008] 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:

[0009] Wherein, the ratio of m / n / k is 7:1:2; a is 2, 4 or 5, and b is 3, 4 or 5;

[0010] The weight average molecular weight of the amino group-containing polymer is 4,000 to 90,000 Da.

[0011] 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.

[0012] In this application, the anticoagulant properties of the product are effectively enhanced by selecting a blend of the three monomers mentioned above. The specific ratio of 2-aminoethyl methacrylate hydrochloride and N-(3-aminopropyl) methacrylamide hydrochloride exhibits more reactive groups, improving the reaction efficiency of the polymer and increasing the probability of free radical reactions.

[0013] 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 will not adsorb and activate platelets, nor 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 reactions 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 the platelet adhesion rate and protein adsorption rate and the polymer molecular weight and amino content. Its anti-adhesion effect is mainly determined by the enrichment and uniformity of the PC end groups successfully grafted to the substrate surface.

[0014] 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 1-6 with an acid solution, then removing water and oxygen, controlling the temperature under inert gas protection for 6-72 hours, and purifying to obtain the amino-containing polymer;

[0015] 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;

[0016] In the step (1), the molar ratio of 2-methacryloyloxyethyl phosphorylcholine, the acrylic acid ester monomer of amino hydrochloride and the acrylamide monomer of amino hydrochloride is 7:1:2.

[0017] As a preferred solution, the reaction temperature in step (3) is 30°C to 100°C.

[0018] As a further preferred embodiment, the reaction temperature in step (3) is 45°C to 60°C.

[0019] Among them, by designing the molar ratio of the three monomers in the polymerization 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 reduces 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.

[0020] As a preferred solution, the acrylic acid ester monomer of the amino hydrochloride is 2-aminoethyl methacrylate hydrochloride.

[0021] As a preferred solution, the acrylamide monomer of the amino hydrochloride is N-(3-aminopropyl)methacrylamide hydrochloride.

[0022] 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.

[0023] As a preferred solution, the reaction solvent is at least one of water, methanol, ethanol, and isopropanol.

[0024] As a preferred solution, the initiator is a peroxide and / or an azo initiator.

[0025] As a preferred embodiment, the initiator is at least one of azobisisobutyronitrile, azobiscyanovaleric acid, azobisisoheptanenitrile, azoisobutylcyanamide, azobisisobutylamidine hydrochloride, dimethyl azobisisobutyrate, benzoyl peroxide, ammonium persulfate, potassium persulfate, tert-butyl benzoyl peroxide and 2-butanone peroxide.

[0026] 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.

[0027] As a preferred solution, the mass ratio of the initiator to the amino hydrochloride acrylate monomer is 0.05-10:90-99.5.

[0028] As a preferred solution, the mass ratio of the initiator to the amino hydrochloride acrylate monomer is 1:99.

[0029] As a preferred solution, the mass ratio of the monomer mixture to the initiator solution is 65-99:1-35.

[0030] As a preferred solution, the mass ratio of the monomer mixture to the initiator solution is 70:30.

[0031] As a preferred solution, the mass ratio of the total amount of monomers to the reaction solvent is 10:60.

[0032] In this application, the change in molecular weight is determined by the selection and addition amount of the reactive monomers and initiators, and the range of molecular weight variation is also within the controllable range of free radical polymerization of compounds such as 2-methacryloyloxyethyl phosphorylcholine. During the exploration of the technical solution, the applicant discovered that when the 2-methacryloyloxyethyl phosphorylcholine monomer is polymerized with an amino-containing acrylate monomer, the 2-methacryloyloxyethyl phosphorylcholine also utilizes its own active groups (double bonds) to synthesize homopolymers, such as poly-2-methacryloyloxyethyl phosphorylcholine. Therefore, in some examples, the increase in polymer molecular weight does not result in a significant increase in amino group content. The purpose of designing amino groups in the compound is actually to promote the grafting rate of PC to the substrate and improve the grafting effect. Although it is generally believed that the higher the amino group content, the easier it is for PC to graft onto the substrate, relevant experiments have shown that after a certain amount of PC is grafted onto the substrate, it reaches "grafting saturation", 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 (4000-7000 Da), the amino-containing polymer can be uniformly grafted onto the substrate surface and achieve a good anticoagulant effect; however, if the substrate surface cannot be grafted with more amino-containing polymer, a certain space effect will occur, and the surface grafting and anticoagulant results will be poor. The technical solution of this application can achieve a wide range of molecular weight selection, which can better meet the use needs of characteristic polymers in the medical field.

