A degradable polymer against protein adsorption and a preparation method and application thereof

Abstract

The application discloses a degradable polymer with protein adsorption resistance, a preparation method of the degradable polymer and application of the degradable polymer in manufacturing protein adsorption resistant materials. Raw material composition of the degradable polymer comprises an initiator, a monomer and a double bond capping molecule. The degradable polymer is a block polymer capped by a carbon-carbon double bond functional group, and a forming process of the degradable polymer comprises: the monomer is subjected to a polymerization reaction under the action of the initiator or under the joint action of the initiator and a catalyst to obtain a first block polymer; and the first block polymer is subjected to a capping reaction with the double bond capping molecule. The initiator comprises at least one of polyethylene glycol with a hydroxyl group as an end group and n-arm polyethylene glycol, wherein n is greater than or equal to 3, and the number average molecular weight of the polyethylene glycol and the n-arm polyethylene glycol is independently 100-10000 g / mol. The mass proportion of the polyethylene glycol block in the degradable polymer is 5%-50%.

Description

TECHNICAL FIELD

[0001] The present application relates to the field of biomedical materials, and particularly relates to a degradable polymer with anti-protein adsorption and a preparation method and application thereof. BACKGROUND

[0002] Medical implants have played an important role in cardiovascular, orthopedics and other fields as a treatment method. However, after the foreign implants enter the body and contact with blood or body fluid, the protein in the blood or body fluid will be adsorbed on the surface of the implants in a very short time, so that the body's immune cells can recognize and trigger a series of foreign body reactions. Taking the blood vessel implant as an example, the plasma protein adsorption of the cardiovascular stent will occur in a few minutes after the implantation is completed, and these adhered plasma proteins will quickly recruit platelet adsorption and trigger a rapid coagulation reaction; further, a large number of platelet adsorption will recruit the adhesion and infiltration of white blood cells in the blood, thereby triggering subsequent inflammatory reactions (Torii, S., Jinnouchi, H., Sakamoto, A., et al. Drug-eluting coronary stents: insights from preclinical and pathology studies [J]. Nat Rev Cardiol: 2019, 17(1): 37-51). Therefore, the cardiovascular implant needs to be treated with long-term anticoagulation and anti-inflammatory therapy during the implantation process and after the implantation is completed. In addition, protein adsorption will cause the colonization of bacteria on the surface of the implant in the body, which will also cause the infection of the implant surface and even septicemia and other serious reactions. Therefore, the anti-protein adsorption function of the implant surface is very important.

[0003] Currently, in clinical applications, hydrophilic coatings with high hydration capacity (such as phosphocholine coatings, polyethylene glycol coatings, etc.) are an important method for achieving anti-protein adsorption on implant surfaces (Wang, Z., Schers, L., Xia, H., et al. Developments and Challenges in Self-Healing Antifouling Materials[J]. Advanced Functional Materials:2020,30(26):1908098). Among them, polyethylene glycol (PEG) molecular brush technology has been widely studied and used to prepare hydrophilic anti-protein adsorption surfaces. PEG forms a hydration layer on the material surface through its excellent hydrophilicity and strong water-binding ability, thereby preventing the non-specific adhesion of proteins, platelets, bacteria, etc. However, the performance of this anti-protein adsorption surface based on molecular brush technology is highly dependent on the modification density and uniformity of the molecular brush. Only molecular brush coatings with high grafting density, close arrangement, and uniform distribution can achieve antifouling effect. Any tiny defects on the material surface may cause the design of the antifouling coating to fail. Therefore, in research, achieving high-density fabrication of PEG molecular brush coatings on material surfaces often requires complex physical and chemical modifications to the substrate material. These modification methods increase the preparation cost of the anti-protein adsorption coating and are not applicable to most chemically inert polymer materials. Furthermore, when these highly hydrating materials are used as bulk materials, their strong hydrophilicity often results in the formation of hydrogels, which have weak mechanical strength and toughness, severely limiting their use as functional implants in vivo. Therefore, developing a simple, widely applicable, and mechanically tunable anti-protein adsorption bulk material and surface coating material and technology remains a significant technological bottleneck. Summary of the Invention

[0004] To address the aforementioned technical problems and shortcomings in the field, this invention provides a degradable polymer resistant to protein adsorption, its preparation method, and its application.