[0033] A third aspect of the present invention provides an application of the above-mentioned amino group-containing polymer, wherein the amino group-containing polymer is used in a surface coating for blood-contact medical devices. Beneficial effects:

[0034] 1. This application provides an amino-containing polymer that can achieve selective design of the polymer's molecular weight, effectively improving the polymer's application in the field of blood-contact medical devices. A ternary random polymer obtained by copolymerizing appropriately proportioned 2-methacryloyloxyethyl phosphorylcholine, an acrylate monomer of amino hydrochloride, and an acrylamide monomer of amino hydrochloride can form a well-defined branched structure. 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 space; on the other hand, because 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 multiple biological activities.

[0035] 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 to 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

[0036] FIG1 is a graph showing the nuclear magnetic resonance data of the polymer prepared in Example 1 of the present application.

[0037] FIG2 is a data diagram showing the molecular weight test results of the polymer prepared in Example 1 of the present application.

[0038] FIG3 is a data diagram showing the molecular weight test results of the polymer prepared in Comparative Example 1 of the present application.

[0039] FIG4 is a data diagram showing the molecular weight test results of the polymer prepared in Comparative Example 2 of the present application.

[0040] FIG5 is a data diagram showing the molecular weight test results of the polymer prepared in Comparative Example 3 of the present application.

[0041] FIG6 is a data graph showing the results of quantitative fluorescence testing of amino groups of the polymer prepared in Example 1 of the present application.

[0042] FIG7 is a graph showing the test results of the anti-platelet adhesion of the polymer prepared in Example 1 of the present application.

[0043] FIG8 is a graph showing the NMR data of the polymer prepared in Comparative Example 4 of the present application. DETAILED DESCRIPTION

[0044] Example 1

[0045] 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 (an acrylate monomer of amino hydrochloride), and N-(3-aminopropyl) methacrylamide hydrochloride (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 3.5 with an acid solution, then removing water and oxygen, controlling the temperature under inert gas protection for 24 hours, and purifying the obtained product.

[0046] The reaction temperature in step (3) is 55°C.

[0047] The reaction solvent is methanol; the initiator is dimethyl azobisisobutyrate; and the acid solution is a methanol solution of phosphoric acid.

[0048] In step (1), the molar ratio of 2-methacryloyloxyethyl phosphorylcholine, 2-aminoethyl methacrylate hydrochloride and N-(3-aminopropyl) methacrylamide hydrochloride is 7:1:2.

[0049] The mass ratio of the total amount of monomers to the reaction solvent in step (1) is 10:60.

[0050] In step (3), the mass ratio of the initiator to the amino hydrochloride acrylate monomer is 1:99.

[0051] The mass ratio of the monomer mixture to the initiator solution in step (3) is 70:30.

[0052] The reaction yield was 89%.

[0053] In a second aspect, this embodiment provides a method for preparing an amino-containing terpolymer, wherein the obtained polymer has the structural formula:

[0054] Among them, the ratio of m / n / k is 7:1:2.

[0055] The peak molecular weight Mp of the polymer is 82615 Da, and the weight average molecular weight Mw is 78561 Da.

[0056] Example 2

[0057] The polymer prepared in Example 1 was coated on the surface of blood-contact medical devices and evaluated by anti-protein and anti-platelet adhesion experiments. The results showed that the polymer can improve the anti-protein adhesion and anti-platelet adhesion of the surface of blood-contact medical devices and improve blood compatibility.

[0058] Comparative Example 1

[0059] The specific implementation of Comparative Example 1 is the same as that of Example 1, except that: the three monomers are 2-methacryloyloxyethyl phosphorylcholine, 2-aminoethyl methacrylate hydrochloride (an acrylate monomer of amino hydrochloride) and N-(4-aminobutyl) methacrylamide hydrochloride (an 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%.

[0060] The structural formula of the obtained polymer is:

[0061] Among them, the ratio of m / n / k is 8:3:3.