[0005] The specific technical solution is as follows:

[0006] [1] A degradable polymer that resists protein adsorption, wherein the raw material composition of the degradable polymer includes an initiator, a monomer and a double-bonded end-capped molecule.

[0007] The biodegradable polymer is a block polymer with carbon-carbon double bond functional groups at the end. Its formation process includes: 1) the monomer undergoes a polymerization reaction under the action of the initiator or under the combined action of the initiator and the catalyst to obtain a first block polymer; 2) the first block polymer undergoes a capping reaction with the double bond-capped molecule.

[0008] The initiator includes at least one of polyethylene glycol with a hydroxyl end group, n-armed polyethylene glycol, n≥3, and the number average molecular weight of the polyethylene glycol and the n-armed polyethylene glycol is independently 100-10000 g / mol, preferably 800-4000 g / mol, such as 1000 g / mol, 2000 g / mol, etc., in consideration of synthesis performance and processing capacity, in order to balance excellent protein adsorption resistance.

[0009] The mass fraction of the polyethylene glycol block in the degradable polymer is 5%-50%, preferably 8%-40%, such as 10% and 30%, etc. Such strict molecular structure ratio setting mainly considers two factors: 1. As a protein adsorption resistant material / coating, the coverage degree of the hydrated PEG chain has a greater impact on the performance of the material. If the PEG content is too low, the hydrated layer cannot completely cover the surface of the material / coating, which will cause the material / coating to fail; 2. However, when the PEG content is too high, the overall material is in a highly water-absorbed state in the underwater environment due to strong hydrophilicity, the PEG molecular chain is straightened due to swelling and loses the structure of close packing, and cannot effectively resist protein adsorption (as shown in the attached Figure 1

[0010] The monomer includes at least one of glycolide, L-lactide, rac-lactide, glycolic acid, lactic acid, ε-caprolactone, 1,4-dioxane-2-ketone, trimethylene carbonate, and polyhydroxyalkanoate.

[0011] The double bond capping molecule includes at least one of methacryloyl chloride, ethyl acryloyl chloride, and isocyanatoethyl methacrylate.

[0012] The catalyst can include at least one of stannous octoate and dibutyltin dilaurate.

[0013] The amount of the catalyst can be 0.01%-0.5% of the total mass of the monomer and the initiator.

[0014] The reaction temperature of the polymerization reaction and the capping reaction can be independently 120-160°C.

[0015] The reaction time of the polymerization reaction can be 1-10 h.

[0016] To ensure the capping degree of the carbon-carbon double bond, considering the chemical reactivity of different capping groups, the amount of the double bond capping molecule can be 1.1-3 times the molar amount of the hydroxyl group in the initiator.

[0017] ​The polymerization reaction can be ring-opening polymerization, direct polycondensation, etc. The ring-opening polymerization is the polymerization of a cyclic monomer after ring-opening under the action of an initiator or an initiator and a catalyst; the direct polycondensation is the reaction of generating a polymer through repeated condensation reactions between bifunctional and / or multifunctional monomers, including melt polycondensation, solution polycondensation, interfacial polycondensation, solid-phase polycondensation, etc.

[0018] [2] The preparation method of the degradable polymer according to [1], comprising the steps of:

[0019] S1, polymerization of the monomer under the action of the initiator or under the joint action of the initiator and a catalyst to obtain a first block polymer;

[0020] S2, end-capping reaction of the first block polymer with the double bond end-capping molecule.

[0021] [3] The application of the degradable polymer according to [1] in making a protein adsorption-resistant material.

[0022] The degradable polymer can be applied to various purposes such as bulk materials and coating materials when making a protein adsorption-resistant material. For example, when used in bulk materials, the product with a specific shape can be obtained through conventional polymer processing methods such as molding, extrusion, injection molding, casting and 3D printing, and the cross-linkable carbon-carbon double bonds at both ends of the molecules can be internally cross-linked through heating or ultraviolet method to ensure the chemical stability of the product; for the requirement of application in coating, different coating methods can be selected to coat the mixed solution containing the degradable polymer on the surface of the material, and the coating methods include but are not limited to ultrasonic atomization spraying, solution dipping, spin coating, etc. The thickness of the mixed solution coated on the surface of the material can be 0.1-50 μm.

[0023] The mechanism of the degradable polymer according to the application in resisting protein adsorption and pollution and in making a protein adsorption-resistant material is as follows: the multi-block polymer is composed of hydrophilic PEG segments and hydrophobic segments, after forming a material / coating and ultraviolet cross-linking, the polymer forms a phase-separated structure on the surface of the material / coating, the hydrophilic PEG segments are stably exposed on the surface and form a firm hydration layer on the surface through hydrogen bonding, thereby hindering the adhesion of proteins, platelets and bacteria on the surface of the material / coating.

[0024] [4] A protein adsorption-resistant material comprising the degradable polymer according to [1].

[0025] The protein adsorption-resistant material can comprise a protein adsorption-resistant coating. Further, the protein adsorption-resistant coating can comprise the degradable polymer.

[0026] [5] The preparation method of the protein adsorption-resistant material according to [4], comprising:

[0027] The degradable polymer and the free radical initiator are dissolved in a solvent to obtain a mixed solution, the mixed solution is crosslinked and cured by ultraviolet and / or heating to obtain the protein adsorption resistant material.

[0028] The solvent can include at least one of dichloromethane, trichloromethane, hexafluoroisopropanol, ethyl acetate, acetone.

[0029] In the mixed solution, the mass fraction of the degradable polymer can be 0.1% to 50%.

[0030] The free radical initiator can include at least one of a thermal initiator and a photoinitiator, and specifically includes at least one of azobisisobutyronitrile (AIBN), benzoyl peroxide (BPO), benzophenone (BP), and I2959.

[0031] The amount of the free radical initiator can be 0.1% to 5% of the mass of the degradable polymer.

[0032] Compared with the prior art, the present application has the following beneficial effects:

[0033] a) The present application strictly limits the molecular weight of polyethylene glycol (PEG) and the content of polyethylene glycol block in the overall molecule: the number average molecular weight of PEG is 800-4000 g / mol, and the mass of PEG is 8%-40% of the total mass of the overall polymer; and the free radical initiator is used to initiate the formation of cross-linked polymer material at the carbon-carbon double bond end group. This unique molecular structure ensures that polyethylene glycol is uniformly distributed between each hydrophobic cross-linking point and forms an orderly and compact stacking structure, thereby significantly improving the anti-fouling ability. Based on this unique molecular structure design, the protein adsorption resistant material prepared by the present application can achieve a protein adsorption amount less than or equal to that of a pure hydrophilic molecule closely arranged material with a very small amount of polyethylene glycol, thereby ensuring excellent processability and mechanical properties of the bulk material. It should be noted that the present application focuses on limiting the specific molecular weight and content of polyethylene glycol, rather than the material synthesis method. Any other method for preparing this type of block copolymer is within the scope of the present application.

[0034] b) Compared with the traditional two-block copolymer based on polyethylene glycol monomethyl ether, the present application strictly limits PEG to be in the middle position of the hydrophobic segment in the material configuration. The unique molecular structure design of the present application ensures that the PEG segment has a more regular arrangement configuration and entropy elasticity in the underwater environment, and therefore has significantly superior protein adsorption resistance performance than the same mass ratio of two-block copolymer (as shown in the accompanying drawings). Figure 2

[0035] ​c) The anti-protein adsorption polymer material obtained by the present application has good processability, and the bulk material can be obtained by molding, extrusion, injection molding, casting and 3D printing, and the anti-adsorption coating can also be prepared by dipping, spraying and other processing methods, so its applicability is much greater than that of most anti-protein adsorption materials on the market. BRIEF DESCRIPTION OF DRAWINGS

[0036] Figure 1 Figure for the influence of different PEG contents on the anti-plasma protein adsorption performance of the material;

[0037] Figure 2 Figure for the anti-plasma protein adsorption performance comparison of two-block and three-block polymer materials;

[0038] Figure 3 Figure for the anti-platelet adhesion performance comparison of the TPU base material, the coating of Comparative Example 1 and the coating of Example 1;

[0039] Figure 4 Figure for the comparison of bacterial adhesion on the surface of the TPU base material and the PCEC208 coating;

[0040] Figure 5 Figure for the cell adhesion on the surface of the TPU base material and the anti-cell adhesion material PLEL210. DETAILED DESCRIPTION

[0041] The present application will be further described below in conjunction with the drawings and specific examples. It should be understood that these examples are only used to illustrate the present application and not to limit the scope of the present application.