[0062] The peak molecular weight Mp of the obtained polymer was 9370 Da, and the weight average molecular weight Mw was 11259 Da.

[0063] Comparative Example 2

[0064] 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 (an acrylate monomer of amino hydrochloride), and N-(5-aminopentyl) methacrylamide hydrochloride (an 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%.

[0065] The structural formula of the obtained polymer is:

[0066] Among them, the ratio of m / n / k is 8:1:1.

[0067] The peak molecular weight Mp of the obtained polymer was 4302 Da, and the weight average molecular weight Mw was 5442 Da.

[0068] Comparative Example 3

[0069] 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 (an acrylate monomer of amino hydrochloride) and N-(4-aminobutyl) methacrylamide hydrochloride (an 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 azobisisobutylamidine hydrochloride, and the reaction yield is 43%.

[0070] Among them, the ratio of m / n / k is 4:3:3.

[0071] The peak molecular weight Mp of the obtained polymer was 7073 Da, and the weight average molecular weight Mw was 7808 Da.

[0072] Comparative Example 4

[0073] 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 monomers (acrylic ester monomers 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 an acid solution, then removing water and oxygen, controlling the temperature under inert gas protection for 24 hours, and purifying the obtained product.

[0074] The reaction temperature in step (3) is 55°C.

[0075] The reaction solvent is methanol; the initiator is dimethyl azobisisobutyrate; and the acid solution is a methanol solution of phosphoric acid.

[0076] In step (1), the molar ratio of 2-methacryloyloxyethyl phosphorylcholine to 2-aminoethyl methacrylate hydrochloride is 8:2.

[0077] The mass ratio of the total amount of monomers to the reaction solvent in step (1) is 10:60.

[0078] In step (3), the mass ratio of the initiator to the amino hydrochloride acrylate monomer is 1:99.

[0079] The mass ratio of the monomer mixture to the initiator solution in step (3) is 50:1.

[0080] The reaction yield was 81%.

[0081] The second aspect of this comparative example provides a method for preparing an amino-containing binary polymer. The structural formula of the obtained polymer is:

[0082] Among them, the ratio of m / n is 8:2.

[0083] The weight average molecular weight Mw of the obtained polymer was 5042 Da.

[0084] Comparative Example 5

[0085] 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.

[0086] The weight average molecular weight Mw of the obtained polymer was 5017 Da.

[0087] Comparative Example 6

[0088] 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.

[0089] 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.

[0090] The weight average molecular weight Mw of the obtained polymer was 9563 Da.

[0091] Comparative Example 7

[0092] 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.

[0093] The weight average molecular weight Mw of the obtained polymer was 40,000 Da.

[0094] Performance Testing

[0095] 1. The results of nuclear magnetic resonance (NMR) testing, molecular weight, amino qualitative analysis, and anti-platelet adhesion testing of the polymer prepared in Example 1, as well as the NMR testing of the polymer prepared in Comparative Example 4, are shown in Figures 1, 2, 6, 7, and 8, respectively. NMR testing was performed using a Bruker 400M H-NMR.

[0096] 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 performed using GPC gel permeation chromatography.

[0097] 3.Amino content, platelet adhesion, platelet activation, and fibrinogen adsorption rate tests:

[0098] Qualitative amino group test: First, prepare a 3 mg / mL fluorescamine acetone solution and refrigerate in the dark. Then, accurately weigh the polymer from Example 1 and dissolve it in phosphate buffered saline (PBS) to create a 1 mg / mL polymer solution. Accurately pipette 1 mL of this polymer solution and add 3 mL of the fluorescamine acetone solution. Mix thoroughly and incubate at room temperature in the dark for 10 minutes. Finally, observe for fluorescence under 380 nm excitation light.

[0099] Amino group quantitative test: First, prepare a 3 mg / mL fluorescein acetone solution and refrigerate it in the dark for use. Subsequently, accurately weigh glycine and dissolve it in phosphate buffered saline (PBS) to make a 1 mg / mL glycine solution. Accurately pipette 1 mL of glycine solution, add it to 3 mL of fluorescein acetone solution, mix and shake well to use as the mother solution of the fluorescein-glycine reaction derivative. Subsequently, dilute the mother solution with PBS to 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 group content of different embodiments and comparative examples according to the standard curve.