[0042] Unless otherwise specified, the unit of molecular weight is g / mol.

[0043] Example 1

[0044] Preparation of PLA-PEG-PLA-110 (PLEL110) degradable anti-protein adsorption material and coating

[0045] (1) Synthesis of double bond end-capped block polymer:

[0046] A 1L glass reaction kettle was vacuum dried at 80℃ for 1h, and 5g of polyethylene glycol with a number average molecular weight of 1000 was dried under vacuum at 120℃ for 2h under nitrogen protection. Then 45g of mixed racemic lactide was added to the reaction kettle under nitrogen protection, 50mg of stannous octoate was added, the temperature was increased to 150℃, and the reaction was carried out at 150℃ under nitrogen protection for 5h, then 0.1g of polymerization inhibitor 4-methoxyphenol was added, and after uniform stirring for 30min, 1.6g of isocyanatoethyl methacrylate was added by dropwise addition, to obtain a double bond end-capped block polymer (PLEL-110) with a number average molecular weight of about 10000.

[0047] (2) Preparation of the biorepelling coating:

[0048] PLEL110 obtained in step (1) was dissolved in dichloromethane, and a photoinitiator BP was added to prepare a mixed solution. The mass fraction of PEL110 in the mixed solution was 20%, and the mass fraction of the photoinitiator BP was 0.2%. A coating with a thickness of 10 μm was prepared by using the dip-coating technique. Subsequently, the coating was crosslinked by using the ultraviolet irradiation method, the irradiation light intensity was 50 mW / cm 2 , and the irradiation time was 3 min.

[0049] According to the synthesis steps and coating preparation method of Example 1, the mass of PEG was kept at 5 g, and 95 g, 45 g, 11.7 g and 5 g of racemic lactide were respectively added to the reaction kettle to obtain the biodegradable polymer coating with the mass ratio of polyethylene glycol block being 5%, 10%, 30% and 50%. The anti-plasma protein adsorption performance of the polymer coating was tested by using a quartz crystal microbalance (QCM), and the results are shown in Table 1. The biodegradable polymer with the mass ratio of polyethylene glycol block being 10% has the best anti-protein adsorption performance. Figure 1

[0050] Comparative Example 1

[0051] Preparation of PEG-PLA-110 (PEL110) two-block biodegradable anti-protein adsorption material and coating

[0052] (1) Synthesis of double bond end-capped block polymer:

[0053] A 1L glass reaction kettle was vacuum dried at 80°C for 1h, and 5g of polyethylene glycol monomethyl ether with a number average molecular weight of 1000 was dried under vacuum at 120°C for 2h under nitrogen protection. Then 45g of racemic lactide was added to the reaction kettle under nitrogen protection, 50mg of stannous octoate was added, the temperature was increased to 150°C, and the reaction was carried out at 150°C under nitrogen protection for 5h. Then 0.1g of polymerization inhibitor 4-methoxyphenol was added, and after uniform stirring for 30min, 0.8g of isocyanatoethyl methacrylate was added by dropwise addition to obtain a double bond end-capped block polymer (PEL-110) with a number average molecular weight of about 10000.

[0054] (2) Preparation of the biorepelling coating:

[0055] PEL110 obtained in step (1) was dissolved in dichloromethane, and a photoinitiator BP was added to prepare a mixed solution. The mass fraction of PEL110 in the mixed solution was 20%, and the mass fraction of the photoinitiator BP was 0.2%. A coating with a thickness of 10 μm was prepared by using the dip-coating technique. Subsequently, the coating was crosslinked by using the ultraviolet irradiation method, the irradiation light intensity was 50 mW / cm​2 irradiation time 3 min.

[0056] The anti-plasma protein adhesion performance of the coating materials of Example 1 and Comparative Example 1 was tested using QCM, and the results are shown in Table 1. Figure 2 As shown in Table 1, the plasma protein adsorption amount of the coating surface of Example 1 was significantly lower than that of the coating material of Comparative Example 1.

[0057] The control substrate (TPU), the coating material of Example 1 and the coating material of Comparative Example 1 were respectively co-imposed with platelet-rich plasma for 2 h, and then after washing, fixing, ethanol dehydration and gold spraying treatment, the adhered platelets on the surface were observed by scanning electron microscopy (SEM). Figure 3 The left, middle and right are SEM images of platelet adhesion on the surfaces of the control substrate (TPU), the coating of Comparative Example 1 and the coating of Example 1, respectively. It can be seen that the control TPU substrate has a relatively significant platelet adsorption, the platelet adhesion on the coating of Comparative Example 1 has a certain decrease, and the coating surface of Example 1 has no platelet adhesion at all, which proves that the coating of Example 1 has more excellent anti-protein adsorption and cell adhesion performance compared with the coating of Comparative Example 1.

[0058] Example 2

[0059] Preparation of PCL-PEG-PCL-208 (PCEC208) degradable anti-protein adsorption material

[0060] (1) Synthesis of double bond terminated block polymer:

[0061] A 1L glass reaction kettle was vacuum dried at 80°C for 1h, and 20g of polyethylene glycol with a number average molecular weight of 2000 was dried under vacuum at 80°C for 2h under nitrogen protection. Then 60g of ε-caprolactone was added to the reaction kettle under nitrogen protection, and the temperature was raised to 120°C. Then 30mg of stannous octoate was added under nitrogen protection, the temperature was increased to 140°C, and the reaction was carried out at 140°C under nitrogen protection for 4h, then 50mg of polymerization inhibitor 4-methoxyphenol was added, and after uniform stirring for 30min, 3.5g of isocyanatoethyl methacrylate was added dropwise to obtain a double bond terminated block polymer (PCEC208) with a number average molecular weight of about 5000.

[0062] (2) Preparation of biological anti-fouling coating:

[0063] The PCEC208 obtained in step (1) was dissolved in ethyl acetate, and a photoinitiator I2959 was added to prepare a mixed solution. The mass fraction of PCEC208 in the mixed solution was 5%, and the mass fraction of photoinitiator I2959 was 0.05%. An ultrasonic spraying technology was used to prepare a coating, and the obtained coating had a thickness of 10μm. Subsequently, the coating was crosslinked by ultraviolet irradiation, and the irradiation light intensity was 50mW / cm2 irradiation time 5 min.

[0064] The substrate material of Example 2 and the coating material of Example 2 were incubated with gram-positive bacteria S. aureus (S.a) and gram-negative bacteria P. aeruginosa (P.a) respectively for 4h, and then washed and dyed with a bacterial live-dead dye. Figure 4 is the amount of bacterial adhesion on the surface of the substrate material TPU and the bio-antifouling coating PCEC208 of Example 2, and it can be found that there is almost no bacterial adhesion on the surface of the coating.

[0065] Example 3

[0066] Preparation of PLA-PEG-PLA-210 (PLEL210) biodegradable anti-protein adsorption material

[0067] (1) Synthesis of double bond terminated block polymer:

[0068] A 1L glass reactor was vacuum dried at 80℃ for 1h, and 20g of polyethylene glycol with a number average molecular weight of 2000 was dried under vacuum at 120℃ for 2h under nitrogen protection. Then 80g of racemic lactide was added to the reactor and vacuum dried at 120℃ for 1h. Then 80mg of stannous octoate was added, the temperature was increased to 150℃, and the reaction was carried out at 150℃ under nitrogen protection for 6h. Then 0.5g of polymerization inhibitor 4-methoxyphenol was added, and after uniform stirring for 30min, 3.5g of isocyanatoethyl methacrylate was added by dropwise addition to obtain a double bond terminated block polymer with a number average molecular weight of about 10000.