[0100] 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. The PRP is removed after incubation at 37°C for 2 hours. According to the requirements of the kit (lactate dehydrogenase (LDH) activity detection kit, Solarbio / Solaibao), antibodies and developer for activating platelets are added, and the absorbance value at a wavelength of 450nm is measured using an enzyme reader. The platelet adhesion rates of different embodiments and comparative examples were tested and calculated according to the standard curve.

[0101] Quantitative testing of platelet activation rate: First, the amino-containing polymer prepared in this application was immobilized on the surface of a titanium sheet. A platelet-rich plasma (PRP) solution was then added. After incubation at 37°C for 2 hours, the PRP was removed. Antibodies and developer for platelet activation were added according to the kit (β-TG ELISA kit, mlbio / Enzyme-Linked Biology). The absorbance at the wavelength specified in the kit was measured using a microplate reader. The platelet activation rates of the various examples and comparative examples were tested and calculated based on the standard curve.

[0102] Fibrinogen (Fg) adsorption quantitative test: First, the amino-containing polymer prepared in this application was fixed to the surface of a titanium sheet, followed by the addition of a Fg solution. After incubation at 37°C for 2 hours, the Fg was removed. Fg antibodies and developer were added according to the kit (BCA protein quantification kit, Cwbio / Kangwei Century), and the absorbance at a wavelength of 562 nm was measured using a microplate reader. The fibrinogen adsorption rate of different examples and comparative examples was tested and calculated based on the standard curve.

[0103] The “ / ” in Table 1 indicates that no relevant tests were conducted. In Table 1, the platelet adhesion rate (%) data is prioritized for comparison. The amino content is a routine test item for the product and does not directly indicate the final application performance of the product.

[0104] Table 1

[0105] As can be seen from the Examples, Comparative Examples, and Table 1, the amino-containing ternary random polymer prepared by the preparation method provided herein, as shown in Example 1, exhibits excellent reactivity, anti-platelet adhesion, anti-platelet activation, and anti-fibrinogen adhesion capabilities. This facilitates stable and efficient chemical fixation to medical device surfaces, leveraging its anticoagulant advantages. Furthermore, due to its unique group structure, it can effectively graft anticoagulant drugs, endothelial cell-targeting peptides, and fluorescent dyes, thereby achieving multiple biological activities, making it suitable for promotion in the medical device field.

Claims

1. A polymer containing amino groups, 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.

2. The amino group-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.

3. A method for preparing an amino-containing polymer, characterized in that: The method 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 according to a proportion to obtain an initiator solution; (3) mixing the monomer mixture obtained in step (1) and the initiator solution obtained in step (2) according to a proportion, adjusting the pH value of the solution to 1-6 with an acid solution, then removing water and oxygen, controlling the temperature under the protection of an inert gas to react for 6-72 hours, and purifying to obtain an 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.

4. The method for preparing an amino-containing polymer according to claim 3, characterized in that: The reaction temperature in step (3) is 30-100°C.

5. The method for preparing an amino group-containing polymer according to claim 3, characterized in that: In the step (3), the mass ratio of the initiator to the amino hydrochloride acrylate monomer is 0.05-10:90-99.

5.

6. The method for preparing an amino group-containing polymer according to claim 3, characterized in that: In the step (3), the mass ratio of the monomer mixture to the initiator solution is 65-99:1-35.

7. The method for preparing an amino group-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.

8. The method for preparing an amino group-containing polymer according to claim 3, characterized in that: The initiator is a peroxide and / or an azo initiator.

9. The method for preparing an amino group-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.

10. A method for preparing an amino-containing polymer, characterized in that: The method 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 according to a proportion to obtain an initiator solution; (3) mixing the monomer mixture obtained in step (1) and the initiator solution obtained in step (2) according to a proportion, adjusting the pH value of the solution to 1-6 with an acid solution, then removing water and oxygen, controlling the temperature under the protection of an inert gas to react for 6-72 hours, and purifying to obtain an amino-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.

11. Use of the amino group-containing polymer according to claim 1 or 2, characterized in that: Application of the amino-containing polymer in surface coatings for blood-contact medical devices.

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