[0069] (2) Preparation of anti-cell adhesion material:

[0070] PLEL210 obtained in step (1) was dissolved in dichloromethane, and a photoinitiator I2959 was added to prepare a mixed solution. The mass fraction of PLEL210 in the mixed solution was 20%, and the mass fraction of the photoinitiator was 0.2%. A thin film material was prepared by using a solution casting technique, and then the coating was crosslinked by ultraviolet light irradiation, with an irradiation light intensity of 50mW / cm 2 irradiation time 5 min.

[0071] Live cell-stained endothelial cells (EC), smooth muscle cells (SMC), mouse embryonic cells (3T3) and macrophages (THP-1) were inoculated on the substrate material of Example 3 and the material of Example 3 respectively, and observed by fluorescence microscopy after incubation for 8h. Figure 5 is the amount of cell adhesion on the surface of the substrate material TPU and the anti-cell adhesion material PLEL210 of Example 3, and it can be found that PLEL210 material significantly reduces the adhesion of different types of cells, which provides a good foundation for reducing inflammatory response after material implantation.

[0072] Example 4

[0073] Preparation of PLA-PEG-PLA-105 (PLEL105) degradable anti-protein adsorption material

[0074] A 1L glass reactor was vacuum dried at 80°C for 1h, and 10g of polyethylene glycol with a number average molecular weight of 1000 was dried under vacuum at 120°C for 2h under nitrogen protection. Then 40g of mixed racemic lactide was added to the reactor, and vacuum drying was continued at 120°C for 1h. Then 50mg of stannous octoate was added, the temperature was increased to 150°C, and the reaction was carried out at 150°C under nitrogen protection for 3h. Then 0.5g of polymerization inhibitor 4-methoxyphenol was added, and after uniform stirring for 30min, 3.5g of isocyanatoethyl methacrylate was added dropwise to obtain a double bond capped block polymer (PLEL105) with a number average molecular weight of about 5000.

[0075] Example 5

[0076] Preparation of PLGA-PEG-PLGA-108 (PLGELG-108) degradable anti-protein adsorption material

[0077] A 1L glass reactor was vacuum dried at 80°C for 1h, and 10g of polyethylene glycol with a number average molecular weight of 1000 was dried under vacuum at 120°C for 2h under nitrogen protection. Then 35g of L-lactide and 50mg of stannous octoate were added, the temperature was increased to 150°C, and the reaction was carried out at 150°C under nitrogen protection for 1h. Then 35g of glycolide was added to the reactor, and the temperature was increased to 160°C, and the reaction was continued under nitrogen protection for 3h. Then 0.2g of polymerization inhibitor 4-methoxyphenol was added, and after uniform stirring for 30min, 3.5g of isocyanatoethyl methacrylate was added dropwise to obtain a double bond capped block polymer (PLGELG-108) with a number average molecular weight of about 8000.

[0078] Example 6

[0079] Preparation of PTMC-PEG-PTMC-212 (PTET-212) degradable anti-protein adsorption material

[0080] A 1 L glass reactor was vacuum dried at 80 °C for 1 h, and 20 g of polyethylene glycol with a number average molecular weight of 2000 was dried under vacuum at 120 °C for 2 h under nitrogen protection. Then 100 g of trimethylene carbonate was added to the reactor under nitrogen protection, 0.1 g of stannous octoate was added, the temperature was increased to 150 °C, and the reaction was carried out at 150 °C under nitrogen protection for 5 h. Then 0.2 g of the polymerization inhibitor 4-methoxyphenol was added, and after uniform stirring for 30 min, 3.5 g of isocyanatoethyl methacrylate was added dropwise to obtain a double bond-capped block polymer (PTET-212) with a number average molecular weight of about 12000.

[0081] Example 7

[0082] Preparation of a PLCL-PEG-PLCL-112 (PLCELC-112) degradable anti-protein adsorption material

[0083] A 1 L glass reactor was vacuum dried at 80 °C for 1 h, and 10 g of polyethylene glycol with a number average molecular weight of 1000 was dried under vacuum at 120 °C for 2 h under nitrogen protection. Then 55 g of racemic lactide and 55 g of ε-caprolactone were added to the reactor under nitrogen protection, 0.1 g of stannous octoate was added, the temperature was increased to 150 °C, and the reaction was carried out at 150 °C under nitrogen protection for 5 h. Then 0.2 g of the polymerization inhibitor 4-methoxyphenol was added, and after uniform stirring for 30 min, 3.5 g of isocyanatoethyl methacrylate was added dropwise to obtain a double bond-capped block polymer (PLCELC-112) with a number average molecular weight of about 12000.

[0084] Example 8

[0085] Preparation of a PPDO-PEG-PPDO-420 (PDED-420) degradable anti-protein adsorption material

[0086] A 1 L glass reactor was vacuum dried at 80 °C for 1 h, and 40 g of polyethylene glycol with a number average molecular weight of 4000 was dried under vacuum at 120 °C for 2 h under nitrogen protection. Then 160 g of 1,4-dioxane-2-one was added to the reactor under nitrogen protection, 0.5 g of stannous octoate was added, the temperature was increased to 140 °C, and the reaction was carried out at 140 °C under nitrogen protection for 4 h. Then 0.5 g of the polymerization inhibitor 4-methoxyphenol was added, and after uniform stirring for 30 min, 3.5 g of isocyanatoethyl methacrylate was added dropwise to obtain a double bond-capped block polymer (PDED-420) with a number average molecular weight of about 20000.

[0087] It is to be understood that even though numerous characteristics and embodiments of the application have been set forth in the foregoing disclosure, the details can be varied without departing from the application, which is defined by the claims.

Claims

1. Use of a degradable polymer resistant to protein adsorption for the manufacture of a material resistant to protein adsorption, characterized in that, The preparation method of the anti-protein adsorption material comprises the following steps: dissolving the degradable polymer and the free radical initiator in a solvent to obtain a mixed solution, crosslinking and curing by ultraviolet and / or heating to obtain the anti-protein adsorption material. The raw material composition of the degradable polymer comprises an initiator, a monomer and a double bond capping molecule. The degradable polymer is a carbon-carbon double bond functional group capped block polymer, and the forming process comprises the following steps: 1) the monomer is polymerized under the action of the initiator or under the joint action of the initiator and a catalyst to obtain a first block polymer; 2) the first block polymer is subjected to capping reaction with the double bond capping molecule. The initiator comprises at least one of polyethylene glycol with a terminal hydroxyl group and n-arm polyethylene glycol, wherein n is greater than or equal to 3, and the number average molecular weight of the polyethylene glycol and the n-arm polyethylene glycol is independently 800-4000 g / mol. The mass fraction of the polyethylene glycol block in the degradable polymer is 8%-40%. The monomer comprises at least one of glycolide, L-lactide, meso-lactide, glycolic acid, lactic acid, ε-caprolactone, 1,4-dioxane-2-ketone and trimethylene carbonate. The double bond capping molecule comprises at least one of methacryloyl chloride, ethyl acryloyl chloride and isocyanatoethyl methacrylate.

2. Use according to claim 1, characterized in that, The catalyst comprises at least one of stannous octoate and dibutyltin dilaurate. The amount of the catalyst is 0.01%-0.5% of the total mass of the monomer and the initiator.

3. Use according to claim 1, characterized in that, The reaction temperature of the polymerization reaction and the capping reaction is independently 120-160 DEG C. The reaction time of the polymerization reaction is 1-10 h.

4. Use according to claim 1, characterized in that, The amount of the double bond capping molecule is 1.1-3 times the molar amount of the hydroxyl group in the initiator.

5. The use according to claim 1, characterized in that, The anti-protein adsorption material comprises an anti-protein adsorption coating. The anti-protein adsorption coating comprises the degradable polymer.

6. Use according to claim 1, characterized in that, The solvent comprises at least one of dichloromethane, trichloromethane, hexafluoroisopropyl alcohol, ethyl acetate and acetone. In the mixed solution, the mass fraction of the degradable polymer is 0.1%-50%. The free radical initiator comprises at least one of a thermal initiator and a photoinitiator. The amount of the free radical initiator is 0.1%-5% of the mass of the degradable polymer.

7. Use according to claim 6, characterized in that, The free radical initiator comprises at least one of azobisisobutyronitrile, benzoyl peroxide, benzophenone and I2959.

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